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Background Patients on dialysis are at higher risk of major bleeding and recurrent thrombosis creating acute venous thromboembolism (VTE) treatment challenges. DOACs represent an interesting option but there are concerns of bioaccumulation and increased bleeding risk. Anti-Xa trough levels may be used to monitor for bioaccumulation but there is little data. Case presentation We describe a case, a 51 yo female, 36 kg on hemodialysis with a provoked acute upper extremity deep vein thrombosis in whom body habitus and calciphylaxis contraindicated the use of standard therapy. She received apixaban 2.5 mg twice daily for 6 weeks. The apixaban anti-Xa trough levels were measured weekly 12 h after the morning dose and ranged from 58 to 84 ng/mL, similar to expected levels with normal renal function. There were no adverse events in the 3 months follow-up. Conclusions We saw no evidence of bioaccumulation indicating a potential role for low dose apixaban for acute VTE in dialysis patients.

Shimaa A Ahmed,1 Ghada EM Abdallah,2 Mai M Aly,2 Eman M Nagiub Abdelsalam,3 Mostafa F Mohammed Saleh2 1Department of Internal Medicine, Faculty of Medicine, South Valley University, Qena, Egypt; 2Clinical Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, EgyptCorrespondence: Mostafa F Mohammed Saleh Tel +201013701057Fax +2088-2332278-2080278Email mostafafaisal2017@yahoo.comIntroduction: A positive direct antiglobulin test (DAT) with or without autoimmune hemolytic anemia is a frequent finding in chronic lymphocytic leukemia (CLL). The heterogenic clinical course of CLL mainly depends on different pathogenetic mechanisms which appears in a form of variable biological and clinical features. These features allow stratification of patients into subsets with different outcomes.Patients and Methods: We evaluated the DAT as a prognostic marker in 120 CLL patients treated with chemoimmunotherapy. Clinical and laboratory features, treatment response, and survival outcomes of CLL patients were assessed in relation to their DAT test status. Additionally, the English literature was extensively reviewed regarding the prognostic impact of a positive DAT in CLL.Results: DAT positivity was detected in 36 patients (30%) and was associated advanced disease staging (P = 0.03). No correlations were found with other clinical, laboratory, or biological factors such as ZAP-70 or CD38. Both a positive DAT and an Eastern Cooperative Oncology Group performance status > 2 were predictors for non-response to first-line treatment in the multivariate analysis (OR = 0.3, 95% CI: 0.12– 0.8 and OR = 0.2, 95% CI: 0.08– 0.8, respectively). The five-year progression-free survival was significantly lower in the DAT-positive group (P = 0.004). No significant association was found with overall survival (P = 0.2). Sixteen reports analyzing more than 11,000 patients were identified in our review.Conclusion: In conclusion, DAT positivity in CLL patients is associated with poor response to treatment and disease progression.Keywords: autoimmunity, chronic lymphocytic leukemia, direct antiglobulin test, autoimmune hemolytic anemia

Tubagus Djumhana Atmakusuma, Anna Mira Lubis Division of Hematology-Medical Oncology, Department of Internal Medicine, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Tubagus Djumhana AtmakusumaDivision of Hematology-Medical Oncology, Department of Internal Medicine, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jalan Diponegoro No. 71, Jakarta Pusat, DKI, Jakarta, IndonesiaTel +622 13162497Email hom_fkui@yahoo.comIntroduction: Iron overload is a common feature of thalassemia intermedia due to regular blood transfusion and increased gastrointestinal iron absorption. Early detection and adequate iron chelator can decrease morbidity and mortality from iron overload. Liver iron concentration (LIC) by MRI T2* is the best non-invasive way to measure body iron stores. However, this method is expensive and not available nationwide in Indonesia. The aim of this study was to identify liver iron overload and correlation of transferrin saturation, serum ferritin, liver MRI T2* and LIC with transient liver elastography in adult thalassemia intermedia patients.Methods: This is a cross-sectional study of 45 patients with thalassemia intermedia with blood transfusion and with and without iron chelator therapy. The study was conducted at Cipto Mangunkusumo Hospital from August through October 2016. We performed measurements of transferrin saturation, serum ferritin level, transient liver elastography and liver MRI T2*. Pearson and Spearman correlation tests were used to evaluate the correlation between transient liver elastography with transferrin saturation, serum ferritin, liver MRI T2*and LIC.Results and Discussion: This study showed that 64.4% of study subjects are β-Hb E thalassemia intermedia. Furthermore, 84.4% of study subjects have regular transfusion. Based on liver MRI T2*all subjects suffered from liver iron overload, 48.9% had severe degree. Median value of liver MRI T2* was 1.6 ms. Mean serum ferritin was 2831 ng/mL, with median transferrin saturation of 66%. Mean of LIC corresponding to liver MRI T2* and mean liver stiffness measurement was 15.36± 7.37 mg Fe/gr dry weight and 7.7± 3.8 kPa, respectively. Liver stiffness correlated with serum ferritin (r=0.651; p=0.000), liver MRI T2* (r=− 0.357; p=0.016), and LIC (r=0.433; p=0.003). No correlation was found between liver elastography and transferrin saturation (r=0.204; p=0.178).Conclusion: Serum ferritin, liver MRI T2*and LIC correlated with liver elastography. No correlation was found between transferrin saturation and liver elastography.Keywords: liver MRI T2*, LIC, serum ferritin, thalassemia intermedia, transient liver elastography

Richard Gooding,1 Jecko Thachil,2 Jayanthi Alamelu,3 Jayashree Motwani,4 Pratima Chowdary5 1Leicester Haemophilia Centre, Haemostasis & Thrombosis Unit, Leicester Royal Infirmary, Leicester, UK; 2Haematology Department, Manchester Royal Infirmary, Manchester, UK; 3Haemophilia Department, Evelina Children’s Hospital – St Thomas’ Hospital, London, UK; 4Haemophilia Comprehensive Care Centre, Birmingham Children’s Hospital, Birmingham, UK; 5Katharine Dormandy Haemophilia Centre, Royal Free Hospital, London, UKCorrespondence: Richard GoodingLeicester Haemophilia Centre, Haemostasis & Thrombosis Unit, Level 2, Osborne Building, The Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UKTel +44 116 258 6500Fax +44 116 258 6120Email richard.gooding@uhl-tr.nhs.ukAbstract: Joint health is a key contributor to quality of life in patients with hemophilia. However, variables that impact long-term joint outcomes have not been comprehensively defined. A systematic literature search identified publications relating to joint health in patients with hemophilia. Studies clearly show that early, sustained prophylaxis with factor replacements improves long-term joint outcomes. However, a subset of patients appear to develop arthropathy despite maintaining excellent bleeding outcomes, which suggests possible recurrent asymptomatic bleeding into the joints in these patients. Furthermore, limited data are available on how long-acting factor VIII and factor IX replacement therapies could impact long-term joint outcomes. Many variables were identified as potential indicators that a patient may develop hemophilic arthropathy, including genetic mutations, endogenous factor VIII and IX levels, bone health, and physical activity levels. Tools for the diagnosis and monitoring of hemophilic arthropathy are critical to detect early joint damage, so that management can be adjusted accordingly. Imaging techniques, particularly magnetic resonance imaging, can detect synovial changes, a strong predictor for the future development of hemophilic arthropathy. In addition, several biomarkers associated with cartilage and bone formation, vascularization, and angiogenesis could potentially identify the onset and progression of early joint damage. Since the development of hemophilic arthropathy is complex, a comprehensive therapeutic approach is necessary for the effective prevention of arthropathy in patients with hemophilia.Keywords: hemophilia, asymptomatic bleeding, joint disease, hemarthrosis, hemophilic arthropathy, hemarthropathy

BackgroundThe purpose of this study is to elucidate the association between peripherally inserted central venous catheter (PICC) in upper extremities and lower extremity deep venous thrombosis (LEDVT) by observing the changes in D-dimer.MethodsThis was a retrospective cohort study with 3452 patients (104 inserted with PICCs and 3348 without PICC) enrolled at the neurology department from April 1, 2017 to April 1, 2020. The patients underwent color Doppler ultrasound (CDU) and D-dimer examinations. LEDVT-related factors and D-dimer value were analyzed before and after PICC insertion. The predictive value of D-dimer for LEDVT was also evaluated.ResultsUnivariate logistic regression analysis showed that PICC insertion increased the risk of LEDVT by 9 times and promoted the increase of D-dimer by 5 times. After risk adjustment, multivariate logistic regression analysis showed that PICC insertion increased the risk of LEDVT by 4 times and tripled the risk of D-dimer increase. The concentration of D-dimer was significantly increased after PICC insertion. D-dimer was unsuitable for excluding venous thrombosis in patients inserted with PICCs.ConclusionsPICC insertion increases the level of D-dimer and the risk of LEDVT. The risks of venous thrombosis need to be assessed in patients inserted with PICCs to ensure the expected clinical outcomes.

Jackie M Helms,1 Kristin T Ansteatt,1 Jonathan C Roberts,1,2 Sravani Kamatam,3 Kap Sum Foong,2,3 Jo-mel S Labayog,4 Michael D Tarantino1,2 1The Bleeding and Clotting Disorders Institute, Peoria, IL, USA; 2Department of Medicine, University of Illinois College of Medicine-Peoria, Peoria, IL, USA; 3Department of Medicine, Saint Francis Medical Center, Peoria, IL, USA; 4Department of Medicine, OSF Sacred Heart Medical Center, Danville, IL, USACorrespondence: Michael D TarantinoChief Medical Officer, The Bleeding and Clotting Disorders Institute, 9128 North Lindbergh Drive, Peoria, IL, 61615, USATel +1 309 692-5337Fax +1 309 693-3913Email mtarantino@ilbcdi.orgAbstract: The rollout of the SARS-CoV-2 vaccine is underway, and millions have already been vaccinated. At least 25 reports of “immune thrombocytopenia” (ITP) or “thrombocytopenia” following the Moderna or Pfizer vaccine have been added to the Vaccine Adverse Event Reporting System (VAERS) in the US. ITP is a rare but known complication of several vaccinations. SARS-CoV-2 vaccine is new, with a novel mechanism of action, and understanding the epidemiology, clinical manifestations, treatment success and natural history of post-vaccination thrombocytopenia is evolving. We report a 74-year-old man who developed refractory thrombocytopenia within one day of receiving the Moderna SARS-CoV-2 vaccine. Several hours after vaccination, he developed significant epistaxis and cutaneous purpura. Severe thrombocytopenia was documented the following day, and he developed extremity weakness and encephalopathy with facial muscle weakness. Over a 14-day period, thrombocytopenia was treated first with high dose dexamethasone, intravenous immunoglobulin, platelet transfusions, rituximab, plasma exchange (for presumed acute inflammatory demyelinating polyneuropathy (AIDP)), and four daily doses of the thrombopoietin receptor agonist (TPO-RA) eltrombopag (Promacta™), without a platelet response. Three days later, he received the TPO-RA romiplostim (Nplate™). Five days later, his platelet count began to rise and by post-vaccination day 25, his platelet count was in the normal range. Thrombocytopenia was refractory to frontline and second-line treatment. The eventual rise in his platelet count suggests that one or both TPO-RAs may have impacted platelet recovery. Possibly, but less likely given the temporality, the drug-induced thrombocytopenia was subsiding. The aggressive use of immunosuppressive treatment may jeopardize the intended purpose of the SARS-CoV-2 vaccine, and earlier use of non-immunosuppressive second-line treatment for vaccine-related severe thrombocytopenia, such as with TPO-RAs, should be considered. While it is imperative to continue the global vaccination program, vigilance to the occurrence of post-vaccination severe thrombocytopenia is warranted.Keywords: immune thrombocytopenic purpura, platelet, SARS-CoV-2, thrombocytopenia, thrombopoietin receptor agonist, vaccine

While rare, abdominal aortic infections remain one of the most technically and emotionally challenging cases that a vascular surgeon may face. Secondary infections of either endovascular, or open aortic reconstructions range from 0.2% to 8%. Primary aortic infections are much more rare. Diagnosis can be elusive, depending upon the virulence of the causative microbes, and extent of the infection. Patients are often brittle, with immunocompromise and malnutrition prevalent in this patient population. The gold standard diagnostic test remains a computed tomographic angiogram. The mainstay of management requires vascular control, and wide debridement of all infected materials and revascularization. Multiple methods exist to reconstruct the vascular supply. The neo-aortoiliac system (NAIS) is attractive as it utilizes the patient’s own femoral veins to reconstruct the vascular supply after the infection has been extirpated. The procedure is demanding upon the patient and surgeons alike. Also, the rarity of aortic infections limit experiences the literature to centers of excellence. However, the NAIS resists infection well, leaving the patient without any remaining foreign bodies. No further costs for conduit are incurred. Moreover, multiple experiences show excellent durability. While comparative effectiveness literature remains sparse, we believe the NAIS to be the optimal method of revascularization for select patients. In this article, we will review the use of NAIS for primary and secondary aortic infections. In particular, we will emphasize procedural details to help enable the reader to apply this procedure most effectively to their own patients.

Intravascular fasciitis (IVF) is a very rare disease that is difficult to diagnose preoperatively. Frequently, it can be misdiagnosed as a malignancy or deep vein thrombosis. A 26-year-old man presented with a 6-month history of intermittent cramping pain in the right calf. Duplex ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography were performed in various hospitals. The work-up revealed a hypermetabolic mass in the femoral vein, suggestive of a malignancy, such as leiomyosarcoma. The tumor was located inside the femoral vein with no invasion, and the mass was resected en bloc with the vein wall. Intraoperative frozen section biopsy revealed no malignancy, and the final pathological diagnosis was IVF. Herein, we report a case of IVF and discuss the role of imaging studies in its preoperative diagnosis, with an extensive literature review.

Purpose: The aim of this study was to analyze changes in stump length over time in patients with saphenous vein incompetence treated with cyanoacrylate closure (CAC) or radiofrequency ablation (RFA). Materials and Methods : : We retrospectively analyzed data collected from patients with saphenous vein incompetence who underwent either CAC or RFA at Seoul National University Hospital between November 2015 and December 2018. The stump lengths were measured using duplex ultrasonography (DUS) within 1 month and 6 months after treatment. The Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) score were used to assess clinical outcomes. Results : : A total of 97 veins (64 great saphenous veins and 33 small saphenous veins) were analyzed. The stump length was not significantly different between the two groups at

Purpose: Native arteriovenous fistula (AVF) is the first choice for hemodialysis access; however, the maturation failure rate remains high. Hence, balloon-assisted maturation (BAM) is increasingly being used to overcome maturation failure. This study evaluated the outcomes of BAM and compared the differences between radial-cephalic (RC) and brachial-cephalic (BC) AVF. Materials and Methods : : Between January 2013 and December 2017, 1,622 new AVFs were created. BAM was considered if the AVF did not satisfy the criteria for hemodynamic maturation (6-mm diameter and 500-mL/min flow rate within 8 weeks after the operation). Results : : Of the 1,622 AVFs, BAM was performed in 142 patients (8.75%). There were 92 RC and 50 BC AVFs. Multivariate analyses revealed that ipsilateral central vein catheter history was the sole risk factor for maturation failure after BAM. Oneyear functional primary patency (FPP) and functional secondary patency (FSP) in RC AVFs were higher than those in BC AVFs without statistical significance (FPP, RC vs. BC: 70.9% vs. 50.9%, P=0.099; FSP, 95.5% vs. 81.1%, P=0.146). Further, based on the multivariate analysis, the independent risk factors for FPP in the RC and BC AVFs were the number of BAMs (odds ratio [OR], 3.05; 95% confidence interval [CI], 1.11-8.37; P=0.03) and age (OR, 1.04; 95% CI, 1.00-1.07; P=0.04), respectively. Conclusion : : BAM is a relatively good salvage method with tolerable patency. However, the risk factors for patency and the outcomes of BAM differ between RC and BC AVFs.

Popliteal artery aneurysm (PAA) is a rare vascular disease, especially in women, and presents with various symptoms, ranging from being asymptomatic to rupture or acute life-threatening ischemia. We have presented a case of PAA in an 81-year-old woman complaining of tingling sensations in her leg. Computed tomography revealed a large 10-cm sized PAA. Because of the compression related symptoms, an open repair approach was selected and performed successfully via a posterior approach, including partial aneurysm resection and interposition graft with a reversed saphenous vein.

We report a case of successful open repair of a 7.5-cm juxtarenal abdominal aortic aneurysm (AAA) in the presence of a left-sided inferior vena cava (LS-IVC) crossing the aorta at the level of the renal arteries in a 72-year-old man. The orifice of the right renal artery was slightly caudal to that of the left renal artery and concomitant occlusive diseases of both iliac arteries were present. Based on the imaging and intraoperative findings, repair of the juxtarenal AAA was performed with mobilization of the LS-IVC, which was encircled twice with soft silicone rubber vessel loops on both sides of operating field and the blood content of the LS-IVC was temporarily evacuated. This procedure allowed proximal control with inter-renal clamping of the aorta and placement of an aortobifemoral polytetrafluoroethylene graft.

Purpose: This study aimed to evaluate and analyze the feasibility and the oncological and functional outcomes of limb salvage surgery in extremity soft tissue sarcomas (ESTS) and bone tumors invading vessels. Materials and Methods : : This single-center retrospective analysis included patients with ESTS encasing or invading major blood vessels that were treated by limb salvage surgery with vascular resection and reconstruction between January 1995 and December 2019. Patients with contiguous involvement of major blood vessels and nerves and patients requiring amputation were excluded from the study. Results : : A total of 24 vessels (14 arteries and 10 veins) in 14 patients were reconstructed. Ten (71.4%) patients underwent both arterial and venous reconstruction, and four (28.6%) underwent only arterial reconstruction. Reconstruction was performed with a reversed saphenous vein (RSV) graft in 12 patients and with a synthetic graft (SG) in the other 12 patients. At a median follow-up of 27 months, RSV grafts were patent in 10 of 12 (83.3%) vessels and SGs were patent in 6 of 12 (50.0%) vessels (log-rank test, P=0.083). Out of 14 arteries and 10 veins, 11 arteries and 5 veins were patent, respectively. No patient developed local recurrence, and 2 (14.3%) patients developed distant metastases. Limb salvage rate was 13/14 (92.9%). The mean Musculoskeletal Tumor Society score was 83.3%. The 5- and 10-year overall survival rates were 80% and 50%, respectively. Conclusion : : Limb salvage surgery in ESTS with vascular resection and reconstruction is feasible and provides favorable oncological and functional outcomes.

Giancarlo Castaman, Silvia Linari Center for Bleeding Disorders and Coagulation, Department of Oncology, Careggi University Hospital, Florence, ItalyCorrespondence: Giancarlo CastamanCenter for Bleeding Disorders and Coagulation, Department of Oncology, Careggi University Hospital, Largo G. Brambilla 3, Florence, 50134, ItalyTel +39 055 7947587Fax +39 055 7947794Email giancarlo.castaman@unifi.itAbstract: Von Willebrand disease (VWD), the most common inherited bleeding disorder, is highly heterogeneous, and its early diagnosis may be difficult, especially for mild cases and in qualitative von Willebrand factor (VWF) defects. Appropriate VWD diagnosis requires the combination of personal and/or family history of bleeding and abnormal VWF laboratory testing. The use of bleeding assessment tools has been helpful in standardizing bleeding history collection and quantification of bleeding symptoms to select patients who may benefit of further hemostatic testing. Type 1 and 3 VWD which represent quantitative VWD variants are relatively easy to diagnose. The diagnosis of type 2 VWD requires multiple assessments to evaluate the effects induced by the responsible abnormality on the heterogeneous functions of VWF. Sensitive and reproducible tests are needed to evaluate different VWF activities, starting from measuring VWF-platelet interaction. In the recent years, several increasingly sensitive, rapid and automated assays have been developed, but they are not widely available so far. Genetic testing for VWD diagnosis is not a common practice because VWF gene is very large and highly polymorphic and therefore it is used only in specific cases. It is evident that the early and correct VWD diagnosis allows optimal management of bleeding and situations at risk. Tranexamic acid, desmopressin, replacement therapy with plasma-derived concentrates with a variable content of VWF and FVIII, or the new recombinant VWF are the different therapeutic options available. Careful VWD classification guides treatment because desmopressin is widely used in type 1 while replacement therapy is the cornerstone of treatment for type 2 and 3 variants.Keywords: von Willebrand disease, von Willebrand factor, bleeding history, laboratory assays, desmopressin, replacement therapy

Background While the number of individuals with hemophilia who are expected to be or have already been included in gene therapy trials has been regularly reported, the number of unscreened or excluded individuals, in addition to the reasons for exclusion, is mostly not reported. Methods We conducted an eligibility assessment of all people with severe hemophilia for gene therapy trials in one large Belgian hemophilia treatment center based on patient selection criteria of gene therapy trials and patients’ profiling. Results Among 87 adult patients with severe hemophilia A and B, 11 aged ≥65 years and two women were excluded from analysis. Six patients were excluded because of inhibitor development. One patient exhibited active hepatitis C infection, one had insufficient exposure to factor VIII, and five had uncontrolled comorbidities, while two were enrolled in other trials and two abused alcohol. Overall, 43 patients were not screened owing to psychosocial factors. Among 14 patients accepting gene therapy, six had adeno‐associated virus type 5 neutralizing antibodies and one had liver fibrosis. The number of patients who would accept gene therapy in the absence of strict clinical trial requirements was estimated at 36 (41.4%), irrespective of any exclusion criteria. Conclusion The majority of individuals with severe hemophilia could not be enrolled in gene therapy trials, almost half of them because of partly modifiable psychosocial reasons (49.4%). The proportion of candidates should substantially increase in the future, as eligibility criteria are likely to change and as more data on long‐term efficacy and safety of gene therapy will become available.

Objective/Background A few case reports in the setting of coronavirus disease 2019 (COVID-19) and multiplex polymerase chain reaction (PCR)-based assays for common respiratory pathogens have shown a higher yield of bronchoalveolar lavage (BAL) samples than upper airway specimens in immunocompromised patients. Methods A retrospective study was conducted reviewing patients diagnosed with COVID-19 at the Medical College of Wisconsin (Milwaukee, WI, USA) between March 13, 2020 and June 11, 2020. All patients tested positive for SARS-CoV-2 via real-time reverse transcriptase PCR (RT-PCR), through a nasopharyngeal or a bronchoscopy specimen. Results During the study period, 53 bronchoscopy procedures were performed at the institution, of which five patients tested positive for COVID-19. Of the five patients, three underwent BAL testing based on high clinical suspicion for COVID-19 after the nasopharyngeal (NP) swab(s) was negative. All three patients had underlying cancers and had lymphopenia for a considerable duration prior to being diagnosed with COVID-19. Two patients had better outcomes that could be attributed to earlier BAL specimen testing resulting in timely medical intervention. Conclusion This study underscores the need for early lower respiratory tract sampling, whenever possible, in patients with cancer and prolonged lymphopenia. High clinical suspicion ought to supersede false-negative NP reverse transcriptase–PCR as early bronchoscopic evaluation in cancer patients, who are either receiving active treatment or are immunosuppressed, can allow timely institution of efficacious treatment, enrollment into clinical trials, as well as effective infection control. In the apt clinical setting in patients with cancer, presumptive treatment may also be considered to minimize exposure to healthcare providers and proceduralists.

Background Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. Method and results This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). Conclusions Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Ashwag S Alsharidah,1 Haifa A Alsuhaibani,2 Basma S Almansour,3 Mansour S Alsharidah1 1Department of Physiology, College of Medicine, Qassim University, Buraidah, Qassim, Saudi Arabia; 2Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraidah, Qassim, Saudi Arabia; 3Department of Medicinal Chemistry, College of Pharmacy, Qassim University, Buraidah, Qassim, Saudi ArabiaCorrespondence: Ashwag S AlsharidahDepartment of Physiology, College of Medicine, Qassim University, Buraidah, Qassim, 51491, Saudi ArabiaTel +966 541719777Email ashriedt@qu.edu.saPurpose: Blood transfusion is a conventional therapeutic procedure; however, the perceptions of general public and healthcare professionals (HCPs), especially physicians and nurses, remain unclear, although the insights of HSPs may affect the treatment decision. This study aimed to assess the awareness of HCPs and the public about blood transfusion risks and consent in Qassim region of Saudi Arabia, to uncover the factors that may influence such perceptions.Patients and Methods: This study used two different closed questionnaires that were distributed electronically between February and March 2018 among the population and HCPs in Qassim region.Results: A total of 400 general public participants and 135 HCPs completed the survey. Among the surveyed participants, 70% believed that blood transfusion therapy was safe. The perceived risk of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) was the highest among all complications (74%). Furthermore, 88.2% of respondents were willing to accept a blood transfusion as a therapeutic measure, primarily from a first-degree relative, although the remaining 11.8% rejected the idea of a transfusion due to fear of medical error. From the HCP survey, 80% were previously involved in a blood transfusion therapy consent process. HCPs typically reported explaining the benefits, risks, and alternatives described in the consent form (74.1%, 67.4%, and 53.3%, respectively).Conclusion: Our results indicated that despite the current high level of acceptance and knowledge regarding blood transfusions, additional educational efforts remain necessary to increase public awareness of blood transfusion therapy.Keywords: consent, blood therapy, alternative therapy, blood bank, adverse reaction

Introduction The thrombin generation (TG) test is a global hemostasis assay sensitive to procoagulant conditions. However, some TG assays may underestimate elevated TG when the thrombin fluorogenic substrate is depleted or fluorescence is attenuated by the inner filter effect (IFE). Objectives We sought to elucidate the extent to which procoagulant conditions require correcting for fluorogenic substrate depletion and/or IFE. Methods We analyzed corrections for substrate depletion and IFE and their effect on TG parameters in plasma samples with elevated blood coagulation factors in the presence or absence of thrombomodulin via commercial calibrated automated thrombogram (CAT) platform and in‐house software capable of internal thrombin calibration with or without CAT‐like artifact correction. Results Elevated thrombin peak height (TPH) and endogenous thrombin potential (ETP) were detected with 2× and 4× increases in blood coagulation factors I, V, VIII, IX, X, and XI, or prothrombin in the presence or absence of artifact correction. The effect of the CAT algorithm was evident in TG curves from both low procoagulant (thrombomodulin‐supplemented) and procoagulant (factor‐supplemented) plasma samples. However, in all samples, with the exception of elevated prothrombin, CAT’s correction was small (

Background Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disorder induced by antiphospholipid antibodies, which occurs exceedingly rarely in pediatric population and even more rarely reported in HIV positive children. Case summary A case of 11 years old boy had a sudden onset of swelling in his left lower leg along with pain which were worsening gradually. Initially, topical ointment was applied for 1 month which were ineffective in reducing pain and swelling. Instead, the symptoms were aggravated and suddenly spread to the proximal thigh, accompanied by dyskinesia of left lower leg. Both color doppler ultrasonography and vascular CT scan of left lower leg revealed deep venous thrombosis. His serum anti-phospholipid antibodies (aPLs) were tested positive. He was a known case of HIV virological failure with substantial HIV viral load (VL) despite receiving regular antiretroviral therapy (ART). His symptoms improved after giving aggressive antithrombotic and high dose corticosteroid treatments. Conclusion When pediatric patients develop thrombotic disease, APS also needs to be ruled out. The autoantibodies levels should be routinely tested to look for recurrent thrombosis in children with HIV/AIDS.

Patients with cancer are prone to develop venous thromboembolism (VTE) that is the second leading cause of mortality among them. Cancer patients with VTE may encounter higher rates of VTE recurrence and bleeding complications than patients without cancer. Treatment of established VTE is often complex in patients with cancer. Treatment of cancer-associated VTE basically comprises initial treatment, long-term treatment, treatment within 6 months, treatment beyond 6 months, treatment of recurrent VTE, and treatment in special situations. Decision of antithrombotic therapy, selection of anticoagulants, duration of anticoagulation, decision of adjuvant therapy, and adjustment of regimen in special situations are the major problems in the treatment of cancer-associated VTE. Therapeutic anticoagulation is the key of the key in the treatment of cancer-associated VTE. In addition to the efficacy and safety of low-molecular-weight heparin (LMWH) that has been fully demonstrated, direct oral anticoagulants (DOACs) are increasingly showing its advantages along with the accompanying concern in the treatment of cancer-associated VTE. The latest ASCO, ITAC and NCCN guidelines agree with each other on most aspects with respect to the treatment of cancer-associated VTE, whereas differ on a few issues. Encompassing recent randomized controlled trials, clinical trials, and meta-analyses, as well as the comparison of the latest authoritative guidelines including the NCCN, ASCO, and ITAC guidelines in this field, the objective of this review is to present current overview and recommendations for the treatment of cancer-associated VTE.

Sophie le Doré,1 Nathalie Grinda,2 Emmanuelle Ferré,1 Valerie Roussel-Robert,3 Birgit Frotscher,4 Pierre Chamouni,5 Sandrine Meunier,6 Sophie Bayart,7 Edita Dolimier,8 Francoise Truong-Berthoz,9 Emmanuelle de Raucourt1 1Haemophilia Treatment Centre, Hôpital Mignot, Versailles, France; 2Regional Hemophilia Centre, Hôpital de Bicêtre (AP-HP), Kremlin-Bicêtre, France; 3Regional Hemophilia Treatment, Hôpital Cochin (AP-HP) Centre, Paris, France; 4Haemophilia Treatment Centre, Hôpital de Brabois, Vandoeuvre-Les-Nancy, France; 5Regional Hemophilia Treatment Centre, Centre Hospitalier Universitaire de Rouen, Rouen, France; 6Hospices Civils de Lyon – Unité d’Hémostase Clinique, Hôpital Cardiologique Louis Pradel, Bron, France; 7Haemophilia Treatment Centre, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France; 8Baxalta France SAS, a Takeda Company, Paris, France; 9Baxalta GmbH, a Takeda Company, Zurich, SwitzerlandCorrespondence: Emmanuelle de RaucourtService d’Hématologie Biologique, Clinique des Anticoagulants (CAC), Unité Inserm U 1148, Hôpital Beaujon, Clichy, FranceTel +33 01 40 87 55 41Fax +33 01 40 87 56 83Email emmanuelle.de-raucourt@aphp.frBackground: Hemophilic arthropathy is a major complication in patients with severe hemophilia. A plastic knee model has been developed for the therapeutic education of patients to promote improved care management and self-treatment skills. The objective of this study was to evaluate the impact of this hemarthrosis-simulating artificial knee (HSAK) on patients’ knowledge of their disease and its treatment.Methods: In this observational study, the impact of HSAK was assessed during individualized education in patients with severe/moderately severe hemophilia A or B at seven hemophilia treatment centers in France. Participants provided written informed consent and completed questionnaires to assess knowledge of their disease (score range: 0– 7) and knowledge of their treatment (score range: 0– 4). Questionnaires were completed before, immediately after and 6 months after HSAK use. The scores obtained before and after the use of the HSAK were compared.Results: The participants comprised 32 children, 29 teenagers, and 31 adults. The mean (SD) disease knowledge score increased significantly in all age groups of patients from 4.5 (2.0) to 5.9 (1.5; p< 0.001) immediately after the training and remained unchanged at 6 months. Mean (SD) treatment knowledge scores were unchanged, but Wilcoxon signed rank testing showed a significant increase after the training course that was maintained at 6 months in children and teenagers.Conclusion: These findings suggest that an individualized training course can enhance the understanding of hemophilia in patients of all ages, especially in children and teenagers, and that the HSAK may assist in improving patients’ management of their disease.Keywords: hemarthrosis, hemophilia, knee joint, patient education as topic, therapeutic education

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a rare disease characterized by aggressive clinical course and short survival. All available data are extracted from case reports and case series. The outcome is dismal and only two reported cases were cured after several lines of therapies including stem cell transplant. We herein present the case of a patient with CD8+ PCAETL who presented with rapidly progressive skin lesions and systemic symptoms. He was treated with aggressive multiagent chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD). The treatment resulted in durable complete remission with no evidence of disease recurrence after 58 months of follow-up. This is the first reported case of durable remission after first-line treatment.

Nahusenay Masresha,1 Esileman Abdela Muche,2 Asmamaw Atnafu,3 Ousman Abdela2 1Hospital Pharmacy, University of Gondar Comprehensive and Specialized Hospital, Gondar, Ethiopia; 2Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 3Department of Health Systems and Policy, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Ousman Abdela Tel +251-912-02-3692Fax +251-58-114 1240Email ousmy2009@gmail.comPurpose: To assess the quality of warfarin anticoagulation and its clinical outcomes on patients treated with warfarin at the University of Gondar comprehensive specialized hospital, North-west Ethiopia.Methods: We reviewed medical records of patients treated with warfarin between June 1, 2016, and May 30, 2018, at the University of Gondar comprehensive specialized hospital. The quality of anticoagulation was evaluated using the percentage of time spent in the therapeutic range. Data were entered into Statistical Product and Service Solutions (SPSS), version 20. Descriptive statistics were used to describe the socio-demographic and clinical characteristics of study participants. Multivariable logistic regression analysis was performed to identify independent predictors of quality of anticoagulation. Statistical significance was declared when the p-value was less than 0.05 at 95% confidence interval (CI).Results: From a total of 202 patients’ charts reviewed, women accounted for 134 (67.3%). The mean participants’ age was 44.33 years (± 17.05years SD). The median time spent in the therapeutic range was 37.91 with an IQR of (0.00– 65.86). More than two-third (143, (70.8%)) of participants had poor anticoagulation quality (time spent in the therapeutic range is less than 65%). Twenty-seven patients (13.4%) experienced adverse medication events of bleeding and thromboembolic events. Logistic regression analysis showed that potential medication interaction [p= 0.003 95% CI Adjusted odds ratio (AOR): 0.32 (0.152– 0.689)] and presence of co-morbidity [p= 0.037 95% CI AOR: 0.70 (1.046– 4.105)] were significantly associated with quality of anticoagulation.Conclusion: The quality of warfarin anticoagulation at the University of Gondar comprehensive specialized hospital was poor. A strong effort is needed to improve the quality of anticoagulation. Patients who had other co-morbidity conditions and potentially interacting medication need special attention.Keywords: warfarin, anticoagulation, University of Gondar, TTR, Ethiopia

Background Transgelin-2 is a 22 kDa actin-binding protein that has been proposed to act as an oncogenic factor, capable of contributing to tumorigenesis in a wide range of human malignancies. However, little is known whether this tiny protein also plays an important role in immunity, thereby keeping body from the cancer development and metastasis. Here, we investigated the functions of transgelin-2 in dendritic cell (DC) immunity. Further, we investigated whether the non-viral transduction of cell-permeable transgelin-2 peptide potentially enhance DC-based cancer immunotherapy. Methods To understand the functions of transgelin-2 in DCs, we utilized bone marrow-derived DCs (BMDCs) purified from transgelin-2 knockout (Tagln2−/−) mice. To observe the dynamic cellular mechanism of transgelin-2, we utilized confocal microscopy and flow cytometry. To monitor DC migration and cognate T–DC interaction in vivo, we used intravital two-photon microscopy. For the solid and metastasis tumor models, OVA+ B16F10 melanoma were inoculated into the C57BL/6 mice via intravenously (i.v.) and subcutaneously (s.c.), respectively. OTI TCR T cells were used for the adoptive transfer experiments. Cell-permeable, de-ubiquitinated recombinant transgelin-2 was purified from Escherichia coli and applied for DC-based adoptive immunotherapy. Results We found that transgelin-2 is remarkably expressed in BMDCs during maturation and lipopolysaccharide activation, suggesting that this protein plays a role in DC-based immunity. Although Tagln2−/− BMDCs exhibited no changes in maturation, they showed significant defects in their abilities to home to draining lymph nodes (LNs) and prime T cells to produce antigen-specific T cell clones, and these changes were associated with a failure to suppress tumor growth and metastasis of OVA+ B16F10 melanoma cells in mice. Tagln2−/− BMDCs had defects in filopodia-like membrane protrusion and podosome formation due to the attenuation of the signals that modulate actin remodeling in vitro and formed short, unstable contacts with cognate CD4+ T cells in vivo. Strikingly, non-viral transduction of cell-permeable, de-ubiquitinated recombinant transgelin-2 potentiated DC functions to suppress tumor growth and metastasis. Conclusion This work demonstrates that transgelin-2 is an essential protein for both cancer and immunity. Therefore, transgelin-2 can act as a double-edged sword depending on how we apply this protein to cancer therapy. Engineering and clinical application of this protein may unveil a new era in DC-based cancer immunotherapy. Our findings indicate that cell-permeable transgelin-2 have a potential clinical value as a cancer immunotherapy based on DCs.

Until recently, acute myeloid leukemia (AML) patients used to have limited treatment options, depending solely on cytarabine + anthracycline (7 + 3) intensive chemotherapy and hypomethylating agents. Allogeneic stem cell transplantation (Allo-SCT) played an important role to improve the survival of eligible AML patients in the past several decades. The exploration of the genomic and molecular landscape of AML, identification of mutations associated with the pathogenesis of AML, and the understanding of the mechanisms of resistance to treatment from excellent translational research helped to expand the treatment options of AML quickly in the past few years, resulting in noteworthy breakthroughs and FDA approvals of new therapeutic treatments in AML patients. Targeted therapies and combinations of different classes of therapeutic agents to overcome treatment resistance further expanded the treatment options and improved survival. Immunotherapy, including antibody-based treatment, inhibition of immune negative regulators, and possible CAR T cells might further expand the therapeutic armamentarium for AML. This review is intended to summarize the recent developments in the treatment of AML.

Introduction Apixaban, a direct factor Xa inhibitor, has been shown to be at least as safe and probably more effective than dalteparin for the treatment of cancer‐associated thrombosis (CAT) as reported in the ADAM‐VTE and Caravaggio studies, which included a low percentage of underweight patients. Lower‐weight–based dosing is supported by cancer‐specific studies such as half‐dose edoxaban in the Hokusai‐VTE cancer trial in individuals weighing 60 kg treated with apixaban 5 mg twice daily, patients weighing ≤60 kg also receiving apixaban 5 mg twice daily, and patients weighing ≤60 kg given half‐dose apixaban (2.5 mg twice daily). Apixaban plasma steady‐state trough levels were determined on a single occasion. Results Mean apixaban plasma trough levels were similar for patients weighing >60 kg on full‐dose apixaban to those weighing ≤60 kg taking 2.5 mg twice daily (mean, 109 ng/dL; 95% confidence interval [CI], 74‐145; standard deviation [SD]: 77.6; and mean,101 ng/dL, 95% CI, 67‐135; SD: 80, respectively). Mean values for low‐weight patients (≤60 kg) on the full 5 mg twice‐daily dosing tended to be higher (mean, 136 ng/dL; 95%CI, 70‐201; SD:114), without statistical significance (P = .22). Conclusions This study supports the rationale for studying weight‐based adjustments in apixaban dosing in prospective studies evaluating safety and efficacy of dose reduction in low‐weight patients with cancer.

Christos Varelas,1 Athina Tampaki,2 Ioanna Sakellari,1 &Agr;chilles Anagnostopoulos,1 Eleni Gavriilaki,1,* Efthymia Vlachaki2,* 1Hematology Department – BMT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; 2Adults Thalassemia Unit, 2nd Department of Internal Medicine, Hippokration Hospital, Thessaloniki, Greece*These authors contributed equally to this workCorrespondence: Eleni GavriilakiHematology Department - BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki, 57010, GreeceEmail elenicelli@yahoo.grAbstract: Sickle cell disease (SCD) is a widely spread inherited hemoglobinopathy that includes a group of congenital hemolytic anemias, all characterized by the predominance of sickle hemoglobin (HbS). Its features are anemia, predisposal to bacterial infections and complications such as vaso-occlusive crisis (VOC) or delayed hemolytic transfusion reaction (DHTR), which lead to increased rate of morbidity and mortality even in the era of hydroxyurea. The interaction between sickle cells, neutrophils, platelets or endothelial cells in small vessels results in hemolysis and has been considered the disease’s main pathophysiological mechanism. Complement activation has been reported in small cohorts of SCD patients, but the governing mechanism has not been fully elucidated. This will be important to predict the patient group that would benefit from complement inhibition. Until now, eculizumab-mediated complement inhibition has shown beneficial effects in DHTR, with limited reports in patients with VOC. In the meantime, several innovative agents are under clinical development Our state-of-the-art review summarizes current data on 1) complement activation in SCD both in steady state and crisis, 2) underlying mechanisms of complement over-activation for the clinician in the context of SCD, 3) actions of hydroxyurea and new therapeutic approaches including indirect involvement in complement activation, and 4) novel paradigms in complement inhibition.Keywords: sickle cell disease, complement system, eculizumab, complement inhibition

Background Richter syndrome (RS) represents an aggressive disease resulting from transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell or Hodgkin lymphoma. In 80% of cases, RS is clonally related to CLL. New therapies like ibrutinib have limited efficacy in RS with anticipated median overall survival (OS) of 3.5 months from the time of CLL transformation. Adriamycin-based regimens combined with rituximab represent the standard induction treatment for RS; and those who demonstrate responsive disease are generally offered an allogeneic hematopoietic cell transplant (allo-HCT) despite the lack of randomized controlled studies. Outcomes following allo-HCT in RS are limited to single-institution case series or registry data. We performed a systematic review of the medical literature to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in RS. Material and methods We performed a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 28, 2018. We extracted data on clinical outcomes pertaining to the benefits (complete remission [CR], OS and progression-free survival [PFS]) and harms (relapse and non-relapse mortality [NRM]), independently by two authors. Our search identified a total of 240 references. Four studies (n= 72 patients) were eligible for inclusion in this systematic review/meta-analysis (Figure 1). Three single-institution studies were from the United States and one data registry study from the European Society for Blood and Marrow Transplantation. Results Reduced intensity conditioning (RIC) regimens were more commonly prescribed (n=50, 69.4%) and the cell source was predominantly peripheral blood stem cells (n=54, 75%). Post-allograft pooled CR rate (3 studies, n=47 patients) was 33% (95%CI=4-71%) with high heterogeneity among studies (I2=84.2%). Pooled OS rate (3 studies, n=52 patients) was 54% (95%CI=28-79%) with high heterogeneity among studies (I2=69.8%) (Figure 2); and these 3 studies reported OS at 4-years, 3-years and 2-years, respectively. Pooled PFS (3 studies, n=52 patients) was 30% (95%CI=18-44%) with no heterogeneity among studies (I2=0). Pooled relapse rates (3 studies, n=52 patients) was 28% (95%CI=9-52%) with high heterogeneity (I2=62.7%). Pooled NRM associated with allo-HCT was 24% (95%CI=29.4%) with low heterogeneity (I2=29.4%). Conclusion Allo-HCT is an effective treatment for RS with a resulting pooled OS rate (between 2-4 years) of 54%. One study identified age (

Introduction The purpose of this study was to review and update the content of the Canadian Hemophilia Outcomes–Kids’ Life Assessment Tool version 2.0 (CHO‐KLAT), in the context of extended half‐life (EHL) factor concentrates (FCs) and to establish the validity and reliability of the updated CHO‐KLAT. Methods Focus groups were conducted with boys with hemophilia, their parents, and health care providers across Canada to review the CHO‐KLAT v2.0 and determine if any modifications were required. The validity of the revised CHO‐KLAT (version 3.0) was then determined in a sample of boys with hemophilia and their parents by calculating its correlation with the Pediatric Quality of Life Core Module (PedsQL‐Core). Test‐retest reliability was assessed using an intraclass correlation coefficient (ICC). Results Thirteen focus groups at 5 pediatric hemophilia treatment centers (HTCs) (n = 71) resulted in 19 changes to the CHO‐KLAT v2.0, generating a revised 40‐item CHO‐KLAT, the CHO‐KLAT v3.0. Thirty‐five boys with hemophilia (median age, 14; range, 7–17 years) and 47 parents participated in the validation of the CHO‐KLAT v3.0. There was a moderate correlation between the CHO‐KLAT v3.0 child self‐report and PedsQL‐Core (r = 0.56, P = .01), and a strong correlation between the CHO‐KLAT v3.0 parent‐proxy and PedsQL‐Core (r = .79, P = .0007). The test‐retest reliability ICC was 0.90 for the child self‐report CHO‐KLAT v3.0 and 0.68 for the parent‐proxy CHO‐KLAT v3.0. Conclusion The CHO‐KLAT v3.0 is a reliable and valid child‐centric tool that effectively measures health‐related quality of life in boys with hemophilia who are receiving standard half‐life or EHL FCs.

Rachelle Mendoza,1 Michael Silver,2,3 Alejandro R Zuretti,1,4 Manan Christian,4 Ballabh Das,5 Allen J Norin,5 Patrick Borgen,6 Jenny Libien,1,4 Martin H Bluth4 1Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; 2School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; 3Department of Medicine, Maimonides Medical Center, Brooklyn, NY, USA; 4Department of Pathology, Maimonides Medical Center, Brooklyn, NY, USA; 5Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; 6Department of Surgery, Maimonides Medical Center, Brooklyn, NY, USACorrespondence: Martin H BluthBlood Transfusion and Donor Services, Clinical Laboratories, Translational Research (Pathology), Maimonides Medical Center, 4802 10 th Avenue, Brooklyn, NY, 11219, USAEmail MBluth@maimonidesmed.orgBackground: We investigated the utility of an automated chemiluminescent SARS-CoV-2 IgG antibody assay platform in quantifying the amount of binding antibodies present in donated convalescent plasma.Methods: A total of 179 convalescent plasma units were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Beckman-Coulter chemiluminescent immunoassay (CLIA) platform. The equipment-derived numerical values (S/Co ratio) were recorded. Aliquots from the same units were subjected to enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 S1 protein. The relationship between ELISA titers and CLIA S/Co values was analyzed using linear regression and receiver operating characteristics (ROC) curve.Results: Twenty-one samples (11.7%) had S/Co values of less than 1.0 and were deemed negative for antibodies and convalescent plasma had S/Co values between > 1.0 and 5.0 (70/179, 39.1%). Fifteen units (8.4%) had negative ELISA titer. The majority of the units (95/179. 53.1%) had titers ≥ 1:1024. The sensitivities of ELISA to CLIA were comparable (90.5% vs 88.3%, respectively; p=0.18). There was positive linear correlation between CLIA S/Co values and ELISA IgG titer (Rho = 0.75; Spearman’s rank = 0.82, p-value = < 0.0001). The agreement between the two methods was fair, with a κ index of 0.2741. Using the ROC analysis, we identified a CLIA S/Co cutoff value of 8.2, which gives a sensitivity of 90% and a specificity of 82% in predicting a titer dilution of ≥ 1:1024.Conclusion: The utility of automated antibody detection systems can be extended from simply a screening method to a semi-quantitative and quantitative functional antibody analysis. CLIA S/Co values can be used to reliably estimate the ELISA antibody titer. Incorporation of chemiluminescent-based methods can provide rapid, cost-effective means of identifying anti-SARS-CoV-2 antibody titers in donated plasma for use in the treatment of COVID-19 infection.Keywords: COVID-19, ELISA, chemiluminescence, antibody, titers

Aberrant DNA methylation is often related to the diagnosis, prognosis, and therapeutic response of acute myeloid leukemia (AML); however, relevant studies on the relationship between bone marrow myeloblast percentage and the DNA methylation level in AML have not been reported. We evaluated the effects of AML blast percentage on DNA methylation level using the MethylC-capture sequencing (MCC-Seq) approach based on next-generation sequencing (NGS) and found that the methylation level of both genome-wide and promoter regions significantly increased when the percentage of AML blasts reached ≥ 40%, indicating that an accurate DNA methylation level in cancer cells can be obtained when the bone marrow samples of AML patients have more than 40% myeloblasts. Supplementary Information The online version contains supplementary material available at 10.1186/s40164-021-00219-0.

Introduction Plasma thrombin generation kinetics as measured by the calibrated automated thrombogram (CAT) assay is a predictor of symptomatic venous thromboembolism after trauma. We hypothesized that data from a new prototype assay for measurement of thrombin generation kinetics in fresh whole blood (near patient testing of thrombin generation), will correlate with the standard CAT assay in the same patients, making it a potential tool in the future care of trauma patients. Methods Patients were enrolled from June 2018 to February 2020. Within 12 hours of injury, blood samples were collected simultaneously for both assays. Variables compared and correlated between assays were lag time, peak height, time to peak, and endogenous thrombin potential. Data are presented as median with interquartile range (IQR). Spearman and Pearson correlations were estimated and tested between both assays; a P value of

Primary malignant aortic tumors are rare and aggressive. Most cases are diagnosed at advanced stages or during autopsies with a median overall survival of 8 months from diagnosis. We present the case of a 59-year-old male with angiosarcoma involving all segments of the thoracic aorta and a large floating thrombus causing acute mesenteric ischemia, which was treated successfully with embolectomy. Graft replacement of the aorta should be considered in cases of localized disease and when patients are fit for surgery. The best medical and surgical treatment remains unclear, and further studies are needed.

Background: The XALIA and XALIA-LEA prospective, noninterventional studies investigated the safety and effectiveness of rivaroxaban versus standard anticoagulation for venous thromboembolism (VTE) treatment in routine clinical practice across global regions. Objectives: This pooled analysis combined their data to determine the incidence of thromboembolic and bleeding events in both treatment groups and addressed specific bleeding patterns in a broad range of patients. Methods: Patients with objectively confirmed VTE and an indication for ≥3months’ anticoagulation treatment received rivaroxaban or standard anticoagulation (eg, initial treatment with heparin/fondaparinux, followed by a vitamin K antagonist [VKA]). Treatment choice, dose, management, and duration were at the physician’s discretion. Primary outcomes (major bleeding, recurrent VTE, and all-cause mortality) were compared between the two treatment groups. Propensity score stratification, and matching were used to reduce bias due to confounding variables. Results: Overall, 7129 patients were enrolled from 36 countries; 6445 and 2714 patients were included in the propensity score–stratified and –matched analyses, respectively. Major bleeding and incidences of recurrent VTE were similar between treatment groups; all-cause mortality was lower with rivaroxaban than with standard anticoagulation. The incidences of genitourinary bleeding were higher with rivaroxaban than with standard anticoagulation therapy (46 and 23 events in the matched analysis, respectively). VKA management in real-world practice was suboptimal. Conclusion: XALIA and XALIA-LEA show similar safety and effectiveness profiles of rivaroxaban and standard anticoagulation for VTE treatment in routine practice in many parts of the world. The observations are consistent with results from the phase III EINSTEIN randomized controlled trials.

Febrile neutropenia (FN) is a hematological emergency requiring urgent investigations to exclude infection and treatment with broad-spectrum antibiotics. Despite frequent blood cultures (BCs) being taking during episodes of FN, in the current literature BC positivity rates remain low in FN. This study aims to determine the BC positivity rate in FN hematology patients and determine the utility of collecting BCs beyond 24 h of commencing broad-spectrum antibiotics.BC results between 2014 and 2016 from all FN hematology patients were analyzed. Patient episodes of FN (PEFNs) were defined as a continuous period of FN where the interval between BC samples was a maximum of two days. In total from 2014 to 2016, 379 patients experienced 914 PEFNs and had 4267 BCs collected.Overall BC positivity rates and BC-positive PEFN rates were 8.16% and 13.35%, respectively. Within the first 24 h, the positivity rate of the first BCs was 3.49%, while subsequent BC positivity within the first 24 h was 11.96%. BC positivity rates declined after 24 h to 2.18%.It is likely that BCs beyond 24 h of commencing broad-spectrum antibiotics will rarely identify relevant microorganisms. Not collecting BCs after 24 h would likely reduce laboratory test costs, patient discomfort, and iatrogenic anemia.Febril nötropeni (FN), enfeksiyonu ve geniş spektrumlu antibiyotiklerle tedaviyi dışlamak için ivedi araştırmalar gerektiren hematolojik bir acil durumdur. FN atakları sırasında sık kan kültürleri (KK) alınmasına rağmen, mevcut literatürde KK pozitiflik oranları FN’de düşük kalmaktadır. Bu çalışma, febril nötropenik hematoloji hastalarında KK pozitiflik oranını belirlemeyi ve geniş spektrumlu antibiyotiklere başladıktan 24 saat sonra KK almanın faydasını belirlemeyi amaçlamaktadır.2014-2016 yılları arasında FN tanısı almış tüm hematoloji hastalarının KK sonuçları analiz edildi. Hasta FN atakları (HFNA), KK örnekleri arasındaki sürenin en fazla iki gün olduğu kesintisiz febril nötropenik dönem bir FN periyodu olarak tanımlandı. 2014’ten 2016’ya kadar toplamda 379 hastada 914 HFNA gözlendi ve 4267 KK örneği alındı.Genel KK pozitiflik oranları ve KK pozitif HFNA oranları sırasıyla %8,16 ve %13,35 idi. İlk 24 saat içinde, ilk KK’lerin pozitiflik oranı %3,49 iken, takip eden KK pozitifliği %11,96 bulundu. KK pozitiflik oranları 24 saat sonra %2,18’e geriledi.Geniş spektrumlu antibiyotikler başlamasını takiben ilk 24 saatten sonra alınan KK’lerin ilgili mikroorganizmaları tanımlaması nadiren muhtemeldir. Febril nötropenili hematoloji hastalarında geniş spektrumlu antibiyotik başlanmasını takiben ilk 24 saatten daha sonra KK’lerin alınmaması, laboratuvar test maliyetlerini, hastanın girişim anksiyetesini ve iyatrojenik anemiyi azaltacaktır.

Background: B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells is crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Factor Runt Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are master regulators of hematopoiesis and are implicated in leukemia.Methods: We worked with BCP-ALL mononuclear bone marrow patients' cells and BCP-ALL cell lines, and performed Chromatin Immunoprecipitations followed by Sequencing (ChIP-Seq), co-immunoprecipitations (co-IP), proximity ligation assays (PLA), luciferase reporter assays and mouse xenograft models.Results: We demonstrated that CBFA2T3 transcript levels correlate with RUNX1 expression in the pediatric t(12;21) ETV6-RUNX1 BCP-ALL. By ChIP-Seq in BCP-ALL patients' cells and cell lines, we found that RUNX1 is recruited on its promoter and on an enhancer of CBFA2T3 located − 2 kb upstream CBFA2T3 promoter and that, subsequently, the transcription factor RUNX1 drives both RUNX1 and CBFA2T3 expression. We demonstrated that, mechanistically, RUNX1 and CBFA2T3 can be part of the same complex allowing CBFA2T3 to strongly potentiate the activity of the transcription factor RUNX1. Finally, we characterized a CBFA2T3-mimicking peptide that inhibits the interaction between RUNX1 and CBFA2T3, abrogating the activity of this transcription complex and reducing BCP-ALL lymphoblast proliferation.Conclusions: Altogether, our findings reveal a novel and important activation loop between the transcription regulator CBFA2T3 and the transcription factor RUNX1 that promotes BCP-ALL proliferation, supporting the development of an innovative therapeutic approach based on the NHR2 subdomain of CBFA2T3 protein.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC). Methods Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis. Results High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway. Conclusions PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.

Background Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium metabolism but also several other cellular effects through extensive binding to the DNA and modification of genome expression. In cancer, it has neoplasia-suppressive effects and various mechanisms of action mediating cancer cell inhibition have been described. Vitamin D deficiency has been linked to increased risk of breast cancer. A role of the vitamin once the disease has been diagnosed is also probable. Methods A systematic review and meta-analysis of studies that report on vitamin D levels (in the form of its main circulating metabolite, 25-hydroxyvitamin D [25-OHD]) in patients with newly diagnosed breast cancer was performed. Outcomes of interest included the levels of serum 25-OHD in patients with breast cancer, those of matched controlled, in studies that included controls, as well as respective percentages of patients and controls with deficient and insufficient 25-OHD levels. Results A total of 25 studies (10 with controls and 15 without controls) provided data on the outcomes of interest. Populations from all continents, besides Australia, were represented in the studies. The mean level of 25-OHD in patients with breast cancer was 26.88 ng/mL (95% CI 22.8–30.96 ng/mL) and the mean level of 25-OHD in control patients was 31.41 ng/mL (95% CI 19.31–43.5 ng/mL). In the patients with breast cancer group, 45.28% (95% CI 24.37%–53.51%) had levels of 25-OHD below 20 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%–45.82%) in controls. Similarly, 67.44% (95% CI 48.32%–86.55%) of patients with breast cancer had a baseline level of 25-OHD below 30 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%–45.82%) in controls. Conclusion A high prevalence of vitamin D insufficiency is observed in patients with newly diagnosed breast cancer and may be linked pathophysiologically with breast cancer development or progression. Therapeutic benefits may be provided by manipulation of the vitamin D pathway in breast cancer.

Background BM-MSCs play an important role in cancer development through the release of cytokines or exosomes. Studies have shown that extracellular exosomes derived from BM-MSCs are a key pro-invasive factor. However, how BM-MSC-exos influence AML cell proliferation, invasion and chemoresistance remains poorly understood. Methods We isolated exosomes from BM-MSCs and used electron microscopy, particle size separation and western blots to identify the exosomes. The invasion of leukemia cells was observed with a transwell assay. The stemness traits and chemoresistance of the leukemia cells were detected by FCM, colony formation and CCK-8 assays. TCGA database was used to investigate the prognostic relevance of S100A4 and its potential role in AML. Results In this study, we found that BM-MSC-exos increased the metastatic potential, maintained the stemness and contributed to the chemoresistance of leukemia cells. Mechanistically, BM-MSC-exos promoted the proliferation, invasion and chemoresistance of leukemia cells via upregulation of S100A4. Downregulating S100A4 clearly suppressed the proliferation, invasion, and chemoresistance of leukemia cells after treatment with BM-MSC-exos. Bioinformatic analysis with data in TCGA database showed that S100A4 was associated with poor prognosis in AML patients, and functional enrichment revealed its involvement in the processes of cell–cell adhesion and cytokine regulation. Conclusions S100A4 is vital in the BM-MSC-exo-driven proliferation, invasion and chemoresistance of leukemia cells and may serve as a potential target for leukemia therapy.

Non-Hodgkin lymphoma (NHL) of the lip is extremely rare. It is usually indolent and in early stages a local approach is often indicated. We present a case report of a patient with extranodal NHL of the lip treated with chemotherapy and low-dose radiation treatment (RT). The patient was affected by B-cell NHL of the marginal zone, Stage IAE. After a few months of observation with progressive disease, the patient was submitted to two cycles of chemotherapy with no response. Therefore, he was treated with very low-dose RT consisting of two fractions of 2 Gy. Complete response was observed and after 1-year follow-up, persistent complete response was recorded. In cases of localized disease, especially in patients with comorbidities of poor performance status (PS), low-dose RT can be an appropriate approach with excellent outcomes in terms of effectiveness and low risk of toxicity.

The prognosis of multiple myeloma (MM) patients is highly heterogeneous. The aim of this study is to determine the impact of patients’ renal functions on the prognostic performance of the International Staging System (ISS). In addition, we aimed to evaluate the results of survival of patients with ISS stages and normal renal functions and those with ISS stages and abnormal renal functions with this study.Two hundred and four patients with newly diagnosed MM who received an autologous stem cell transplantation after induction chemotherapy in our tertiary care center between the years of 2001 and 2018 were evaluated.There were 153 (75%) MM patients who had a glomerular filtration rate (GFR) of ≥60 mL/min and 51 (25%) MM patients who had GFR of60 mL/min at the time of diagnosis in this study. There was a strong correlation between ISS stage and GFR. The ISS stages were higher in patients who had GFR of60 mL/min than patients who had GFR of ≥60 mL/min (p0.001). Patients with GFR of60 mL/min were significantly more prevalent in the ISS III group than ISS I and II (p0.001).This study showed that the ISS provides significant prognostic information in MM patients with GFR of ≥60 mL/min at diagnosis. However, in patients with impaired renal function at the time of diagnosis, B2-microglobulin may not be a good prognostic indicator since it may be affected by renal dysfunction as well as tumor burden.Multipl miyelom (MM) hastalarının prognozu oldukça heterojendir. Bu çalışmanın amacı, hastaların böbrek fonksiyonlarının Uluslararası Evreleme Sistemi’nin (ISS) prognostik performansı üzerindeki etkisini belirlemektir. Ayrıca bu çalışma ile ISS evreli ve böbrek fonksiyonları normal ve anormal olan hastaların ISS evresine göre sağkalım sonuçlarını değerlendirmeyi amaçladık.2001-2018 yılları arasında üçüncü basamak merkezimizde indüksiyon kemoterapisi sonrası otolog kök hücre nakli yapılan yeni tanı konmuş MM’li 244 hasta değerlendirildi.Tanı anında glomerüler filtrasyon hızı (GFR) ≥60 mL/dak olan 153 (%75) MM hastası ve GFR’si60 mL/dak olan 51 (%25) MM hastası vardı. ISS evresi ile GFR arasında güçlü bir ilişki vardı. ISS evreleri, GFR değeri60 mL/dak olan hastalarda GFR’si ≥60 mL/dak olan hastalara göre daha yüksekti (p0,001). GFR değeri60 mL/dak olan hasta sayısı, ISS 3 grubunda ISS 1 ve 2’ye göre anlamlı olarak daha saptandı (p0,001).Bu çalışma, ISS’nin GFR’si ≥60 mL/dak olan MM hastalarında tanıda önemli prognostik bilgi sağladığını göstermiştir. Bununla birlikte, tanı anında böbrek fonksiyon bozukluğu olan hastalarda B2-mikroglobulin, böbrek fonksiyon bozukluğundan ve tümör yükünden etkilenebileceğinden iyi bir prognostik gösterge olmayabilir.

Sarcoma (Src) family kinases (SFKs) have occupied a central place in platelet research for over 40 years. Discovered by virologists and oncologists as the proto proto‐oncogene, Src tyrosine kinase spurred a phenomenal burst of research on reversible tyrosine phosphorylation and signal transduction. For a time, platelets were adopted as the model of choice for studying the biological functions of Src, owing to their ease of isolation, high Src expression, and lack of a nucleus, only to be abandoned due to challenges of culturing and manipulating using common molecular biology‐based techniques. For platelet biologists, SFKs have remained an important area of investigation, initiating and amplifying signals from all major adhesion, activation, and inhibitory receptors, including the integrin αIIbβ3, the collagen receptor complex glycoprotein VI–Fc receptor γ‐chain, the G protein–coupled ADP receptor P2Y12 and the inhibitory receptors platelet endothelial cell adhesion molecule‐1 and G6b‐B. The vital roles of SFKs in platelets is highlighted by the severe phenotypes of null and gain‐of‐function mutations in SFKs in mice and humans, and effects of pharmacologic inhibitors on platelet activation, thrombosis, and hemostasis. The recent description of critical regulators of SFKs in platelets, namely, C‐terminal Src kinase (Csk), Csk homologous kinase (Chk), the receptor‐type protein‐tyrosine phosphatase receptor type J (PTPRJ) helps explain some of the bleeding side effects of tyrosine kinase inhibitors and are novel therapeutic targets for regulating the thrombotic and hemostatic capacity of platelets. Recent findings from Chk, Csk, and PTPRJ knockout mouse models highlighted that SFKs are able to autoinhibit by phosphorylating their C‐terminal tyrosine residues, providing fundamental insights into SFK autoregulation.

The immune system is the core defense against cancer development and progression. Failure of the immune system to recognize and eliminate malignant cells plays an important role in the pathogenesis of cancer. Tumor cells evade immune recognition, in part, due to the immunosuppressive features of the tumor microenvironment. Immunotherapy augments the host immune system to generate an antitumor effect. Immune checkpoints are pathways with inhibitory or stimulatory features that maintain self-tolerance and assist with immune response. The most well-described checkpoints are inhibitory in nature and include the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Molecules that block these pathways to enhance the host immunologic activity against tumors have been developed and become standard of care in the treatment of many malignancies. Only a small percentage of patients have meaningful responses to these treatments, however. New pathways and molecules are being explored in an attempt to improve responses and application of immune checkpoint inhibition therapy. In this review, we aim to elucidate these novel immune inhibitory pathways, potential therapeutic molecules that are under development, and outline particular advantages and challenges with the use of each one of them.

Muhamad R Abdel Hameed,1,2 Howiada A Nafady,1,2 Mona Ibrahim Mostafa,3 Douaa Sayed,4 Ahmad A Obiedallah5 1Hematology Unit, Department of Internal Medicine, Assiut University Hospitals, Assiut University, Assiut, Egypt; 2Bone Marrow Transplantation Unit, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 3Department of Internal Medicine, Assiut General Hospital, Assiut, Egypt; 4Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 5Critical Care Unit, Department of Internal Medicine, Assiut University Hospitals, Assiut University, Assiut, EgyptCorrespondence: Muhamad R Abdel HameedHematology Unit, Department of Internal Medicine, Assiut University Hospitals, Assiut University, Assiut, 71515, EgyptTel +20 1097510010Email dr.muhamadramadan@yahoo.comBackground and Objectives: Immune thrombocytopenia (ITP) is one of the autoimmune diseases that presented by thrombocytopenia and increased risk of bleeding. Etiology of immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important role in ITP. The aim of this study was evaluation of expression of CD11a on lymphocytes to explore its possible role in primary ITP patients also, regarding severity and response to immunosuppressive treatment.Patients and Methods: This is a cross-sectional case-control study. Forty adult patients aged (18:58) years, 29 females and 11 males were enrolled as newly diagnosed primary ITP. Forty age and sex matched control subjects were randomly selected. The expression of CD11a on lymphocyte subpopulations (CD3+ T cells, CD3+CD4+ T cells and CD19+ B cells) was analyzed by flowcytometry at the start of the study and after 6 months of follow-up.Results: The mean fluorescence intensity (MFI) of CD11a on CD3+ T and CD19+ B lymphocytes was significantly highly increased in ITP patients compared to healthy controls while MFI of CD11a on CD3+ CD4+Tclls was non-significant. MFI of CD11a on CD3+ and CD19+ B lymphocytes showed non-significant elevation with platelet count or bleeding score. MFI of CD11a on CD3+ showed significant highly increased level in refractory ITP compared with responder cases.Conclusion: CD11a had possible role in the pathogenesis of ITP. Immunosuppressive therapy in ITP did not affect the level of CD11a expression on T and B lymphocytes. Levels of CD11a do not reflect the severity of ITP neither platelet count nor bleeding score. Increased MFI of CD11a in CD3+T lymphocytes of ITP patients may cause resistance to immunosuppressive therapy.Keywords: Primary immune thrombocytopenia, immunosuppressive therapy, LFA-1, CD11a, B cells, T cells

Ana Marco,1,2 Pascual Marco1– 3 1Thrombosis and Hemostasis Department, Hematology Service, University General Hospital in Alicante, Alicante, Spain; 2Biomedical Health Research Institute, University General Hospital in Alicante, Alicante, Spain; 3Department of Clinical Medicine, Miguel Hernández University, Alicante, SpainCorrespondence: Ana MarcoUniversity General Hospital in Alicante, Pintor Baeza 12, Alicante, 03010, SpainTel +34 965913863Fax +34 965913869Email marco_anaric@gva.esAbstract: Autoimmune acquired factor XIII (FXIII) deficiency is a rare disorder characterized by severe spontaneous hematomas and autoantibodies against FXIII. High mortality rates have been reported (18% within a year of diagnosis). We present a 70-year-old patient with recurrent muscular hematomas. The basic hemostasis study and the coagulation factors were within normal ranges. The aggregation platelet study was also normal and von Willebrand disease was excluded. Bearing in mind the recurrent bleeding history and the described laboratory results, we considered a FXIII deficiency, that was confirmed (FXIII< 10%). In addition, we suspected an acquired FXIII deficiency since the patient did not report a personal or family history of bleeding and FXIII gene sequencing study was normal. Non-immune causes were ruled out, and plasma autoantibodies against FXIII were detected. Immunosuppression was rapidly initiated to eradicate inhibitor as was hemostatic treatment to obtain bleeding control. Currently, the patient is asymptomatic, but a low level of FXIII inhibitor remains.Keywords: acquired disease, autoantibodies, factor XIII deficiency, hematoma, spontaneous

Background Patients diagnosed with pulmonary embolism (PE) are reported to experience symptoms of posttraumatic stress disorder (PTSD) and existential anxiety following their diagnosis. They may also experience negative changes in perspective and hypervigilance of PE symptoms. Objective The aim of this study was to document the mental and emotional experience associated with PE diagnosis through the lens of PTSD, to better understand the factors involved in psychological distress following receipt of a PE diagnosis. Patients/Methods This was a mixed‐methods study in two parts: (i) measurement of self‐reported PTSD symptoms among patients attending thrombosis clinic and (ii) semistructured interviews with patients about their experience of receiving a diagnosis of PE and its psychological aftermath. Results Of 72 patients who participated in the survey, two met the criteria for a tentative diagnosis of PTSD. The semistructured interviews with 37 patients suggested that around half of respondents experienced some degree of ongoing psychological distress. Those with psychological distress often recalled painful symptoms, recalled diagnosis delivery as stressful, worried about PE recurrence, and had anxieties about stopping their anticoagulant medication. Few patients reported inclination to seek support from professional mental health services. Conclusions We found ongoing and untreated psychological distress among people who were previously diagnosed with PE.

Direct oral anticoagulants (DOACs) are currently the preferred oral anticoagulant treatment for most of the patients with deep vein thrombosis of the lower extremities and/or pulmonary embolism. DOACs have several advantages over vitamin K antagonists, such as availability of fixed dosages, fewer drug interactions, faster onset of action, shorter half-life, and lower risk of major and intracranial bleeding. Although the evidence on the use of DOACs in patients with unusual-site venous thromboembolism (VTE) is limited to a few, small randomized controlled trials, these drugs are increasingly used in clinical practice, and several observational cohort studies have been published recently. This narrative review will describe the latest evidence for the use of the DOACs in patients with thrombosis in atypical locations (splanchnic, cerebral, upper extremity, ovarian, and renal vein thrombosis) and will provide some practical advice for their use in patients with unusual-site VTE., peer-reviewed

Ugochi O Ogu,1 Nnenna U Badamosi,2 Pamela E Camacho,3 Amado X Freire,4 Patricia Adams-Graves1 1Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN, USA; 2Division of Pediatric Hematology and Oncology, Medical College of Georgia, Augusta, GA, USA; 3Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; 4Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, Memphis, TN, USACorrespondence: Patricia Adams-Graves Tel +1 901-545-8538Fax +1 901-545-6454Email padamsgraves@uthsc.eduAbstract: Sickle cell disease results in numerous complications that can lead to significant morbidity and mortality. Amongst them, acute chest syndrome is the leading cause of mortality. As a result, most providers are in tune with this complication and well versed with management. As sickle cell patients now live longer, they face a multitude of other complications that if left unattended, can lead to significant morbidity and mortality as well. It is critical to look beyond acute chest syndrome and adopt a more comprehensive approach to the management of the sickle cell patient.Keywords: sickle cell disease, acute chest syndrome, complications