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Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin exposure with potential for significant morbidity and mortality. Early identification and treatment can prevent catastrophic thrombosis. Herein, we report the performance of a platelet count-based clinical decision support system (CDSS) where providers received a notification when a patient had a platelet count decline of ≥50 %. In the 90-day study period, the CDSS sent 302 notifications on 270 patients. Notifications were frequently inappropriate; 25 % had an expected platelet count decline (organ donation, stem cell transplant), an inaccurate count, or no heparin exposure. Patient testing for HIT prompted by the CDSS was not in accordance with best practice guidelines in most circumstances. For example, 36 % had a low probability 4Ts score, while 42 % with an intermediate or high probability 4Ts score were not tested. Due to concern for lack of efficacy, the CDSS was discontinued. Analysis of an 8-month period before and after discontinuation showed a significant decrease in the number of enzyme immunoassays ordered (547 vs. 386) without a change in the number of patients with HIT identified (13 vs. 13) or the rate of thrombosis in those with confirmed HIT (62 % vs. 62 %). In conclusion, a CDSS based on platelet count decline contributed to "alert fatigue" via inappropriate notification and did not improve evidence-based HIT testing. In addition, its removal did not decrease or delay HIT identification. Additional efforts are needed to better define how CDSS can support the rapid diagnosis and appropriate treatment of patients with HIT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder caused by antibodies against platelet factor 4 (PF4) and heparin complexes. Rapid immunoassays (IAs) for detection of these antibodies mark a milestone in HIT diagnosis, despite a higher false-positive rate compared with functional platelet-activation assays. However, combining different rapid IAs may help to improve their diagnostic specificity. Here, we compared the individual performance of the latex immunoturbidimetric assay (LIA; HemosIL HIT-Ab [PF4-H]; sensitivity 91.7%, specificity 68.4%) and chemiluminescence immunoassay (CLIA; HemosIL AcuStarHIT-Ab [PF4-H]; sensitivity 92.4%, specificity 85.8%) with their combined performance using two unique diagnostic algorithms in a single prospective cohort of suspected HIT patients. Using the simultaneous algorithm adapted from Warkentin et al, the combined LIA-CLIA had a sensitivity of 99.0% and specificity of 64.3%. The sequential algorithm adapted from Rittener-Ruff et al was applied in two theoretical scenarios to reflect real-world circumstances in diagnostic laboratories where access to clinical information is limited: (1) assuming all patients had an intermediate 4Ts score and (2) assuming all patients had a high 4Ts score. This algorithm correctly predicted HIT in 94.5% (high 4Ts) and 96.0% (intermediate 4Ts) and excluded HIT in 82.6% (high 4Ts) and 80.1% (intermediate 4Ts) of patients in either scenario, respectively. Although both combined algorithms improved diagnostic performance of individual IAs, the simultaneous algorithm showed fewer false predictions (7.9%) than the sequential algorithm (intermediate 4Ts: 37.6% and high 4Ts: 41.5%) and proved more practical as it does not rely on physician evaluations. Our findings highlight the importance of accounting for clinician and interlaboratory variability when evaluating diagnostic tests for HIT., Competing Interests: I.N. and T.E.W. have received research funding from Instrumentation Laboratory (Werfen). T.E.W. has received lecture honoraria from Instrumentation Laboratory (Werfen), and royalties from Informa (Taylor & Francis) and UptoDate (Wolters Kluwer); has provided consulting services to Arbor Biotechnologies, Paradigm Pharmaceuticals, and Veralox Therapeutics; has provided expert witness testimony relating to HIT and non-HIT thrombocytopenic and coagulopathic disorders., (Thieme. All rights reserved.)

Background: Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT., Methods: After institutional review board (IRB) approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. The demographic and clinical variables were collected as follows: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes., Results: 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either noncardiac, nonvascular surgery, or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing), and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77 days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K ( ± 104.6 K) within an average of 2.3 days and 364K ( ± 273.9 K) within 30 days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30 days., Conclusions: Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pseudothrombocytopenia caused by platelet clumping (PC) can lead to unnecessary platelet transfusions or underdiagnosis of hematologic neoplasms. To overcome these limitations, we assessed the capacity of the Sysmex DI-60 digital morphology analyzer (Sysmex, Kobe, Japan) for detecting PC and determining an accurate platelet count in the presence of PC. For this purpose, 135 samples with or without PC (groups Y and N, respectively) were processed by an examiner (a hematologic specialist) using both the Sysmex XN-9000 and DI-60 analyzers. Although the platelet aggregate (PA) and giant platelet (GP) counts reported by the DI-60 and the examiner exhibited strong correlations, they proved inadequate as effective indicators for screening samples containing PC. Between the PA and GP counts and four platelet indices (the platelet distribution width [PDW], mean platelet volume [MPV], platelet large cell ratio [P_LCR], and plateletcrit [PCT]) reported by the XN-9000, we observed statistically significant correlations (both overall and with group Y), but they were relatively weak. The platelet counts determined using the DI-60 and light microscopy in group Y showed substantial variations. Although the performance of the DI-60 was reliable for detecting PA and GP in smear images, such fixed areas are not representative of whole samples. Further, in the presence of PC, the resulting platelet counts determined using the DI-60 were not sufficiently accurate to be accepted as the final count.

Background: EDTA-induced pseudothrombocytopenia (PTCP) during whole blood collection requires significant laboratory resources to obtain accurate results. We evaluated platelet-deaggregation function in EDTA-induced PTCP and platelet-clump flagging by the BC-6800Plus hematology analyzer using integrated digital image analysis., Methods: We prospectively collected 132 whole blood samples suspected of platelet clumping (102 in EDTA and 30 in sodium citrate) from 88 individuals. We compared platelet counts determined using the platelet count by impedance (PLT-I) function of the DxH 900 hematology analyzer and the PLT-I or optical platelet count (PLT-O) function of the BC-6800Plus. Platelet clumping was verified through manual inspection and the MC-80 digital image analyzer., Results: Among the 132 whole blood samples, 43 EDTA samples showed platelet clumping. The DxH 900 PLT-I and BC-6800Plus PLT-I results demonstrated a strong correlation (r=0.711) for the EDTA samples but only a moderate correlation with the BC-6800Plus PLT-O results (r=0.506 and 0.545, respectively). The BC-6800Plus PLT-O results were consistent with the sodium citrate platelet counts, with a median dissociation rate of 102.5% (range, 74.9%-123.1%). The DxH 900 and BC-6800Plus analyzers had sensitivity values of 0.79 and 0.72, respectively, for platelet-clump flagging. When integrating the MC-80 digital image analysis results, the sensitivity of BC-6800Plus improved to 0.89 (standard mode) or 1.0 (PLT-Pro mode)., Conclusions: BC-6800Plus PLT-O measurement results are close to the actual values obtained by platelet deaggregation with PTCP samples. Integrating the BC-6800Plus with a digital imaging analyzer effectively improved the diagnosis of PTCP and reduced the requirement for additional laboratory procedures.

A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (C min ) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid C min additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid C min , and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid C min had better predictive capability than that containing linezolid C min for predicting linezolid-induced thrombocytopenia in patients with renal impairment., (© 2024. The Author(s).)

A female in her 60s was admitted via the emergency department following a respiratory collapse at home. She was profoundly hypoxic and hypertensive. For 1 week prior, she had been self-administering subcutaneous (SC) low molecular weight heparin (LMWH) for a small postoperative pulmonary embolism (PE) and reported worsening, self-resolving episodes of breathlessness 1 hour post-injection. Repeat imaging revealed a new small PE and blood tests showed a significant platelet drop. Her heparin-induced thrombocytopaenia (HIT) antibody test was positive. A diagnosis of HIT-associated anaphylactoid reaction was made. She was switched to a direct oral anticoagulant and fully recovered. This condition is well described, often presenting with profound respiratory compromise that can be misdiagnosed as 'massive PE'. A key differentiation is that there is often hypertension instead of hypotension. This case, however, is unusual as it was triggered by SC LMWH not intravenous heparin as previously described in the literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Thrombocytopenia in cirrhosis is causing puzzlement in clinical practice. Therefore, in order to help clinical practitioners grasp quickly and standardize the diagnosis and treatment of thrombocytopenia in cirrhosis, liver fibrosis, and portal hypertension, the Group of the Chinese Society of Hepatology of the Chinese Medical Association has organized relevant field experts to formulate the "Concise Guidelines for Clinical Management of Thrombocytopenia in Cirrhosis" with aim of providing guidance for the clinical diagnosis and treatment.

Pseudothrombocytopenia (PTCP) is defined by the occurence of spouriously low platelet count as a consequence of in vitro platelet aggregation. It is a rare and benign artifact, not associated with any specific disorder or therapy, that becomes clinically relevant when it is not timely and reliably recognized. Thus, it may result in inappropriate clinical decisions ( i.e. unnecessary further testing, misdiagnoses and potential patients' mismanagement) unavoidably compromising patient safety. The most common form of PTCP is caused by ethylenediaminetetraacetic acid (EDTA). Several approaches for the management of samples with EDTA-induced PTCP have been described in the literature. However, expert recommendations are scarce. The scope of these recommendations is to assist in achieving national harmonisation in laboratory management ( i.e. detecting and reporting platelet counts) of samples with EDTA-induced PTCP. These minimal recommendations were prepared by the members of the joint working group of the Croatian Chamber of Medical Biochemists and Working group for Laboratory Hematology of the Croatian Society of Medical Biochemistry and Laboratory Medicine, and might be customized according to specific conditions ( i.e. personnel and equipment) of each individual laboratory. These recommendations are primarily intended to all laboratory professionals involved in the management of samples with EDTA-induced PTCP, but also to other healthcare professionals involved in collecting samples and interpreting complete blood count results., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Background: Vancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed., Case Presentation: A 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 10 9 /L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient's fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 10 9 /L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as "Certain" according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment., Conclusion: This case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases., (© 2024. The Author(s).)

Severe febrile thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease that is endemic in parts of eastern Asia. Few pediatric cases have been reported. We describe a case of SFTS in a seven-year-old girl who presented with prolonged fever and gastrointestinal symptoms. Leukopenia and thrombocytopenia on hematology, and a history of outdoor activity led us to diagnose SFTS, although the patient had no tick bite marks. We also review the literature and discuss the characteristics of pediatric SFTS. Physicians should consider SFTS in the differential diagnosis of fever with thrombocytopenia in children living in endemic areas., Competing Interests: No potential conflict of interest relevant to this article was reported.

India contributes to 26% of the global tuberculosis (TB) burden, with very high mortality and morbidity. The exact incidence of disseminated TB cannot be established among the general population but accounts for <2% of cases among immunocompromised hosts and constitutes 20% of all extrapulmonary TB cases. Disseminated TB has a very high mortality rate of around 25-30%. Miliary TB, a disseminated form, is another entity of TB that poses a health burden due to its difficulty in diagnosis. This entity usually presents with subclinical symptoms and poses a diagnostic challenge in the absence of specific diagnostic tests. We present a case of a young female with epistaxis and thrombocytopenia who was diagnosed with disseminated TB [miliary, bone cyst, bone marrow (BM) involvement]., (© Journal of the Association of Physicians of India 2024.)

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), whose diagnostic criteria changed over time to achieve a timelier diagnosis. Recently, pediatric-specific criteria presented by the European Society for Blood and Marrow Transplantation (pEBMT) incorporated transfusion-refractory thrombocytopenia (RT) as an early indicator of SOS in children. However, a comparison of all individual diagnostic parameters belonging to pEBMT and former SOS diagnostic criteria has never been performed. This retrospective study conducted at a pediatric tertiary care hospital analyzed all pediatric HSCT cases diagnosed with SOS among 170 children transplanted from 2009 to 2023. Eleven patients developed SOS during this period (incidence: 11/170, 6.5%). pEBMT, Seattle, and Baltimore criteria were retrospectively applied to the 11 cases and compared, showing that RT was the earliest fulfilled parameter (median onset: 6 d post-HSCT). pEBMT and Seattle criteria identified 11/11 SOS cases, with pEBMT leading to an earlier diagnosis. RT typically manifested before diagnosis, with significantly higher platelet transfusion requirements before diagnosis than after. RT is the earliest satisfied criterion in pediatric SOS and typically occurs in the initial stages of the disease before diagnosis. Further research is needed to identify additional early indicators of pediatric SOS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A rare lymphoproliferative disorder involving thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), renal dysfunction (R), and organomegaly (O), called TAFRO syndrome, was first reported in 2010. Considered a variant of idiopathic multicentric Castleman's disease, the recent discovery and rarity of this syndrome pose challenges to diagnosis and management. Herein, we review three pediatric cases, including an infant, that illustrate the heterogeneity of TAFRO syndrome. Despite differences in presentation and treatment responses, all patients experienced excellent outcomes. This multi-institutional case series highlights the need to work toward earlier diagnosis and improved long-term management recommendations for patients with TAFRO syndrome., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD. An LZD trough concentration of 8 mg/L was set as the cutoff value for thrombocytopenia occurrence among critically ill patients who received parenteral LZD therapy at a dose of 600 mg every 8 h during ECMO. Eleven patients were included in this prospective observational study. Median LZD trough concentrations were 7.85 (interquartile range (IQR), 1.95-11) mg/L. Thrombocytopenia was found in 81.8% of patients. Based on the median LZD trough concentrations cutoff value, patients were divided into two groups, 1.95 (IQR, 0.91-3.6) and 10.3 (IQR, 9.7-11.7) mg/L, respectively. Median platelet values differed significantly between groups on admission, ECMO day 0, ECMO day 1, and LZD sampling day [194 and 152.5, (p < 0.05)], [113 and 214, (p < 0.05)], [76 and 147.5, (p < 0.01)], and [26 and 96.5, (p < 0.01)], respectively. Duration of LZD therapy was similar between the groups. Significant platelet reduction was observed in both groups, emphasizing the need for closer monitoring to prevent LZD-associated thrombocytopenia., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Endogenous DNA damage is a significant factor in the damage of hematopoietic cells. Megakaryopoiesis is one of the pathways of hematopoiesis that ends with the production of platelets and plays the most crucial role in hemostasis. Despite the presence of efficient DNA repair mechanisms, some endogenous lesions can lead to mutagenic alterations, disruption of pathways of hematopoiesis including megakaryopoiesis and potentially result in human diseases., Areas Covered: The complex regulation of DNA repair mechanisms plays a central role in maintaining genomic integrity during megakaryopoiesis and influences platelet production efficiency and quality. Moreover, anomalies in DNA repair processes are involved in several diseases associated with megakaryopoiesis, including myeloproliferative disorders and thrombocytopenia., Expert Opinion: In the era of personalized medicine, diagnosing diseases related to megakaryopoiesis can only be made with a complete assessment of their molecular aspects to provide physicians with critical molecular data for patient management and to identify the subset of patients who could benefit from targeted therapy.

Purpose: To determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 10 9 /L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies., Materials and Methods: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm., Results: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 10 9 /L (interquartile range, 26-43 × 10 9 /L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9-31.7) compared with SOC group (100%; 95% CI, 88.1-100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9-31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2-27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1-17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups., Conclusions: TEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Immune thrombocytopenia (ITP) in paediatric patients is a complex and heterogeneous disorder characterized by isolated thrombocytopenia and an increased risk of bleeding. The diagnosis of ITP involves a careful exclusion of other causes of thrombocytopenia, supported by clinical evaluation and laboratory findings. Management strategies have evolved significantly, emphasizing individualized treatment approaches based on disease severity, bleeding risk, and patient-specific factors. This comprehensive review provides an in-depth analysis of the current diagnostic criteria, including the role of novel biomarkers and genetic testing in distinguishing ITP from other haematological disorders. We also explore the latest therapeutic options, ranging from observation and first-line treatments such as corticosteroids and intravenous immunoglobulin (IVIG) to second-line therapies, including thrombopoietin receptor agonists and immunosuppressive agents. The review addresses the challenges of managing chronic ITP in pediatric patients, focusing on balancing treatment efficacy with the potential side effects and long-term outcomes. Additionally, we discuss the emerging role of personalized medicine in optimizing care for children with ITP, highlighting recent advances in targeted therapies and the potential for future research to refine diagnostic and treatment paradigms to refine diagnostic and treatment paradigms further., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thakur et al.)

Evans syndrome (ES) is a rare autoimmune disorder characterized by the presence of at least two autoimmune cytopenias (AIC), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). Secondary ES accounts for 21%-50% of cases. ES is characterized by recurrent relapses, serious complications such as thrombosis and infection, and high mortality. The management of ES is highly heterogeneous, necessitating treatment for AIC, the primary disease, as well as associated complications. However, there remains a lack of prospective evidence, randomized clinical trials for ES. To standardize the diagnosis and management of ES in China effectively, this consensus was developed by the Red Blood Cell Diseases (Anemia) Group under the Chinese Society of Hematology within the Chinese Medical Association. It aims to provide valuable guidance for diagnosing and managing ES in clinical practice based on international consensus and comprehensive review of both domestic and international literature.

Background: Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin treatment caused by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Accurate diagnosis of HIT is essential but remains challenging. The aim of our study was to explore the performance of our optimized diagnostic laboratory algorithm, based on Chemiluminescence (CliA) and ELISA immunoassays, on suspected HIT patients. The study compared the prevalence of HIT diagnosis in A.O. Mauriziano with the literature., Methods: 163 consecutive patients were investigated for suspected HIT with CliA HemosIL Acustar HIT-IgG, Werfen. HIT was ruled out in all patients with CliA <0.13 U/mL. All patients with CliA >0.13 U/mL were further investigated with Zymutest-HIA anti-PF4 IgG ELISA immunoassay. In these patients, HIT was ruled out on the combination of CliA between 0.13 and 1.0 U/mL followed by ELISA assay <0.300 OD. HIT was ruled in patients whose plasma tested positive or doubtful with CliA and positive with ELISA immunoassay and confirmed positive with a platelet aggregation test (PAT). Suspicion of HIT was revealed with clinical 4Ts score or recent suggestive anamnestic history., Results: Our diagnostic algorithm ruled out HIT diagnosis in 144/163 patients (88%) and predicted a positive PAT in 5/19 (26%) of CliA positive (4/5) or ELISA positive and CliA doubtful (1/5) patients., Conclusions: Our prevalence was 3.1%, comparable with the literature. The approach combining 2 quantitative immunoassays' (CliA and ELISA) results and 4Ts score probability was able to rule out the diagnosis within 1 h in 66% of patients with suspected HIT and within 24 h in 88% of patients. In the remaining 12% of cases, management decisions have to be based on individualized judgment while awaiting functional confirming results (48-72 h)., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This article provides a comprehensive overview of Heparin-Induced Thrombocytopenia (HIT) with an emphasis on laboratory testing and advantages of automation. HIT is a critical condition arising from heparin exposure, leading to a contradictory combination of thrombocytopenia with an increased thrombosis risk. The article discusses HIT's history, clinical presentation, laboratory diagnosis, and management strategies. It highlights the importance of interdisciplinary collaboration for effective diagnosis and treatment, underscoring advancements in technology and targeted therapies that are shaping future approaches to HIT management., Competing Interests: Disclosure The authors have nothing to disclose including funding., (Copyright © 2024 Elsevier Inc. All rights reserved.)

TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The diagnosis of TAFRO syndrome can be challenging; however, prompt diagnosis is vital because TAFRO syndrome is a progressive and life-threatening disease. We have showcased five patients with TAFRO syndrome who had similar bone marrow (BM) findings that could be considered the findings that characterize TAFRO syndrome. All patients were treated with corticosteroids and tocilizumab; three of the five patients (60 %) responded positively to the treatment. The unique BM findings observed in this study were megakaryocytes with distinct multinuclei and three-dimensional and indistinct bizarre nuclei ("dysmorphic megakaryocyte"), similar to the megakaryocyte morphology observed in myeloproliferative neoplasms (MPNs). Notably, dysmorphic megakaryocytes were observed in all five cases, whereas only two of the five patients tested positive for reticulin myelofibrosis, and three of the five patients had megakaryocytic hyperplasia, which are considered typical findings of TAFRO syndrome. Thus, the BM findings of dysmorphic megakaryocytes could help in the correct and immediate diagnosis of TAFRO syndrome., Competing Interests: Declaration of competing interest The authors declare no conflict-of-interest relevant to this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD 405 ] of 0.93 (SD = 1.21) units, and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD 405  ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody-negative patients. We observed statistical differences between antibody-positive and -negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody-positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context.—: In the Sysmex DI-60 digital morphology system, a platelet estimate factor (PEF) is used to calculate the estimated platelet count (PLT)., Objective.—: To determine the most accurate PEF by analyzing various specimens, including those with abnormal flag alerts, using both impedance (PLT-I) and optical fluorescent (PLT-F) PLT methods. A validation study was then conducted using random specimens to evaluate the accuracy of the PEF., Design.—: This study included 120 blood specimens without flag alerts, and 120 blood specimens with flag alerts related to platelet abnormalities to determine the PEF. Each group was equally divided into thrombocytopenia, normal count, and thrombocytosis specimens. The PEF values obtained from the PLT-I and PLT-F methods were analyzed. An additional 120 specimens were used to compare the estimated PLT from PEF with the PLT-F count. Unadjusted PEF disregarded platelet ranges and flag alerts, whereas adjusted PEF incorporated them., Results.—: The mean PEF values ranged within 9.95 to 12.99 for PLT-I-obtained values (PEF-I) and within 10.32 to 11.69 for PLT-F-obtained values (PEF-F) across different PLT ranges. The mean PEF values were significantly higher in specimens with flags compared with those without flags. The values were 12.43 compared with 10.19 for PEF-I and 11.45 compared with 10.4 for PEF-F. A significant difference was found between PEF-I and PEF-F in flagged specimens, with respective values of 12.43 and 11.45. There was excellent agreement between estimated PLTs using adjusted PEF and PLT-F. However, proportional biases were observed between estimated PLT using unadjusted PEF and PLT-F., Conclusions.—: Adjustment of PEF values according to specific platelet ranges and flag alert presence was shown to enhance the accuracy of PLT estimation using the Sysmex DI-60 system., Competing Interests: The author has no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thrombocytopenia is a common hematologic finding in children and adolescents. Immune thrombocytopenia (ITP) is the most common cause of this finding, but the differential diagnosis includes a growing list of genetic disorders. We aimed to report differences in phenotypes of patients with ITP, inherited platelet disorder (IPD)/primary immunodeficiency disorder (PID), and other causes, with a focus on differentiating ITP from inherited thrombocytopenia., Procedure: This retrospective, population-based observational cohort from 2006 to 2020 involved 506 Finnish children under 16 years of age presenting with isolated thrombocytopenia., Results: Of the 506 participants, 79.7% had ITP, 6.7% had IPD/PID, and 13.6% had other causes of thrombocytopenia. A platelet count of ≤12 × 10 9 /L best distinguished between ITP and other reasons with a sensitivity of 60% and a specificity of 80%. Among patients with the lowest platelet count of less than 10 × 10 9 /L, 95.9% had ITP, 3.3% had IPD/PID, and 0.8% had other causes. Severe bleeding events were reported in 20 patients (4.0%), but there were no cases of intracranial or fatal bleeding due to thrombocytopenia. Up to 50% of patients with a high suspicion of inherited thrombocytopenia remained without a specific diagnosis despite genetic testing., Conclusions: ITP remains the most common cause of thrombocytopenia. A platelet count of ≤12 × 10 9 /L often leads to an ITP diagnosis. Genetic disorders are rare but should be suspected in patients with persisting thrombocytopenia, especially with platelet counts constantly above 12 × 10 9 /L, a positive family history, or atypical clinical features., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Prolonged thrombocytopenia (PT) is a serious complication after haematopoietic stem cell transplantation (HSCT). PT has been suggested to be associated with an increased platelet transfusion requirement and poor outcomes after transplantation. Due to the complex mechanism of PT development, it is difficult to diagnose in the early post-transplant period. Our study aimed to identify an early predictive marker for PT after HSCT. Previous studies showed that the clinical utility of immature platelet fraction (IPF) predicts platelet recovery after chemotherapy and successful engraftment. However, the relationship between IPF and PT after HSCT remains unclear. Fifty-two patients with malignant haematological diseases who underwent HSCT were included in the study. We observed the kinetics of recovery of haematological parameters after transplantation and performed receiver operating characteristics (ROC) curve analysis using data from the 52 HSCT patients. The days to rise and peak of IPF, absolute IPF count (A-IPF) and highly fluorescent IPF (H-IPF) were almost synchronised in all patients, at day 10 and day 15, respectively. The begin to rise levels of IPF, H-IPF and A-IPF were all significantly lower in the PT group than in the good engraftment (GE) group (p=0.0016, p=0.0094, p=0.0086, respectively). The peak levels of IPF were significantly lower in the PT group than the GE group (p=0.0036). However, the peaks of H-IPF and A-IPF were not statistically significant between the two groups (p=0.3383, p=0.0887, respectively). The area under the ROC curve (AUC) of IPF rise was 0.739 (95% CI 0.583-0.896; p<0.05) and the cut-off value was 3.5%, while the AUC of IPF peak was 0.800 (95% CI 0.637-0.962; p<0.01) and the cut-off value was 8.0%. In conclusion, early low levels of IPF predict the development of PT after HSCT. These findings may help improve the management and treatment strategies for PT after HSCT., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale: Gaucher disease (GD) is a rare hereditary lysosomal storage disorder disease progression and inappropriate treatment. However, not all patients with GD receive timely diagnosis and treatment., Patient Concerns: Early diagnosis is important for initiating proper treatment and preventing complications., Diagnoses: Two patients were diagnosed as GD in this study., Interventions and Outcomes: These 2 patients received the imiglucerase enzyme replacement and symptoms significantly improved by the follow-up., Lessons: Herein, we report 2 patients with a delayed diagnosis of GD to increase awareness and improve education regarding rare diseases. However, noninvasive β-glucocerebrosidase activity or GBA gene testing had not been done before bone marrow aspiration, which are the noninvasive and reliable tests that indicate the diagnosis of GD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There is scant evidence regarding the safety of antiplatelet therapy in acute ischemic stroke (AIS) patients with thrombocytopenia. Our study aims to address this concern by examining AIS patients with thrombocytopenia from a large database in real-world settings., Methods and Results: We included patients with AIS with a platelet count <100×10 9 /L who had complete records of antiplatelet drug use. Those requiring anticoagulation or having contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was 1-year all-cause mortality. A good clinical outcome was defined as functional independence, indicated by a modified Rankin Scale score of 0 to 2 at discharge. Propensity score matched analyses were used. We screened 169 423 patients with AIS from 90 stroke centers in the CASE II register, ultimately enrolling 2808 noncardioembolic patients with thrombocytopenia. In the propensity score matched analyses, no significant difference was observed between the antiplatelet and nonantiplatelet groups in terms of intracranial hemorrhage (odds ratio=0.855 [95% CI, 0.284-5.478]; P =0.160) or gastrointestinal bleeding (odds ratio=2.034 [95% CI, 0.755-5.478]; P =0.160). Antiplatelet therapy was associated with improved functional outcomes at discharge (odds ratio=1.405 [95% CI, 1.028-1.920]; P =0.033), and showed a trend towards reducing 1-year mortality (odds ratio=0.395 [95% CI, 0.152-1.031]; P =0.058)., Conclusions: The use of antiplatelet therapy lessened as platelet count decreased in patients with AIS with thrombocytopenia. However, our findings suggest that antiplatelet medications remain safe and effective for this population.

We herein report a 64-year-old man with heparin-induced thrombocytopenia accompanied by anaphylactoid reaction during hemodialysis. The patient was admitted to our hospital with acute myocardial infarction and developed acute kidney injury after percutaneous coronary intervention. When maintenance hemodialysis with heparin was initiated, the patient developed an anaphylactoid reaction with dyspnea, hypotension, nausea, and vomiting. Laboratory tests revealed thrombocytopenia. Immunoglobulin G antibodies to heparin-platelet factor 4 complexes were positive, and a functional assay showed heparin-independent platelet activation. These results provide a definitive diagnosis of heparin-induced thrombocytopenia. The onset timing supported a diagnosis of 'rapid-onset' heparin-induced thrombocytopenia.

Rationale: TAFRO syndrome is a systemic inflammatory disorder, manifesting as thrombocytopenia (t), anasarca (a), fever (f), reticulin myelofibrosis/renal insufficiency (r), and organomegaly (o), and considered as a unique clinical subtype of idiopathic multicentric Castleman disease (iMCD). Such syndrome gave rise to a clinical picture similar to that of either a connective tissue disease or an autoimmune disease., Patient Concerns: A Chinese young female initially presenting with arthralgia, Raynaud phenomenon, generalized edema, and a positive anti-small nuclear ribonucleoprotein particle antibody was diagnosed as mixed connective tissue disease. The kidney biopsy showed thrombotic microangiopathy. Bone marrow smear showed bone marrow hyperplasia and biopsy revealed suspected light chain restricted expression, megakaryocyte proliferation, and moderate to severe bone marrow fibrosis. A lymph node biopsy was conducted and the histopathological findings were consistent with the subtype of mixed Castleman disease. The clinical symptoms were relieved after regular chemotherapy., Diagnoses: After above examination results and clinical manifestations, the final diagnoses was TAFRO syndrome., Intervention: The she was started on chemotherapy with bortezomib, cyclophosphamide, and dexamethasone., Outcome: After chemotherapy, symptoms such as thrombocytopenia, hematuria and proteinuria disappeared, lymphadenopathy and VEGF level decreased, and bone marrow fibrosis relieved., Lessons: Our case illustrated the first cases of shared characteristics of mixed connective tissue disease and iMCD-TAFRO syndrome. Cytokines may play a role in the shared pathogenicity of the iMCD-TAFRO syndrome and systemic autoimmune diseases. Therapy directly against inflammatory factors such as corticosteroids or chemotherapy have an important therapeutic implication., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Osteopetrosis encompasses rare inherited metabolic bone disorders with defect in the osteoclast activity. Severe forms of presentation such as malignant infantile osteopetrosis are seen in infants and milder forms in older children. The clinical presentation includes failure to thrive, severe pallor, optic atrophy and hepatosplenomegaly. The disorder is characterised by dense bone on radiography, hence the name marble bone disease. A 10-month-old boy who presented with developmental delay, failure to thrive, nystagmus (which the mother described as wandering eye movements), splenomegaly of 16 cm and hepatomegaly of 8 cm. Investigations demonstrated severe anaemia (5.7 g/dL) and thrombocytopenia (34 x 109/L). Radiological signs which help in the diagnosis include diffuse sclerosis, bone within bone appearance, sandwich vertebrae and Erlenmeyer flask deformity. Plain radiography is an easily available and cost effective tool which can aid in the diagnosis of osteopetrosis.

Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice., Competing Interests: Declaration of interests WB has received consultancy or advisory board honoraria and speaker's bureau from Alexion, Novartis, Agios, Pfizer, Sanofi, and Sobi. BF has received consultancy or advisory board honoraria and speaker's bureau from Agios, Alexion, Apellis, Janssen, Novartis, Roche, Samsung, Sanofi, and Sobi. HF has received research support from Sanofi and Novartis. AG has received consultancy and research funds from Agios, Bristol Myers Squibb, Novo Nordisk, Saniona, Sanofi, Pharmacosmos, Novartis, AbbVie, and Vertex Pharmaceuticals. TJG-L has received research support from Sobi, Novartis, Amgen, Grifols; speakers bureau from Sobi, Novartis, Amgen, Grifols, argenx, Sanofi, Momenta, and Alpine; and fees for participation in data safety monitoring for Novartis and Alpine. IM has received consultancy honoraria from Alexion, Janssen, Novartis, Apellis, and Sanofi. MaM has received consultancy or speaker's bureau from Alexion, argenx, Sanofi, Novartis, and Sobi. MoM has received consultancy from Gilead, Novartis, AbbVie, and Pfizer. M-EM has received research support, consultancy and speaker's bureau from Amgen, Novartis, Novo Nordisk, Sanofi, Grifols, Sobi, Takeda, and CSL Bering. MN has received speaker fees from Sobi, Novo Nordisk, Amegn, Novartis, Kedrion, Bayer, Takeda, CSL Behring, and Sanofi, and consultancy honoraria from Bayer and CSL Behring. AP has received consultancy or speaker's bureau from Sanofi, Alexion, Novartis, Sobi, Pfizer, Gilead, and Morphosys. SR has received consultancy honoraria from Sanofi, Novartis, and Alexion. NV has received speaker's bureau from Sanofi, Amgen, and Grifols. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Objective: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis., Methods: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 10 9 /L), mild thrombocytopenia (100 ≤ PC < 150 × 10 9 /L), normal PC (150 ≤ PC ≤ 450 × 10 9 /L), and thrombocythemia (PC > 450 × 10 9 /L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes., Results: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 10 9 /L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02)., Conclusions: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 10 9 /L, especially PC < 100 × 10 9 /L. It indicated that PC < 100 × 10 9 /L is a reasonable contraindication to thrombolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Cardiogenic shock (CS) is associated with high mortality. Patients treated for CS mostly require heparin therapy, which may be associated with complications such as heparin-induced thrombocytopenia (HIT). HIT represents a serious condition associated with platelet decline and increased hypercoagulability and remains a poorly researched field in intensive care medicine. Primary purpose of this study was to: 1) determine HIT prevalence in CS, 2) assess the performance of common diagnostic tests for the workup of HIT, and 3) compare outcomes in CS patients with excluded and confirmed HIT., Design: Retrospective dual-center study including adult patients 18 years old or older with diagnosed CS and suspected HIT from January 2010 to November 2022., Setting: Cardiac ICU at the Ludwig-Maximilians University hospital in Munich and the university hospital of Bonn., Patients and Interventions: In this retrospective analysis, adult patients with diagnosed CS and suspected HIT were included. Differences in baseline characteristics, mortality, neurologic and safety outcomes between patients with excluded and confirmed HIT were evaluated., Measurements and Main Results: In cases of suspected HIT, positive screening antibodies were detected in 159 of 2808 patients (5.7%). HIT was confirmed via positive functional assay in 57 of 2808 patients, corresponding to a prevalence rate of 2.0%. The positive predictive value for anti-platelet factor 4/heparin screening antibodies was 35.8%. Total in-hospital mortality (58.8% vs. 57.9%; p > 0.999), 1-month mortality (47.1% vs. 43.9%; p = 0.781), and 12-month mortality (58.8% vs. 59.6%; p > 0.999) were similar between patients with excluded and confirmed HIT, respectively. Furthermore, no significant difference in neurologic outcome among survivors was found between groups (Cerebral Performance Category [CPC] score 1: 8.8% vs. 8.8%; p > 0.999 and CPC 2: 7.8% vs. 12.3%; p = 0.485)., Conclusions: HIT was a rare complication in CS patients treated with unfractionated heparin and was not associated with increased mortality. Also, HIT confirmation was not associated with worse neurologic outcome in survivors. Future studies should aim at developing more precise, standardized, and cost-effective strategies to diagnose HIT and prevent complications., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Systemic lupus erythematosus (SLE) is often seen with antiphospholipid antibody syndrome (APS), and these conditions may occur concurrently with severe immune thrombocytopenia (ITP) and even acute kidney injury (AKI); however, post-renal AKI due to bleeding is uncommon. Here, we describe a case of post-renal AKI and anuria in a patient with SLE and APS, which were attributable to urinary tract obstruction due to massive blood clots caused by secondary ITP. A 50-year-old Japanese woman was admitted to our hospital with anuria, abdominal tenderness, purpura in the trunk and in both legs, and severe thrombocytopenia. She had been receiving medical treatment for APS and SLE till the age of 45 years. Computed tomography revealed a blood clot without extravasation in both urinary tracts, and she was diagnosed with post-renal AKI due to complete obstruction of the urinary system. Additionally, based on her medical history, elevated platelet-associated Immunoglobulin G (IgG) levels, and increased megakaryocyte count, she was diagnosed with secondary ITP complicated by SLE and APS. She also had elevated APS-related autoantibodies, including antiphosphatidylserine/prothrombin Immunoglobulin M (IgM), and IgG. However, concomitant serositis such as lupus enteritis or cystitis was not seen. She was treated with a combination of glucocorticoids, intravenous immunoglobulin, and continuous haemodialysis/haemofiltration, which resulted in rapid improvement of her symptoms and renal dysfunction. Secondary ITP-induced massive bleeding of urinary tract can cause post-renal AKI. Appropriate diagnosis and aggressive treatment are necessary to improve prognosis in such patients., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition induced by platelet-activating IgG antibodies that recognize PF4/heparin complexes. Diagnosis of HIT relies on enzyme immunologic assays (EIAs) and functional assays [serotonin release assay (SRA)]. Our institution uses a latex immunoturbidimetric assay (LIA), which has shown a positive-predictive value (PPV) of 55.6%, and a negative-predictive value (NPV) of 99.7%. The low PPV of EIAs/LIAs, in combination with the clinical delay in obtaining results of a SRA, commonly leads to a false-positive diagnosis of HIT and inappropriate treatment. We performed a single-institution retrospective study at a large tertiary center to assess patient management decisions and economic costs following a false-positive HIT (LIA) test. This study found an 89.5% incidence of false-positive HIT (LIA) tests. 97.4% of patients underwent anticoagulation changes. 69.6% of patients were switched to argatroban. Of patients with a false-positive HIT immunoassay (LIA), 42 (40.7%) patients were on a prophylactic dose of anticoagulation at the time of HIT (LIA) positivity, of which 22 (52.4%) were switched to full anticoagulation with either argatroban or fondaparinux. Of the 22 patients switched to full anticoagulation, 15 (68%) had low-probability 4T scores. Seven (8.8%) of patients had bleeding events after HIT (LIA) positivity. All seven patients were switched to argatroban from a full-dose heparin anticoagulation. Five of the seven patients were considered major bleeds. Utilization of argatroban incurred substantial costs, estimated at approximately $73 000 for false-positive HIT cases. False-positive HIT (LIA) tests contribute to unwarranted anticoagulation changes, increased bleeding risks, and substantial healthcare costs. Incorporating the 4T score into diagnostic algorithms may help mitigate these risks by guiding appropriate clinical decisions. Future research should focus on refining diagnostic approaches and standardizing management strategies to improve patient outcomes and cost-effectiveness in HIT diagnosis and management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The most ordered laboratory test worldwide is the complete blood count (CBC)., Content: In this primer, an introduction to platelet testing in the context of the CBC is provided with a discussion of the laboratory evaluation of platelet abnormalities including thrombocytopenia and thrombocytosis., Summary: As clinical chemists continue to be tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This primer is dedicated to that effort., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Bernard-Soulier syndrome (BSS) is caused by defects in GP1BA, GP1BB, or GP9 genes. Patients with 22q11.2 deletion syndrome (22q11.2DS) are obligate carriers of BSS because GP1BB resides on chromosome 22q11.2. A 15-month-old girl without bleeding symptoms had giant platelets and thrombocytopenia. Physical findings and macrothrombocytopenia suggested 22q11.2DS, which was confirmed by fluorescence in situ hybridization. Flow cytometry showed decreased GPIbα on the platelets. Gene panel testing revealed a novel variant in GP1BB, p.(Val169&#95;Leu172del). These findings confirmed that the patient had BSS. This case suggests that any patient with 22q11.2DS and macrothrombocytopenia should be further tested for BSS., (© 2024. Japanese Society of Hematology.)

Context.—: Laboratories face the challenge of providing quality patient care while managing costs and turnaround times (TATs). To this end, we brought the heparin-induced thrombocytopenia (HIT) antibody test in-house with the goal of reducing costs and the time to diagnosis., Objectives.—: To determine the cost-effectiveness and return on investment of our in-house HIT antibody test by comparing it to send-out assays with TATs of 2, 3, or 4 days., Design.—: We performed a retrospective chart review of all patients with a HIT antibody assay and analysis of laboratory financial records. Analysis included the percentage of patients receiving alternative treatment, cost of treatment, startup costs of bringing the test in-house, and average TAT of the in-house test., Results.—: We found significant reductions in the cost of treatment for patients and the overall cost to the health care system. The in-house assay became cost-effective at between 8 and 20 tests, with a return on investment of up to 298%., Conclusions.—: Bringing the HIT antibody assay in-house becomes cost-effective at a very low test volume with excellent return on investment. This novel analysis can provide a framework for other laboratory medicine professionals to analyze the benefits of bringing this and other assays in-house., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background and Objectives: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare adverse effect characterized by thrombocytopenia and thrombosis occurring after COVID-19 vaccination. VITT pathophysiology is not fully unravelled but shows similarities to heparin-induced thrombocytopenia (HIT). HIT is characterized by the presence of antibodies against platelet factor 4 (PF4)/heparin complex, which can activate platelets in an FcγRIIa-dependent manner, whereas IgG-antibodies directed against PF4 play an important role in VITT., Materials and Methods: We characterized all clinically suspected VITT cases in the Netherlands from a diagnostic perspective and hypothesized that patients who developed both thrombocytopenia and thrombosis display underlying mechanisms similar to those in HIT. We conducted an anti-PF4 ELISA and a functional PF4-induced platelet activation assay (PIPAA) with and without blocking the platelet-FcγRIIa and found positivity in both tests, suggesting VITT with mechanisms similar to those in VITT., Results: We identified 65 patients with both thrombocytopenia and thrombosis among 275 clinically suspected VITT cases. Of these 65 patients, 14 (22%) tested positive for anti-PF4 and PF4-dependent platelet activation. The essential role of platelet-FcγRIIa in VITT with mechanisms similar to those in HIT was evident, as platelet activation was inhibited by an FcγRIIa-blocking antibody in all 14 patients., Conclusion: Our study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti-PF4-inducing, FcɣRIIa-dependent platelet activation, suggesting an HIT-like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology ('non-HIT like') leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies., (© 2024 International Society of Blood Transfusion.)

A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but elements of her presentation and workup including brain magnetic resonance imaging were not consistent with isolated CMV infection. To avoid premature diagnostic closure, a multidisciplinary workup was initiated and ultimately established her diagnosis., (Copyright © 2024 by the American Academy of Pediatrics.)