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Hepatectomy-induced coagulation disturbances have been well studied over the past decade. Cumulative evidence supports the superiority of global coagulation analysis compared with conventional coagulation tests (i.e., prothrombin time or activated partial thromboplastin time) for clinical decision making. Cancer, however, represents an acquired prothrombotic state and liver resection for cancer deserves a more thorough investigation. This prospective observational study was conducted to assess the perioperative coagulation status of patients undergoing major hepatectomies for primary or metastatic hepatic malignancy. Patients were followed up to the 10th post-operative day by serial measurements of conventional coagulation tests, plasma levels of coagulation factors, and thrombin generation assay parameters. An abnormal coagulation profile was detected at presentation and included elevated FVIII levels, decreased levels of antithrombin, and lag time prolongation in thrombin generation. Serial hematological data demonstrated increased Von Willebrand factor, FVIII, D-dimer, fibrinogen and decreased levels of natural anticoagulant proteins in the early post-operative period predisposing to a hyper-coagulable state. The ratio of the anticoagulant protein C to the procoagulant FVIII was low at baseline and further declined post-operatively, indicating a prothrombotic state. Though no bleeding complications were reported, one patient experienced pulmonary embolism while under thromboprophylaxis. Overall, patients with hepatic carcinoma presenting for elective major hepatectomy may have baseline malignancy-associated coagulation disturbances, aggravating the hyper-coagulable state documented in the early post-operative period.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.

A B S T R A C T Important progress has been made in the development of risk assessment models (RAM) for the identification of outpatients on anticancer treatment at risk of venous thromboembolism (VTE). Since the breakthrough publication of the original Khorana risk score (KRS) more than 10 years ago, a new generation of KRS-based scores have been developed, including the Vienna Cancer and Thrombosis Study, PROTECHT, CONKO, ONCOTEV, TicOnco and the CATS/MICA score. Among these the CATS/MICA score showed that a simplified score composed of only two calibrated predictors, the type of cancer and the D-dimer levels, offers a user-friendly tool for the evaluation of cancer-associated thrombosis (CAT) risk. The COMPASS-CAT score is the first that introduced a more synthetic approach of risk evaluation by combining cancer-related predictors with patient comorbidity in a score which is designed for the types of cancer frequently seen in the community (i.e. breast, lung colon or ovarian cancers) and has been externally validated in independent studies. The Throly score is registered as part of the same group as it has a similar structure to the COMPASS-CAT score and is applicable in patients with lymphoma. The incorporation of specific biomarkers of hypercoagulability to the RAM for CAT offers the possibility to perform a precision medicine approach in the prevention of CAT. The improvement of RAM for CAT with artificial intelligence methodologies and deep learning techniques is the challenge in the near future.

The increase in fetal and neonatal morbidity and mortality associated with twin pregnancies correlates with an increased risk of preterm delivery, low birth weight, and intrauterine growth restriction (IUGR). Although the pathogenesis of IUGR is unclear and thus management remains a major challenge, feto-placental blood vessels are compromised, and altered umbilical blood flow is observed. In this pilot observational study we investigated the effects of pravastatin plus l-arginine on umbilical artery (umb art) blood flow. Between 2013 and 2016, five women received daily doses l-arginine and pravastatin when an umb art pulsatility index above limits for gestational age was observed and concerns about selective growth restrictions arose. All patients showed selective absent or reversed end-diastolic umbilical artery Doppler flow (AREDV) associated with increased perinatal mortality. Pravastatin (PRAV) plus l-arginine (l-Arg) treatment diminished umb art resistance significantly and allowed pregnancy to continue. No signs of acidosis or hypoxia, normal cardiotocography tracing, normal fetal movement and fetal weight gain were observed in the twins that showed abnormal umb art Dopplers. All neonates were born around 33 weeks (median 33 weeks, IQR [31.4–33.0]), thus diminishing substantially the chances for any prematurity-associated adverse neonatal outcomes. The infants now show normal growth and development. In in vitro studies, pravastatin induced relaxation of aortic rings. Murine studies identified were performed to investigate the mechanism behind PRAV+L-Arg beneficial effects. A nitric oxide (NO)-dependent synergistic vasorelaxant effect of PRAV+L-Arg was demonstrated using aortic rings. Increased levels of placental NO and increased synthesis of eNOS in placental endothelial cells were observed in mice treated with PRAV+L-Arg compared to untreated mice and mice treated with PRAV- or L-Arg alone. This study suggests that PRAV plus L-Arg might be a good therapeutic option to improve blood flow in umbilical arteries prolonging pregnancy and improving pregnancy outcomes in twins. A RCT should be organized to confirm these results.

A previous pilot study showed that pravastatin supplementation improved pregnancy outcomes in women with obstetric antiphospholipid syndrome (OAPS) that developed placental insufficiency despite standard of care treatment low molecular weight heparin plus low dose aspirin (LMWH + LDA). In this study we investigated the mechanism behind the beneficial effects of the triple therapy LMWH + LDA + pravastatin in improving uteroplacental vascular function and reducing pregnancy complications in OAPS. We hypothesized that nitric oxide (NO) is involved in the vasculoprotective effects of the triple therapy. A mouse model of OAPS that resembles the clinical scenario was used to test this hypothesis.Eleven women with OAPS that developed preeclampsia (PE) and/or intrauterine growth restriction (IUGR) associated with uteroplacental vascular dysfunction despite treatment with LMWH + LDA participated in this study after given informed written consent. Seven women were supplemented with pravastatin at the time abnormal uterine artery Dopplers were detected and 4 remained on LMWH + LDA treatment only. Wire myography was used to identify the mechanisms underpinning the protective effects of the triple therapy in the mouse model of OAPS.The triple therapy increased serum NO levels, diminished uteroplacental vessels resistance improving placental function and prolonged pregnancies compared to conventional treatment LMWH + LDA, leading to live births in women with OAPS. Comparable to the observations in women, the triple therapy protected pregnancies in OAPS-mice, increasing placental perfusion and pregnancy outcomes. A synergistic vasculoprotective effect of the triple therapy on uterine arteries and aorta was demonstrated in OAPS-mice. LMWH + LDA showed a partial protection on endothelial function. Addition of pravastatin increase eNOS synthesis, expression and activity/signaling leading to a significant increment in nitric oxide (NO) generation, resulting in improved placental vascular function and total protection of pregnancies.LMWH + LDA + PRAV increased serum NO levels and significantly improved placental haemodynamics and maternal and neonatal outcomes in women and mice with OAPS. A role for eNOS/NO in mediating the placental vasculoprotective effects in OAPS-mice was demonstrated, strengthening the concept that impaired NO production is a crucial mediator in the pathogenesis of OAPS and a potential target for pharmacological interventions. The efficacy of pravastatin supplementation should be confirmed in a larger clinical trial.

Uteroplacental vascular dysfunction, characterized by diminished uterine artery (UtA) blood flow in the second trimester is a clinically useful predictor of the further development of preeclampsia, fetal growth restriction and stillbirth. Efforts to develop effective treatments to protect pregnancies with abnormal UtA Dopplers would be of significant clinical benefit for mothers and their fetuses.The aim of this pilot non randomized control study was to use pravastatin +L-arginine to improve uteroplacental haemodynamics and prevent adverse maternal and neonatal outcomes in women with abnormal Dopplers and high risk for developing adverse pregnancy outcomes.This study was performed between 2015 and 2018. All women received primary care at OB/GYN Polyclinic Jurisic and Narodni Front University Hospital, University of Belgrade Medical School, Serbia. Approval for investigational drug use was obtained and all women gave informed consent. 10 pregnant women with a poor obstetric history that developed uteroplacental dysfunction (UtA pulsatility index (PI) above the 95th percentile and notching) at 20.5 weeks IQR [17.7-22] gave consent to be treated daily with pravastatin (40 mg) and L-arginine (1.5 g) to improve placental blood flow and pregnancy outcomes. 5 women remained untreated after diagnosis at 21 weeks [20-22] (control group). Due to presence of risk factors for pregnancy complications, close maternal and fetal monitoring was undertaken in all patients. Doppler examinations were performed to monitor changes in placental vascular resistance and fetal well-being and growth.PRAV+L-arginine improved uteroplacental haemodynamics, increased fetal growth and prevented early onset preeclampsia leading to delivery close to term (delivery date: median 38 weeks, IQR[36.5-39]) and appropriate weight for gestational age compared to controls, in which placental blood flow did not improve and 2 women developed severe early onset preeclampsia. Neonates from the control group were born preterm (25 weeks IQR[23.5-25]), growth restricted and spent several months at NICU. Two neonates died due to prematurity-associated complications. PRAV+L-arginine treatment prolonged pregnancies for 4.1 months, compared to 26 days in the untreated group, preventing neonatal complications associated with prematurity. The infants are now 1-3 years old and show normal growth and development.This study describes the successful management with pravastatin+L-arginine of 10 pregnant patients with uteroplacental vascular dysfunction and high risk of adverse maternal and fetal outcomes. A larger study is being organized to confirm these observations.

In addition to its role in calcium homeostasis and bone formation, a modulatory role of the active form of vitamin D on cells of the immune system, particularly T lymphocytes, has been described. The effects of vitamin D on the production and action of several cytokines has been intensively investigated in recent years. In this connection, deficiency of vitamin D has been associated with several autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Hashimoto Thyroiditis (HT), and multiple sclerosis (MS). In a successful pregnancy, the maternal immune response needs to adapt to accommodate the semiallogeneic fetus. Disturbances in maternal tolerance are implicated in infertility and pregnancy complications such as miscarriages (RM) and preeclampsia (PE). It is well-known that a subset of T lymphocytes, regulatory T cells (Tregs) exhibit potent suppressive activity, and have a crucial role in curtailing the destructive response of the immune system during pregnancy, and preventing autoimmune diseases. Interestingly, vitamin D deficiency is common in pregnant women, despite the widespread use of prenatal vitamins, and adverse pregnancy outcomes such as RM, PE, intrauterine growth restriction have been linked to hypovitaminosis D during pregnancy. Research has shown that autoimmune diseases have a significant prevalence within the female population, and women with autoimmune disorders are at higher risk for adverse pregnancy outcomes. Provocatively, dysregulation of T cells plays a crucial role in the pathogenesis of autoimmunity, and adverse pregnancy outcomes where these pathologies are also associated with vitamin D deficiency. This article reviews the immunomodulatory role of vitamin D in autoimmune diseases and pregnancy. In particular, we will describe the role of vitamin D from conception until delivery, including the health of the offspring. This review highlights an observational study where hypovitaminosis D was correlated with decreased fertility, increased disease activity, placental insufficiency, and preeclampsia in women with APS.

During pregnancy the physiological changes in the haemostatic system tend to improve the mild inherited bleeding disorders. However, thrombocytopenia and coagulation problems unique to pregnancy may occur. In this review, we discuss and provide recommendations for the management of bleeding problems seen in pregnancy, such as thrombocytopenia, von Willebrand disease, haemophilias and thrombotic microangiopathies. In the majority of cases complicated by haematological disease, pregnancy, delivery and the puerperium should be managed by a multidisciplinary team, which includes obstetricians, haematologists and obstetric anaesthetists.

BACKGROUND. Administration of conventional antithrombotic treatment (low-dose aspirin plus low–molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency–associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes. METHODS. We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated. RESULTS. In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients. CONCLUSION. The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy.

Background Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome. Methods Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5–8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of βHCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point. Results Positive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome. Conclusions Diagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials.

Evans' syndrome, the coexistence of immune thrombocytopenia (ITP) with autoimmune haemolytic anaemia (AIHA), is rare in pregnancy, with a few published cases. Concerns about the teratogenic effect of pharmacological agents used in the management of Evans' syndrome limit the treatment options in pregnancy. In this paper we performed a systematic review of the literature of all published cases with Evans' syndrome in pregnancy and we report two new cases. The review was performed by searching the electronic databases PubMed, EMBASE, Cochrane Library and Google scholar up to the end of December 2008. The selection criteria were Evans' syndrome in pregnancy; autoimmune haemolytic anaemia; immune thrombocytopenia. Thirteen papers reporting 14 pregnancies in women with Evans' syndrome have been published: 7 papers are written in English. Evans' syndrome can be diagnosed with a full blood count, film and Coombs testing. It runs a more benign course in pregnancy than in non-pregnant state (notably neutropenia does not occur) and very often resolves post-delivery. The fetal outcome may be less favourable: a minority of fetuses are affected by transplacental passage of antibody and have a significant morbidity and mortality. With appropriate treatment, women with Evans' syndrome can have successful pregnancies, with a good response to conventional treatment. More detailed studies of Evans' syndrome in pregnancy, especially of fetal outcome, are required.

The objective of the present study was to evaluate the Taipan snake venom time (TSVT) assay in the detection of lupus anticoagulant in patients receiving or not receiving oral vitamin K antagonists. Blood samples were collected from individuals requiring investigation for the presence of a lupus anticoagulant. The TSVT test was run in parallel with the dilute Russell viper venom time (dRVVT) assay and anticardiolipin antibody assays. Results were assessed by Bayesian statistics. Two thousand and five plasma samples were obtained from 1335 individuals. One thousand, one hundred and eleven individuals were not receiving oral vitamin K antagonists; of these, 451 had a lupus anticoagulant by conventional testing, and the TSVT showed a sensitivity of 22%, specificity of 98%, positive predictive value of 80%, negative predictive value of 78%, positive likelihood ratio of 12.3 and a negative likelihood ratio of 0.790. Two hundred and ten of the 224 patients receiving oral vitamin K antagonists were known to have a persistent lupus anticoagulant prior to oral anticoagulation. In this setting, TSVT had a sensitivity of 39% and specificity of 93%, but the dRVVT had a 50% false-positive rate, which meant that despite having a higher sensitivity at 61% than the TSVT, its specificity was only 53%. TSVT is a specific but insensitive assay for the lupus anticoagulant in individuals not receiving oral vitamin K antagonists, when assessed against the dRVVT as the gold standard. It can be argued that despite the TSVT's poor sensitivity in patients taking oral vitamin K antagonists, its high specificity and positive predictive value make it a preferable assay to the dRVVT to diagnose lupus anticoagulant in this group.

Obstetric haemorrhage (OH) remains the leading cause of maternal morbidity and mortality worldwide, 140 000–160 000 women die annually. Uterine atony (70%), and retained and invasive placentae remain the commonest causes. Rarely OH is due to an inherited bleeding disorder. Although risk factors and preventive strategies are documented, not all cases are expected or avoidable. Haematological management includes regular monitoring of full blood count and coagulation screen, with the appropriate use of blood products: red cells to maintain a Hb>8 g/dl; if APPT ratio and/or INR>1.5 then 15 ml/kg of fresh frozen plasma; if fibrinogen 9 then one single donor pool. As fibrinolytic activation occurs with blood loss, 1–2 g tranexamic acid is suggested as it is safe, but as yet no studies of its use in OH have been undertaken. The use of rFVIIa is also reviewed. Women with OH are at high risk of venous thromboembolism post delivery and thromboprophylaxis is recommended for these women once bleeding has ceased.

International audience; BackgroundIn breast cancer patients routine thromboprophylaxis is not recommended but individualized risk assessment is encouraged. The incorporation of hypercoagulability biomarkers could increase the sensitivity of risk assessment models (RAM) to identify patients at VTE risk. To this aim we investigated the impact of cancer-related characteristics on hypercoagulability biomarkers.MethodsThrombin generation (TG) assessed with the Thrombogramme-Thrombinoscope®, levels of platelet derived microparticles (Pd-MP) assessed with flow cytometry, procoagulant phospholid dependent clotting time (PPL-ct) measured with a clotting assay and D-Dimers (were assessed in a cohort of 62 women with breast cancer and in 30 age matched healthy women.ResultsPatients showed significantly higher TG, Pd-MP, D-Dimers levels and shortened PPL-ct compared to the controls. The PPL-ct was inversely correlated with the levels of Pd-MP, which were increased in 97% of patients. TG and D-Dimers were increased in 76% and 59% of patients respectively. In any stage of the disease TG was significantly increased as compared to the controls. There was no significant difference of TG in patients with local, regional of metastatic stage. There was no significant difference in Pd-MP or Pd-MP/PS+ between the subgroups of patients with local or regional stage of cancer. Patients with metastatic disease had significantly higher levels of Pd-MP and Pd-MP/PS+ compared to those with regional stage. The D-Dimers increased in patients with metastatic stage. In patients on chemotherapy with less than 6 months since diagnosis TG was significantly higher compared to those on chemotherapy who diagnosed in interval > 6 months. Patients with metastatic disease had significantly higher levels of Pd-MP and D-Dimers compared to those with non-metastatic disease.ConclusionIn breast cancer patients the stage, the time elapsed since the diagnosis and the administration of chemotherapy are determinants of cellular and plasma hypercoagulability. The levels and the procoagulant activity of Pd-MP are interconnected with the biological activity and the overall burden of cancer. TG reflects the procoagulant properties of both breast cancer and chemotherapy in the initial period of cancer diagnosis. Thus the weighted incorporation of the biomarkers of cellular and plasma hypercoagulabilty in RAM for VTE might improve their predictive value.

The clinical hallmarks of the antiphospholipid syndrome (APS) are thrombosis and adverse obstetric outcomes. Women with APS have a higher incidence of preeclampsia.1 Currently, treatment of APS focuses on anticoagulation therapy, treatment mostly given empirically and often ineffective. Similarly, treatment for preeclampsia remains symptomatic and also ineffective. Studies in animal models support the hypothesis that pravastatin may be an effective therapy to prevent pregnancy complications in APS and in preeclampsia.2–5 Here, we describe a patient, with a previous history of preeclampsia, thrombosis, and APS, presenting with preeclampsia at 23 weeks’ gestation in her second pregnancy that was treated with pravastatin, which resulted in marked clinical improvement and successful pregnancy outcome. A 30-year-old woman with no previous medical history had a first pregnancy complicated with early preeclampsia with bilateral notching (22 weeks and 0 days) and hypertension and edema at 24 weeks, leading to a still birth at week 26. She developed deep vein thrombosis 2 days postpartum. Based on her history of deep vein thrombosis, early preeclampsia, and twice positive lupus anticoagulant, with an interval of 3 months between the tests, the patient was diagnosed with APS. The patient received therapeutic doses of low-molecular-weight heparin for 3 months and prophylactic doses while trying to conceive again. Her blood pressure and proteinuria remained normal. Ten months later, she got pregnant and was started on intermediate doses of enoxaparin (0.6 OD) and aspirin (100 mg OD). Blood pressure …

Background Parental history of coronary artery disease (CAD) is considered an important risk factor for early atherosclerosis Hypothesis The onset of the inflammatory process of atherosclerosis initiates early during childhood in children with positive family history (PFH) of CAD. Methods We studied 55 healthy children (5–15 years), 30 (16 male) with PFH and 25 age and sex matched control subjects. Blood samples were taken to measure white blood count (WBC), glucose, total cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), erythrocyte sedimentation rate (SDE), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-a). We performed cultures on monocytes (from peripheral blood) measuring in the cell culture supernatants the proinflammatory cytokines IL-6 and TNF-a, by using the immunoassay ELISA method. Results: Higher values of body mass index (BMI), total cholesterol, LDL, cholesterol, TG, SDE, leucocytes, and CRP were calculated in children with PFH. Significantly higher values of cytokines in monocell cultures were measured in the PFH group compared to the control group (IL-6 = 139.32 ± 80.84 pg/ml versus 14.30 ± 12.97 pg/ml, p < 0.001 and TNF-a = 39.91 ± 11.80 pg/ml versus 8.65 ± 4.35 pg/ml, p < 0.001). IL-6 values in plasma and cultures were found independently associated with PFH of premature CAD (p < 0.001, p = 0.005, respectively). A similar relation was found for TNF-a values measured in cultures (p = 0.005) and CRP values in plasma (p < 0.001). The values of IL-6 were found proportionally related to TG. Conclusion In individuals with PFH of CAD the inflammatory process of atheromatosis appears to begin early in childhood. Except for triglycerides, this inflammatory process appears to occur independently of several traditional cardiovascular risk factors. Copyright © 2010 Wiley Periodicals, Inc.

Kawasaki disease (KD) is characterized by persistent fever, mucous membrane hyperaemia, cervical lymph node enlargement, exanthema and periungual desquamation. It is seen mainly in children, with

Increased life expectancy in patients with homozygous beta-thalassaemia consequently increases the risk for neoplastic diseases. This study was conducted to assess the levels of five common tumour markers in thalassaemic patients and to investigate possible correlations to demographical, clinical and laboratory data. Eighty-five patients (44 female and 41 male) with homozygous beta-thalassaemia (mean age = 27.92 +/- 12.5), on regular blood transfusions and adequate chelation treatment, and 60 sex and age- matched healthy controls were enrolled in the study. Blood samples for the determination of carcinoma antigen (CA) 15.3, CA 125, CA 19.9, carcinoembryonic antigen (CEA) and alpha-fetoprotein (a-FP) were collected from every subject. Results showed that 69% of the thalassaemic patients had abnormal levels of CA 15.3, whereas only sporadic cases had increased levels of CA 125 and CA 19.9. On the contrary, all controls had normal levels of CA 15.3, CA 19.9 and CA 125. CEA and a-FP were within reference ranges both in the thalassaemic and in the control group. Levels of CA 15.3 were significantly lower in patients aged less than 20 years compared to older patients. Male patients had significantly increased levels of CA 15.3 compared to female patients. Relatively recent studies show an increased expression of CA 15.3 on progenitor cells of the erythroid lineage and increased amounts of circulating progenitor cells even in well-transfused thalassaemic patients. However, it seems that there are also other factors contributing to this phenomenon. In conclusion, our results indicate that CA 15.3 seems to be an unreliable marker of occult malignancy in patients with beta-thalassaemia. However, more studies are needed to support these preliminary results.

Summary. Congenital afibrinogenaemia is a rare bleeding disorder characterized by absence of fibrinogen and varying bleeding tendency. Treatment with fibrinogen concentrates is considered to be the best choice for afibrinogenaemic patients who experience bleeding. We report the case of a 22-year-old Greek patient who presented with large muscular haematomas and was treated with fibrinogen concentrates. The efficacy of this treatment and the problems that arose during his hospitalization are being discussed.

Introduction: Obstetric haemorrhage (OH) is a major cause of maternal mortality and morbidity worldwide. Appropriate management requires understanding of normal peripartum haemostatic changes during labour, and yet there are few studies. Aim: In this pilot study we aimed to evaluate peripartum haemostatic changes in healthy women. Methods: We collected blood samples from 20 women peripartum, into 0.102 M trisodium citrate tubes (ratio9:1) (Becton Dickinson) from the antecubital fossa using flawless venepuncture at the following time-points: antepartum; after delivery of the placenta; 24hrs post-partum and 48hrs post-partum. Plasma was aliquoted and stored in −70°C until the following ELIZA assays were performed: D-Dimer levels (Dade Behring, Sysmex UK), prothrombin fragments 1+ 2 (PF 1+2) (Dade Behring, Sysmex, UK) and tissue plasminogen activator antigen (t-PA:Ag) (Biopool, Trinity Biotech, UK). Prothrombin time (PT) (PT-Fib HS), activated partial thromboplastin time (APTT) (APTT micronized silica) and clauss fibrinogen (Fib-C), reagents were from Instrumentation Laboratories Ltd UK. Statistical analysis was performed using XLSTAT 2008. Results: The median (range) age was 28 (19–36) years and the body mass index (BMI) 28.9 (21.7– 35.3). Table 1: To show the median (range) for the haemostatic assays Assay (normal ranges) D-dimers (4–52ug/l) PF1+2 (0.2–1.2 pmol/l) t-PA:Ag: 3–11 ng/ml) PT (12–16s) APTT (26–38s) Fibrinogen (1.52–4.12 g/l) * p Conclusion: These findings demonstrate that peripartum haemostasis is prothrombotic with shortened PT, APTT and prolonged fibrinogen. There is increased thrombin generation and fibrinolytic activity. t-PA antigen is most notably elevated immediately post delivery.