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This document is a letter to the editor discussing a French field study on the cross-reactivity of human anti-FVIII antibodies to porcine rFVIII. The study aimed to validate the modified Nijmegen method used in French laboratories for the titration of anti-porcine FVIII inhibitors. The study compared the stability of rpFVIII in different dilution media and assessed the cross-reactivity of plasma samples from patients with AHA and congenital hemophilia A with inhibitors. The results showed a decrease in rpFVIII activity after incubation, but no statistical difference between dilution media. The study provides valuable information for the laboratory assessment of rpFVIII in the treatment of AHA. Another study discussed in the letter found that cross-reactivity with rpFVIII was detected in 26% of AHA samples and 75% of PWA samples, but high cross-reactivity above 20 BU/mL was rare and not observed in the AHA population. The study confirmed the feasibility of using imidazole buffer to detect anti-rpFVIII antibodies. [Extracted from the article]

Introduction Factor XIII ( FXIII) deficiency is a rare hemorrhagic disorder whose early diagnosis is crucial for appropriate treatment and prophylactic supplementation in cases of severe deficiency. International guidelines recommend a quantitative FXIII activity assay as first-line screening test. FXIII antigen measurement may be performed to establish the subtype of FXIII deficiency ( FXIIID) when activity is decreased. Methods The aim of this multicenter study was to evaluate the analytical and diagnostic levels of performance of a new latex immunoassay, K-Assay® FXIII reagent from Stago, for first-line measurement of FXIII antigen. Results were compared to those obtained with the Berichrom® FXIII chromogenic assay for measurement of FXIII activity. Of the 147 patient plasma samples, 138 were selected for analysis. Results The accuracy was very good, with intercenter reproducibility close to 7%. Five groups were defined on FXIII activity level (<5% ( n = 5), 5%-30% ( n = 23), 30%-60% ( n = 17), 60%-120% ( n = 69), above 120% ( n = 24)), without statistical differences between activity and antigen levels ( P value >0.05). Correlation of the K-Assay® with the Berichrom® FXIII activity results was excellent (r = 0.919). Good agreement was established by the Bland and Altman method, with a bias of +9.4% on all samples, and of −1.4% for FXIII levels lower than 30%. One patient with afibrinogenemia showed low levels of Berichrom® FXIII activity but normal antigen level and clot solubility as expected. Conclusions The measurement of FXIII antigen using the K-Assay® is a reliable first-line tool for detection of FXIII deficiency when an activity assay is not available. [ABSTRACT FROM AUTHOR]

We present here a 63-year old woman with a long history of immune thrombocytopenia. She was hospitalized for a traumatic intracranial hemorrhage with thrombocytopenia. Following inefficient treatment of four platelet transfusions, immunoglobulins, and corticosteroids, we initiated treatment with a thrombopoietin (TPO) receptor agonist (eltrombopag 25 mg/d) with a good efficacy. Her mother and sister also had chronic thrombocytopenia. Clinical history, hemostasis results, and gene analysis revealed von Willebrand disease (VWD) type 2B with the mutation (c.3946G>A; p.V1316M), which combines a von Willebrand factor defect with severe thrombocytopenia, as well as a thrombocytopathy. The efficacy of TPO receptor agonists appears to counterbalance, at least to some extent, the thrombocytopathy associated with this mutation. As such, the use of TPO receptor agonists could represent an alternative therapeutic approach in cases of VWD type 2B with severe thrombocytopenia. [ABSTRACT FROM PUBLISHER]

The article offers information on a study conducted by the authors on discrepancies between chromogenic substrate assay and one stage assay in patients who are treated with coagulation factor VIII. Topics discussed include evaluation of the ReFacto antihemophilic factor in clinical practice, testing of plasma samples of the patients, and mentions the need for guidelines to be followed for postinfusion monitoring and pharmacokinetic assessment of coagulation factor FVIII concentrates.

Abstract: Antithrombin (AT) is a natural anticoagulant and serine protease inhibitor. Hereditary AT deficiencies are uncommon and are associated with a higher risk of venous thrombo-embolism (VTE) compared to other thrombophilias. They are either quantitative (type I) or qualitative (type II) and various mutations have been reported. The II HBS deficiency is caused by a defect in the heparin-binding region (HBS) of AT. This homozygous deficiency increases the risk of VTE. The association with arterial thrombosis is weak but a few cases have been reported. We report a 20-year-old female with recurring arterial thrombosis associated with an AT type II HBS deficiency, due to a homozygous mutation Leu99Phe. In young patients, with recurrent and unexplained arterial thrombosis, a biologic thrombophilia has to be comprehensively searched. [Copyright &y& Elsevier]

PURPOSE: Review of the frequency, clinical and biological features and treatment of type II heparin-induced thrombocyopenia.METHODS: Case report and literature review.RESULTS: A 65 years old woman received as antithrombotic prophylaxis low molecular weight heparin (LMWH) after prosthetic knee replacement. Day 8, asymptomatic deep vein thrombosis was discovered after systematic echodoppler examination. Curative anticoagulation was started with LMWH. A fall in the platelet count (17 G/L) was noted day 12. Danaparoid was immediately introduced and heparin discontinued. However, day 16 a massive pulmonary embolism occurred which required transfer to an intensive care unit. Danaparoid was changed for lepirudin the same day. It took longer than three weeks for platelet count to return to normal value after heparin discontinuation. The suspicion of heparin-induced thrombocyopenia was confirmed by specific tests.DISCUSSION: HIT type II are rare but life-threatening and thrombosis events are the most frequent complications. The diagnosis is a high probability proved by both clinical and biological patterns. The treatment consists in alternative thrombin inhibitors such as danaparoid and lepirudin. The platelet count usually requires less than ten days to recover normal values after heparin withdrawal. Cases in which the delay to a normal platelet count exceeds 3 weeks have been reported specially after LMWH therapy.CONCLUSION: Type II HIT are rare but life-threatening events can occur. The platelet count check-up during heparin therapy must be systematic. [Copyright &y& Elsevier]

Abstract: Purpose: Acquired haemophilia A (AHA) is a rare bleeding disorder, due to the presence of an inhibitor directed against factor VIII (FVIII). About 50% of the AHA are idiopathic, while the remaining 50% are related to an underlying disorder or condition (autoimmune diseases, malignancies, postpartum, etc.). Patients and methods: We report on a monocentric retrospective cohort of 39 patients with AHA. Data were collected and compared to recent published data. Results: Thirty-nine patients were admitted for AHA between 1993 et 2011. Mean age at diagnosis was 71.3 years, and we noted a marked male predominance. Although the majority of patients presented a bleeding event at diagnosis (94.9%), the hemorrhagic mortality was low (2.6%). On the contrary, immunosuppressive morbidity and mortality were high in this elderly population. There was a clear correlation between initial FVIII inhibitor titer and complete remission delay. We did not identify prognostic factor for global survival. Conclusion: AHA is a rare but potentially fatal disorder. Rapidity of diagnosis and treatment initiation is crucial. Morbidity and mortality, particularly of infectious cause, due to immunosuppressive treatment, should lead to consider other available therapeutical options. [Copyright &y& Elsevier]

Purpose.– Moderate hyperhomocysteinemia is a risk factor for deep venous thrombosis. The homozygous C677T methylenetetrahydrofolate reductase (MTHFR) mutation is associated with increased level of total plasma homocysteine. The association between homozygous C677T mutation and deep venous thrombosis is still controversial.Method. – In order to evaluate this association, we studied the prevalence of C677T mutation in 168 patients with confirmed deep venous thrombosis; 31 with an idiopathic deep venous thrombosis (group A) and 137 with thromboembolic event explained by one or more clinical and/or biological risk factors (group B).Results.– The distribution of genotypes was different between group A and B [++/+ –/– –(n(%))] : 9(29)/10(32)/12(39) vs 16(12)/57(42)/64(46) (χ2 : 6.03 ; P: 0.049). The comparison between homozygotes and the two other genotypes showed significant statistical relationship between homozygous genotype and idiopathic character of deep venous thrombosis (χ2 : 6.01 ; P : 0.014 ; OR : 3.09 [IC 95% : 1.06–8.53]).Conclusion. – These results suggest that homozygous C677T methylenetetrahydrofolate reductase mutation could be considered as a genetic risk factor for venous thrombosis. [Copyright &y& Elsevier]