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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]

Objectives: To determine if inherited thrombophilia and immunological disorders represent risk factors for small for gestational age infants, and to assess their relationship with neonatal status., Design: Case-control study., Population: Ninety-seven consecutive women who had pregnancies complicated by unexplained small for gestational age infants, defined as a birthweight below the third centile and 97 women as controls who delivered infants with a birthweight > or = 10th centile., Methods: Patients were included in the immediate postpartum period and tested for antithrombin III, protein C, protein S, anticardiolipin and antinuclear antibodies, lupus anticoagulant, Factor V Leiden mutation, prothrombin 20210A mutation, and methylenetetrahydrofolate reductase (MTHFR) polymorphism. Women with small for gestational age infants were then divided into subgroups depending on haemostatic and immunologic status in order to compare neonatal events., Results: Frequencies for anticardiolipin and antinuclear antibodies were higher in women with small for gestational age infants compared with controls (P = 0.02 and P = 0.004, respectively), and overall prevalence of inherited thrombophilia were comparable in cases and controls (19.6% and 18.6%, respectively). The subgroups of patients with small for gestational age infants were women with only one inherited thrombophilia (n = 10), only one immunological disorder (n = 14), combined disorders (n = 9), and no detected abnormality (n = 64). Admission to paediatric ward significantly increased in the group with combined disorders (P = 0.002) compared with the other groups. Also one-third of the babies from this group had a poor neonatal outcome. However, most of the neonatal deaths (6/7 = 85.7%) occurred in the group with no detected abnormality., Conclusion: The prevalence of inherited thrombophilia was considered to be similar between the case and the control groups even when immunological disorders were significantly elevated in pregnancies complicated by the baby being small for gestational age. Combined disorders may represent a potential risk factor for severe small for gestational age infants. However, the aetiology of small for gestational age infants with poor neonatal outcomes remains unknown in most cases.

The factor V (FV) Arg 506 to Gln mutation is the most common abnormality observed in familial thrombophilia. Many studies have shown that its clinical expression differs among families and among carriers. Some thrombotic patients carry an additional genetic risk factor such as protein C, protein S or antithrombin deficiency. We sought to identify other genetic risk factors potentially favouring expression of the thrombotic phenotype in 370 members of 43 families with the FV Arg 506 to Gln mutation. We analysed three candidate polymorphisms in genes involved in the PC anticoagulant pathway, consisting of two polymorphic sites in the 5' non-transcribed region of the PC gene, -1654 C/T and -1641 A/G, with three known combinations (TA, CA and CG) that influence the protein C plasma level; one polymorphic site (4070 A/G) in exon 13 of the FV gene, which influences the plasma factor V concentration, and one polymorphic site (677 C/T) in the methylenetetrahydrofolate reductase gene, which is often associated with moderate hyperhomocysteinaemia. The distribution of these different polymorphisms was similar in patients with a history of thrombosis and those who remained asymptomatic, ruling out the possibility that each of these polymorphisms alone can play a role in the onset of thrombosis in carriers of the FV Arg 506 to Gln mutation.