Extended persistence of antiphospholipid antibodies beyond the 12-week time interval: Association with baseline antiphospholipid antibodies titres.

INTRODUCTION: The confirmation time interval for the presence of antiphospholipid antibodies (aPL) has been extended to 12 weeks as epiphenomenal antibodies may disappear after 6 weeks. Our aim was to analyse extended persistence of aPL positivity beyond the 12-week interval. METHODS: We retrospectively analysed our database of 23 856 aPL test samples collected between 2005 and 2017 from 17 367 consecutive patients. Two groups of patients were identified among aPL-positive patients, confirmed at 12 weeks: with or without extended persistence beyond confirmatory testing. Percentages of extended persistence are given according to the initial aPL positivity profiles, and baseline laboratory variables are compared between the two groups. RESULTS: Three hundred and twenty-seven patients confirmed aPL-positive had subsequent testing. The vast majority of them displayed extended persistence in the long term: 89.6% and up to 97.9% for patients with initial triple positivity. In extended persistent positive patients, there were more LA-positive initial samples, and baseline LA test values and IgG aCL titres were higher than in nonpersistent positive patients. CONCLUSION: Data from a large database of an aPL referral laboratory showed that the time interval of 12 weeks defining persistence of aPL positivity was appropriate for the majority of patients. Furthermore, we found baseline features associated with extended persistence.

Possible relationship between antiphospholipid antibodies and embolic events in infective endocarditis.

OBJECTIVE: Antiphospholipid (aPL) antibodies may activate platelets and contribute to vegetation growth and embolisation in infective endocarditis (IE). We aimed to determine the value of aPL as predictors of embolic events (EE) in IE. METHODS: We studied 186 patients with definite IE (Duke-Li criteria, all types of IE) from the Nanc-IE prospective registry (2007-2012) who all had a frozen blood sample and at least one imaging procedure to detect asymptomatic or confirm symptomatic EE. Anticardiolipin (aCL) and anti-ß2-glycoprotein I (ß2GPI) antibodies (IgG and IgM) were assessed after the end of patients' inclusion. The relationship between antibodies and the detection of EE after IE diagnosis were studied with Kaplan-Meier and Cox multivariate analyses. RESULTS: At least one EE was detected in 118 (63%) patients (52 cerebral, 95 other locations) after IE diagnosis in 80 (time interval between IE and EE diagnosis: 5.9±11.3 days). At least one aPL antibody was found in 31 patients (17%).Detection of EE over time after IE diagnosis was more frequent among patients with anti-ß2GPI IgM (log-rank P=0.0036) and that of cerebral embolisms, among patients with aCL IgM and anti-ß2GPI IgM (log-rank P=0.002 and P<0.0001, respectively).Factors predictive of EE were anti-ß2GPI IgM (HR=3.45 (1.47-8.08), P=0.0045), creatinine (2.74 (1.55-4.84), P=0.0005) and vegetation size (2.41 (1.41-4.12), P=0.0014). Those of cerebral embolism were aCL IgM (2.84 (1.22-6.62), P=0.016) and anti-ß2GPI IgM (4.77 (1.79-12.74), P=0.0018). CONCLUSION: The presence of aCL and anti-ß2GPI IgM was associated with EE, particularly cerebral ones, and could contribute to assess the embolic risk of IE.

[A case of dysfibrinogenemia without hemorrhagic diathesis or thromboembolism linked to a new mutation p.H103N in fibrinogen γ chain]. / Un cas de dysfibrinogénémie sans complication hémorragique ni thrombotique lié à une nouvelle mutation p.H103N de la chaîne γ du fibrinogène.

This work describes a dysfibrinogenemia linked to a new mutation in the gene coding for fibrinogen γ chain. Dysfibrinogenemia was fortuitously discovered in a 9-year old boy consulting for symptoms suggesting meningitis. DNA was extracted from blood, the fibrinogen genes coding for Aα, Bß and γ chains were sequenced, and compared with consensus sequences. Apart from the patient, dysfibrinogenemia and the mutation p.H103N in the γ chain of fibrinogen with heterozygous status were found in his mother, without any symptom. This mutation is unknown in fibrinogen variant databases and seems to affect mostly fibrin polymerisation. The reporting of this new p.H103N mutation in the γ chain has a great interest for improving the knowledge of the fibrinogen gene and its expression. Even if no haemorrhage was observed in this case, the expression of this mutation impaired the function of the molecule, particularly polymerisation, and could induce bleeding during an important surgery.

Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant.

Several genome-wide association studies (GWAS) have identified a strong association between serum vitamin B12 and fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. Hazra et al. conducted a meta-analysis of three GWAS and found three additional loci in MUT, CUBN and TCN1. Other GWAS conducted in Italy and China confirmed the association for FUT2 gene. Alpha-2-fucosyltransferase (FUT2) catalyzes fucose addition to form H-type antigens in exocrine secretions. FUT2 non-secretor variant produces no secretion of H-type antigens and is associated with high-plasma vitamin B12 levels. This association was explained by the influence of FUT2 on H. pylori, which is a risk factor of gastritis, a main cause of vitamin B12 impaired absorption. However, we recently showed that H. pylori serology had no influence on FUT2 association with vitamin B12, in a large sample population, suggesting the involvement of an alternative mechanism. GIF is another gene associated with plasma levels of vitamin B12 and gastric intrinsic factor (GIF) is a fucosylated protein needed for B12 absorption. Inherited GIF deficiency produces B12 deficiency unrelated with gastritis. We report 2 families with heterozygous GIF mutation, 290T>C, M97T, with decreased binding affinity of GIF for vitamin B12 and one family with heterozygous GIF mutation 435_437delGAA, K145_N146delinsN and no B12 binding activity of mutated GIF. All cases with vitamin B12 deficit carried the FUT2 rs601338 secretor variant. Ulex europeus binding to GIF was influenced by FUT2 genotypes and GIF concentration was lower, in gastric juice from control subjects with the secretor genotype. GIF290C allele was reported in 5 European cases and no Africans among 1282 ambulatory subjects and was associated with low plasma vitamin B12 and anaemia in the single case bearing the FUT2 secretor variant. We concluded that FUT2 secretor variant worsens B12 status in cases with heterozygous GIF mutations by impairing GIF secretion, independently from H. pylori-related gastritis.

[Prophylactic use of a recombinant activated factor VII in delivery haemorrhage by caesarean in a woman with major factor VII deficiency: a case report]. / Utilisation prophylactique du facteur VII activé recombinant dans l'hémorragie de la délivrance par césarienne chez une patiente atteinte de déficit majeur en facteur VII : à propos d'un cas.

Taking in charge the delivery of pregnant women with inherited major deficiency of factor VII (FVII) is poorly reported in literature. We report here the haemorrhagic prophylaxis of delivery by recombinant activated FVII (rFVIIa) in a 27-year-old women, gravida 1, para 0, with major deficiency FVII by missense mutation (p.Arg337Cys). Her parents, first germen, presented a FVII deficiency. She has four brothers and three sisters, of which only one brother has major FVII deficiency with hemorrhagic diathesis in childhood (hematochezia). At her birth, because of dystocia, a right sterno-cleido-mastoid muscle hematoma and left clavicle fracture occurred. The FVII concentration was 0.08 U/mL. At the age of fifteen, a surgery of appendicitis was performed with substitution by FVII from plasma donors without any haemorrhagic complication. Because of anatomic specificity (bifid uterus and vagina), caesarean was planned. After reviewing of the literature, caesarean was performed at 38th week of gestation with haemorrhagic prophylaxis consisting in administration of rFVIIa (eptacog alfa) at a dose of 20 µg/kg, 30 min before surgery, then every 3 h during 48 h. No haemorrhagic complication occurred. Thrombosis prophylaxis was ensured by enoxaparin (4000 UI a day subcutaneously started 6 h after surgery for 5 days). Clinical examination of the newborn was normal. In future, modalities of taking in charge have to be evaluated by prospective studies involving a sufficiently numerous group of woman with FVII major deficiency, or by retrospective studies with the means of national or European registers.