Antiphospholipid Antibodies and Procoagulant Profile in Tunisians With Inflammatory Bowel Diseases.

The hypercoagulable state accompanying inflammatory bowel diseases (IBDs) is still poorly understood. The aim of this study was to assess antiphospholipid antibodies (APAs) and a large panel of inherited and acquired thrombotic markers simultaneously in a sample of Tunisian patients with IBD. In total, 89 consecutive patients with IBD (mean age 38 ± 15 years; 48 with Crohn disease and 41 with ulcerative colitis) and 129 controls were prospectively evaluated for immunoglobulin (Ig) G, IgM, and IgA antibodies against cardiolipin (aCL), ß2glycoprotein I (aß2GPI), and prothrombin (aPT); IgG and IgM antibodies against phosphatidic acid (aPA), phosphatidylinositol (aPI), and annexin V (aAnnV); lupus anticoagulant (LA); coagulation factors; natural inhibitors; and thrombotic genetic polymorphisms. Levels of fibrinogen, factors II, V, and VIII and von Willebrand factor, antithrombin, and protein C were significantly higher in patients with IBD than in controls (P < .05 for all comparisons). At least 1 APA subset was detected in 54 patients. The frequencies of antibodies against anionic phospholipids-aCL, aPI, and aPA-in patients with IBD were 15.9%, 21.3%, and 14.6%, respectively. The frequencies of antiphospholipid cofactor antibodies were 39.8% for aß2GPI and 15.7% for both aAnnV and aPT. Isolated aß2GPI IgA was detected in 22 patients, and 12 (13.5%) patients had LA. The IgA aß2GPI antibodies were frequently detected in Tunisian patients with IBD. These results are of potential diagnostic, prognostic, and therapeutic interest.

Hemodialysis duration, human platelet antigen HPA-3 and IgA isotype of anti-ß2glycoprotein I antibodies are associated with native arteriovenous fistula failure in Tunisian hemodialysis patients.

INTRODUCTION: Arteriovenous fistula (AVF) failure is a major cause of morbidity and mortality in hemodialysis patients. We assessed the role of a large panel of acquired and inherited thrombophilic markers in cases of AVF thrombosis among 101 Tunisians on chronic hemodialysis, all with native AVF. MATERIALS AND METHODS: In this case-control study, we considered the levels of fibrinogen, factor II, factor VII, factor VIII, factor IX, factor X, factor XI, factor XII, von Willebrand factor, natural coagulation inhibitors, D-Dimer, homocysteine, IgG, IgM and IgA anticardiolipin and anti-ß2glycoprotein I (anti-ß2GPI), and anti-H/PF4 antibodies; the presence of Lupus Anticoagulant; and genetic markers (Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C). RESULTS: Multivariate analysis indicated that dialysis for >69 months (OR=10.12; 95% CI, 2.53 to 40.52; p=0.001), HPA-3aa genotype (OR=3.58; 95% CI, 1.36 to 9.4; p=0.01) and anti-ß2GPI IgA isotype (OR=3.4; 95% CI, 1.21 to 9.55; p=0.02) were independent risk factors for AVF thrombosis in Tunisian hemodialysis patients. Kaplan-Meier analysis showed that AVF survival was significantly lower for patients with anti-ß2GPI IgA than for patients without this isotype (log-rank test, p=0.014). CONCLUSIONS: IgA anti-ß2GPI may be of clinical relevance among Tunisians. Further studies on the polymorphism of ß2GPI and HPA systems would be helpful for identifying patient groups at high risk of AVF failure.

Frequency of specific coagulation inhibitors and antiphospholipid antibodies in Tunisian haemophiliacs.

Production of factor VIII or factor IX inhibitors is a major complication limiting the efficiency of substitutive therapy in haemophiliacs. Moreover, viral infections, the second serious complication of replacement therapy, may be associated to the occurrence of antiphospholipid antibodies which paradoxically lead to thrombosis. We investigated the prevalence of coagulation inhibitors (factor VIII and factor IX inhibitors, antiphospholipid antibodies) in Tunisian haemophiliacs, and we assessed concomitant coagulation factor deficiencies. Thirty-two previously treated haemophiliacs (20 haemophiliacs A; 12 haemophiliacs B) were screened for factor VIII and factor IX inhibitors by APTT mixing study, Bethesda test and modified Nijmegen method, and investigated for the presence of anticardiolipin, anti-ß2 glycoprotein I, lupus anticoagulant and associated coagulation factors deficiencies. The frequency of factor VIII and factor IX inhibitors was low (5%) in contrast to the high prevalence of antiphospholipid antibodies (28.1%). Four and nine patients were positive for anticardiolipin and anti-ß2 glycoprotein I, respectively. No lupus anticoagulant was detected. The prevalence of antiphospholipid antibodies was higher in patients with positive hepatitis C virus infection serology as compared to patients with negative serology (41.6% vs. 20%). Concomitant factor VII and/or factor V deficiency was found in 10 patients. In conclusion, the occurrence of factor VIII and factor IX inhibitors is rare among Tunisian haemophiliacs. The clinical relevance of antiphospholipid antibodies requires further investigations. We emphasize the importance of screening for concomitant deficiencies in haemophiliacs when the clinical presentation is suggestive.

Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C, and homocysteinemia in Tunisian blood donors.

Specific genetic conditions are known to be associated with high risk of venous thromboembolism. This genetic basis varies widely between ethnic groups. We investigated the distribution of four inherited polymorphisms in 113 unselected Tunisian blood donors by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The allele frequencies of Factor V Leiden (FVL), prothrombin 20210G>A, methylenetetrahydrofolate reductase (MTHFR) 677C>T, and MTHFR 1298A>C mutations were 3, 0.9, 30, and 31%, respectively. The MTHFR 677C>T polymorphism was influenced by age. Twenty-nine of the 113 blood donors demonstrated more than one genetic markers. Hyperhomocysteinemia was found in 12 subjects, and it was statistically associated to the MTHFR 677TT genotype. Principal component analysis allowed disclosing the resemblance between Mediterranean populations. Our findings may be helpful for population genetics study, and provide epidemiologic database for further studies in thrombosis field among Tunisians.