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.

Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report.

BACKGROUND: Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. CASE PRESENTATION: Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. CONCLUSIONS: The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.

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.

[Primary renal non-Hodgkin lymphoma]. / Lymphome non-Hodgkinien rénal primitif.

Primary renal non Hodgkin lymphoma is rare and unusual because the renal parenchyma does not have lymphatics. We report a case of bilateral primary lymphoblastic T lymphoma presenting with renal insufficiency in a 14 year old girl. We discuss clinical, pathological particularity and prognosis.

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.

A prospective study of the prevalence of heparin-induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis.

Heparin, which is used at high doses in hemodialysis patients, may induce antibodies favoring thromboembolic complications. We prospectively investigated the prevalence of heparin-induced platelet-reactive antibodies in a cohort of 38 pediatric hemodialysis patients, by means of heparin/platelet factor 4 (H/PF4) ELISA and heparin-induced platelet activation assay (HIPA). We also assessed other acquired and congenital hypercoagulable states. Heparin-induced antibodies were detected in 13 and 21% of patients with HIPA and ELISA, respectively. Anti-H/PF4 antibodies were negatively correlated with the number of hemodialysis sessions. These antibodies disappeared after a median time of 6 months despite continuing heparin treatment. The prevalence of antiphospholipid antibodies was 21% (anticardiolipin 10.5%, anti-beta2GPI 13%, and lupus anticoagulant 5%). Blood levels of homocysteine, factor VIII, and fibrinogen were significantly higher and factor II levels were significantly lower in hemodialysis patients than in controls, whereas factor VII, factor IX, and natural coagulation inhibitor levels were similar in patients and controls. Overall, 26 of 38 patients had at least one biomarker of hypercoagulability, but only 1 patient, without anti-H/PF4 antibodies, presented with thrombosis. In conclusion, heparin induces the transient production of anti-H/PF4 antibodies in children undergoing hemodialysis, but other abnormalities probably contribute to hypercoagulability. These findings may help to improve the diagnosis and management of thrombotic events in hemodialysis patients.

Platelet and granulocyte alloimmunisation in multitransfused Tunisian patients.

We determined the frequency of post-transfusion alloimmunisation against platelet and granulocyte antigens in 51 Tunisian polytransfused patients with haematological diseases. Serum samples were analysed by a standard and an antiglobulin-augmented lymphocytotoxicity technique, a granulocyte agglutination test, a granulocyte immunofluorescence test, a platelet immunofluorescence test and the monoclonal antibody-specific immobilisation of platelet antigens assay. No granulocyte-specific antibodies were detected. HLA antibodies were found in 58.8% of patients. Platelet-specific antibodies were detected in four patients and were directed against human platelet antigen (HPA)-5b, HPA-1b and HPA-3a. The three patients with Glanzmann's thrombasthenia developed anti-GPIIb/IIIa antibodies. This study provides immunogenetic information that could improve the management of transfusion therapy in Tunisia.