Heparin, which is used at high doses in hemodialysis patients, may induce antibodies favoring thromboembolic complications. We prospectively investigated the prevalence of heparininduced 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-b2GPI 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. Am. J. Hematol. 81:328-334, 2006. V V C 2006 Wiley-Liss, Inc.

Gene frequencies of mainly human platelet antigens (HPA) -1 to -6 and -15 were determined in 116 Tunisian blood donors. The distribution of HPA-1, -3 and -5 systems approach those found in other Maghrebian populations. Tunisians have the highest frequency of HPA-1b and -5b alleles. The distribution of HPA-1a allele and HPA-4, -6 and -15 systems is similar to Caucasians. Phylogenetic study using the neighbor-joining method and principal component multivariate analysis demonstrate that Tunisians are more closely related to western than to eastern Mediterraneans. This immunogenetic study highlights the relatedness between Mediterranean populations and will serve as a baseline study for future clinical research involving platelet disorders among Tunisians.

Pregnancy may allow alloimmunization against human platelet antigens (HPA), which can lead to neonatal alloimmune thrombocytopenia (NAIT). The specificities of alloantibodies are closely related to the distribution of the HPA systems. A total of 281 Tunisian multiparous women (mean number of pregnancies: 4.5) were phenotyped for the HPA-1, -3 and -5 systems, by monoclonal antibody immobilization of platelet antigens (MAIPA). We searched for antibodies against HPA-1a, HPA-3a, HPA-5b and HPA-5a in HPA-1b1b, HPA-3b3b, HPA-5a5a and HPA-5b5b individuals, respectively. The gene frequencies were: 0.83 for HPA-1a, 0.17 for HPA-1b, 0.78 for HPA-3a, 0.22 for HPA-3b, 0.82 for HPA-5a and 0.18 for HPA-5b. Anti-HPA-5b antibodies were present in eight sera and anti-HPA-3a antibodies were present in one serum. The anti-HPA-5b system is the most frequently involved in platelet alloimmunization in Tunisian multiparous women. However, prospective trials are required to confirm this result and to determine the exact frequencies and clinical relevance of platelet alloantibodies in pregnant Tunisian women.

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