Abstract
Patients with essential thrombocythemia (ET) and polycythemia vera (PV) have a high risk of thrombosis. Inherited thrombophilias are established risk factors for thrombosis. To determine if inherited thrombophilic abnormalities might contribute to the thrombotic risk in ET and PV, we investigated antitrombin III (ATIII), protein C (PC) and protein S (PS), polymorphisms of clotting factors V (FVQ506) and II (G20210A) and methylenetetrahydrofolate reductase (MTHFR) mutation in patients with ET and PV and we tried to correlate these results with prothrombotic markers such as bthromboglobulin (bTG), platelet factor 4 (PF4), prothrombin fragment 1+2 (F1+2) and d-dimer (DD). In addition, we analysed a possible association between inherited coagulopathy and thrombosis. ATIII, PC and PS antigen levels were assayed by ELISA as well as bTG, PF4 and F1+2. PCR-based assays were used for FVQ506, prothrombin and MTHFR. DD was measured by immunoturbimetric latex agglutination. The study involved 101 patients diagnosed with ET (71 patients, 30 men, 41 women, mean age 62.3 years) or PV (30 patients, 21 men, 9 women, mean age 65.4 years) according to conventional criteria. The duration of disease ranged between 1 to 12 years. Of 101 patients, 53 (52,47%) were non-carriers of mutations and among these 24 (45.28%) experienced thrombosis, 48 (47.52%) were carriers and 27 (56.25%) had thrombosis. With reference to carriers, 9/48 (14.58%) had combined mutations such as PC and PS (2/9), PS and G20210A (1/9), PC and MTHFR (4/9), G20210A and MTHFR (2/9). The prevalence of studied defects was 31.25% (15/48) and 18.75% (9/48) for deficiency of PC and PS, respectively, 8.33% (4/48) and 14.58% (7/48) for heterozygosity of FVQ502 and G20210A, respectively, and 45.83% (22/48) for MTHFR mutation. Deficiency of ATIII was not present. All patients had higher bTG, PF4 and F1+2 (365±654 IU/ml, 133±64 IU/ml and 2.6±2.5 nmol/L, respectively) than to controls (23.8±9.1 IU/ml, 5.5±2.8 IU/ml and 0.60.2 nmol/L, respectively) (p<0.0001) and normal DD (144±92 ng/L). No correlation between studied polymorphisms genetic and bTG, PF4, F1+2 and DD was found as well as with thrombotic complication. The frequency of thrombosis was not statistically different between non-carriers and carriers. Based on these data, it appears that inherited thrombophilias are not an additional risk factor for thrombosis in ET and PV and that the thrombotic phenomena are due to the abnormal platelet function that is part of the myeloproliferative disorders.
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