Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders

Abstract

Chronic myeloproliferative disorders (MPD) are characterized by a high incidence of thrombohaemorrhagic complications, possibly related to platelet abnormalities and disturbances of the coagulation system. In an attempt to de®ne abnormalities in coagulation and ®brinolysis, we investigated risk markers for venous thromboembolism, ®-brinolytic, and haemostatic system activation markers and antiphospholipid antibodies in blood samples from 50 MPD patients and 30 controls. Compared with controls median levels of protein S free and protein C were signi®cantly decreased in the patients (0.27 vs. 0.38 arbitrary units; P < 0.001 and 0.86 vs. 0.99 arbitrary units; P < 0.001, respectively), and activated partial thromboplastin time was signi®cantly prolonged in patients (33 vs. 27 sec; P < 0.001). No dierences were observed in levels of antithrombin, thrombin± antithrombin complex, and ®brin D-dimer. In patients the median value of thrombomodulin was signi®cantly increased indicating perturbed endothelial function. Anticardiolipin antibodies of IgM subtype (median 38 U/mL, 33±99) were detected in 11 patients (22%) and only in one control (3%) (P < 0.021; patients vs. controls). Seven patients were heterozygous for the Factor V Leiden, one patient was heterozygous for the prothrombin G20210A mutation, and one patient was homozygous for the Factor V Leiden mutation. Among controls, two were heterozygous for the Factor V Leiden mutation. Comparing the allele frequency of the Factor V Leiden mutation in patients with MPD and the background population disclosed a signi®cantly increased allele prevalence of the Factor V Leiden mutation in the patients (9% vs. 3.4%; P = 0.003). Alterations in the level of anticoagulant proteins, disturbances of endothelial cell function, and the presence of cardiolipin antibodies and Factor V Leiden mutation may increase the cumulative thrombotic risk in MPD besides the risk imposed by platelet activation. Am.

Myeloproliferative neoplasms and thrombosis

“…The frequency of genetic thrombophilic factors, such as factor V Leiden or prothrombin mutations, was higher in MPN with venous thrombosis, suggesting that these tests should be performed in younger patients with a familial or personal history of thrombosis. [65][66][67] On the contrary, in regard to the role of antiphospholipid antibodies 68,69 and hyperhomocysteinemia, 70,71 data so far produced are too limited to recommend their evaluation in the work-up of patients with MPN.…”

Association Between the G20210A Polymorphism of Prothrombin Gene and Myocardial Infarction in Tunisian Population

“…Various studies showed that carrier frequency of The prothrombin G20210A polymorphism in healthy southern europeans was around 3 % (Rosendaal et al Bykowska et al 2000), nearly twice as high as data from the north of Europe (Poort et al 1996;Rosendaal et al 1998;Jensen et al 2002).…”

Platelets and Thrombosis in Myeloproliferative Diseases

“…The largest study of 304 ET and PV patients identified an association between presence of the factor V Leiden mutation and venous thrombosis (16%) compared with its absence (3%). 30 An increased prevalence of antiphospholipid antibodies has been reported in ET 31,32 and correlated with thrombosis in one report. 31 Small sample sizes and limited confirmatory testing of the detected antibodies limit the impact of these findings.…”