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.