Thrombophilic genotypes, natural anticoagulants, and plasma homocysteine in myeloproliferative disorders: Relationship with splanchnic vein thrombosis and arterial disease

Abstract

The contribution of pro-thrombotic factors towards the development of arterial disease (AD) and splanchnic vein thrombosis (SVT) was retrospectively evaluated in 79 patients (39M, 40F, mean age 55 ± 16 years) with myeloproliferative disorders (MPD) (essential thrombocythemia [n = 26], primary proliferative polycythemia [n = 27], and idiopathic myelofibrosis [n = 26]). Of these, 18 had AD and 17 SVT, the remaining 44 were nonthrombotic (NT). Plasma concentrations of natural anticoagulants, plasma homocysteine (HC), IgG anticardiolipin antibodies (aCL), and thrombophilic genotypes (methylenetetrahydrofolate reductase C 677 T, factor V Leiden, prothrombin G 20210 →A) were determined. Isolated protein C deficiency was found in 23% of patients from the SVT group, in 5% from the AD group, in 6.8% from the NT group, and in 1% of historical controls (P = 0.0001). The prevalence of thrombophilic genotypes and that of the other natural anticoagulants did not differ across the groups. The proportion of patients with elevated plasma HC was 66% in the AD group, 27% in the non-thrombotic group, 12% in the SVT group and 4.5% in the control group (P < 0.0001). Patients with AD had higher plasma HC (24.4 ± 23 µmol/L) than NT patients (12.3 ± 7.7 µmol/L), SVT patients (9 ± 4.9 µmol/L), and healthy controls (7.9 ± 3 µmol/L) (P < 0.0001). In a logistic regression model lower protein C was independently associated with SVT, whereas elevated plasma HC was independently associated with AD. Measurement of plasma HC and protein C in MPD may identify patients more likely to suffer arterial disease and splanchnic vein thrombosis and who may require plasma HC lowering in the former case. Am. J. Hematol. 72:75-81, 2003.

Predictive factors of thrombosis for patients with essential thrombocythaemia: A single center study

“…8 The systematic review and meta-analysis of 2,436 patients with ET shows that JAK2 positivity correlated with a clear increase in the odds of thrombosis (OR = 1.83) 9 , and this was also observed by others. [10][11][12] Our findings are in line with the results of Schwartz et al, 13 who have proven, on the basis of an analyzed cohort of 1,179 thrombocythemic Ph-myeloptroliferations, that JAK2 mutation affected significantly the incidence of thrombosis (both arterial and venous). The JAK2 mutation has been included recently into the major criteria for ET 14,15 , and is also considered as a major prothrombotic risk factor in the International Prognostic Score in Essential Thrombocythemia (IPSET) risk factor study in WHO-defined ET.…”

“…10 Schwartz et al have shown that in ET the specific thrombophilic markers, e.g. FVLeiden mutation and protein C deficiency, were connected with thrombotic venous events.…”

Factor V G1691A (Leiden) and prothrombin G20210A gene mutation status, and thrombosis in patients with chronic myeloproliferative disorders

“…In the general Caucasian population the prevalence of the PT 20210A allele is 2% showing difference according to geographic variation approximately 2%, with some geographic variation [5]. The prevalence of FVL and PT mutation in Turkey was reported to be 7.4%-10.8% and 2.6%, respectively [6][7][8][9][10], which differs from the reported incidence of FVL and PT mutation in patients with ET and PV [11][12][13]. To the best of our knowledge the frequency of FVL and PT mutation in patients with IMF has not been reported.…”

Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation

“…68 Several studies have demonstrated elevated homocysteine levels among patients with MPN. 69,70 Many MPN patients develop hyperhomocysteinaemia during the course of the disease, 71 and this has been attributed to vitamin folic acid deficiency. 72 Hyperhomocysteinaemia is likely to increase the thrombotic risk of MPN patients.…”