High prevalence of hyperhomocysteinemia due to marginal deficiency of cobalamin or folate in chronic myeloproliferative disorders

Hyperhomocysteinemia is an established risk factor for thrombosis. In patie nts with myeloproliferative disorders, thrombotic events are common. Our ai m was to investigate whether the increased burden of proliferating cells pr esent in these patients implies a risk of homocysteine (HCY) accumulation s econdary to depletion of folate and/or cobalamin. Fifty patients (PV, 25; E T, 10; IMF, 15) and 163 healthy volunteers (HV) participated in the study. The prevalence of hyperhomocysteinemia was 56.0% in PV, 70.0% in ET, 60.0% in IMF, and 34.9% in HV. The mean P-homocysteine (P-HCY) was 13.88 +/- 4.24 mu mol/L in PV, 12.78 +/- 3.70 in ET, 11.34 +/- 4.22 in IMF, and 9.71 +/- 2.76 in HV. In PV and ET, but not in IMF, the mean P-HCY was significantly higher than in the HV group (P < 0.001, P = 0.028, and P = 0.163, respectiv ely). Thirty-three percent of the patients with hyperhomocysteinemia displa yed metabolic changes compatible with cobalamin deficiency (P-HCY and P-met hylmalonic acid both elevated), while 67% were folate deficient (P-HCY elev ated, P-methylmalonic acid normal). Supplementation therapy with the releva nt vitamin was implemented in 11 vitamin-deficient patients and led to norm alization of metabolite levels in all cases. No correlation between hyperho mocysteinemia and thrombosis was found, Our data indicate that patients wit h PV, ET, and IMF frequently develop hyperhomocysteinemia due to discrete d epletion of cobalamin or folate. Vitamin therapy leads to normalization of P-HCY and should be considered, even though hyperhomocysteinemia does not s eem to be of crucial importance for the thrombotic tendency in the myelopro liferative disorders. (C) 2000 Wiley-Liss, Inc.