Evaluation of inherited and acquired thrombophilia defects in essential thrombocythemia

HELLER PAULA G; KORNBLIHTT LAURA I; CORREA GABRIEL; GENOUD VALERIA; CASTAÑÓN MARÍA M; VASSALLU PATRICIA S; KORDICH LUCÍA; MOLINAS FELISA C

París

Congreso; XVIII Congress of the International Society of Thrombosis and Haemostasis; 2001

International Society of Thrombosis and Haemostasis

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by an increased frequency of arterial and venous thrombosis. To investigate whether genetic or acquired thrombophilic defects contribute to the thrombotic risk, we evaluated the prevalence of factor V Leiden (FVL), prothrombin G20210A (PT) and methylentetrahydrofolate reductase C677T (MTHFR) polymorphisms by restriction fragment analysis, protein C, protein S and ATIII activity, activated protein Cresistance (APCr) by a modified APC sensitivity ratio, lupus anticoagulant tests (LA), anticardiolipin (aCL), antiphospholipid (aPh) and anti B2 glycoprotein I (aB2GPI) antibodies (IgG, IgM) by ELISA, and homocysteinemia (HCY) by ELISA. We studied 43 patients with ET, age 43 (11-83), F/M 31/12, platelet count 1300 (400-3126), 37.5% had spontaneous platelet aggregation and 35% presented vascular risk factors. Nine patients (21%) had thrombosis (T) (1 AMI, 6 stroke, 1 iliac artery, 1 portal, mesenteric and splenic vein,1 arterial and venous splenic) and 19 had microvascular disturbances (MV) (erythomelalgia, TIAs, visual symptoms). Seven patients were evaluated at diagnosis and 36 at follow-up; 38 were treated with anagrelide with a median follow-up after starting treatment of 38 months (4-92) without thrombosis recurrence. The prevalence of FVL (1/43, 2.8%, heterozygous), PT (3/43, 7.2%, 1 was homozygous) and homozygous MTHFR (4/43, 9.3%) was not significantly different from a control argentinian population (n=418, 2.43%, 2.63%15.5%, respectively). PC, PS and ATIII activity was normal in all patients, APCr was detected in 2 patients (1 with FVL), 2 hd aCL, 1 aPh, 1 aB2GPI, 1 aB2GPI+aPh and 1 LA. Median HCY levels were slightly higher than normal and 5 patients had hyperHCY (>15mmol/l). Two patients had two concomitant thrombophilia conditions (1 FVL+LA, 1 APCr+PT). No significant difference in the frequency of each of the evaluated risk factors was found between patients with T or MV with respect to those asymptomatic. Overall 17/43 (40%) patients had an associated thrombophilia defect, of whom 29% had T versus 15% of those without these thrombophilic markers. Normalization of platelet counts by anagrelide treatment decreased the risk of thrombosis in our patients. Routine screening for hereditary or acquired thrombophilia conditions in ET might not be justified. However, diagnosis and treatment of these defects in ET patients with thrombosis may help minimize thrombotic recurrence.