Thrombotic risk factors in pulmonary hypertension

Thrombotic lesions are consistently observed in chronic thromboembolic pulm onary hypertension (CTEPH) and frequently found in primary pulmonary hypert ension (PPH), It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thr ombotic risk factors in CTEPH and PPH, One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH . In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibod ies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined . Antithrombin, protein C and protein S activities were measured by functio nal assays, Mutations of factor V and factor IT were identified by polymera se chain reaction, The prevalence of hereditary thrombotic risk factors was not increased in p atients with either PPH or CTEPH. In contrast, a high frequency of phosphol ipid-dependent antibodies was observed in PPH (10%) and more notably in CTE PH (20%), Moreover, in PPH, antibodies were present only in low titre where as in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus antic oagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phosphol ipid-dependent antibodies but their clinical relevance appears to be differ ent in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low ti tre probably reflect endothelial dysfunction. In contrast, in chronic throm boembolic pulmonary hypertension the presence of antibodies in high titre a ssociated with lupus anticoagulant, underlines the role of thrombosis in th e pathogenesis of this condition.