Thrombotic lesions are consistently observed in chronic thromboembolic
pulmonary hypertension (CTEPH) and frequently found in
primary pulmonary hypertension (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 thrombotic 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
antibodies (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 functional assays. Mutations of
factor V and
factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of
phospholipid-dependent
antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH,
antibodies were present only in low titre whereas in CTEPH, half of the patients with
antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with
lupus anticoagulant also had
antiphospholipid antibodies. The most striking finding of this study was the high prevalence of
phospholipid-dependent
antibodies but their clinical relevance appears to be different in
primary pulmonary hypertension and chronic thromboembolic
pulmonary hypertension. In
primary pulmonary hypertension, these
antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic
pulmonary hypertension the presence of
antibodies in high titre associated with
lupus anticoagulant, underlines the role of
thrombosis in the pathogenesis of this condition.