Prevalence of High Levels of Antiphospholipid Antibodies in Otherwise Unexplained Juvenile Venous Thromboembolism

According to an accepted diagnostic procedure patients who suffer from juvenile venous thromboembolism (VfE), in absence of overt clinical predisposing factors, are submitted for laboratory coagulation screening to assess biochemical changes leading to a condition of thrombophilia. Inherited thrombophilic clotting and fibrinolytic defects are found in 15 to 25% of the cases (1) while other factors, such as fibrinolytic system impairment (2) and presence of lupus anticoagulant (LA,3) , are found with varying prevalence in patients with non familial VTE. Although all the mentioned predisposing factors are customarily screened in young patients with VTE, a possible cause of thrombophilia remains undetected in many cases. In recent years several thrombotic diseases have been reported in association with high anticardiolipin or, more generally, antiphospholipid antibodies (APA) levels (3-6). These antibodies, while not necessarily affecting the phospholipid dependent blood coagulation tests (7), could represent a factor for thrombophilia We assessed the APA levels by means of the Asserachrom APA test (ELISA assay, Diagnostica Stago, France), which measures both IgG and IgM antibodies against cardiolipin, phosphatidylserine and phosphatidic acid (8). The test was carried out in 92 patients (50 males, 12-45 years) referred to our Department from May 1988 to Janu ary 1990 for VTE episodes, including recurrent and/or migrant superticial thrombophlebitis. Their first or single episode of VTE occurred before 45 years, without any overt disease predisposing to thrombosis (malignancy, nephrotic syndroffie, diabetes, clinical collagenosis, polytrauma, orthopedic surgery etc.). Patients who suffered from VTE during pregnancy or postpartum, oral contraception and after general surgery, were, however, included since such conditions may precipitate VTE in thrombophilic subjects (9). All patients were investigated at least 3 months after the last VTE episode, and at least 15 days after suspension of any anticoagulant or antithrombotic treatment. An inherited coagulation defect, confirmed in at least one relative, was present in 23 (inherited defect subgroup) out of the 92 patients: deficiency of antithrombin III in 4 patients, protein C in 8 patients, protein S in 8 patients, plasminogen and factor XII in L patient each, dysfibrinogenemia in L patient. Fibrinolytic alterations were present in 16 patients (fibrinolytic defect subgroup): 13 patients had increased PAI levels and 3 reduced t-PA release after venous occlusion. In the 6 patients with prolonged aPTT (normal in all the other patients) the presence of lupus anticoagulant (LA subgroup) was confirmed by the positivity of a mixing study with normal plasma and of tissue thromboplastin inhibition test or platelet neutralization procedure . In 47 patients (unexplained subgroup) none of the forementioned blood changes was found. This distribution is in accordance with recent studies (10). The APA test was also carried out in 68 healthy young subjects (control group, 32 males, 18 43 years) so as to obtain the normal range values for our laboratory. The APA test results were expressed as phospholipid