Lupus anticoagulant and thrombosis: role of von Willebrand factor multimeric forms.

OBJECTIVE: Patients with lupus anticoagulant (LA) have an increased incidence of venous and arterial thrombosis whose pathogenesis is still unclear. High molecular weight von Willebrand Factor (vWF) multimers seem to play a causal role in shear stress-induced platelet aggregation and thrombus formation. We studied whether in patients with LA, alterations in the vWF multimers might coexist. METHODS: The multimeric composition of plasma vWF was analysed by SDS-electrophoresis and immunoblotting in 43 subjects positive for LA. About 2/3 of the patients had had either ischemic stroke, recurrent abortions, deep vein thrombosis (DVT) or a combination of these; the remaining subjects had never had any thrombotic events. RESULTS: An abnormal vWf multimeric pattern was found in 16 patients (37.2%); no correlation was found with the diagnosis, but the presence of abnormal vWF significantly correlated with the site of the thrombosis: indeed, it was never detected in subjects with DVT, but was found in 71.4% of patients with multiple abortions, in 50% of those with stroke and even in 25% of non-thrombotic patients. CONCLUSION: The hypothesis is put forward that abnormal VWF may represent an additional risk factor to LA for arterial thrombosis.

[Anomalies of coagulation and fibrinolytic activity in patients with chronic pulmonary thromboembolism]. / Anomalie della coagulazione e dell'attività fibrinolitica nei pazienti con tromboembolia polmonare cronica.

INTRODUCTION: Haemostatic and fibrinolytic parameters were evaluated in patients with chronic pulmonary hypertension following pulmonary embolism (CPE). The diagnosis of CPE was based on lobar or segmental defects on perfusion lung scans and by pulmonary angiograms which showed complete or partial obstruction of main or segmentary lobar arteries. METHODS: Antithrombin III (AT III), protein C, protein S, and lupus anticoagulant (LA) were assayed in 8 patients with CPE; in 6 out of 8 patients plasma fibrinolytic activity was assessed both under basal conditions and after venous stasis. The control group consisted of 4 normal subjects. Protein C and protein S antigens were assayed by an electrophoretic method. Protein C and protein S biological activities were assayed by a manual clotting system. AT III was assayed by chromogenic method. Fibrinolytic total activity was studied on fibrin plates, tPA and PAI-1 activities by chromogenic method; tPA and PAI-1 antigens by ELISA technique. RESULTS: One patient out of 8 showed a protein C deficiency and 3 patients out of 8 were positive for a LA. All patients had a statistically significant reduction of plasma fibrinolytic activity (p < 0.001) and of tPA activity (p < 0.0005) after venous stasis as compared to the control group. CONCLUSIONS: Our data show that significant haemostatic abnormalities may underlie this disease. In particular, a) an impairment of fibrinolytic plasma activity and low levels of plasminogen activator may be found, and b) the undiagnosed presence of a LA may be the cause of these thrombotic events. The meaning of these results needs further assessment.

Lupus anticoagulant: interference with in vivo prostaglandin production and with platelet sensitivity to prostacyclin.

The hypothesis has been made that inhibition of prostacyclin (PG12) production may play a role in the pathogenesis of thrombosis in patients with the lupus anticoagulant (LA), but so far no evidence of reduced PG12 levels in vivo has been produced. We have tested the plasma levels of PG12 and thromboxane A2 (TXA2) and the platelet sensitivity to PG12 in 14 patients with and without LA and in 14 healthy controls. No significant difference in the prostanoid basal levels was detected among the groups; however, in some patients PG12 increments seemed to parallel the clinical course of the disease. Platelet sensitivity to exogenous PG12 was significantly enhanced in the LA + patients and correlated with PG12 values. We suggest that in these subjects additional factors, other than reduced PG12, may predispose to thrombosis.