A 23-year-old woman has had altered consciousness and slurred speech for the past 24 hours. A head CT scan shows a right temporal hemorrhagic infarction. Cerebral angiography shows a distal right middle cerebral arterial occlusion. Within the past 3 years, she has had an episode of pulmonary embolism. A pregnancy 18 months ago ended in miscarriage. Laboratory studies show a false-positive serologic test for syphilis, normal prothrombin time (PT), elevated partial thromboplastin time (PTT), and normal platelet count. Which of the following is the most likely cause of these findings?
These findings are characteristic of a hypercoagulable state. The patient has antibodies that react with cardiolipin, a phospholipid antigen used for the serologic diagnosis of syphilis. These so-called antiphospholipid antibodies are directed against phospholipid-protein complexes such as b2 -glycoprotein I and thrombin and are sometimes called lupus anticoagulant because they are present in some patients with systemic lupus erythematosus (SLE) or other autoimmune states. Patients with antiphospholipid syndrome have recurrent arterial and venous thrombosis and repeated miscarriages. In vitro, these antibodies inhibit coagulation by interfering with the assembly of phospholipid complexes, and a "mixing study" with normal serum will not correct the PTT (which primarily measures factors II, V, VIII, IX, X, XI, and XII and fibrinogen in the "intrinsic pathway" of in vitro coagulation). In vivo, the antibodies induce a hypercoagulable state by unknown mechanisms. Disseminated intravascular coagulation is an acute consumptive coagulopathy characterized by elevated PT and PTT, and decreased platelet count. The PT and PTT are normal in patients with factor V (Leiden) mutation. Hypercholesterolemia promotes atherosclerosis over many years, and the risk of arterial thrombosis increases. Von Willebrand disease affects platelet adhesion and leads to a bleeding tendency, not to thrombosis.
Antiphospholipid antibody
Disseminated intravascular coagulation
Factor V mutation
Hypercholesterolemia
Hemodynamics