antibodies) are immunoglobulins that interfere with phospholipid dependent coagulation assays. Typically, the aPTT is the first assay affected. If a strong lupus inhibitor is present, the aPTT may be moderately to markedly prolonged and will not completely correct on 1:1 mix. The prothrombin time may also be prolonged. The prothrombin time prolongation may be due to either the antiphospholipid antibody and/or decreased factor II. Hypoprothrombinemia (decreased factor II) has been reported in patients with lupus inhibitors; these patients are at risk for bleeding. Lupus inhibitors are associated with arterial and venous thrombosis. PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1 (PAI-1) ACTIVITY Method: Immunofunctional assay. Citrated plasma is added to a microtiter plate containing bound, active tPA. Active PAI-1 in the sample binds tPA forming tPA/PAI-1 complex. The amount of bound PAI-1 is quantitated using a peroxidase conjugated anti-PAI-1 antibody. The amount of active PAI-1 in the sample is proportional to the amount of PAI-1 bound to the plate. One unit of PAI-1 activity is defined as the amount of PAI-1 that inhibits one international unit of tPA. Fibrinolytic activity in blood follows a circadian rhythm. Peak levels of PAI-1 occur in the morning with the lowest levels occurring in the evening. For this reason the optimal time to draw blood is between 0800 and 0900. Blood drawn between 0700 and 1000 is acceptable. It is important that the time of blood collection be indicated on the requisition form. Increased PAI-1 activity indicates impaired fibrinolytic function and may be associated with increased risk of arterial thrombosis. PAI-1 is an acute phase reactant. Increased levels are found in pregnancy, sepsis, deep venous thrombosis and after myocardial infarction. Absent PAI-1 activity and antigen indicate PAI-1 deficiency which is associated with a mild to moderate delayed bleeding syndrome. PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1 (PAI-1) ANTIGEN Method: Enzyme immunoassay Measures total level of PAI-1 in blood including active PAI-1 (see PAI-1 activity above), tPA/PAI-1 complex and latent PAI-1. Typically parallels PAI-1 activity. Useful for diagnosis of elevated PAI-1 in patients with arterial thrombotic disease and in patients with PAI-1 deficiency associated bleeding. Care must be taken when drawing the sample to avoid release of PAI-1 from platelets. 30 Fibrinolytic activity in blood follows a circadian rhythm. Peak levels of PAI-1 occur in the morning with the lowest levels occurring in the evening. For this reason the optimal time to draw blood is between 0800 and 0900. Blood drawn between 0700 and 1000 is acceptable. It is important that the time of blood collection be indicated on the requisition form. PROTEIN C ACTIVITY Method: Chromogenic based assay. The patient should be off oral anticoagulant therapy for at least a week and should be tested at least one month after resolution of the thrombus. Protein C is a vitamin K dependent protein synthesized in the liver. Protein C is present in plasma as a proenzyme that is converted to its active form by the thrombin/thrombomodulin complex on the endothelial surface. When activated, protein C in the presence of protein S regulates thrombosis by inactivating factors Va and VIIIa. A qualitative or quantitative protein C deficiency may exist. Type I deficiency has decreased function (activity) and antigen levels. Type II patients have decreased function and normal antigen determination. There is no difference in the risk of thrombosis between the two types of protein C deficiency. The protein C activity assay screens for both types of deficiency. Hereditary protein C deficiency is inherited as autosomal dominant. Approximately 3% of patients with venous thrombophilia have protein C deficiency. Half of patients heterozygous for protein C deficiency present with venous thrombosis before age 40. Thrombosis of the lower extremity occurs most often; less common is thrombosis of the mesenteric or cerebral veins. Surgery, pregnancy or immobilization may be an added risk factor in these patients. A protein C deficiency combined with the factor V Leiden mutation increases the risk of venous