Are the new reagents really more sensitive?
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Biomedical subjects
Publications and source records attributed to M J Sanfelippo.
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The Lupus Anticoagulant (L.A.) is an antibody that prolongs the clotting time of in-vitro laboratory tests by binding phospholipid in the test system. Patients with the L.A. are at increased risk for development of venous and arterial thrombosis but not hemorrhage. Therefore, many patients with the L.A. are being treated with warfarin sodium to prevent reoccurrence of thrombosis. This oral anticoagulant therapy is traditionally regulated by periodic determination of the Prothrombin Time (PT). This test is usually unaffected by the L.A. However, we have recently identified a small series of patients with the L.A. in whom the PT is affected by the L.A. This interference is manifest as an artifactually increased International Normalized Ratio (INR). These patients were identified by failure to achieve significant correction of the PT with addition of an equal volume of normal plasma to the patient plasma and a Factor X level discordant with the PT INR Interference in determination of the PT by the L.A. was found to occur in 6.5% of patients identified with the L.A. by our laboratory. It is suggested that patients with this complication of anticoagulant therapy be monitored by measurement of Factor X levels rather than the PT INR. Failure to recognize this complication may result in inadequate anticoagulation and recurrent thrombosis.
The 5-year experience with a panel of laboratory tests designed to identify patients with high risk of thromboembolism was reviewed. This panel included an activated partial thromboplastin time and reptilase time as well as specific assays for antithrombin III, protein C, protein S, and plasminogen. One hundred and nine patients were evaluated by this panel. Conditions predisposing to thrombosis were identified in 24 of these patients and these conditions included: dysfibrinogenemia, lupus anticoagulant, and deficiencies of antithrombin III, protein C and protein S. The limitations of this panel are also discussed.
A 29-year-old female with no prior history of bleeding tendencies had gingival bleeding develop after 10 days of treatment with hydroxyethyl starch (HES), 1,000 mL/day. Laboratory studies revealed a marked reduction in Factor VIII coagulant activity (VIII:C), von Willebrand's factor antigen (vWF:Agn), and (VIII R:RCo), resembling severe type I von Willebrand's disease. The HES was stopped and the bleeding subsided. The levels of Factor VIII:C, vWF:Agn, and Factor VIII R:RCo gradually increased to normal over the following 17 days.
The lupus anticoagulant was identified in three patients. Laboratory studies gave evidence of inhibitory activity directed against phospholipid and prekallikrein. Inhibition of prekallikrein has not been reported previously. When exposed to kaolin, all three patients' plasmas failed to develop the level of fibrinolytic activity achieved by similarly treated normal plasma. The data suggest that compromised fibrinolytic capacity may be a contributing factor in the development of thrombosis in patients with the lupus anticoagulant.
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