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Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa).

Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive

Absorption↗

Inhibitors of plasma thromboplastin antecedent (factor XI): studies on mechanism of inhibition.

Acquired inhibitors of plasma thromboplastin antecedent (PTA) have been described in several recent studies, which collectively emphasize the heterogeneity of PTA functions that are impaired by this class of circulating anticoagulants. To clarify whether acquired inhibitors of PTA exhibit inhibitory properties that vary widely from one patient to the next, IgG inhibitors from four patients were isolated. The effect of these inhibitors on the binding of PTA to glass, the activation of kaolin-bound PTA, the coagulant activity of both kaolin-bound and fluid phase activated PTA (aPTA), and the enzymatic activity of aPTA against a low molecular weight substrate was quantified. The relative inhibition of these individual components of PTA activation and function by the four anticoagulants was quite similar. The results indicate that the principal binding sites for acquired inhibitors of PTA are PTA domains involved with surface binding and conversion of PTA to aPTA, with less effective steric impairment of aPTA enzymatic activity.

Adult↗

Hemorrhage in a cat caused by inhibition of factor XI (plasma thromboplastin antecedent).

A coagulation profile from a 5-year-old neutered male cat with severe epistaxis revealed an intrinsic coagulation defect characterized by prolonged activated partial thromboplastin time, with normal bleeding time, platelet count, and prothrombin time. Subsequent factor XI analyses, using bovine factor XI-deficient plasma, revealed factor XI deficiency. Hematologic and clinical studies on the cat failed to reveal an underlying disease process that might have resulted in acquired factor XI inhibition.

Animals↗

Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay.

A specific, sensitive, and reproducible radioimmunoassay for human plasma thromboplastin antecedent (PTA, factor XI) has been developed with purified PTA and monospecific rabbit antiserum. Precise measurements of PTA antigen were possible for concentrations as low as 0.3% of that in normal pooled plasma. Normal plasma contained approximately 6 microgram PTA/ml. A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females). PTA antigen was markedly reduced in plasma of 13 patients with congenital homozygous PTA deficiency (range less than 0.003-0.128 U/ml) and 9 patients with hepatic cirrhosis (0.35+/-0.17 U/ml), but was normal in those of 9 patients under treatment with warfarin, 8 patients with disseminated intravascular coagulation and 16 patients with other congenital clotting factor abnormalities, including prekallikrein deficiency (Fletcher trait) and high molecular weight kininogen deficiency (Fitzgerald trait).

Adult↗