PubMed · 10543189
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K Fukutake, A Tanaka. 1999. [Factor VII].. https://pubmed.ncbi.nlm.nih.gov/10543189/
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BACKGROUND: Lupus anticoagulant (antiphospholipid antibodies) is associated with venous and arterial thrombosis in patients with and without autoimmune disorders. Vitamin K antagonists are the treatment of choice in patients with thrombosis, of which the dose is titrated by INR monitoring. Several recent reports suggest that the presence of the lupus anticoagulant disturbs the INR test and may lead to unreliable results with a large variation in INR values, dependent on the reagents used. METHODS: We studied 11 lupus anticoagulant positive patients and 11 lupus anticoagulant negative patients, all using vitamin K antagonists. The INR value was determined using seven different tests and the variation in INR values was compared between the two groups. The amidolytic Factor X levels were used as an phospholipid independent measure for intensity of warfarin therapy. Factor VII and X activity were measured to assess the stability of warfarin therapy. RESULTS: The variation of the results with different INR tests within one patient was minimal and comparable in the two groups for INR's in the therapeutic range. The coefficient of variation for the cases and control group was 10.43 and 9.35, respectively. Variation in both groups increased at supratherapeutic levels of anticoagulation and when the anticoagulation was unstable (measured with Factor X/Factor VII ratio). The relationship between INR values and Factor X analysis revealed no influence of the lupus anticoagulant. CONCLUSIONS: In this study, lupus anticoagulant antibodies do not disturb INR laboratory tests. Differences in INR measurements are seen in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved. Abbreviated Abstract. This study investigates the influence of lupus anticoagulant on INR determination tests in patients treated with warfarin. Eleven cases and eleven lupus anticoagulant negative control patients, also on warfarin therapy, were included. Seven INR results per patient were obtained using different laboratory tests. A factor X assay was performed to obtain an independent measure for the intensity of warfarin therapy. The variation of INR results between the cases and controls revealed no difference in these groups. In addition, the relationship between INR values and Factor X analysis indicated no influence of the lupus anticoagulant. What was observed was an increased difference in INR values in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved
The development of factor VIII and factor IX concentrates markedly improved the management of hemophilia A and B and made home therapy possible. However, treatment of hemophilic patients with acquired inhibitors remained difficult. The preparation of prothrombin complex concentrates, nonactivated or activated, addressed this difficult clinical problem, but their use was associated with serious side effects. Factor VIIa was found to be a safer treatment modality. Factor VIIa per se is inactive and needs tissue factor (TF) to become biologically active. TF serves as the receptor for factor VIIa. TF is expressed from vessel walls only upon injury. Treatment of inhibitor patients with plasma-derived factor VII was found to be successful. This led to the development of recombinant factor VIIa, which was also found to be successful in managing hemophilia patients with inhibitors. Up to this point, large numbers of patients have been treated and few serious side effects have been noted. Because of its unique effects on the hemostasis system, recombinant factor VIIa will be useful for other indications as well, including patients with congenital factor VII deficiency, patients with bleeding and liver function impairment, patients with quantitative and qualitative platelet defects, and individuals who have sustained multiple trauma. The development of recombinant factor VII is reviewed in detail.