Topical bovine thrombin preparations are used extensively in cardiovascular, neurosurgical, and otolaryngologic procedures. Patients who are treated with these topical thrombin preparations may develop antibodies to bovine coagulation factors that may cross-react with the endogenous human clotting proteins. We have identified four patients with acquired factor inhibitors following exposure to topical thrombin at Duke University Medical Center and summarize these cases in addition to 13 patients previously reported in the literature. In most cases, the inhibitor developed following a second (or subsequent) exposure to topical thrombin. The clinical course was extremely variable, ranging from totally asymptomatic to life-threatening hemorrhage. The most consistent laboratory abnormality was a prolonged bovine thrombin clotting time, which corrected, at least partially, when human thrombin was substituted for bovine thrombin. Some of these patients also developed factor V inhibitors with prolonged prothrombin and activated partial thromboplastin times. Although these patients have prolonged clotting times, they should not be considered "autoanticoagulated," since thromboembolic complications can still occur. Therapeutic intervention is largely empirical and depends on the clinical manifestations of the individual patient.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem-cell disorder in which the glycolipid-anchored membrane proteins, including the cell-surface complement inhibitors, CD55 and CD59, are partially or completely deleted from the plasma membranes of mature blood cells. To gain insight into the pathogenesis of thrombosis that is frequently observed in this disorder, the procoagulant responses of PNH platelets exposed to the human terminal complement proteins C5b-9 were investigated. C5b-9 complexes were assembled on gel-filtered platelets by incubation with purified C5b6, C7, C9, and limiting amounts of C8. Platelet microparticle formation and exposure of plasma membrane- binding sites for coagulation factor Va were then analyzed by flow cytometry. PNH platelets exhibiting undetectable levels of surface CD59 antigen showed an approximately 10-fold increase in sensitivity to C5b- 9-stimulated expression of membrane-binding sites for factor Va when compared with platelets from normal controls. Expression of catalytic surface for the prothrombinase complex (VaXa) paralleled the exposure of factor Va-binding sites; the rate of prothrombin conversion by C5b-9- treated PNH platelets exceeded that of C5b-9-treated normal controls by approximately 10-fold at the maximal input of C8 tested (500 ng/mL). These data indicate that PNH platelets deficient in plasma membrane CD59 antigen are exquisitely sensitive to C5b-9-induced expression of prothrombinase activity, and suggest that the tendency toward thrombosis in these patients may be due, at least in part, to the deletion of this complement inhibitor from the platelet plasma membrane.
Transmittance waveforms are the optical data generated during clot formation on photo-optical coagulation analyzers and are used to define specific events of the clotting reactions. Thus, a prothrombin time (PT) or an activated partial thromboplastin time (aPTT) can be divided into a pre-coagulation phase, a coagulation phase, and a post-coagulation phase. These phases are further characterized by parameters that define the timing, the rate, the 'slope', and the magnitude of the signal change of the reactions. We investigated the transmittance waveform parameters obtained during PT and aPTT of patients with antiphospholipid antibodies (APLA) who were or were not taking warfarin, normal donors, and non-APLA patients taking warfarin. An abnormal deflection in the pre-coagulation phase of the PT (called slope 1) was observed in 61.5% of the patients with APLA, in contrast to 5.9% of non-APLA patients taking warfarin (P= 0.0015). The presence of an abnormal PT slope 1 was reagent specific and was inversely correlated with the anticardiolipin antibody immunoglobulin G (IgG) level, which suggests that the abnormal PT slope 1 may reflect interactions between patient IgG and components from the thromboplastin, possibly phospholipids. The abnormal PT slope 1 values may be of diagnostic utility in the identification of patients with antiphospholipid syndromes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.