Causal relationships between drug-induced hypercoagulability and priapism.
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Hartert's thromboelastography has been used in the diagnosis of abnormal blood clotting for more than 20 years. From a thromboelastogram three parameters are obtained, viz, the reaction time 'r', the rate of formation of fibrin clot 'k', the maximum elasticity of thrombus 'amax'. It is desirable, however, to know the equation that describes the thromboelastogram both in the period in which the complex modulus increases with time because of coagulation, and in the period in which the complex modulus decreases with time because of fibrinolysis. The parameters of the equation could then be used as a diagnostic criterion; yielding information on the mechanism of coagulation and fibrinolysis. Based on our experimental results on human blood in normal and abnormal subjects, we found that the complex modulus of thromboelastograms can be expressed by the sum of two terms, one describing the increase of the complex modulus during coagulation, G1 = G'1 Exp (-tau 1/t), the other describing the decrease of the complex modulus during fibrinolysis, G2 = G'2 Exp (-tau 2/(t-D) when t greater than D. G2 = 0 when t less than D. The compound complex modulus from coagulation to fibrinolysis is G = G1 - G2. Here t is the clotting time, and G'1, G'2, tau 1, tau 2, and D are five constants to be identified. These five constants can be used for diagnostic and prognostic purposes.
CONTEXT: Patients with sickle cell disease suffer from a variety of vaso-occlusive events that may be related to activation of the hemostatic system. Thromboelastography assesses the functionality of this system from a global standpoint and has demonstrated some utility in detecting hypercoagulable states in varied clinical settings, but it has not been systematically evaluated in patients with sickle cell disease. OBJECTIVE: To characterize the findings of thromboelastography in patients with sickle cell disease during periods of steady state and illness, to compare these results with those of healthy controls, and to correlate these profiles with other measured hemostatic parameters. DESIGN: In this cross-sectional study, we obtained thromboelastographic and other hemostatic data on specimens from 46 patients with sickle cell disease (35 with hemoglobin SS, 7 with hemoglobin SC, and 4 with hemoglobin S-beta thalassemia) and 20 healthy race-matched controls. Data were obtained from patients with sickle cell disease at baseline conditions (n = 41) and in the setting of acute illness (n = 5). RESULTS: Patients with hemoglobin SS had lower reaction time and higher angle, maximum amplitude, and coagulation index values on thromboelastography than the control group. Hemoglobin SC patients had higher angle, maximum amplitude, and coagulation index values than controls. Hemoglobin S-beta thalassemia patients showed no significant differences compared with controls. Five hemoglobin SS patients with recent or current illness demonstrated increased maximum amplitude and coagulation index compared with hemoglobin SS patients at baseline conditions. CONCLUSIONS: Patients with sickle cell disease demonstrated a significant hypercoagulable state in thromboelastography profiles, with the degree of abnormality dependent on the type of sickle cell disease and perhaps the presence of acute illness. Continued follow-up of this patient cohort, as well as further study of larger and more homogeneous patient groups, is required to adequately assess the utility of thromboelastography in predicting complications of sickle cell disease.
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A total of 168 patients with atherosclerotic cardiosclerosis and different stages of chronic circulatory insufficiency were subjected to an examination of the state of their blood coagulation (thromboelasto- and coagulogramme) and fibrinolytic systems (indices of the general fibrinolytic activity of the blood, some components of fibrinolysis). In cases of circulatory insufficiency at its early stages (especially IIA) distinct signs of blood hypercoagulation were found to develop at the expense of an elevation of the level of fibrinogen A and B fibrinstabilizing factor, a reduction of the content of antithrombins and heparin, as well as signs of fibrinolysis inhibition at the expense of an increase of the level of plasminogen and antiplasmins activation inhibitors, fast acting including. During Stages IIB and III of circulatory insufficiency the signs of hypercoagulation of the blood and fibrinolysis inhibition are noted to decrease, although they do not disappear completely.
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Patients undergoing intraaortic balloon pump (IABP) therapy are at risk for developing coagulopathies due to the adverse effects of prolonged exposure of the synthetic surface of the polyurethane balloon to blood components. Hemorrhagic risk has been attributed to a number of factors including thrombocytopenia, vascular injury, and/or platelet degranulation which increase the potential of receiving autogeneic blood transfusions. The present study is a prospective evaluation of coagulation using a viscoelastic monitor (Thrombelastograph--TEG) that measures functional aspects of clot development and stabilization in patients being treated with IABP therapy. Following Institutional Review Board approval, six patients undergoing IABP therapy for hemodynamic instability were enrolled in this study. Blood samples were taken prior to balloon insertion, at 8, 16, 24, 48, 72, and 96 hours on IABP therapy, and 24 hours following the removal of the balloon when applicable. Samples were incubated with heparinase to degrade heparin and TEG profiles were subsequently determined in duplicate. Measured parameters on the TEG included R-time, K-time, maximum amplitude, alpha angle, and lysis at 30 and 60 minutes with calculation of the TEG index. Mortality was 33% following IABP discontinuation. Transfusion of packed red blood cells occurred in 50% of the patients during their balloon pump therapy. Patients demonstrated a significant deviance in fibrinolytic potential from pre-IABP lysis (1.6% +/- 1.8) at both 24 hours (18.8% +/- 22.9) and 48 hours (21.9% +/- 28.5) of therapy (p < 0.05) which returned to baseline shortly after balloon removal. Activation of coagulation factors appeared evident by a steadily increasing alpha angle from pre-IABP data (3.1 +/- 9.2) throughout the duration of therapy and 24 hour recovery (53 +/- 14; p < .005), and by a steadily trending increase in the TEG index pre-IABP (.251 +/- 1.4) to post-IABP (2.6 +/- 1.7; p < 0.05). The results indicate that IABP therapy induces an increase in fibrinolytic potential at 24 to 48 hours of balloon pump therapy with a paradoxical trend toward increased coagulability, potentially predisposing the patient to hemorrhagic risk.
The effect of antioxidant compounds ionol and mexidol and the new phenol derivative N9-imidazo-(1,2 alpha)-benzymidazol (PY-185) on the functional activity of blood platelets was studied. All the compounds under study effectively inhibited blood platelet aggregation both in vitro and in administration into rats, a result of which the blood thrombogenic potential reduced.
Changes in blood coagulation and fibrinolysis were followed up in 255 patients of intensive care wards during 5 days after effective treatment of grave and terminal stages of traumatic hemorrhagic shock. Four stages in the development of disseminated intravascular coagulation (DIC) were distinguished. Special attention is paid to the time course of the third stage with repeated hypercoagulation, suppressed fibrinolysis, and microthrombolysis in organs and tissues leading to multiple organ failure. The fourth stage of DIC is described, when involvement of the organs and generalized inflammation or sepsis is associated with remote (on days 3-5 and later) hemorrhages. These hemorrhages are apparently caused by disorders in fibrin production but not by acute fibrinolysis and consumption coagulopathy, as during the second stage of DIC.