A hitherto undescribed plasma factor acting at the contact phase of blood coagulation (Flaujeac factor): case report and coagulation studies.
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This paper reports an asymptomatic coagulation defect responsible for an abnormality at the contact phase of blood coagulation in vitro, distinct from Hageman factor and Fletcher factor deficiencies. Coagulation studies in a 50-yr-old French woman without bleeding tendency revealed the following results: whole-blood clotting time in glass tubes and activated partial thromboplastin time with kaolin and ellagic acid were greatly prolonged; one-stage prothrombin was normal; no circulating anticoagulant was detected, and the infusion of normal plasma corrected the coagulation defect with an estimated half-life of 6.5 days; the levels of factor VIII, IX, XI, and XII were normal; mutual correction was obtained with a Fletcher factor-deficient plasma; the level of whole complement was normal. Studies of the contact phase of blood coagulation and contact-induced fibrinolysis showed the same abnormalities as in Hageman factor- and Fletcher-deficient plasmas. These results indicate that the patient's plasma is deficient in a previously undescribed coagulation factor, which participates in the initial stage of the blood coagulation process in vitro. Family studies revealed consanguinity in the propositus' parents. The assay of this newly described factor in the propositus' children revealed a partial defect, compatible with a heterozygous state, in three of the four tested children. This indicates a recessive inheritance of this new blood coagulation defect. (+info)
Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome.
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BACKGROUND: The hemolytic-uremic syndrome is a thrombotic complication of Escherichia coli O157:H7 infection. It is not known whether the coagulation abnormalities precede, and potentially cause, this disorder. METHODS: In 53 children infected with E. coli O157:H7, we measured a panel of markers indicating activation of the clotting cascade and renal function within four days after the onset of illness. These markers were measured again in as many as possible of the 16 children in whom the hemolytic-uremic syndrome developed. RESULTS: The children in whom the hemolytic-uremic syndrome subsequently developed had significantly higher median plasma concentrations of prothrombin fragment 1+2, tissue plasminogen activator (t-PA) antigen, t-PA-plasminogen-activator inhibitor type 1 (PAI-1) complex, and D-dimer than children with uncomplicated infection. These abnormalities preceded the development of azotemia and thrombocytopenia. When the hemolytic-uremic syndrome developed, the urinary concentrations of beta2-microglobulin and N-acetyl-beta-glucosaminidase rose significantly (P=0.03 for both increases); the plasma concentrations of t-PA antigen, t-PA-PAI-1 complex, D-dimer, and plasmin-antiplasmin complex also increased significantly. The concentration of t-PA antigen correlated with that of the t-PA-PAI-1 complex in a linear regression model (squared correlation coefficient, 0.80; P<0.001). CONCLUSIONS: In the hemolytic-uremic syndrome, thrombin generation (probably due to accelerated thrombogenesis) and inhibition of fibrinolysis precede renal injury and may be the cause of such injury. (+info)
Prevention of venous thromboembolism in Wales: results of a survey among general surgeons.
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OBJECTIVE: To examine the current attitudes towards the prevention of venous thromboembolism among a cohort of surgeons. DESIGN: A postal survey, comprising a questionnaire covering various aspects of venous thromboembolism prophylaxis was sent to all (n=84) consultant general surgeons in Wales. RESULTS: Replies were received from 57 surgeons (68%), all of whom routinely used prophylaxis, the most frequent modalities used being heparin (100%) and graded compression stockings (79%). A combination of physical and pharmacological methods was used by over 89% of surgeons, with 60% starting prophylaxis more than two hours before operation. All surgeons continued prophylaxis after surgery, 53% until patients were mobile, 45% until they were discharged, and one surgeon continued prophylaxis for seven days after discharge. The thrombosis risk factors considered most important by surgeons when deciding about prophylaxis were (i) a previous history of venous thromboembolism, (ii) hypercoagulability, and (iii) malignancy. CONCLUSIONS: This study confirms that Welsh surgeons conform to standard methods, but also highlights some uncertainties that are present in current surgical practice. Those who responded all routinely used prophylaxis, the timing of which was variable. The main risk factors identified when considering prophylaxis were previous history of deep vein thrombosis/pulmonary embolism, hypercoagulability, and the presence of malignancy. Suggestions for future practice are made. (+info)
Coagulopathy as a result of factor V inhibitor after exposure to bovine topical thrombin.
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We describe a case of severe coagulopathy after mesenteric revascularization. Laboratory investigation results revealed the presence of plasma inhibitors of factor V believed to result from exposure to bovine thrombin used for intraoperative hemostasis. Vascular and cardiothoracic surgeons commonly use topical thrombin for surgical hemostasis, and many patients undergo multiple exposure. More patients likely have factor V inhibitors develop than has previously been realized, and this may account for some otherwise unexplained postoperative coagulation disorders. This report may alert surgeons to coagulation disturbances that can result from exposure to bovine thrombin and provide guidelines for diagnosis and management. (+info)
Impaired platelet aggregation in melanoma patients treated with interferon-alpha-2b adjuvant therapy.
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BACKGROUND: High-dose interferon (INF)- alpha-2b is the only Food and Drug Administration-approved adjuvant treatment for patients with melanoma who are at high risk of recurrence. Although circumstantial evidence points to a potentially harmful effect of INF-alpha-2b on platelet function, to the authors' knowledge this has never been studied in humans. METHODS: The study group was comprised of patients who had undergone surgery for melanoma and were free of disease but at a high risk of recurrence. All patients were candidates for adjuvant INF treatment (high-dose) and were undergoing routine evaluation to which platelet aggregation was added. Aggregation was triggered in standard fashion with adenosine diphosphate, epinephrine, collagen, thrombin, arachidonic acid, and ristocetin. Blood samples were drawn immediately before treatment, during the intravenous loading phase, during the subcutaneous maintenance phase, and 3-6 weeks after cessation of treatment. Patients receiving low-dose, long-standing INF-alpha-2b treatment also were tested. All results at each phase were compared with those of normal controls. RESULTS: In those patients receiving high-dose INF-alpha-2b, ristocetin-induced aggregation did not appear to be affected. However, the response to > or = 1 of the other agonists was impaired in 5 of 6 samples during loading, 14 of 15 samples during the maintenance phase, and 8 of 13 samples after treatment, compared with only 1 of 8 samples before treatment (P = 0.025, P = 0.002, and P = 0.067, respectively). During treatment with low-dose INF, platelet function was affected to a lesser extent. CONCLUSIONS: INF treatment in melanoma patients appears to be associated with severe impairment of platelet aggregation, which appears to be dose-dependent and cumulative-dose-dependent. This is not detectable by the standard coagulation profile. This effect has significant implications in the event of accidental injury or elective surgery. The antiaggregation activity may be the mechanism by which INF delays, reduces, or prevents the formation of melanoma metastases. (+info)
Accelerated atherosclerosis in patients with systemic lupus erythematosus: a review of the causes and possible prevention.
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Systemic lupus erythematosus is an autoimmune disorder affecting multiple organ systems. Patients with systemic lupus erythematosus exhibit a bimodal pattern of mortality, with those who have had the disease for 5 to 10 years being at increased risk of cardiovascular disease, particularly myocardial infarction. Elevated levels of conventional cardiovascular risk factors promote vascular damage resulting in impairment of normal endothelial function. In addition, autoantibodies directed against oxidised lipoproteins, along with chronic secretion of inflammatory cytokines and suppression of fibrinolytic parameters, are thought to increase atherogenesis. Treatment with corticosteroids may also contribute to the accelerated atherosclerosis observed in these patients. This review discusses the accentuated relationship between conventional cardiovascular risk factors, systemic lupus erythematosus-induced inflammatory changes and the early stages of atherogenesis and how careful monitoring of risk factors and use of appropriate therapies may reduce the progression of atheroma development in patients with systemic lupus erythematosus. (+info)
Aberrations in hemostasis and coagulation in untreated discordant hepatic xenotransplantation: studies in the dog-to-pig model.
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Discordant liver xenotransplantation is a poorly explored entity. Data from the few large animal studies of hepatic xenotransplantation suggest that severe hemorrhage is encountered. The purpose of the studies described here is to characterize the nature of the hemorrhage that accompanies liver xenotransplantation. Canine livers were transplanted into porcine recipients, and lethal hemorrhage was encountered. Analysis of recipient blood showed that factors V, IX, and X were present in adequate levels until after the hemorrhage appeared, suggesting that coagulation factor loss was the result and not the cause of hemorrhage. Platelet counts decreased dramatically in recipients within minutes of graft reperfusion. There also was no evidence of clotting activity in the blood of recipients of liver xenografts within minutes of graft reperfusion. This loss of clotting activity was specific to liver xenografts, was not seen in renal xenografts with or without venovenous bypass, and also was absent in pig-to-pig liver allografts. In brief, the hemorrhage that accompanies liver xenotransplantation occurs because of a decrease in the number and function of circulating platelets in the recipient. (+info)
Predictors of mortality and stenosis after transjugular intrahepatic portosystemic shunt.
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Transjugular intrahepatic portosystemic shunts (TIPSs) are used to treat variceal hemorrhage and refractory ascites. We sought to determine factors associated with stenosis and mortality after TIPS placement in patients with end-stage liver disease. This is a retrospective review of 90 TIPSs placed over a 3-year period. Demographic, clinical, and biochemical parameters were analyzed in univariate analyses to determine their association with stenosis and death. Multivariate analyses were conducted using logistic regression and Cox proportional hazard modeling. Thirty-five TIPSs were placed for recurrent variceal bleeding; 14 TIPSs, for uncontrolled variceal bleeding; 34 TIPSs, for refractory ascites; and 7 TIPSs, for other causes. The overall mortality rate was 33%, and 18 patients died within 30 days of TIPS placement. The 1-year stenosis rate was 49%. Fourteen patients underwent liver transplantation a mean of 116 +/- 143 days after TIPS placement. Prothrombin time greater than 17 seconds, serum creatinine level greater than 1.7 mg/dL, total bilirubin level greater than 3 mg/dL, and uncontrolled variceal bleeding as an indication for TIPS placement were significant predictors of 30-day mortality. Serum creatinine level was a predictor of 30-day mortality in individuals with recurrent variceal hemorrhage or ascites. Multivariate analyses showed that creatinine level greater than 1.7 mg/dL and uncontrolled variceal bleeding as an indication for TIPS placement were independently associated with 30-day mortality. Individuals with both coagulopathy and renal insufficiency had a 30-day mortality rate of 78%. Urgent placement of TIPS was associated with an increased risk for stenosis (hazard ratio = 4.5; 95% confidence interval, 1.9 to 10.1; P <.001), but no other clinical variables were associated with stenosis. Uncontrolled variceal bleeding as an indication for TIPS placement, coagulopathy, hyperbilirubinemia, and renal insufficiency were associated with increased mortality in patients with TIPSs. Individuals with both coagulopathy and renal insufficiency had high mortality. Urgent TIPS placement for uncontrolled variceal bleeding was associated with stenosis. (+info)