Pulmonary responses of unilateral positive end expiratory pressure (PEEP) on experimental fat embolism.
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The role of positive end expiratory pressure (PEEP) was evaluated in preventing the deleterious mechanical respiratory effects of fatty acid pulmonary embolism. One group of animals had ventilation without PEEP, while the second group had PEEP of 10 cm H2O applied only to the right lung. In the right lung, PEEP slightly reduced the blood flow, increased the vascular resistance, but reduced intersititial edema and reduced the degree of shunting to almost normal. Hypoxemia was prevented in the right pulmonary venous system, but was prominent in the left. The hypoxemia and shunting in the left lung were comparable to the Group I animals without PEEP to either lung. These studies confirm the value of PEEP in the therapy of the pulmonary manifestations of fat embolism which are the lethal factors in the fatty embolism syndrome. (+info)
High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.
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BACKGROUND: A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII. METHODS: We studied 360 patients for an average follow-up period of 30 months after a first episode of venous thromboembolism and discontinuation of oral anticoagulants. Patients who had recurrent or secondary venous thromboembolism, a congenital deficiency of an anticoagulant, the lupus anticoagulant, hyperhomocysteinemia, cancer, or a requirement for long-term treatment with antithrombotic drugs or who were pregnant were excluded. The end point was objectively documented, symptomatic recurrent venous thromboembolism. RESULTS: Recurrent venous thromboembolism developed in 38 of the 360 patients (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosis was 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII. Among patients with a factor VIII level above the 90th percentile of the values in the study population, the likelihood of recurrence at two years was 37 percent, as compared with a 5 percent likelihood among patients with lower levels (P<0.001). Among patients with plasma factor VIII levels above the 90th percentile, as compared with those with lower levels, the overall relative risk of recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden or the G20210A prothrombin mutation, and the duration of oral anticoagulation. CONCLUSIONS: Patients with a high plasma level of factor VIII have an increased risk of recurrent venous thromboembolism. (+info)
Prophylactic vena caval filters in trauma: the rest of the story.
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OBJECTIVE: The purpose of this study was to describe outcomes for patients with trauma who had vena caval filters placed in the absence of venous thromboembolic disease (group P) and compare them with outcomes for patients with trauma who had filters placed after either deep venous thrombosis or pulmonary embolism (group T). DESIGN: The study is a case series of consecutive patients who received vena caval filters after traumatic injury. Data were collected prospectively at the time of filter placement from reports of diagnostic studies obtained for clinical indications and during the annual follow-up examinations. Event rate findings are based on objective tests. Data were obtained from the Michigan Vena Cava Filter Registry. RESULTS: Filters were placed in 385 patients with trauma; 249 of these filters were prophylactic (group P). Event rates were similar in the two groups. New pulmonary embolism was diagnosed in 1.5% of the patients in group P and 2% of the patients in group T. Caval occlusion rates were 3.5% for group P and 2.3% for group T. In all, 15.6% of the patients in group P had deep venous thrombosis or pulmonary embolism after placement. The frequencies of lower extremity swelling and use of support hose were higher in group T than in group P (43% vs 25% and 25% vs 3.5%, respectively; P <.005). Outcomes were comparable in the two groups with respect to mechanical stability of the filter. CONCLUSIONS: The prophylactic indication for vena caval filter placement in patients with trauma is associated with a low incidence of adverse outcomes while providing protection from fatal pulmonary embolism. The current challenge is to limit the number of unnecessary placements through improved methods of risk stratification. (+info)
Urokinase mediates fibrinolysis in the pulmonary microvasculature.
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The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in fibrinolysis remains unsettled. The contribution of uPA may depend on the vascular location, the physical properties of the clot, and its impact on tissue function. To study the contribution of urokinase within the pulmonary microvasculature, a model of pulmonary microembolism in the mouse was developed. Iodine 125 ((125)I)-labeled fibrin microparticles injected intravenously through the tail vein lodged preferentially in the lung, distributing homogeneously throughout the lobes. Clearance of (125)I-microemboli in wild type mice was rapid and essentially complete by 5 hours. In contrast, uPA(-/-) and tissue-type plasminogen activator tPA(-/-) mice, but not uPAR(-/-) mice, showed a marked impairment in pulmonary fibrinolysis throughout the experimental period. The phenotype in the uPA(-/-) mouse was rescued completely by infusion of single chain uPA (scuPA). The increment in clot lysis was 4-fold greater in uPA(-/-) mice infused with the same concentration of scuPA complexed with soluble recombinant uPAR. These data indicate that uPA contributes to endogenous fibrinolysis in the pulmonary vasculature to the same extent as tPA in this model system. Binding of scuPA to its receptor promotes fibrinolytic activity in vivo as well as in vitro. The physical properties of fibrin clots, including size, age, and cellular composition, as well as heterogeneity in endothelial cell function, may modify the participation of uPA in endogenous fibrinolysis. (Blood. 2000;96:1820-1826) (+info)
Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis.
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PURPOSE: Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR. PATIENTS AND METHODS: In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0. RESULTS: In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0. CONCLUSION: Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy. (+info)
Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension.
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The transfer factor of the lung for carbon monoxide (TL,CO) is decreased in patients with pulmonary hypertension. The pulmonary membrane diffusion capacity (Dm) and pulmonary capillary blood volume (Vc), were studied to establish: 1) the relative contribution of the components of the transfer factor to the decrease in TL,CO; 2) whether differences exist between primary pulmonary hypertension (PPH) and chronic thromboembolic pulmonary hypertension (CTEPH); and 3) the relationship between these parameters and haemodynamic parameters. Dm and Vc were determined in 19 patients with PPH and in eight patients with CTEPH. The patients had been referred for consideration for lung transplantation. Haemodynamic parameters were assessed by heart catheterization. In the PPH group, Vc was reduced in 12 of 19 patients (mean+/-SD Vc 72+/-14% of the predicted value) and Dm in 17 of 19 patients (60+/-22% pred). In the CTEPH group, Vc was reduced in six of eight patients and Dm in seven of eight patients. The mean TL,CO Dm and Vc values were similar to those in the PPH group. The reduction in pulmonary membrane diffusion capacity was significantly greater than that in pulmonary capillary blood volume. No differences in pulmonary and cardiovascular functional values were found between the groups. Right atrial pressure showed a significant negative correlation with pulmonary capillary blood volume and an increased pulmonary vascular resistance was associated with a decrease in pulmonary membrane diffusion capacity. These results suggest pronounced functional impairment of the alveolocapillary membrane in these patients. (+info)
Long-term results of inferior vena cava filters: experiences in a Japanese population.
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OBJECTIVE: In this prospective, non-controlled observational study, we evaluated the middle- to long-term results of placement of inferior vena cava (IVC) filter devices in Japanese patients. METHODS AND RESULTS: In 42 Japanese patients with deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) who underwent percutaneous insertion of IVC filters, follow-up examinations at fixed intervals of 2 years were performed, and the data was evaluated including complications. There were no fatal complications during IVC filter implantation. About 5% of patients with an inserted IVC filter developed symptomatic PTE, another 5% developed asymptomatic PTE. The trapped thrombus was demonstrated in about 22% of the inserted IVC filters. Lower rates of PTE development, occlusion of IVC, and captured thrombus were found in the cases where concurrent use of anticoagulation therapy with filters was used. Trapped thrombi were found in half of IVC filters inserted prophylactically for proximal femoral venous thrombosis. CONCLUSION: These experiences with IVC filters suggest that they are safe and effective for the prevention of PTE in the Japanese population. (+info)
Catalytic life of activated factor XIII in thrombi. Implications for fibrinolytic resistance and thrombus aging.
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BACKGROUND: Because the increased fibrinolytic resistance of older thrombi may be caused by the continuous cross-linking action of fibrin-bound activated factor XIII (FXIIIa), we examined the persistence of FXIIIa catalytic activity in clots of various ages. METHODS AND RESULTS: The time-related changes in FXIIIa activity in clots was measured with (1) alpha(2)-antiplasmin (alpha(2)AP), a physiological glutamine substrate; (2) alpha(2)AP(13-24), a peptide; and (3) pentylamine, a nonspecific lysine substrate. The cross-linking of alpha(2)AP, alpha(2)AP(13-24), and pentylamine into fibrin by clot-bound FXIIIa declined rapidly with half-lives of 19, 21, and 26 minutes, respectively. Mutational studies showed that glutamine 14 (but not glutamine 3 or 16) and valine 17 of alpha(2)AP(13-24) were required for efficient cross-linking to fibrin. The loss of activity was not due primarily to FXIIIa proteolysis and was partially restored by reducing agents, suggesting that oxidation contributes to the loss of the enzyme's activity in clots. In vivo, the ability of thrombus-bound FXIIIa to cross-link an infused alpha(2)AP(13-24) peptide into existing pulmonary emboli also declined significantly over time. CONCLUSIONS: FXIIIa cross-links alpha(2)AP and an alpha(2)AP peptide, in a sequence-specific manner, into formed clots with a catalytic half-life of approximately 20 minutes. This indicates that FXIIIa activity is a hallmark of new thrombi and that the antifibrinolytic cross-linking effects of FXIIIa are achieved more rapidly in thrombi than previously believed. (+info)