[Treatment of coagulopathy in severe sepsis].
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Biomedical subjects
Publications and source records attributed to L J García Frade.
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Three different assays for fibrin/fibrinogen degradation products (FDP) were evaluated in patients with suspected pulmonary embolism (PE) as rapid screening tests with the aim of evaluating whether they could be used either as a substitute of ventilation/perfusion lung scanning or to supplement scintigraphy in patients in whom the scan was inconclusive (low or intermediate probability). D-Dimer by enzyme-linked immunosorbent assay (ELISA) and latex and total FDP by ELISA were measured prospectively in 85 consecutive patients with suspected PE. With a cutoff of 500 ng/ml, D-dimer by ELISA presented a 96% sensitivity and a 42% specificity, with positive and negative predictive values of 49 and 96%, respectively. D-Dimer by latex, also with a cutoff of 500 ng/ml showed a 93% sensitivity and 29% specificity, with positive and negative predictive values of 43 and 89%. For total FDP, with a cutoff of 900 ng/ml, the sensitivity and specificity were 96 and 26% respectively, with positive and negative predictive values of 42 and 93%. A normal assay may have reduced the necessity of a ventilation/perfusion only in 28% patients with D-dimer ELISA, 21% with D-dimer latex and 17% with total FDP ELISA and with a possible error of 4, 11 and 7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To check out the reproducibility and costs of prothrombin time (PT) determination as a control of oral anticoagulant therapy (OAT) in plasma and capillary blood. PATIENTS AND METHODS: The study was carried out in two phases: along two years, 1,700 patients with OAT were controlled, 700 of them in the hospital outpatient clinic. In 149 patients INR was simultaneously determined in both capillary and venous blood. The 700 patients receiving acenocoumarin who had been controlled in 1991 according to the conventional plasma-sample fashion, were controlled in the second year (i.e., 1992) by means of capillary blood testing, a comparison of the costs of each method and the need for anticoagulant drugs being undertaken. Venous blood PT was assessed with reagent thromboplastin (Tromborel S) in an Electra-1000 (MLA) system. An automated Trombotrack system was used for the capillary blood tests using Thrombotest as current procedure. The results were expressed as INR in both methods. The statistical evaluation of the results was carried out by means of Student's t, variance analysis, and correlation study. RESULTS: No significant differences were found in the anticoagulation intervals attained from venous or capillary blood samples. No significant differences were seen in 87 patients on whom the test was repeated in two samples drawn from a single capillary puncture. The weekly OAT doses of 30 patients along six months were analysed. The need for anticoagulant drugs was similar (17.4 vs 17.2 mg/patient/week). The mean INR in 1991 was 2.82 and the mean drug-need was 15.24 mg/week, whereas in 1992 the mean INR was 2.86 and the need for anticoagulant was 15.49 mg/week. The costs of the conventional method were 103.6 Pta, this being 70 Pta for capillary blood, which means a 32% savings. CONCLUSIONS: OAT control by means of PT performed on capillary blood must be considered a substitutive method for the venous blood assay due to its efficacy, simplicity and lower costs.
Resistance to activated protein C (RAPC) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia.
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Thrombolytic therapy yields a 80% repermeabilitation in the acute myocardium infarct if applied soon. In other thrombotic sites such as deep venous thrombosis, pulmonary thromboembolism and peripheral arterial thrombosis, with no large cooperative randomized clinical trials, its usefulness is clear, tough selectively. The high rethrombosis frequency is the major drawback of this therapy. The concomitant use of an anti-thrombotic and/or anti-aggregant agent, even tough the possible higher risks of hemorrhages, seems a key element to improve the results obtained with thrombolysis.
An exaggerated hemorrhagic syndrome is a characteristic in acute non-lymphoblastic leukemia (ANLL) and it determines the patient's outcome. Disseminated intravascular coagulation as a result of a procoagulant factor release and primary hyperfibrinolysis due to plasminogen activators also released by leukemic cells have been implicated in the development of this syndrome. The aim of this work was to evaluate urokinase-type plasminogen activator (u-PA) and related parameters of the fibrinolytic system in 14 ANLL patients. Our results showed an increased u-PA concentration in ANLL patients compared to controls [2.63 (1.61-4.62) vs. 0.95 (0.77-1.48) ng/ml, p < 0.01]. u-PA levels correlated positively with tissue-type plasminogen activator. The relevance of the enhancement of u-PA in this clinical setting was supported by the fact that it was the only analytical parameter positively correlated with patient mortality (p < 0.05). Though u-PA levels do not seem to be the determining factor in the development of the hemorrhagic syndrome of ANLL patients, a contributory role of this plasminogen activator is suggested from our results.
A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.
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Fibrinolysis and lipid disturbances have been considered as independent risk factors for coronary artery disease. Besides this, lipoprotein(a), which is characterized by its homology with plasminogen may interfere with the fibrinolytic function. To evaluate the eventual correlation between fibrinolytic parameters, lipoprotein (a) and other risk factors, 46 patients with coronary artery disease (34 with chronic angina pectoris and 12 with myocardial infarction) were studied. Increased basal values of t-PA antigen (8.2 and 6.6 vs. 4.2 ng/ml) but decreased response after stimulus (2.2 and 1.8 vs. 3.8 ng/ml) and increased levels of lipoprotein(a) (24.7 and 35.9 vs. 10.5 mg/dl) were the most relevant differences between coronary artery disease patients and controls. No correlation between lipoprotein(a) and fibrinolytic parameters was found. Therefore plasma concentration of the main plasma fibrinolytic parameters and lipoprotein(a) seem to be unrelated though the relevance of this interaction at a local level needs to be studied.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder characterized by the presence of generalized mucocutaneous and visceral telangiectasias associated with recurrent bleeding. In order to analyze the mechanism of bleeding in HHT we studied the hemostatic system and platelet in vitro aggregation in 7 unrelated patients suffering from HHT. Unlike the authors of previous reports, we could not find any significant alteration of the parameters measured suggesting a possible local role of the affected endothelial cells.
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It is well known that in thrombotic disease the alteration of biological factors such as antithrombin III, protein C, and protein S deficiency, and congenital disfibrinogenimias and displasminogenemias are determining factors being the acquired alterations not so well known. With this in mind was studied 85 patients with arterial thrombosis and 196 with venous thrombosis, who were again divided into three groups: unique or of repetition, less or more than 35 years and with or without immediate apparent cause. The general clinical-biological profile in patients with thrombosis in whom a congenital deficit is not detected, can help establish prognosis and treatment in these patients. In our patients, together with the importance of factors such as obesity, hyperlipemia, and tabaquism, an increase in fibrinogen (Fg), antigenic Factor VII (vWF:Ag), total protein S is observed as well as a decrease in total fibrinolytic activity related to an increase in the inhibitor of the plasminogen tissue activator (PTA).