Thrombus age and tissue plasminogen activator mediated thrombolysis in rats.

Thrombolytic efficacy is directly related to thrombus age. We used recombinant tissue plasminogen activator (rt-PA), Streptokinase (SK) and Urokinase (UK) on a seven days old inferior vena cava thrombus model. "In vitro" clot lysis assays with fibrinogen-I125 were also evaluated with the same agents at 1, 3 and 7 days. Fibrinogen, D-D dimer and t-PA were measured. Experiments with 40 controls and 27 rt-PA treated animals showed a significant decrease in thrombus weight (8.5 +/- 1.1 mg) vs. (4.2 +/- 0.6 mg) (p less than 0.01). Fibrinogen concentration in rt-PA group decreased significantly (1032 +/- 123 mg/dl) vs. (202 +/- 32 mg/dl) (p less than 0.001). "In vitro" rt-PA showed a marked lytic effect in a wide range (100-4 IU/ml). Fibrin selective agents as rt-PA may be more effective than non selective ones in the treatment of fully developed thrombus.

Fibrinolytic parameters and lipoprotein (a) levels in plasma of patients with coronary artery disease.

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.

Hypofibrinolysis associated with vasculopathy in non insulin dependent diabetes mellitus.

The pathogenesis of diabetic vasculopathy has been related to modifications in hemostasis and fibrinolysis. 50 non insulin dependent diabetes mellitus patients have been studied. Euglobulin clot lysis time, fibrin plate, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, Protein C and S, cholesterol, triglycerides and Hb A1c were determined in blood samples. Diabetic patients showed decreased fibrinolytic activity, as measured by ECLT, with clearly increased PAI levels. Fibrinolytic response to venous occlusion was lower than normal. Vascular complications were associated both with an even higher PAI activity and with a decreased fibrinolytic response to venous occlusion. Elevated PAI activity and decreased fibrinolytic response to stimulus may contribute to vascular disease in diabetes.

[Thrombolytic agents: efficacy in relation to evolution time and dose]. / Agentes trombolíticos: efectividad en relación con el tiempo de evolución y dosis.

"In vitro" efficacy of urokinase (UK), streptokinase (SK) and tissue-type plasminogen activator (t-PA) was studied. Lytic action was measured by dry clot weight, 125I counts released from previously incorporated 125I-fibrinogen and fibrin fragment quantification at 1, 3 and 7 days using different doses. t-PA doses between 100 and 0.8 IU/ml were efficient. t-PA (40 IU/ml), SK (200 IU/ml) and UK (200 IU/ml) showed an equivalent activity in 1, 3 and 7 day-old clots. Fibrin fragment (D-D dimer) production was highest when t-PA and UK were used. "In vitro" lytic capacity up to 7 days after clot formation has been proved with the different fibrinolytic agents.

High plasma urokinase-type plasminogen activator levels are present in patients with acute nonlymphoblastic leukemia.

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.

[Hemostasis profiles in thrombotic disease]. / Perfiles de hemostasia en la enfermedad trombótica.

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).

A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia.

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.