L.J. Garcia Frade

Diabetes mellitus as a hypercoagulable state: Its relationship with fibrin fragments and vascular damage

Haemostatic variables were assessed in 43 patients, 28 insulin-dependent and 15 non insulin-dependent. Maximum aggregation by low concentrations of adenosine diphosphate (ADP) or arachidonic acid and elevated plasma concentrations of TxB2, Factor VIII, vWF:Ag, RCoF and fibronectin (Fnct) indicated a hypercoagulable state. The manifestation of vasculopathy was associated with elevated concentrations of RCoF, Fnct, Hbalc, cholesterol and triglycerides, while impaired fibrinolysis was demonstrated by decreased t-PA levels and the absence of crosslinked fibrin degradation products (XL-FDP).

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.

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.

Hereditary Hemorrhagic Telangiectasia: Analysis of Platelet Aggregation and Fibrinolytic System in Seven Patients

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.

PAI and D-D Dimer Levels are Related to Severity of Injury in Trauma Patients

Abstract Trauma patients present a hypercoagulable state that predisposes to thromboembolism. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), plasminogen, α2-antiplasmin, D-D dimer fibrin fragments, protein C, protein S, antithrombin III (AT-III), fibrinogen, factor II Ag, Von Willebrand factor related antigen (VWF:Ag), prothrombin time and Kaolin-cephalin clotting time were studied on admission to the intensive care unit and sequentially after 24 and 48 h in 32 adult trauma patients. Decreased levels of AT-III and protein S pointed to an early activated coagulation. An increase in D-D dimer crosslinked fibrin degradation products associated with low levels of t-PA indicates fibrin deposition and consumption of this fibrinolysis activator. PAI and D-D dimer levels were directly related to the trauma severity injury score. All these data indicate that trauma patients must be evaluated in respect to hypercoagulability and hypofibrinolysis whose intensity may be related to trauma severity.

Silent myocardial ischaemia episodes in non-insulin dependent diabetes mellitus: relationship with haemostatic alterations

A hypercoagulable state possibly associated with metabolic alterations may contribute to the development of vascular damage in diabetes mellitus. The aim of this study was to evaluate the coagulation-fibrinolysis system in patients with non-insulin dependent diabetes mellitus (NIDDM), silent myocardial ischaemia (SMI). Fifty NIDDM patients were studied (24 men and 26 women) age 58.3±0.9 (mean ± M.S.E.) years and diabetes duration 9.2±0.8 (mean ± M.S.E.) years. None of the patients showed basal ECG alterations and all were under continuous ambulatory electrocardiographic monitoring for 48 h. A SMI episode was defined as an asymptomatic downslope of ST segment ⩾ 0.1 mV with a duration 0.08 s after J point of QRS complex, remaining at least for 1 min. Peripheral vasculopathy was evaluated from clinical data and physical examination. Pre and post venous occlusion blood samples were collected, measuring tissue-type plasminogen activator (t-PA) levels, tissue plasminogen activator fast acting inhibitor (PAI) activity, antithrombin III (AT-III) and glycosylated haemoglobin (Hb A1c). Ninety-eight control persons matched by age and sex were studied. Twenty-nine patients showed SMI, 7 had peripheral vasculopathy; none of the patients without SMI had peripheral vasculopathy (p<0.01). Hb A1c levels were higher in patients with SMI than those without it (p<0.01) and the same occurred with the AT-III levels (p<0.05). PAI levels were significantly higher in patients with SMI when compared to controls (p<0.05). A lack of t-PA liberation was demonstrated as a response to venous occlusion in patients with peripheral vasculopathy as related to those without it (p<0.01), nevertheless, patients with SMI did not show this lack of liberation. The increase of PAI levels in patients with SMI in comparison to controls may indicate an inhibition in fibrinolytic activity. The increase of AT-III may be considered as a reaction to hypercoagulability. Fibrinolytic response to stimulous was decreased in patients with peripheral vasculopathy and normal in the ones with SMI, which suggest that there are different stages in the evolution of vascular damage.