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Biomedical subjects

M Cucuianu

Publications and source records attributed to M Cucuianu.

At least 73 records · Page 4Linked to original sources

Hemostatic variables in nephrotic patients.

The paper reviews data in the literature as well as the authors' own investigations, performed during the last seven years, concerning the hemostatic balance in nephrotic patients. The obviously increased plasma levels of fibrinogen, fibronectin, fibrin-stabilizing factor XIII, clotting factors V and VIII, von Willebrand factor as well as the enhanced platelet aggregability of such patients, associated with a decreased plasma antithrombin III, are compatible with a thrombotic tendency. On the other hand the increased plasma protein C may provide a compensative antithrombotic mechanism. A rather complex behaviour of the fibrinolytic system was noted in the nephrotic syndrome. Actually the enhanced release of tissue plasminogen activator (t-PA) from the endothelia of nephrotic patients is accompanied by an accelerated lysis of dilute blood clots, although the inhibitors of fibrinolysis such as alpha 2-macroglobulin and alpha 2-antiplasmin are increased. Failure or exhaustion of the compensative antithrombotic mechanisms would accentuate the hemostatic imbalance and favour the occurrence of thrombotic events. It is considered that increased urinary loss of antithrombin III and the enhanced hepatic synthesis of clotting factors would represent the main mechanisms involved in the production of this precarious hemostatic balance of nephrotic patients.

Antithrombin III↗

Serum electrophoretic lipoprotein factors and pseudocholinesterase activity in thyroid disease.

Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.

Butyrylcholinesterase↗

Clinical studies on alpha 2 plasmin inhibitor.

Plasma levels of alpha 2 plasmin inhibitor (alpha 2 PI) were measured by both an immunological and a functional assay, and a good correlation (r = 0.793; p less than 0.001) was found between the two methods. When compared to values recorded in 17 control subjects (69.55 micrograms/ml +/- 2.04) alpha 2 PI antigen levels were found to be obviously decreased in the 10 patients with decompensated cirrhosis of the liver (41.06 micrograms/ml +/- 4.66) and slightly increased in the 13 nephrotic patients (79.73 micrograms/ml +/- 2.35) and in the 23 hypertriglyceridemic and obese patients (78.59 micrograms/ml +/- 2.23). In spite of similar plasma levels of alpha 2 PI, dilute blood clot lysis was rather accelerated in patients with the nephrotic syndrome (240 min +/- 12) and obviously delayed in patients with endogenous hypertriglyceridemia (739 min +/- 131). Apparently the rate of clot lysis is mainly determined at an earlier stage of the fibrinolytic process, represented by the balance between tissue plasminogen activator and its inhibitor. Severe decrease of alpha 2 PI may nevertheless contribute to accelerated clot lysis as noted in a patient with familial heterozygous alpha 2 PI deficiency. On the other hand increased level of factor XIII and alpha 2 PI associated to an impaired plasminogen activation would render the fibrin network more resistant to fibrinolysis.

Acute-Phase Reaction↗

Plasma von Willebrand factor antigen and activity and platelet aggregability in patients with proteinuria.

Using a complex stimulating mixture containing ADP, epinephrine and collagen, a significantly (p less than 0.002) enhanced platelet aggregability, expressed as platelet sensitivity factor (PSF) was noted in platelet rich plasma of patients with proteinuria (PSF = 472 +/- 125), as against normal weight normolipidemic control subjects (PSF = 32.76 +/- 2.67). A significantly negative correlation (r. -0.579; p less than 0.001) was found between serum albumin concentration and the logarithmic values of platelet sensitivity factor. Plasma von Willebrand factor activity expressed as a percentage of normal was also significantly (p less than 0.001) higher in proteinuric patients (287% +/- 25.8) than in control subjects (99% +/- 5.02), but this hemostatic variable did not correlate with the logarithm of platelet sensitivity factor. Platelet aggregability was higher in hyperlipidemic nephrotic patients than in proteinuric patients with normal serum lipids, while renal failure led to a decrease of platelet function. The raised plasma levels of von Willebrand factor noted in proteinuric patients were not influenced by either hyperlipidemia or by chronic renal failure. It is concluded that changes affecting platelet function in the nephrotic syndrome are produced by other mechanisms than these leading to an increase of endothelia-derived von Willebrand factor. Both changes may, however, contribute to the thrombotic tendency of nephrotic patients.

Adult↗

Hyperlipoproteinemia, hemostatic variables and thromboatherosclerosis.

A concept is gradually being established that certain forms of hyperlipoproteinemia are apt to be accompanied by disturbances of the hemostatic balance favouring fibrin deposition and the incorporation of microthrombi into the arterial wall. Author's clinical and laboratory observations emphasized that endogenous hypertriglyceridemia is often accompanied by raised plasma levels of fibrin stabilizing factor XIII, fibronectin and fibrinolytic inhibitors rendering the fibrin clots more resistant to fibrinolysis and more readily attached to the subendothelial layers of the vessel wall. Increased activity of vitamin K-dependent clotting factors partially counterbalanced by a rather high level of antithrombin III were also detected. Since endogenous hypertriglyceridemia is characterized by an accelerated synthesis and turnover of lipoproteins it may be suggested that this process somehow stimulates the hepatic production of the above-mentioned hemostatic variables. The subsequent alteration of the hemostatic balance is compatible with the localized character and the slow progression of thromboatherosclerosis.

Arteriosclerosis↗

Plasma fibronectin and factor XIII in nephrotic syndrome.

When compared to control subjects plasma fibronectin and factor XIII as well as plasma fibrinogen, factor VIII-related antigen and serum cholinesterase were found to be significantly increased in nephrotic patients. Factor XIII activity was positively correlated with serum cholinesterase, while plasma fibronectin displayed weak correlations with plasma fibrinogen and factor VIII-related antigen. It is considered that increased levels of factor XIII and fibronectin should be related to the intensity of the liver's compensative response to proteinuria, although their turnover rates and the signals triggering this response may differ. It is however difficult to assess possible consequences of the above-mentioned changes for the evolution of the nephrotic syndrome.

Adult↗

Influence of some inhibitors and activators of fibrinolysis on transcapillary transport of macromolecules.

The RISA transcapillary transport in the posterior paw was followed up under the influence of some substances inhibiting and activating fibrinolysis (Trasylol, EACA and Streptokinase and Salyrgan, respectively) in 11 dogs under narcosis with chloralose and the cannulation of the lymphatics in the popliteal space. It was found that EACA inhibits the transcapillary RISA transport and streptokinase activates it. Trasylol and Salyrgan produced no changes, the slope of the vanishing curve of the tracer being identical with that of the controls.

Animals↗

Behaviour of fibrinolysis in the nephrotic syndrome.

When compared to 39 normal-weight normolipidemic control subjects, the dilute blood clot lysis time was found to be slightly (p less than 0.05) accelerated in the 49 investigated nephrotic patients, although their plasma fibrinogen, factor XIII as well as the inhibitors of fibrinolysis, are markedly increased. These findings indicate that the fibrinolytic system as a whole is not markedly depressed in the nephrotic syndrome. Although the fibrinolytic activity of euglobulins tested on agarose-fibrin plates was not significantly increased in nephrotic patients, one cannot definitely preclude an enhanced secretion of plasminogen activators in this pathological condition. A different quality of the inhibitors which may be less active in retarding dilute blood clot lysis time could also be considered.

Adolescent↗

Lupus anticoagulant and transient severe bleeding tendency in a girl aged nine years.

A 9-year old girl admitted in our clinic for severe hemorrhagic syndrome was found to display a high level of lupus anticoagulant (LA) leading to an important prolongation of phospholipid-dependent coagulation. Positive antinuclear and anti DNA antibodies, as well as very low levels of complement C3 and C4 proteins confirmed the diagnosis of systemic lupus erythematosus. Therapy with cortisone and cyclophosphamide led to normalization of the clotting tests but could not arrest the development of renal and hepatic lesions. The patient is one of the few cases with presence of lupus anticoagulant associated with severe hemorrhagic diathesis, in opposition to the more frequently reported thrombotic tendency connected with antiphospholipid antibodies.

Acute Disease↗

Clinical studies on plasma antithrombin III using an antiserum prepared in our laboratories.

Using an antiserum obtained in rabbits injected with antithrombin III purified in our laboratories, the plasma level of this inhibitor of coagulation was found to be significantly (p less than 0.001) decreased in 8 patients with decompensated cirrhosis of the liver (15.66 mg/dl +/- 2.22) and in 18 nephrotic patients (21.74 mg/dl +/- 1.75). When compared to values noted in 22 normal-weight normolipidemic control subjects (31.54 mg/dl +/- 0.81), the plasma level of antithrombin III was slightly (p less than 0.05) higher in the 18 hyperlipidemic subjects (36.11 mg/dl +/- 1.9). Owing to an extremely wide dispersion of individual values, the mean level of antithrombin III noted in 16 critically ill postoperative patients (28.16 mg/dl +/- 2.98) did not significantly differ from control values, although this protease inhibitor was obviously decreased in those postoperative patients who developed multiple organ failure or disseminated intravascular-coagulation. Among the 11 patients with recurrent venous thrombosis, two subjects with familial deficiency in antithrombin III were detected. The results provide evidence that the antiserum prepared in our laboratories is a useful tool for detecting acquired and inherited antithrombin III deficiencies.

Adult↗

Increased level of plasma factor VIII-related antigen in peripheral arterial disease.

When compared to age-matched control subjects factor VIII-related antigen was found to be significantly increased in patients with peripheral arterial diseases, while there were no significant differences concerning its plasma level between patients with thrombangitis obliterans and those with atherosclerosis of the lower limbs or between the various stages of the disease. Acute phase reactants such as plasma fibrinogen and alpha 1 antitrypsin were changed to a much lesser extent in the initial stages of peripheral arterial disease, and the afore mentioned antiprotease increased significantly only in stage IV. It is considered that the increased plasma level of factor VIII-related antigen occurring already in the initial stages of arterial disease, should be interpreted as an expression of widespread endothelial lesions and not as the mere result of an acute phase reaction. The relevance of changes affecting factor VIII-related antigen for the development of thrombotic complications could be assessed only in the context of other abnormalities of the hemostatic variables.

Adult↗

Plasma fibronectin in peripheral arterial disease.

When compared to values obtained in 24 age-matched normal weight normolipidemic control subjects, plasma fibronectin level was not significantly changed in the 28 patients with peripheral arterial disease, although endothelial cell-derived factor VIII related antigen was found to be obviously increased. On the other hand the 15 patients with obliterative atherosclerosis of the lower limbs who were hyperlipidemic (mainly hypertriglyceridemic) displayed a plasma fibronectin level (46.3 +/- 2.8 mg/dl) which was higher than the mean values recorded in both control subjects (36.2 +/- 1.66 mg/dl) and in normolipidemic patients with peripheral arterial disease (34.5 +/- 4.14 mg/dl). The results suggest that an increased level of plasma fibronectin should be connected rather to a peculiar pattern of hepatic protein synthesis occurring in overweight and hypertriglyceridemic subjects than to a release of this glycoprotein from an ongoing arterial lesion.

Adult↗

Increased plasma level of clotting factors VII and X in hyperlipoproteinemia.

When compared to values obtained in healthy normal-weight normolipidemic controls, the combined activities of clotting factors VII and XI, as well as serum cholinesterase were found to be significantly higher in hyperlipidemic and especially in hypertriglyceridemic subjects. The levels of the vitamin K-dependent clotting factors are positively correlated with the concentration of serum cholesterol, the logarithm of serum triacylglycerol level and serum cholinesterase activity. Based on these data as well as on previous observations concerning an increased plasma level of other liver secretion enzymes in endogenous hypertriglyceridemia, a possible interrelationship between accelerated turnover of lipoproteins, enhanced hepatic protein synthesis and thromboatherosclerosis is suggested.

Adult↗