Biomedical subjects
Publications and source records attributed to M Manasia.
Two cases of necropsy and 5 cases of renal biopuncture were studied on the occassion of an epidemic of "hemorrhagic fever with renal syndrome" identified in mountainous areas of Transylvania. The prevalent pathogenic process was capillary toxicosis which injured the renal tubules and vessels. The severity of the disease was determined by the phenomena of tubular failure, by the hemorrhagic syndrome and shock.
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.
In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena.
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.
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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.
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.
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