Beatriz Sassetti

Influence of homocysteine on fibrin network lysis.

To elucidate some of the links between homocysteine and vascular disease, we have evaluated the effect of the amino acid on the formation (by kinetics studies), structure (by electron microscopy) and lysis of the fibrin network, using tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have studied whether homocysteine could alter the activity of the components involved in fibrinolysis (by amidolytic and thrombolytic methods). The results showed that homocysteine-associated networks were more compact and branched than controls (52 ± 6 vs 44 ± 5 fibers/field, P = 0.008), and were formed by shorter and thicker fibers. This clot proved to be more resistant to fibrinolysis with u-PA than control [lysis time 50%: 257 ± 16 (homocysteine) vs 187 ± 6 min (control); P < 0.004], but there were no differences with t-PA. Homocysteine did not affect the biological activities of plasmin, or plasminogen activation by t-PA and u-PA. Defective fibrinolysis with u-PA was therefore associated with homocysteine–fibrin structural alterations rather than the homocysteine effect on the biological activities of the fibrinolytic components evaluated. Results suggest that hyperhomocysteinemic patients could produce tight clots, were more resistant to lysis, and generated a procoagulant environment in situ. We believe that our findings may contribute to understanding the mechanisms involved in the homocysteine harmful effect.

Nitric oxide in liver transplantation.

Abstract Liver transplantation is the only therapeutic option for patients with end-stage liver disease. Nitric oxide, a free radical produced from L-arginine, a potent vasodilator, also inhibits platelet adhesion and aggregation, reduces adhesion of leukocytes to the endothelium and suppresses proliferation of vascular smooth muscle cells. The inducible form of the nitric oxide synthase may generate large quantities of nitric oxide, and may be induced by the action of cytokines and lipopolysaccharides. Nitric oxide can be released from the hepatic vascular endothelium, platelets and Kupffer cells as a response to ischemia-reperfusion injury and circulatory shock. We analyzed the relationships between the levels of nitric oxide, hepatic enzymes and other clinical parameters (glucose, total proteins, total bilirubin, creatinine, albumin) obtained in serum samples before liver transplantation and every 48 h till day 15 in 15 patients aged 40 ± 13 years. Aspartate aminotransferase and alanine aminotransferase levels changed from high at the beginning, to almost normal at the end of the study, cholinesterase levels remained decreased throughout the study and nitric oxide remained high, never reaching normal values.

Glanzmann thrombasthenia in children from Argentina

Purpose Glanzmann thrombasthenia is a well-defined inherited disorder of platelet function characterized by a decrease or absence of functional platelet glycoprotein (GP) GPIIbIIIa. The diagnosis must be considered in patients presenting with mucocutaneous bleeding, purpura, a normal platelet count, abnormal platelet aggregation, and a prolonged bleeding time. In most of the patients, the presence of small amounts of either GPIIb or GPIIIa was detected in their platelets. These observations could provide a basis for determining the clinical and laboratory heterogeneity of the disease. Patients and Methods We studied 10 patients of seven unrelated families with the usual methods and an immunoalkaline phosphatase technique (APAAP) to analyze the biosynthesis of GP in megakaryocytes. Results The results allowed us to classify six patients as GT type I, three as type II, and one as a variant. Conclusion The nature and severity of the bleeding manifestations, in our patients, were not predictible by the laboratory findings. These confirm the clinical and laboratory heterogeneity of the disease.