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Orthotopic liver transplantation: an experimental study on mechanisms of hemorrhagic diathesis and thrombosis.

The hemorrhagic diathesis after transplantation of preserved livers generally is attributed to intravascular coagulation, whereas postoperative "hypercoagulability" of the blood is considered the main cause of thrombosis of the hepatic artery anastomosis. Since our preliminary studies, however, suggested other mechanisms, parameters of coagulation, fibrinolysis, and platelet function were prospectively studied before and after 28 orthotopic liver transplantations, with and without preservation, in dogs and pigs. In addition, the arterial anastomoses were evaluated routinely by angiography and, after removal at reintervention or autopsy, inspected for thrombosis and tested for fibrinolytic activity and fibrin deposition. Concerning the hemorrhagic diathesis, prolongation of bleeding time without concomitant thrombocytopenia was the main abnormality found and occurred only in the nine dogs with liver transplants previously preserved for 3 to 6 hours. As only two of the nine dogs had postoperative hemorrhage of clinical significance, we consider surgically imperfect hemostasis facilitated by an acquired platelet dysfunction the principal cause of hemorrhage. Thrombosis of the arterial anastomosis was found in 38 percent of animals in which an end-to-end anastomosis was made but was not encountered with celiac artery-aorta anastomoses. Local factors due to surgical technique therefore appear most important in the pathogenesis of thrombosis of the hepatic artery anastomosis, although the postoperative hyperfibrinogenemia and diminished local and systemic fibrinolytic activity may contribute as well.

Animals↗

A familial hemorrhagic diathesis in a Dutch family: an inherited deficiency of alpha 2-antiplasmin.

This study concerns a case of congenital homozygous deficiency in alpha 2-antiplasmin associated with a severe hemorrhagic diathesis. Heterozygous family members also show a mild bleeding tendency. The propositus is a 17-yr-old male born of white parents and showing a severe hemorrhagic diathesis characterized by spontaneous bleeding in the joints since his early childhood. He was originally suspected of having factor XIII deficiency but was found to have normal functions of the coagulation system and the platelets. Except for alpha 2-antiplasmin, all protease inhibitors showed normal plasma values. With the immediate plasmin inhibition test (synthetic substrate), only 2% of normal functional inhibition was detected, while no reaction with monospecific antisera for alpha 2-antiplasmin was observed. Inhibition of activator-induced fibrinolysis in vitro was reduced. No enhanced spontaneous in vitro fibrinolysis was detected nor were there signs of increased in vivo fibrinolysis during an asymptomatic period. During recovery from a hemorrhagic episode, signs of previous consumption of antithrombin III, alpha 2-macroglobulin, factor XIII, and inter-alpha-trypsin inhibitor were noted. After the diagnosis was made, treatment with tranexamic acid (4 daily doses of 1 g) was effective for about 2 yr. Among the 37 family members studied, a separate group of 16 individuals (including the father and mother of the propositus) with approximately one-half normal plasma levels of alpha 2-antiplasmin both functionally (59% +/- 6%) and immunologically 48% +/- 8%) was discovered. The defect appeared to be inherited as an autosomal recessive gene; no ancestral consanguinity could be shown. The group of apparent heterozygotes as a whole showed increased levels of alpha 1-antitrypsin (142% +/- 39%; p less than 0.01), indicating systemic consequences of the deficiency and reduced binding (+/- 50%) of alpha 2-antiplasmin to fibrin. Six exhibited a mild hemorrhagic diathesis for which no explanation was provided by routine screening of coagulation and platelet functions; also, within the group of heterozygotes, the occurrence of the bleeding tendency did not correlate with differences in residual alpha 2-antiplasmin levels and functions. It is concluded that not only the absence of alpha 2-antiplasmin but also a reduction in its plasma level to +/- 60% of normal may predispose to a hemorrhagic diathesis.

Adolescent↗

An electron microscopic study of the vascular factor in hemorrhagic diathesis.

Experimental diapedetic hemorrhage (oozing) was produced by streptokinase in rabbits and the fine structures of mesenterial microvessels were observed. Diapedesis of erythrocytes was seen in the venular side of microcirculation. On the contrary, no diapedesis was seen in true capillary on the arteriolar side. Sticking of erythrocytes to venular wall prior to diapedesis was proved, electron microscopically, to be the state in which red blood cells were trapped in the gaps on the endothelial junction. It was considered to be the morphological findings of the prediapedetic state. Erythrocytes passed through gaps on the endothelial junctions with high plasticities under any diapedetic conditions mentioned above. Furthermore, in author's experiments by ruthenium red staining, erythrocytes were observed just passing through the basement membrane under electron microscopy, in spite of its high speed process. It was found that the basement membrane is a very important barrier in erythrocyte diapedesis.

Animals↗

[Hemorrhagic diathesis and oral surgery].

Dental and/or periodontal diseases are an important clinical and social problem in patients with hemorrhagic diathesis. The possibility to overcome it successfully depends on the type of hemorrhagic disease and on the organization of hematological and odontostomatological centres: in fact, the best results in the surgery of these patients are obtained through the balanced combination of general and local treatments. The right diagnosis of coagulopathy is the first important goal: it can be obtained through the screening tests of hemostasis and, when necessary, through additional tests. Therapeutic protocols are available for each congenital or acquired hemorrhagic diathesis to prepare the patient for surgery; by so doing the risk of hemorrhagic complications is negligible. A better homogeneity in the approach to these patients in the different centres is highly desirable: the present review can offer a contribute in this respect.

Blood Coagulation Disorders↗