1,720,988 research outputs found
Venocclusive disease of the liver after bone marrow transplantation: The role of hemostasis
No full textNewer fibrinolytic agents in patients with acute myocardial infarction
No full textFibrinolytic agents with higher specificity for fibrin in the thrombi and little systemic activation of the fibrinolytic system have been developed and tested in preliminary clinical trials of patients with acute myocardial infarction. The largest published experience available has been with recombinant tissue plasminogen activator, which seems to be more effective than streptokinase in lysing coronary thrombi. The acylated streptokinase-plasminogen complex BRL 26921 and pro-urokinase also gave promising preliminary results. All these agents, however, were accompanied by unexpectedly high incidence of systemic activation of the fibrinolytic system and by hemorrhagic complications with frequencies similar to those accompanying streptokinase. Hence, their superior clinical efficacy must be clearly proven before they are substituted for a more widely available and less expensive drug, such as streptokinase
Poor relationship between phenotypes of protein S deficiency and mutations in the protein S alpha gene
No full textBy single strand conformational polymorphism, nucleotide sequencing and enzyme restriction, we analyzed the protein S α gene in 17 protein S-deficient probands and in their available family members. The relationship between genotype and phenotype was also evaluated. Twelve different sequence variations were identified in 17 probands. Ten were putative causal mutations distributed in 16 probands: 4 were nonsense, 5 missense and one a splice site mutation. In most families in which a mutation was identified, more than one phenotype of PS deficiency was present. The same splice site mutation (intron j G-A, exon 10 + 5) was associated with type I deficiency in one family and with type I/III in another unrelated family. A phenotypic discrepancy was also observed for the Arg474Pro, Gly597Asp and Arg410stop mutations. Glu26Ala, previously reported in kindreds with type I deficiencies, was found in association with I, II and III phenotypes in four unrelated kindreds. Phenotypic analysis of protein S deficiency is poorly related to the underlying genetic defect
Heightened thrombin generation in individuals with resistance to activated protein C
No full textWe chose to evaluate whether or not a state of biochemical hypercoagulability was present in 74 individuals (69 heterozygotes and 5 homozygotes) resistant to activated protein C (APC) due to the Arg506 → Gln mutation in the factor V gene. To this end, plasma levels of two markers of thrombin formation, prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT), were measured. High levels of F1 + 2 and TAT were found in 32% and 23% of APC-resistant individuals vs 4% in controls. The levels of these markers tended to be particularly elevated in three homozygous subjects. A significant positive correlation between F1 + 2 and TAT was present in APC-resistant individuals. No relationship between marker values and the previous occurrence of thrombotic episodes was found. Therefore, by measuring F1 + 2 and TAT a state of biochemical hypercoagulability has been identified in about one-third of APC-resistant individuals. This frequency is similar to that previously observed in comparable individuals with inherited deficiencies of protein C and protein S, which are usually associated with a stronger thrombotic tendency than APC-resistant individuals
Activation of the protein C pathway in hereditary thrombophilia
No full textLevels of free activated protein C are a measure of the activation of the protein C pathway in vivo. The aim of this study was to establish if the protein C pathway is triggered in familial thrombophilia and if activated protein C levels correlate with type of defect or symptoms. We measured activated protein C in 133 patients with a deficiency of antithrombin (n = 31), protein C (n = 24) or protein S (n = 27) or with resistance to activated protein C (n = 51). Levels of activated protein C were evaluated also in 97 healthy individuals. Results indicate that the levels of activated protein C are higher in patients who have experienced a thrombotic event than in patients who have not and that 71% of patients with levels of activated protein C above the normal reference range had had a venous thromboembolic event. We conclude that the protein C pathway is triggered in patients with thrombophilia and that in symptomatic patients, activated protein C levels are increased and may reflect heightened coagulation activation and scavenging through the protein C pathway
Resistance to activated protein C mimicking dysfunctional protein C: Diagnostic approach
No full textIt has been reported that resistance to activated protein C interferes with functional plasma-based coagulation assays of protein C, mimicking a type II deficiency. In this study we confirm and extend these findings. In our laboratory approximately 25% of patients with resistance to activated protein C have an apparent type II protein C deficiency. It is important for rapid and accurate diagnosis to be able to confirm or exclude a dysfunction of protein C associated with resistance. We therefore propose a new coagulation assay that requires first adsorption of protein C from plasma, activation with a snake venom and measurement of its anticoagulant activity. This assay is quick, reproducible and can be automated. It is also insensitive to the presence of resistance to activated protein C and allows detection of all types of protein C deficiency. This is important when screening for inherited causes of thrombophilia since more than one defect might be present and interference from resistance to activated protein C is common
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