Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034065 (pulmonary embolism)
14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma fibrinopeptide A (FPA) concentrations were measured in clinical blood samples incubated in the collecting syringe for different time periods before addition to heparin and Trasylol, and the rate of in vitro generation of FPA was calculated as the mean increment in FPA concentration per minute over the linear portion of the generation curve. 36 normal individuals had a mean plasma FPA level of 0.64 +/- 0.56 pmol/ml and an FPA generation rate of less than 0.5 pmol/ml per min. Clinical samples with elevated plasma FPA levels manifested slow (less than 1 pmol/ml per min) (28 patients) or rapid FPA generation (greater than 1 pmol/ml per min) (33 patients). Slow FPA generation was found in 10/10 patients with venous thrombosis, in 4/4 with aortic aneurysm, and in several patients with acquired hypofibrinogenemia. In one such patient, addition of fibrinogen resulted in rapid FPA generation whereas thrombin addition was without effect. Rapid FPA generation was generally linear, was usually associated with slower fibrinopeptide B generation and was inhibited by parenteral or in vitro heparin. It is thought to reflect increased thrombin activity and was seen in patients with pulmonary embolism, active systemic lupus erythematosus, renal transplant rejection, and after infusion of prothrombin concentrates. The initial rate of FPA cleavage by thrombin at fibrinogen concentrations from 0.05 to 4 mg/ml showed little change between 2 and 4 mg/ml with a Km of 2.99 muM. At a fibrinogen concentration of 2.5 mg/ml the FPA cleavage rate was 49.2 +/- 1.6 nmol/ml per min per U of thrombin. Exogenous thrombin added to normal blood generated 21.7 nmol/ml per U of thrombin FPA in the first minute with a nonlinear pattern reflecting inactivation of thrombin and the presence of alternative substrates. Hence, the thrombin concentration in the blood cannot be calculated from the FPA generation rate. The FPA generation rates in clinical samples with rapid generation (1-28 pmol/ml per min) could be produced by 2 X 10(-5) to 5.6 X 10(-4) thrombin U/ml acting on purified fibrinogen at physiological conditions of pH, ionic strength, and temperature.
...
PMID:The generation of fibrinopeptide A in clinical blood samples: evidence for thrombin activity. 99 37

A 29-year-old woman sustained an acute massive pulmonary embolism in the 32nd week of pregnancy. Rapid clinical improvement followed the use of streptokinase. Treatment was continued for 41 hours, including labour and the first three hours after delivery. There was slow but severe postpartum haemorrhage. Partial uterine atony occurred, and may have been due, at least in part, to fibrin degradation products arising from thrombolysis. No adverse effects were noted in the baby.Our experience suggests that streptokinase may be given during labour but that an oxytocic agent may be needed; and that reversal of fibrinolysis before delivery is best achieved by the use of aprotinin (Trasylol) rather than aminocaproic acid.
...
PMID:Treatment of acute massive pulmonary embolism by streptokinase during labour and delivery. 453 33

The inhibitory effects of antifibrinolytic amino acids on clot lysis induced with recombinant staphylokinase (SakSTAR) or with streptokinase (SK) were evaluated in a human plasma milieu in vitro and in a hamster pulmonary embolism model in vivo. Addition of tranexamic acid to a system composed of 60 microliters 125I-fibrin-labeled plasma clots submerged in 0.5 ml human plasma, caused dose-dependent inhibition of lysis; complete lysis in 120 min required 30 nM SakSTAR or 100 nM SK and was reduced to 50% with 0.015 mM or with 0.07 mM tranexamic acid, respectively. Aprotinin also produced dose-dependent inhibition; lysis with SakSTAR or with SK was reduced to 50% of the control value with 8 KIU/ml or with 10 KIU/ml aprotinin, respectively. Thus, in human plasma in vitro the antifibrinolytic potency of tranexamic acid was 5-fold higher towards SakSTAR than towards SK, whereas that of aprotinin was comparable towards both agents. In hamsters with pulmonary embolism given 0.063 mg/kg SakSTAR or 0.20 mg/kg SK over 30 min, the antifibrinolytic potency of tranexamic acid, administered as a single bolus injection or as a bolus injection followed by continuous infusion, was 8- to 10-fold higher towards SakSTAR than toward SK (50% reduction of clot lysis with SakSTAR at 12.5 mg/kg, as compared to 100-150 mg/kg with SK). In contrast, aprotinin was equipotent towards SakSTAR and SK (50% reduction of clot lysis with 2,000 to 2,700 KIU/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Differential inhibition with antifibrinolytic agents of staphylokinase and streptokinase induced clot lysis. 748 14

Aprotinin is a potent pharmacological agent that reduces bleeding and limits blood transfusion requirements in current surgical practice. Many studies have been conducted in orthopedic surgery. In several trials performed in total hip replacement (THR) and total knee replacement (TKN) patients, aprotinin only moderately decreased blood-loss-replacement requirements. Conversely, when aprotinin was used in patients at high risk for bleeding (cancer, sepsis, redone surgery), it developed a potent hemostatic activity and decreased blood transfusion significantly. No increase in deep vein thrombosis and pulmonary embolism was observed. The only major side effect could be the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk major orthopedic operations. The decision to use aprotinin should be guided by a risk/benefit analysis.
...
PMID:Aprotinin and major orthopedic surgery. 1523 43

Aprotinin is a potent pharmacological agent that reduces bleeding. In current surgical practices, the rate of blood transfusions has decreased with the use of aprotinin. Recently, studies using aprotinin have been conducted in orthopedic surgery. Several trials have been performed in patients undergoing total hip replacement and total knee replacement. Aprotinin moderately decreased blood loss in these patients. When aprotinin was used in patients with a high-risk of bleeding (ie, patients with cancer, sepsis, or undergoing reoperation), potent hemostatic activity occurred and the rate of blood transfusions significantly decreased. No increase in deep vein thrombosis and pulmonary embolism was observed. One adverse effect was the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk orthopedic operations. The decision to use aprotinin can be guided by a risk/benefit analysis.
...
PMID:A direct antifibrinolytic agent in major orthopedic surgery. 1523 56

Aprotinin is an antifibrinolytic drug that reduces blood loss during orthotopic liver transplantation (OLT). Case reports have suggested that aprotinin may be associated with an increased risk of thromboembolic complications. Recent studies in cardiac surgery also have suggested a higher risk of renal failure and postoperative mortality. Despite these concerns, no large-scale safety assessment has been performed in OLT. In a retrospective observational study involving 1492 liver transplants, we studied the occurrence of postoperative thromboembolic or thrombotic events and mortality in patients who received aprotinin (n = 907) and patients who did not (n = 585). The overall incidence of hepatic artery thrombosis and central venous complications (pulmonary embolism or inferior vena cava thrombosis) was 3.2% and 0.9%, respectively. In propensity score-adjusted analyses (C-index = 0.79), aprotinin was not associated with an increased risk of hepatic artery thrombosis [odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.50-2.01, P = 0.86]. Although central venous complications were found more frequently in patients receiving aprotinin, the difference was not statistically significant (OR = 2.95, 95% CI = 0.54-16.23, P = 0.32). In addition, no significant differences were found in 1-year mortality (OR = 1.21, 95% CI = 0.86-1.71, P = 0.32). In conclusion, this study did not demonstrate an increased risk of thrombotic complications or mortality when aprotinin is used during OLT.
...
PMID:Aprotinin and the risk of thrombotic complications after liver transplantation: a retrospective analysis of 1492 patients. 1956 8