Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detailed haemostatic changes were investigated during eight liver transplantations. The patients were divided into two groups; group 1 had minor operative bleeding (four cases) and group 2 had major bleeding (four cases). Group 2 had lower levels of platelets, fibrinogen, factor V (FV), and alpha 2-antiplasmin than group 1, and the thromboelastography showed fibrinolysis. In both groups, plasma tissue-plasminogen activator levels rose slightly. After revascularization of the graft liver, reductions in the values of PT, fibrinogen, FV and FVII were noted, along with a prolongation of the PTT and an increase in thrombin-antithrombin III complex levels. Plasma levels of protein C, protein S, antithrombin III, and plasminogen remained relatively stable throughout the operation. These results show that the preceding fibrinolysis and subsequent superimposed activation of the clotting system are the main causes of coagulopathy during liver transplantation, which correlate with the amount of operative haemorrhage and the abnormalities found in haemostatic tests.
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PMID:Coagulation disorder during liver transplantation. 177 95

The levels of prothrombin fragment F1 + 2 were measured by a double antibody radioimmunoassay in blood samples collected into different anticoagulant solutions. We evaluated healthy males between the ages of 42 and 77, asymptomatic patients with hereditary deficiencies of protein C or protein S, and persons receiving tumor necrosis factor infusions. The results in specimens collected in an anticoagulant containing ACD, EDTA, adenosine, and 25 U/ml of heparin (a) were highly correlated with those collected in an anticoagulant containing a synthetic thrombin inhibitor, EDTA, and aprotinin (b). However, in asymptomatic patients with congenital antithrombin III deficiency, we found that the plasma levels of F1 + 2 in blood collected in anticoagulant (a) were usually substantially higher than those collected in anticoagulant (b). We determined that this phenomenon was not attributable to the venipuncture procedure itself, but rather appears to be due to the action of low concentrations of heparin in the presence of reduced blood levels of antithrombin III. Our data show that the previously documented elevations in plasma F1 + 2 levels in patients with congenital antithrombin III deficiency appear to be caused by the above in vitro anticoagulant effect, and that this population does not exhibit evidence of a prethrombotic state as defined by the F1 + 2 assay.
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PMID:Influence of anticoagulants used for blood collection on plasma prothrombin fragment F1 + 2 measurements. 178 Aug 6

6 patients with deep vein thrombosis triggered by drug therapy, that is oral contraceptives in 5 and the anticonvulsant tranexamic acid in 1, are described. These cases were among 40 symptomatic patients out of a total group of 81 with congenital coagulation inhibitor defects studied over 10 years at the Institute of Medical Semiotics, Padua, Italy. The 5 women with deep vein thrombosis ranged in age from 20-34, and had typically taken oral contraceptives containing 35 mcg ethinyl estradiol in combined or phasic preparations, for 1 to 8 cycles. One women, however, had been prescribed sequential pills containing 50 mcg mestranol. Another had taken oral contraceptives with impunity for 3 years, but developed deep vein thrombosis after taking tranexamic acid for 10 days. All recovered after heparin or oral anticoagulant therapy, except a 21 year old whose condition evolved into complete ileo-caval obstruction up to the renal veins, and was treated with urokinase. the congenital defects involved were 3 probable heterozygous true deficiencies of antithrombin III (low ATIII antigen and activity); a decreased protein C antigen to factor X antigen ratio; a heparin cofactor II deficiency; and a type I protein S deficiency (low free protein S, with normal total protein S and normal levels of C4B-bp.) While 5 of these 6 women had family histories of thromboembolic disease, the drug was prescribed without knowing that they were heterozygous for a coagulation inhibitor deficiency. The incidence of drug-induced thromboembolism was low in this series overall, where most of the events were triggered by surgery or trauma.
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PMID:The role of drugs, particularly oral contraceptives, in triggering thrombosis in congenital defects of coagulation inhibitors: a study of six patients. 178 39

Thromboembolism remains a major cause of maternal morbidity and mortality. The incidence of thrombosis associated with pregnancy is stated to be around 0.09%1 but is greater in women with familial or acquired thrombophilia. Around 50% of pregnancies in women with antithrombin III deficiency are complicated by thrombosis. Anticoagulation throughout pregnancy and the puerperium is recommended in women with antithrombin III deficiency. Because thrombosis is less common in women with protein C or protein S deficiency less aggressive management may be appropriate during pregnancy but anticoagulation post partum is generally recommended. The most important acquired thrombophilic abnormality is the development of antiphospholipid antibodies ('lupus anticoagulants'). Women with these antibodies may present major problems but no clear guidelines for their management currently exist. The majority of women with a history of thrombosis have no identifiable haemostatic abnormality. Management of pregnancy in these patients depends on individual circumstances.
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PMID:Management of thrombophilia in pregnancy. 178 82

It is well known that in thrombotic disease the alteration of biological factors such as antithrombin III, protein C, and protein S deficiency, and congenital disfibrinogenimias and displasminogenemias are determining factors being the acquired alterations not so well known. With this in mind was studied 85 patients with arterial thrombosis and 196 with venous thrombosis, who were again divided into three groups: unique or of repetition, less or more than 35 years and with or without immediate apparent cause. The general clinical-biological profile in patients with thrombosis in whom a congenital deficit is not detected, can help establish prognosis and treatment in these patients. In our patients, together with the importance of factors such as obesity, hyperlipemia, and tabaquism, an increase in fibrinogen (Fg), antigenic Factor VII (vWF:Ag), total protein S is observed as well as a decrease in total fibrinolytic activity related to an increase in the inhibitor of the plasminogen tissue activator (PTA).
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PMID:[Hemostasis profiles in thrombotic disease]. 178 55

To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgkin's lymphoma. Patients received either weekly (standard dose group) or daily (high dose group) vitamin K supplements with their total parenteral nutrition. By day 14 there had been a significant drop in protein C activity (mean of 95% of normal to 52%), protein C antigen (mean of 105% of normal to 70%), and antithrombin 3 activity (111% of normal to 83%), and an increase in fibrinogen (471-621 mg/dl) and tissue plasminogen activator (6.9-13.8 ng/ml). No changes were seen in free or total protein S, plasminogen activator inhibitor, prothrombin time or partial thromboplastin time. The decreases in protein C and antithrombin 3 persisted through day 28 after transplantation. The drop in protein C correlated strongly with decrease in serum albumin, suggesting impaired synthesis of these proteins by the liver. No differences were seen in any of these parameters between the standard and high dose groups. Deficiencies in anticoagulant proteins antithrombin 3 and protein C and a rise in fibrinogen without a concomitant improvement in fibrinolytic variables create a potentially hypercoagulable state which may contribute to the thrombotic complications of autologous BMT.
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PMID:High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma. 179 Apr 30

Phospholipids bearing a proportion of anionic species such as phosphatidylserine are necessary to promote the anticoagulant potential of the protein C pathway. Factor Xa (200 or 350 pM) was found to activate protein C in a thrombomodulin-independent reaction requiring only phospholipids in Al(OH)3,-adsorbed plasma resupplemented with physiological concentrations of protein C (70 nM) and protein S (130 nM). All experiments were performed in the presence of an excess of hirudin. The activity of activated protein C was assessed by the survival of factor Va. The optimal phospholipid concentration range was 5 to 25 microM with a proportion of phosphatidylserine of 50% (mol/mol) resulting in a half-life of factor Va of 7.5 min in the absence of protein S and 4.2 min in its presence. Dns-EGR-Xa, an inactive derivative of factor Xa, behaved as an apparent protector of factor Va. When replacing factor Xa, thrombin at 10 nM was not an efficient protein C activator in the absence of purified human placenta thrombomodulin. In the presence of 100 pM activated protein C, factor Va half-life was 2 min in the absence of protein S and 1.1 min in its presence in the above optimal phospholipid concentration range. The presence of protein S allowed reduction of phospholipid requirements. Annexin-V (placental anticoagulant protein-I), a potent phospholipid antagonist, fully protected factor Va from degradation by phospholipid-dependent mechanisms. Factor Va was partially protected in the plasma of a patient having experienced thrombosis associated with lupus-like anticoagulant and anti-phospholipid auto-antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The catalytic role of anionic phospholipids in the activation of protein C by factor Xa and expression of its anticoagulant function in human plasma. 179 56

This study concerns 20 patients with cerebrovascular disease in the course of oral contraception with estrogens/progestins. The assumption of oral contraceptives appears to be related to the cerebrovascular manifestations, which could be caused by alterations of the blood vessel walls or of the coagulative process induced by estrogens/progestins. The thrombogenic action of these substances could be enhanced by preexisting conditions such as protein C or protein S deficiency.
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PMID:[Cerebrovascular manifestations while taking combined estrogens and progestins for contraceptive purposes. Clinical cases]. 181 77

Protein C, a potent vitamin K-dependent protein activated by an endothelial cell cofactor, thrombomodulin, has anticoagulant and profibrinolytic activity. Free protein S, a cofactor for protein C, potentiates protein C activity at the endothelial cell surface. Pulmonary thromboemboli are a consistent finding in adult respiratory distress syndrome (ARDS). To determine if protein S or protein C were affected by widespread endothelial cell damage in ARDS, we measured bound and free protein S levels and protein C antigenic and functional levels in 18 patients with acute lung injury, 6 critically ill patients without lung history, and 22 normal subjects. Free (PS:F) and bound (PS:Ag) protein S and protein C antigen (PC:Ag) levels were measured using an enzyme-linked immunoassay and protein C function (PC:Fn) by measuring its anticoagulant activity. We found a significant decrease in bound and free protein S levels of both patient groups in comparison to normal and a shift toward the inactive, bound protein S form. In addition, a significant decrease in free protein S compared to bound protein S in both patient groups was observed. While both PC:Ag and PC:Fn were significantly reduced compared to normal, the PC:Fn was significantly and severely decreased out of proportion to the PC:Ag in both patient groups. There was no difference between those with and without lung injury for both protein S and protein C. Analyzed according to etiology of lung injury, there was no difference in the bound and free protein S, nor in PC:Ag and PC:Fn levels between patients with sepsis and trauma. However, there were significant decreases in both protein S and protein C levels compared with normal subjects. Levels of both PS and PC levels in patients who survived did not differ from those who died. In summary, our data show that both protein S and C are markedly deranged in acutely ill patients who suffered from either sepsis or trauma, and these changes are independent of lung injury. The marked reductions in functional activity of PS and PC may be contributing factors to the thromboembolic complications often observed in these patients.
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PMID:Protein S and C alterations in acutely ill patients. 182 9

We studied the effect of hemodialysis on natural coagulation inhibitors including protein C (PC), protein S (PS), and antithrombin III (AT III), as well as the correlations between the antigen level (immunological activity) and functional activity of individual coagulation inhibitor. Plasma AT III, PS, and PC were measured in 20 uremic patients on maintenance hemodialysis immediately before, during, and after dialysis treatment. These values were compared with those obtained from 20 matched healthy controls. Plasma PC and total PS antigen levels were measured by enzyme immunoassay. The plasma AT III antigen level was determined by Laurell rocket immunoelectrophoresis. Functional activities of PC and AT III were determined by the amidolytic method. Free PS antigen level was quantitated by measuring the free PS-related antigen after the sample was treated with polyethylene glycol to remove the C4b-binding protein. Uremic patients on maintenance hemodialysis had a higher total PS antigen level, but a lower free PS antigen level compared with the controls. Both the antigen level and functional activity of AT III in uremic patients were significantly lower than those of controls. Their predialysis plasma PC antigen level and functional activity were not different from those of normal controls. A significant correlation between the antigen level and functional activity of PC, PS, and AT III was demonstrated in healthy controls, but not in hemodialysis patients. No significant change in the level of AT III or PS was observed with hemodialysis, but a progressive increase of functional activity of PC was documented with hemodialysis. Furthermore, the coefficient of correlation between the antigen level and functional activity of PC improved significantly with dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hemodialysis on protein C, protein S, and antithrombin III levels. 182 35


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