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)

The hemostatic system is assumed to be similar in children and adults and reference ranges established for adults are commonly used to evaluate children suspected of having congenital or acquired hemostatic problems. However, we know that the hemostatic system is not fully mature by 6 months of age and comprehensive studies of healthy older children have not been published. Therefore, we conducted a prospective cohort study of the hemostatic system in healthy children having minor, elective day surgery. After obtaining informed consent, a 3-mL blood sample was obtained at the time routine preoperative blood work was drawn. The plasma was fractioned and stored at -70 degrees C for batch assaying. We measured the concentration of 33 components of the hemostatic system (functional and immunologic assays) and the bleeding time (automated pediatric device) in 246 children aged 1 to 16 inclusive (a minimum of four subjects at each age). Eleven components of hemostasis (fibrinogen, prekallikrein, high-molecular weight kininogen, factors VIII and XIII, antithrombin III [ATIII], heparin cofactor II [HCII], alpha 1-antitrypsin [alpha 1AT], protein S, plasminogen, alpha 2-antiplasmin [alpha 2AP]) had mean values and ranges of normal that were similar to adults. Mean values of seven coagulants (II, V, VII, IX, X, XI, XII) were significantly lower than adult values and varied with age. Values for three inhibitors, alpha 2-macroglobulin (alpha 2M), protein C, and protein C1-inhibitor (C1-Inh) also differed from adults. Alpha 2M and C1-Inh inhibitor levels were elevated throughout childhood, whereas protein C levels were low, with a lower limit of normal of 0.40 U/mL until the age of 11. Finally, the upper limit of normal for the bleeding time was longer in children during the first 10 years of life, but decreased to adult values in the teenage years. In summary, there are important physiologic differences in the hemostatic system in children compared with adults. The decreased levels of several critical coagulants and increased levels of alpha 2M may contribute in part to the lower risk of thrombotic events in childhood. Age-matched controls should be used for evaluation of the hemostatic system in children with suspected congenital or acquired defects.
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PMID:Maturation of the hemostatic system during childhood. 139 57

A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VII hyperactivity were detected in this family. To study the effects of protein C and factor VII on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VII to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VII was enhanced by low protein C levels, suggesting that concomitant factor VII hyperactivity may cause acute myocardial infarction in patients with protein C deficiency.
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PMID:Congenital protein C deficiency and myocardial infarction:concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis. 144 May 17

This article has summarized known congenital and acquired alterations of hemostasis leading to thrombosis. Decreases in coagulation inhibitors, including antithrombin III, heparin cofactor II, and protein C and protein S, are of major importance in assessing patients with hypercoagulable states or patients with unexplained thrombosis. Newer assays for components of the fibrinolytic system, plasminogen, t-PA and t-PA inhibitor are also now readily available and are important for defining congenital or acquired fibrinolytic defects leading to hypercoagulability and thrombosis. By judicious use of these assays, combined with clinical evaluation, many patients with thrombosis will have an underlying etiologic blood protein defect defined. Delineating reasons for a thrombotic event is of obvious importance for planning long-term prophylactic therapy and for diagnosing and counseling afflicted family members. In this manner, newly found patients can be treated prophylactically before unalterable morbidity or mortality occurs.
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PMID:Hypercoagulability and thrombosis. 145 21

The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cases of acute liver damage (n = 8) and in patients with non-alcoholic cirrhosis (n = 15) (35 +/- 7% and 36 +/- 4%, respectively). A significant correlation was found between protein C and Normotest, antithrombin, heparin cofactor II, (r = 0.83, r = 0.82, r = 0.81, respectively, p less than 0.001). There was also a significant correlation between protein C and serum concentrations of albumin (r = 0.61, p less than 0.001), but a negative association to bilirubin (r = -0.56). No significant association was found between protein C and aspartate aminotransferase, alaline aminotransferase, and gamma-glutamyltranspeptidase. In conclusion, protein C is low in advanced liver diseases and gives the same amount and type of information as Normotest, antithrombin and heparin cofactor II.
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PMID:Protein C in patients with alcoholic cirrhosis and other liver diseases. 150 Jun 80

Previous studies of patients with thromboembolic disease have revealed an association either with hereditary anticoagulant protein deficiencies or with defects in the fibrinolytic system. To obtain a more comprehensive picture and to investigate which analyses are useful in the evaluation of such patients, we have performed an extensive laboratory investigation in 439 individuals with thromboembolic disease. Anticoagulant protein deficiencies were found in 24 patients. Deficiencies of protein C (n = 10) and protein S (n = 9) were most common followed by deficiencies of antithrombin III (n = 3) and plasminogen (n = 2). Six of the nine protein S deficient patients demonstrated a selective deficiency of free protein S with normal total protein S concentrations. To diagnose protein C and S deficiencies among the 201 patients receiving oral vitamin K antagonists, the concentrations of protein C and S were compared with the mean concentration of several other vitamin K-dependent proteins. One protein C and three protein S deficiencies were identified among the treated patients. The number of protein C deficiencies found in this group was significantly lower than the number found among untreated patients. Although fewer protein S deficiencies were also identified among the treated patients, than in the untreated group, the difference was not statistically significant. The results suggest that protein C deficiencies went undetected in the treated group and that oral anticoagulant therapy should be discontinued before efforts to diagnose protein C deficiency are made. We found no cases with heparin cofactor II deficiency. Lupus anticoagulant was present in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thromboembolic disease--critical evaluation of laboratory investigation. 832 78

Anabolic steroids are known to increase the plasma concentrations of certain plasma proteins. In four patients given treatment with danazol, an attenuated androgen, the concentrations of heparin cofactor II, Hageman factor (factor XII), protein C, and both free and total protein S increased significantly when tested 39 to 103 days after the start of therapy. The titers of these proteins in samples obtained 21 days to 5 years after therapy was discontinued were similar to those before treatment, except for total protein S, the titer of which remained elevated. No significant changes in the titers of C4b binding protein or plasma plasmin inhibitory activity were found.
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PMID:Some clotting factors in plasma during danazol therapy: free and total protein S, but not C4b-binding protein, are elevated by danazol therapy. 153 44

This study analyzed the coagulation changes in twenty patients after orthotopic liver transplantation. The procoagulant, anticoagulant, and fibrinolytic systems were studied during the first two postoperative weeks. Within the first postoperative day all extrinsic and intrinsic pathway factors became normal except factors IX, VII, and X, which recovered within the next 24 hr. Of interest are the changes in factor VIII, which reached a high concentration with an increase in its antigenic fraction during the study. However, coagulation inhibitors showed a different pattern. In fact, antithrombin III (AT-III) and protein C (PC) needed from 7 to 14 days to reach normal values. Total protein S (TPS) and free protein S (FPS) did not recover until day 7, whereas heparin cofactor II (HC-II) remained at subnormal levels throughout the study. Thrombin-antithrombin III complex (TAT) values were strikingly elevated in the immediate postoperative period. Fibrinolysis parameters showed plasminogen (PL) levels in the normal range until day 4. Antiplasmin (AP) followed a curve parallel to that of plasminogen but its levels were higher during this observation period. Similarly the initial elevation in plasminogen activator inhibitor 1 endothelial type (PAI-1) levels remained high until days 4 and 7. In summary, it can be concluded that during the postoperative phase after OLT a hypercoagulable state is developed as a result of diminished anticoagulant and fibrinolytic activity. This coagulation might be a nontechnical factor contributing to the thrombotic vascular complications of some liver recipients.
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PMID:Diminished anticoagulant and fibrinolytic activity following liver transplantation. 160 81

To study the effect of the severe loss of hepatic synthetic function on the inhibitors of coagulation we have measured protein S (total and free), protein C, heparin cofactor II and antithrombin III in 30 patients with fulminant hepatic failure. The results showed severe reduction in all inhibitor levels with mean (+/- SE) values of: protein S, 0.26 +/- 0.03 U/ml; protein C, 0.26 +/- 0.03 U/ml; heparin cofactor II, 0.12 +/- 0.02 U/ml and antithrombin III, 0.21 +/- 0.02 U/ml. Heparin cofactor II was significantly lower than the other inhibitors (P less than 0.01). Although the reduction in free protein S was significant in fulminant hepatic failure as compared to normal subjects (0.40 +/- 0.05 U/ml compared to 1.02 +/- 0.08 U/ml, P less than 0.001), the ratio of free to total protein S was significantly increased (0.67 +/- 0.02 compared to 0.40 +/- 0.04, P less than 0.01). Prothrombin time (INR) was significantly inversely correlated with total protein S (r = -0.56, P less than 0.001) and free protein S (r = -0.48, P less than 0.01), but not with the ratio of free to total protein S. No significant correlation between the different coagulation inhibitors and other measures of hepatic function could be detected. Although the loss of hepatic synthetic function appears to be the major cause of the loss of coagulation inhibitors, other effects such as increased consumption and rate of clearance may play a role. The balance of these will be reflected in the circulating levels of the coagulation inhibitors.
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PMID:Physiological inhibitors of coagulation in fulminant hepatic failure. 164 1

The relationship between thrombomodulin-associated O-linked glycosammoglycans (GAGs) and the exogenous GAGs heparin or dermatan sulfate was studied in the inhibition of thrombin by antithrombin III (AT III) or heparin cofactor II (HC II). Both rabbit thrombomodulin (TM) and two glycoforms (a high-Mr form containing GAGs and a low-Mr form lacking the majority of O-linked GAGs) of a recombinant human TM deletion mutant (rec-TM) were used. The rapid inactivation of thrombin by HC II in the presence of dermatan sulfate was prevented by both the high-Mr rec-TM and the rabbit TM. In contrast, both rabbit TM treated with chondroitin ABC lyase to remove O-linked GAGs and the low-Mr form of rec-TM had only weak protecting effects. In the absence of exogeneous dermatan sulfate, thrombin inhibition by a high concentration of HC II was slightly accelerated by the high-Mr form of rec-TM but protected by rabbit TM. When thrombin inhibition by AT III in the presence of heparin was studied, both high-Mr rec-TM and rabbit TM again invoked a similar reduction of inactivation rates, whereas in the absence of exogenous heparin, both high-Mr forms accelerated thrombin inhibition by AT III. The diverse reactivities of various forms of TM towards HC II and AT III were also observed during protein C activation by the thrombin-TM complex. These results suggest that thrombin activity at the vessel wall or in fluid phase may undergo major kinetic modulations depending on the type of protease inhibitor, the presence or absence of exogenous GAGs and the glycosylation phenotype of TM. The dependence of TM anticoagulant function on the presence of an intrinsic GAG moiety suggests that variant glycoforms of this endothelial cell cofactor may be expressed differently in a species-, organ-, or tissue-specific manner as a means to regulate TM function in diverse vasculatures.
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PMID:Different glycoforms of human thrombomodulin. Their glycosaminoglycan-dependent modulatory effects on thrombin inactivation by heparin cofactor II and antithrombin III. 164 16

Inherited defects of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and the fibrinogens are thought to be responsible for between 10 and 15% of all patients presenting with recurrent venous thrombosis. The structure, function and expression of these genes and the nature of the gene lesions underlying the deficiency states are reviewed in detail.
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PMID:The molecular genetics of familial venous thrombosis. 167 36


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