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

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

Although Virchow postulated 100 years ago that hypercoagulability states exist, it has only been in recent years that methods of documenting hypercoagulability have been developed. These clotting tendencies can be acquired or congenital. The common causes of acquired clotting tendencies include conditions which result in tissue and cellular damage, shock, transfusion reactions, and tissue necrosis. Certain drugs and drug reactions, and certain disease states which include blood dyscrasias and cancer are also associated with clotting problems. In certain diseases such as homocystinuria, hyperlipidemia, and lupus erythematosus, abnormal clotting tendencies may also develop. Important advances in the recognition of hypercoagulability have come with the documentation that congenital clotting abnormalities exist. Moreover, these abnormalities are proving to be more common than are congenital bleeding syndromes. Patients who appear to have spontaneous clotting manifestations and are under 40 years of age should be screened for one of these abnormalities. These congenital clotting tendencies can be classified as defects in thrombosis inhibitors, dysfibrinogenemias, or defects in fibrinolysis. The first thrombotic inhibitor defect recognized was antithrombin III deficiency which was reported in 1965. Subsequently, Protein C, Protein S, and Heparin cofactor II deficiencies have been recognized as contributing to thrombotic tendencies. Dysfibrinogenemias are relatively rare and most are associated with bleeding problems; however, 11% of the abnormal fibrinogens are associated with a clotting tendency. The reason appears to be that these fibrins are resistant to fibrinolysis. The most common defects which are associated with thrombotic tendencies appear, at the present time, to be due to defects in fibrinolysis. These include hypoplasminogenemia, decreases in plasminogen activator, increases in plasminogen activator inhibitor, and Factor XII deficiency.
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PMID:Acquired and congenital clotting syndromes. 223 69

A series of coagulation tests is described by which an increased thrombotic tendency is likely to be detected. These tests were carried out in 268 patients with venous thromboembolic disease and in 583 patients with arterial thrombotic manifestations. In venous thromboembolism alterations which point to hypercoagulability were found in 50% of all cases. Most frequent findings were a diminished availability of t-PA followed by low levels of Protein C, AT III and of Heparin cofactor II. In arterial thrombotic disease alterations of the clotting system were found in 77% of the patients. There was a high frequency of increased spontaneous platelet aggregation, of a diminished t-PA availability and of a combination of both alterations. Other abnormal results were rare with the exception of a diminished Heparin cofactor II which was found in 3% of the patients. The consequences which arise for prophylaxis and therapy when the defect is known are discussed.
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PMID:New diagnostic possibilities for the detection of thrombophilic states. 246 11

Heparin cofactor II (HC II) was measured by a chromogenic activity assay in normal preterm infants (gestational age, 28-36 weeks; n = 17; 29% +/- 11.5 [mean +/- 1 SD], range 11-51), normal full-term infants (n = 18; 49% +/- 6.6 [mean +/- 1 SD], range 36-58), and normal adults (n = 38; 101% +/- 14 [mean +/- 1 SD], range 73-130). Normal children attained adult levels at approximately 5 to 7 months of age. The lower values in preterm and term infants most likely reflect immature liver function. Neither adults and children with a history of thrombosis with prior negative evaluation (n = 74), patients with documented protein C and protein S deficiency (n = 4), nor sick infants without evidence of consumptive coagulopathy (n = 15) had significantly lower levels of HC II activity. Infants with disseminated intravascular coagulation (n = 2) had strikingly lower levels of HC II activity.
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PMID:Heparin cofactor II in adults and infants with thrombosis and DIC. 252 33

Heparin cofactor II (HC II) levels were measured by electroimmunoassay in plasmas and urines from 68 patients with nephrotic syndrome. In addition, antithrombin III (AT III) and protein C (PC) activities and antigens were measured also in the same group of patients. Seven of these patients had histories of thrombosis. Plasma HC II levels (mean +/- SD 105 +/- 43) were not different from levels in healthy subjects (94 +/- 17). Only 5 patients had low plasma levels of HC II. None of the patients with thrombosis had low HC II levels. Even though measurable amounts of HC II were found in 25 urines from 50 patients. There was a relationship in the urinary excretion between HC II and AT III and their urinary clearances were quite similar. However, no correlation was found between plasma HC II and AT III levels, and levels of AT III activity and antigen were significantly lower than in healthy subjects. Three patients with histories of thrombosis had low AT III levels. Most patients (including those with thrombosis histories) had high plasma PC levels and increased urinary loss. It is suggested that HC II does not play an important role in the pathogenesis of thrombosis in nephrotic syndrome.
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PMID:Plasma and urinary heparin cofactor II levels in patients with nephrotic syndrome. 321 13

A 15-year-old woman with a history of transient dysarthria two years before, suddenly developed weakness of right upper extremity, right facial palsy, and dysarthria. She was admitted to our hospital on the third day. She had no hypertension, heart murmur and oedema. On neurological examination, she had mild right hemiparesis including face muscles and mild dysarthria. The right knee jerk was brisk with no Babinski's sign. Ataxia and sensory disturbance were not present. T2-weighted MRI showed a hyperintensity at the posterior limb of the left internal capsule. Cerebral angiography was unremarkable. Ultracardiography and 24-hour electrocardiography were normal. Laboratory data revealed no inflammatory findings, liver dysfunction, hyperglycemia and hyperlipidemia. Antinuclear and anticardiolipin antibodies were negative. Prothrombin time was normal, but activated partial thromboplastin time was slightly prolonged (35.4 sec, normal 25.2-34.4). Protein C, protein S and antithrombin III were normal. Heparin cofactor II (HC II) activity was decreased (44%) with normal HC II antigen (79%) and so she was diagnosed as heparin cofactor II deficiency type II (heparin cofactor II abnormality). Her father manifesting thromboangitis obliterans also had low HC II activity with normal HC II antigen. However, on her genetic analysis, we didn't detect any mutations in the coding region of HC II gene. Until now she has no recurrence of cerebrovascular attacks. On the basis of these results, we suspect that HC II deficiency was a possible risk factor of cerebral infarction in this case because she was so young and had no general risk factors except for HC II. No stroke associated with HC II deficiency type II has been reported up to date. This case is worth considering etiologies of juvenile cerebral infarction.
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PMID:[Juvenile cerebral infarction associated with heparin cofactor II abnormality. A case report]. 1096 62

The authors examined the changes in the haemostasis during the use of the oral contraceptive combination with 20 microg ethynil estradiol/150 microg desogestrel at 35 women, a basic group, who used the oral contraceptive in the duration of 12 months and a control group (n=35), who do not use the pills. We found statistically significant increase of Antithrombin III (ATIII) (p<0.011), Cofactor II of Heparin (HCII) (p<0.001), the activity of plasminogen (p<0.026) and beta2-antiplasmin (0.026), significant decrease of Protein C (PrC) (p<0.0001) and of total Protein S (TPrS) (p<0.03) in the basic group in comparision with the control one. We do not observe significant changes in the rest of the haemostatic variables between the two groups. During the use of the oral contraceptive combination with 20 microg ethynil estradiol/150 microg desogestrel the changes in the system of the natural inhibitors are balanced by these in the system of fibrinolysis.
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PMID:[Effect of the monophase oral contraceptive combination with 20 ug ethinyl estradiol/150 ug desogestrel on haemostasis]. 1531 40