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)

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estrogen-associated thromboembolism. 134 94

1. Guinea-pig blood clots rapidly and the clots retract in glass tubes. The prothrombin time is long and the activated partial thromboplastin time short compared to human. The Russel viper venom time is similar to human. 2. Factors VII and X assay at levels far below and factors V, VIII and XII assay far above human levels. Other coagulation factors (fibrinogen, II, IX, XI, Fletcher and Fitzgerald) assay within or close to the human range. 3. The thromboplastin generation test results for guinea-pigs and humans are similar. 4. Platelets are numerous and small. They aggregate with ADP, arachidonic acid and pig plasma, variably with ristocetin and poorly with bovine collagen or thrombin. On electron microscopy, platelets appear small with many dark granules (dense bodies). There is an open canicular system. Glycogen particles are sparse. Microtubules are occasionally seen, mitochondria are rare and alpha-granules are not readily distinguished from dark granules. 5. Ristocetin cofactor is very low, assaying at < 16% of human (< 0.16 U/ml). 6. Leukocyte counts are variable (6300-17,000 per microliters) and differential counts show neutrophils slightly lower and lymphocytes slightly higher than average human counts. 7. Guinea-pig erythrocyte parameters fall within human ranges. 8. Protein electrophoresis shows total protein and albumin to be slightly lower than human. 9. Antithrombin III, Protein C and alpha 2-antiplasmin assay within the human range and plasminogen at very low levels. 10. Bleeding times are consistently about 4 min.
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PMID:Comparative hematology: studies on guinea-pigs (Cavia porcellus). 135 40

Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.
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PMID:Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. 144 May 30

Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.
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PMID:Modulators of coagulation. A critical appraisal of their role in sepsis. 162 18

The prevalence of inherited thrombotic syndrome in the general population appears to be higher than that of inherited bleeding disorders. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40 years: In 18 children and adolescents suffering from "idiopathic" vein thrombosis laboratory screening has been performed: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin. Compared to an age matched healthy control group in children with idiopathic vein thrombosis we could demonstrate in vitro platelet activation with significant enhanced platelet aggregation and elevated levels of von Willebrand factor in the onset of the disease. Antithrombin III, protein C, alpha-2-antiplasmin and alpha-2-macroglobulin were significantly decreased. These changes turned to be normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and c1-inactivator showed no alterations compared to the control. Platelet activation and alteration of platelet function in vivo and in vitro is established to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The decreased inhibitors of the hemostatic system antithrombin III and protein C in the onset period of thrombotic diseases are discussed to be an increased turnover, whereas the decreased levels of alpha-2-antiplasmin and alpha-2-macroglobulin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.
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PMID:[Hemostatic changes in idiopathic venous thrombosis in childhood and adolescence]. 175 45

Antithrombin III and protein C are the major inhibitors of the plasma clotting system. Since adequate thromboembolism protection requires a cofactor AT III for heparin to provide full antithrombotic coverage, the preoperative AT III and protein C levels in the plasma of 105 patients treated with marcumar are measured. The understanding of the physiological role of these inhibitors of the plasma clotting system and of the causes for their decrease should directly lead to the indications for laboratory analysis.
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PMID:[Antithrombin III control in patients with long-term anticoagulant therapy]. 184 95

A longitudinal study has been undertaken in 125 pregnant women between 25 and 40 weeks of gestation, to provide systematic information on the changes that occur in a wide range of haemostasiological and haemorheological variables. Fibrinogen, D-Dimer, Factor VIIIR: Ag, erythrocyte aggregation and plasma viscosity rose markedly throughout pregnancy. Antithrombin III and alpha 2-antiplasmin were unchanged during pregnancy. There were no significant differences between women in the pre-eclamptic group (N = 16) and the control group. HELLP syndrome (N = 7) was associated with high D-Dimer (p less than 0.05), and TAT (p less than 0.05), low antithrombin III (p less than 0.03), protein C (p less than 0.01) and platelets (p less than 0.001). Our results demonstrate that during pregnancy (also, however, in pre-eclamptic women) alterations of the coagulation system occur, but these changes do not affect the overall haemostatic balance. Findings in patients with "true" HELLP syndrome are consistent with an increased tendency for intravascular coagulation.
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PMID:[Hemostasis and pre-eclampsia]. 205 97

We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L-ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series.
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PMID:Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia. 209 99

The influence of a disturbed hemostasis as one of the causes of retinal or ciliary vascular occlusions is still controversial. Antithrombin III, protein C and its cofactor protein S were investigated in 25 patients; 14 of them with a retinal vein occlusion, five showed an occlusion of retinal arteries and six of ciliary arteries. Patients with a preceding thromboembolic disease were excluded from the investigations. The mean values (+/- SEM) of antithrombin III (12.1 IU/ml +/- 0.4), protein C (116% +/- 4), total protein S (102% +/- 3) and free protein S (46% +/- 2) were equivalent to the mean values of a normal population. Neither does a defect or a lack of coagulation inhibitors have an essential influence on the development of an isolated retinal or ciliary vascular occlusion nor does the local occlusive vascular disorder influence the activity of systemic inhibitors.
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PMID:[Inhibitors of blood coagulation in vascular occlusion of the retina and optic nerve]. 214 89

Several reports have appeared on the increased risk of thromboembolic diseases associated with the use of oral contraceptives (OCs). The increased risk of thromboembolism has been related to increased circulating blood levels of certain factors of both the clotting and fibrinolytic systems seen in OC users. These changes have been associated primarily with the estrogen component of the OC preparations. The two new oral contraceptives under study contain reduced levels of ethinyl estradiol, 30 micrograms and each utilizes a new progestogen--75 micrograms gestodene or 150 micrograms desogestrel. A prospective randomized study was performed with 50 women over one year in which several factors of the hemostatic system were investigated; blood samples were taken in treatment cycles 1, 3, 6 and 12 and 6-8 weeks after cessation of therapy. During treatment with both preparations, factors II, VII, IX, X, XI, XII, VIII clotting activity, and prekallikrein were elevated; factor V was not elevated. Antithrombin III which controls these factors, was decreased by 8-10% after 12 months; Protein C which controls factors V and VIII was not changed. Markedly elevated levels of plasminogen and its unaffected inhibitor alpha antiplasmin were seen in the first and all subsequent treatment cycles; this represents increased potency of the lytic system, which can be looked upon as a compensatory mechanism. There were no differences seen between the gestodene and desogestrel preparations regarding changes in the hemostatic system. As with all other low-dose pills, a history of thromboembolism is a contraindication to their use.
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PMID:Influence of modern low-dose oral contraceptives on hemostasis. 214 6


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