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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)

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.
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PMID:Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group. 1089 70

The pathogenesis of portal vein thrombosis (PVT) in cirrhotic liver patients is not known. PVT has been related to liver dysfunction, neoplasm, hemodynamic factors, and hypercoagulability states. PVT has been reported in patients with antiphospholipid syndrome without liver cirrhosis. Our aim was to find the role of antiphospholipid antibodies (APAs) and coagulation inhibitors in PVT in patients with liver cirrhosis. We present a case-controlled study, matched by age, liver function, and etiology, to discover the role of APAs and anticoagulant protein activity in PVT in cirrhotic patients. We studied 30 cirrhotic patients: 6 of 10 (60%) patients with PVT were APA-positive, whereas only 2 of 20 (10%) in the cirrhotic control group were APA-positive (p < 0.005). Low serum levels of protein C, protein S antithrombin III, and plasminogen were found in cirrhotic patients; and, no differences were found between patients with and without PVT. Significantly lower protein S and antithrombin III levels were found in patients with Child-Pugh class C. Therefore, APAs were related to PVT in cirrhotic patients; but, a lower concentration of coagulation inhibitors was associated with liver dysfunction alone.
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PMID:Antiphospholipid antibodies are related to portal vein thrombosis in patients with liver cirrhosis. 1103 5

Thrombosis is a major clinical feature of the antiphospholipid syndrome. Interactions between genetic and acquired factors could contribute to thrombosis development. In this study, we evaluated 40 patients with antiphospholipid syndrome and thrombosis, 31 primary and nine secondary to systemic lupus erythemathosus, to estimate the carrier rates of factor V Leiden, 20210A --> G prothrombin variant and 677C --> T in the MTHFR gene. Protein C, protein S and antithrombin were measured in 30 patients, with a median of 100.66 +/- 23.86, 93.57 +/- 36.44 and 98.8 +/- 5.67%, respectively. None of the patients were deficient on these natural anticoagulants. No significant variation was found between the patient group and the controls, regarding the prevalence of homozygotes for the mutated 677T allele (2.5 versus 5.4%), or heterozygotes for factor V Leiden (0 versus 0.7%). Despite the fact that these mutations are relatively common in Brazilian thrombophilic patients, its low prevalence in this cohort of patients suggest that these genetic alterations are not risk factors for thrombosis in antiphospholipid syndrome. The prevalence of the mutated allele 20210A of the prothrombin gene was higher in patients when compared with controls (5 versus 0.7%; P = 0.01), suggesting that prothrombin variant could increase the risk of thrombosis in patients with antiphospholipid syndrome.
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PMID:The impact of the search for thrombophilia risk factors among antiphospholipid syndrome patients with thrombosis. 1108 90

Increased thrombin generation associated with resistance to activated protein C makes the latter a likely candidate for an increased risk of acute coronary events. Activated protein C resistance (factor V Leiden) on its own, however, appears to have no significant effect in this regard. We describe a case of recurrent myocardial infarction caused by coronary thrombosis in a patient with persistent thrombocytopenia who was found to have a coexistence of heterozygous factor V Leiden and primary antiphospholipid syndrome. Since both thrombophilic disorders interfere with the protein C anticoagulant system, the simultaneous existence of inherited and acquired resistance against activated protein C could account for an increased thrombophilia with manifestation in the coronary arteries. This case suggests that evaluation of patients who present with recurrent acute coronary events should also consider these coagulation defects.
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PMID:Coexistence of factor V Leiden and primary antiphospholipid syndrome: a patient with recurrent myocardial infarctions and thrombocytopenia. 1120 Oct 21

Evaluation of inherited thrombophilia in patients with venous thromboembolism includes testing for functional activity of antithrombin, protein C and protein S, and resistance to activated protein C (factor V Leiden), which can be assessed with plasma and DNA-based assays. The antiphospholipid syndrome is an acquired disorder related to the development of antibodies against phospholipid-protein complexes. Testing for the antiphospholipid syndrome includes measurement of antibodies to phospholipid-protein complexes by immunoassay or by detecting interference of anti-phospholipid antibodies in sensitive phospholipid-based assays. Other genetic risk factors have been listed, including a common polymorphism in prothrombin gene (3'-untranslated region) related to an increase of prothrombin level (> 115%) and a common polymorphism in the methylene tetrahydrofolate reductase (enzyme involved in homocysteine metabolism) gene related to a mild increase of homocysteine blood level. More recently high plasmatic levels of factor VIII (> 150%) or factor XI (> 120%), not related so far to a molecular defect, have been identified as risk factors for deep vein thrombosis. As a candidate gene, factor XIII gene polymorphisms are under investigation. Beside the acquired or genetic risk factors involved in thrombophilia, the gene-environment interactions are of importance in the onset of thrombosis.
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PMID:[Laboratory testing for venous thromboembolism]. 1120 40

Congenital and acquired thrombophilias are the most common predisposing factors for thromboembolism, but they may also contribute to pathophysiological processes involved in recurrent pregnancy loss, fetal death, intrauterine growth restriction, placental abruption, placental infarction, and pre-eclampsia. The most common thrombophilias are deficiencies of antithrombin III, protein C, and protein S, acquired protein C resistance, genetic mutation encoding for factor V Leiden, prothrombin gene, and inherited hyperhomocysteinemia, and antiphospholipid syndrome. Although adverse pregnancy outcomes are more common in women with thrombophilia, the current evidence does not support routine thrombophilia screening of all pregnant women. Selective thrombophilia screening may be justified in certain group of women, particularly those with a history of thromboembolism. More research is required to confirm or refute the causal link between thrombophilia and abnormal placentation, and assess effectiveness and safety of thromboprophylaxis in pregnant women.
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PMID:Thrombophilia and adverse pregnancy outcome. 1125 34

We present a patient with membranous glomerulonephritis, several clinical complications of the antiphospholipid syndrome and ulcerative colitis, but without lupus anticoagulant and antiphospholipid/cofactor antibodies. Immunological studies--other antibodies--were negative and failed to show enough criteria for any autoimmune diseases. Evaluation of her laboratory tests for hereditary thrombophilia revealed a heterozygous form of the Leiden mutation that might be associated with widespread vasculopathy. An interesting possibility is that the inherited activated protein C resistance could be an additional risk factor for vaso-occlusive manifestations appearing as a clinical sign of cardiovascular diseases and nephropathy.
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PMID:Membranous glomerulonephritis in a patient with inherited activated protein C resistance. 1130 13

Antiphospholipid syndrome (APS) occurs as a primary or secondary syndrome and has various manifestations, including arterial and venous thrombosis, thrombocytopenia, fetal loss, livedo reticularis, and cardiac and neurological sequelae. APS is linked with autoantibodies that were originally thought to have specificity for negatively charged phospholipids. Recent data suggest specificity for different phospholipid-binding plasma proteins, including 2-glycoprotein I, prothrombin, protein C, and protein S. The most well-known antiphospholipid antibodies are lupus anticoagulant and anticardiolipin antibody. These antibodies are detected through lupus anticoagulant assays, anticardiolipin assays, and certain serologic tests for syphilis. This article describes 2 cases encountered in our clinical work and reviews the literature on APS.
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PMID:Antiphospholipid antibody syndrome. A literature review. 1136 16

Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis and fetal loss. Two hundred eighty-nine patients with a history of recurrent spontaneous abortion were subjected to screening examinations for the etiology of these abortions. Endocrine abnormality (28.0%), uterine abnormality (10.4%), autoimmune diseases (1.4%), antiphospholipid antibody syndrome (4.5%), and balanced type chromosome translocation (4.2%) were found as underlying causes of recurrent abortions, and the remaining 55.0% of the 289 patients were classified as having an unexplained etiology. Congenital thrombophilia such as protein C (PC) deficiency, protein S (PS) deficiency, antithrombin deficiency, and factor V Leiden mutation was not frequently detected; only one patient had PS deficiency. A reduced factor XII activity was found at a frequency of 4.2%. The frequency of methylene tetrahydrofolate reductase gene C677T mutation in recurrent aborters (0.38) was the same as that found in a fertile control group. Although the prevalence of anti-beta2-glycoprotein I antibody (abeta2-GPI) syndrome was very low (1.7%), patients with a high titer of immunoglobulin G (IgG) class abeta2-GPI, despite anticoagulation therapy, experienced severe fetomaternal complications in subsequent pregnancies. The rate (13.8%) of positive tests for serum IgA class abeta2-GPI in patients with unexplained etiology was higher than that in the controls (0%) (P < .05). We conclude that congenital thrombophilia is rare in Japanese patients who had experienced consecutive spontaneous abortions.
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PMID:Recurrent pregnancy loss: etiology of thrombophilia. 1137 65

Antiphospholipid antibodies(APA) have been reported to be a heterogeneous family of immunoglobulins. Some APA can be detected via phospholipid dependent coagulation assays when they present as an aspecific coagulation inhibitor, lupus anticoagulant(LA), other antibodies can be measured via immunological assays mostly via their capability to bind to immobilized cardiolipin (anticardiolipin antibody; aCL). Despite their name, APA associated with antiphospholipid syndrome(APS) do not bind phospholipids, but are directed at plasma proteins bound with anionic phospholipids. The antigenic targets of these antibodies include beta 2 glycoprotein I(beta 2 GP I), prothrombin, high- and low-molecular-weight kininogens, annexin V, protein C and protein S. In this article, the current knowledge on the methods of detection and their functional properties are reviewed, and the interaction of these antibodies and acquired activated protein C resistance are discussed.
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PMID:[Laboratory tests for detection of antiphospholipid antibodies]. 1139 41


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