Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The composition of antibodies against phospholipids (PLa) was analysed in 54 PLa-positive thrombophilic women, different in the factor V genotype (Arg506-Gln mutation carriers, n=23; and noncarriers, n=31). The presence of antibodies against prothrombin was also studied. The incidence of cardiolipin antibodies (CLa) and lupus anticoagulant (LA) activity was similar among the carriers and noncarriers, while phosphatidylserine antibodies (PSa) were often the only PLa detected in the carriers of the mutation (7/23 vs. 2/31; chi2=5.47, p<0.05). Antibodies against prothrombin were found in 11 of 54 patients. They segregated with PSa (8/19 vs. 3/35; chi2=8.54, p<0.025), but were equally distributed between carriers and noncarriers. The analysis of nAPC-ratio in patients with different PLa showed that it was consistently lower in the mutation carriers in whom none of the PLa caused further suppression. The noncarrier group positive for LA in several assays was associated with a reduction of nAPC-ratio (0.82+/-0.25 vs. 1.12+/-0.22, p<0.05). Our findings indicate that PLa contributing to the development of APC resistance are restricted to those possessing LA activity.
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PMID:Production of phospholipid antibodies in selected thrombophilic women differing in genotype at the 506 site of factor V. 968 88

We evaluated 81 thalassaemia major and 4 thalassaemia intermedia patients (48 M, 37 F), median age 17 years; 62/85 patients were HCV-positive, 3/85 HIV-positive, 19/85 were splenectomized. Forty normal healthy children were recruited as the control group. The number of thrombotic events was studied retrospectively. Platelet poor plasma was filtered and quick-frozen at -70 degrees C until time of assay. APC resistance was measured in an activated thromboplastin time and results were expressed as normalized ratio. All tests were done with diluted 1 in 5 (v/v) factor V deficient plasma and with undiluted plasma. Molecular genetic investigation of factor V gene was performed with polymerase chain reaction, followed by digestion of amplified products with restriction enzyme Mnl I. Data obtained with molecular investigation revealed the presence of 4 heterozygous subjects for factor V Leiden (4.7%). Functional tests were able to detect all heterozygotes for factor V Leiden both with undiluted and with diluted plasma, and there were no false negative subjects. However, undiluted plasma revealed a greater number of false positive subjects (n=15) than did diluted plasma. Therefore, tests done with undiluted and diluted plasma revealed a 100% sensitivity, while specificity was 81% for undiluted plasma and 97% for diluted plasma. Only one thrombotic event was observed in one of the 85 studied patients, as a case of stroke in a thalassaemia intermedia patient with APC resistance. In the same patient an additional thrombogenic risk factor was represented by a pronounced haematocrit increase at the beginning of her transfusion regimen.
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PMID:Resistance to activated protein C in thalassaemic patients: an underlying cause of thrombosis. 971 25

The factor V (Arg506-->Gln) mutation confers an increased risk of deep vein thrombosis, whereas its role in saphenous vein graft closure after coronary artery bypass grafting (CABG) remains unclear. This study examined the anticoagulant response to activated protein C (APC ratio) in relation to the surgical trauma and the significance of the factor V Leiden mutation in determining postoperative thrombin generation and fibrin formation and the risk of early vein graft occlusion. A total of 108 men undergoing elective CABG for exertional angina pectoris (mean age 61.1 +/- 8.7 years) were examined. The patency of saphenous vein grafts was studied at routine reangiography three months after CABG. Of 100 patients who underwent reangiography, 23 had one or more occluded vein grafts at reangiography. Heterozygosity for the factor V (Arg506-->Gln) mutation tended to be associated with early saphenous vein graft occlusion (5/11 carriers vs. 18/89 non-carriers with graft occlusion, chi2 = 3.52, p = 0.06), whereas pre- and postoperative APC ratios did not. Pre- and postoperative determinations of prothrombin fragment 1+2, thrombin-antithrombin complexes and soluble fibrin levels did not differ between patients with and without the mutation. Early saphenous vein graft occlusion after CABG could tentatively be added to deep vein thrombosis as a vascular complication that can be attributed to the factor V (Arg506-->Gln) mutation.
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PMID:Coagulation factor V (Arg506-->Gln) mutation and early saphenous vein graft occlusion after coronary artery bypass grafting. 971 41

We compared the sensitivity and specificity of a tissue factor-based assay (FVR) with the addition of a phospholipid/silica preparation, to the commercially available aPTT-based method, APCR (CoatestTM), and a modified aPTT-based method (APCM) which utilized factor V-depleted plasma, for the detection of the factor V Leiden mutation. A total of 110 patients were included in this study. This included 32 patients on coumadin therapy, 7 patients on heparin therapy, 5 patients on both anticoagulants therapy, and 24 patients who were positive for anticardiolipin antibody (ACL) and/or lupus inhibitor (LI). Our data demonstrate that the FVR is not affected by anticoagulation treatment or ACL/LI antibodies, whereas in the APCR method, 33 patients cannot be determined either due to the anticoagulant therapy or presence of the ACL and/or LI. With the APCM method, the clotting endpoint could not be determined in 1 patient due to the presence of a strong LI. The additional phospholipid/silica material utilized in the FVR enhanced the APC degradation of factor Va and therefore sharpened the demarcation between the factor V Leiden-positive and -negative patients. The sensitivity for the APCR, APCM and FVR was 42, 97 and 100% respectively. The specificity for the APCR, APCM and FVR was 94, 96 and 100% respectively.
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PMID:A highly specific functional test for factor V leiden: A modified tissue factor assay for activated protein C resistance. 973 Nov 10

Genetic defects of antithrombin (AT) or one of the components of the protein C pathway are associated with hereditary thrombophilia. Laboratory assays are currently available to diagnose and type hereditary thrombophilia due to deficiency or dysfunction of one of the anticoagulant factors antithrombin (AT), protein C (PC) and protein S (PS), and APC resistance without the need of DNA analysis. There are no functional tests for the prothrombin mutant G20210A and thrombomodulin mutations, which can be diagnosed by a PCR-based test or by gene analysis, respectively. Hereditary AT deficiency is classified in a quantitative type I and three functional type II deficiencies affecting the reactive site (RS), heparin binding site (HBS), or pleiomorphic site of the AT protein. All four types of hereditary AT deficiencies can be diagnosed by a heparin cofactor assay and one immune assay in combination with crossed immunoelectrophoresis of the AT protein. The combination of an enzyme-linked immunoadsorbent assay (ELISA) and a functional Protac-APTT-based assay for PC will detect quantitative type I and dysfunctional type II PC deficiencies. There is a significant overlap in PC antigen and functional levels between heterozygotes of PC deficiency and normals leaving a gray zone of uncertainty in differentiating congenital PC deficiency and normal individuals. Accurate diagnosis of hereditary PS deficiency should be a combination of tests aimed to measure free PS activity and antigen and total PS antigen levels. APTT-, Xa-, and RVVT-based APC-resistance tests, when test plasmas are diluted in factor V deficient plasma, have increased in sensitivity and specificity to 100% for the discrimination of normal individuals from heterozygotes and homozygotes for factor V Leiden. The RVVT-based APC-resistance test provides better separation of factor V Leiden and normals in the various clinical settings, lupus anticoagulant in particular. The modified APC-resistance tests also claim a separation between heterozygotes and homozygotes for factor V Leiden in the normal population, asymptomatic subjects, and thrombosis patients. Below a certain cut-off level, a minor overlap of normalized APC ratios between heterozygotes and homozygotes for factor V Leiden of thrombosis patients has been shown in one study, which still points to the need to perform the more time consuming and expensive DNA test to identify heterozygotes from the more clinically significant homozygotes. The prothrombin-based APC-resistance test, which measures thrombin activated factor Va in highly diluted test plasma, appears to be the most sensitive and specific of all APC-resistance tests and separates normal individuals from heterozygotes and heterozygotes from homozygotes for factor V Leiden without the need of confirmation by a DNA test.
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PMID:Laboratory diagnosis of hereditary thrombophilia. 976 48

A new automated method for screening defects in the Protein C Pathway (PCP) was evaluated. The "PCP test" is based on a phospholipid-rich Russells viper venom reagent, insensitive to heparin and lupus anticoagulants. To minimize interference from other clotting variables, ratios of the clotting time with and without the addition of a protein C activator were usually determined. Plasma samples from healthy volunteers, patients untreated or on oral anticoagulants, patients with factor V Leiden with and without treatment, and patients with protein C and/or S deficiencies were tested. Mixing patient plasmas 1:1 with individual plasmas deficient in factor V, protein C or S was evaluated for identifying the nature of defects by shortening the screening test. The PCP test was found to be sensitive to APC resistance due to factor V Leiden and by mixing with factor V deficient plasma was also useful despite the effects of oral anticoagulants. Results in the group of patients with previous low protein C or S levels suggest that the method has a better sensitivity to protein C than to protein S deficiency. The automated test was simple to use and gave a between-run coefficient of variation below 3% on normal plasmas.
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PMID:A protein C pathway (PCP) screening test for the detection of APC resistance and protein C or S deficiencies. 976 52

Identifying a defect affecting the protein C/protein S (PC/PS) anticoagulant system, using a single global test, has recently become possible thanks to a new methodological approach based on the activation of endogenous plasma PC by Protac, derived from Agkistrodon Contortix snake venom (ACV). The introduction of a commercial test (ProC Global), ACV-based, provides a useful tool for the screening of thrombotic patients since the most frequent causes of inherited thrombophilia are found in the PC/PS system. The test provides information only on the global activity of the anticoagulant pathway but not on PC and PS activity or on the factor V related conditions (e.g., FV Leiden). The present study shows that by carrying out the test alternating the presence of PC-, PS-, or FV-deficient plasma and using appropriate amounts of ACV, it is possible to increase the specificity of the test to correctly evaluate respectively the PC or PS activities or the activated protein C resistance condition (APC-R). These simple modifications applied to the original commercial test allow to detect exactly, using a single, basic methodology, the principal defects affecting the PC/PS anticoagulant pathway. Furthermore, carrying out the tests on an automated coagulometer, in combination or not with the classic ProC Global assay, it is possible to use a unique reagent profile to simultaneously investigate in the same or different samples, the PC, PS, and APC-R defect.
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PMID:A modified functional global test to measure protein C, protein S activities and the activated protein C-resistance phenotype. 980 66

Activated protein C resistance is an inherited thrombophilia caused by a point mutation in the factor V gene (G to A transition in nucleotide 1691 in the factor V gene with replacement of arginine (R) 506 by glutamine (Q) in the factor V molecule). The mutation is commonly named factor V R506Q or factor V Leiden. The mutation results in a poor anticoagulant response to activated protein C. APC resistance is inherited autosomally, and approximately 5-10% of the Norwegian population are carriers of the mutation. It is present in 20-50% of all cases of venous thromboembolism. Among asymptomatic heterozygous family members of affected individuals there is a five to eight-fold increase in the risk of venous thromboembolism, whereas there may be a 100-fold increased risk among homozygous individuals. The risk for asymptomatic carriers without a family history is yet not known. Activated protein C resistance is a major risk factor for venous thromboembolism, and the detection of activated protein C resistance is vital for proper prophylaxis and treatment of this disorder. It is essential therefore that as many medical specialists as possible acquire knowledge of activated protein C resistance. This report describes a family with activated protein C resistance and the main indications for screening for inherited thrombophilia.
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PMID:[Activated protein C resistance--a recently discovered hereditary thrombophilia]. 982 2

Today, more than 40% of all patients who develop a thrombosis are found to have inherited thrombophilia. The most common cause of this is APC resistance, which can usually be traced back to factor V-Leiden. In the commonly heterozygous patients the risk of thrombosis is increased about 7-fold (life-long risk of thrombosis 10 to 15%). In most cases, however, additional thrombogenic stimuli are required (oral contraception, pregnancy, surgery, immobilization). In combination with oral contraceptives, the risk is increased roughly 30-fold. In contrast, APC resistance does not present an increased risk for thrombosis in the arterial system (myocardial infarction, stroke). Four further inherited or acquired disorders of the hemostatic system are known: prothrombin dimorphism, antithrombin, protein C and protein S deficiencies. Prothrombin dimorphism, the second most common form of inherited thrombophilia, has been known only for the past two years and elevates the risk of thrombosis only to a moderate degree. Today, a search for thrombophilic factors should be carried out not only in young patients with spontaneous development of thrombosis, but also in elderly patients, even when an additional risk for the occurrence of thrombosis such as traumatization or immobilization is present. Therapeutic consequences are discussed.
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PMID:[Thrombophilia caused by congenital disorders of blood coagulation]. 984 71

Thirty-seven young patients (less than 42 years of age) presenting with sudden onset of idiopathic nonembolic cerebrovascular disease were evaluated for underlying prothrombotic factors. Activated protein C resistance (APC-R) was measured by Dahlback's method and the modified method using factor V-deficient plasma. Activities of antithrombin (AT) III, protein C and S were measured. Anticardiolipin antibody was estimated by ELISA and lupus anticoagulant by kaolin clotting tests. APC-R was the most common defect (21.62%) followed by AT III deficiency and presence of anticardiolipin antibodies (5.6% each). The latter two were present together in one case. It is thus concluded that APC-R is the most common defect underlying idiopathic nonembolic cerebrovascular infarction in young individuals.
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PMID:Risk factors for thrombosis in nonembolic cerebrovascular disease. 1007 19


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