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)

Very little data is available assessing the clinical utility of coagulation-based APC resistance assays compared to DNA-based analysis for the factor V Leiden mutation in children. Therefore, the clinical utility of four aPTT-based assays for APC resistance was evaluated in 169 children, ages 3 months through 16 years. The prevalence of the Arg506 to Gln mutation was 7/169 (4.1%). Using cutoff points derived from the normal PCR-screened population (n = 162), two assays for APC resistance (APC-SR and n-APC-SR) gave poor concordance with the PCR assay (sensitivity 29% and 57%, respectively). Two modified assays (FDAPC-SR and n-FDAPC-SR), in which patient plasma was prediluted 1:5 in factor V deficient plasma, gave excellent concordance (sensitivity 100%). The predictive value of a positive test was 0.25, 0.44, 1.00 and 0.88 for the APC-SR, n-APC-SR, FDAPC-SR and n-FDAPC-SR, respectively. The FDAPC-SR and n-FDAPC-SR tests gave excellent discrimination using cutoff values derived from the total population (n = 169) without regard to previous PCR screening results.
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PMID:Sensitivity, specificity and predictive value of modified assays for activated protein C resistance in children. 953 Oct 42

Activated protein C resistance (APCR) is a recently discovered, medically important cause of venous thrombosis. More than 95% of cases are due to factor V Leiden (FVL), a mutated form of factor V that is resistant to degradation by activated protein C. The prevalence of this disorder, which is inherited in an autosomal dominant fashion, is approximately 5% among asymptomatic people of European heritage. In addition, 20 to 60% of patient cohorts with previous thrombosis demonstrate APCR, making it the most common known genetic cause of abnormal thrombophilia. Current laboratory techniques available for diagnosis include functional assays, such as the APC ratio, as well as DNA-based tests that detect the specific genetic anomaly responsible for FVL. A case report is presented, along with a review of the literature highlighting epidemiology, pathogenesis, clinical features and methods for laboratory diagnosis.
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PMID:The diagnosis and clinical manifestations of activated protein C resistance: a case report and review of the literature. 955 83

Hypercoagulable states are a group of conditions associated with increased predisposition to thromboembolic events. Most of the inherited abnormalities recognized to date are associated with venous thromboembolism (VTE) rather than arterial thrombosis. The well-recognized inherited hypercoagulable states are the deficiencies of antithrombin, protein C and protein S, and the resistance to APC (factor V Leiden). These entities represent aberrations in the natural anticoagulant systems that exist in plasma. Other causes of inherited thrombophilia include abnormalities in the proteins of the fibrinolytic system, dysfibrinogenemias, deficiency of heparin cofactor II, abnormal thrombomodulin, elevated levels of histidine-rich glycoprotein, and the recently described variation in the prothrombin gene. One entity that has become firmly established as a predisposing factor for recurrent VTE is hyperhomocysteinemia. About half of VTE episodes in patients with inherited thrombophilias occur in relation to events that are generally recognized as predisposing states, such as surgery, pregnancy (particularly puerperium) and immobilization. In this review, the risks of VTE associated with inherited risk factors are discussed, and guidelines for the diagnosis and management are presented.
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PMID:Inherited hypercoagulable states. 957 5

Resistance to activated protein C (APC resistance) was described recently as a cause for thrombophilia. APC inactivates coagulation co-factors Va and VIIIa. A single base-pair mutation changing Arg506 to Gln at the APC cleavage site of the factor V gene leads to a factor V Leiden variant, which is the most frequent cause of APC resistance. Recently, its role in peripheral venous thrombosis during pregnancy was described. We here report a case with thrombosis of the venous anastomoses after finger replantation with resistance to activated protein C associated with factor V Leiden mutation.
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PMID:Venous thrombosis in a replanted finger with underlying factor V Leiden mutation. 957 20

In order to evaluate the actual incidence and clinical repercussion of activated protein C resistance (APCR) in our area, we performed a coagulation and thrombophillic study on 65 young patients diagnosed with deep vein thrombosis and 53 controls. Family and genetic study was carried out in APC-resistant patients. We found APCR in 26.15% of patients and the 77.7% of these and their relative were heterozygous for factor V Leiden. There's a clear relationship between phenotype APCR and thrombosis, and also between factor V Leiden and thrombosis.
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PMID:Incidence and clinical manifestations of activated protein C resistance and factor V Leiden in young patients with venous thromboembolic disease in Spain. 959 91

The discovery of plasma resistance towards activated protein C, APC resistance, and its main genetic background, the presence of a single-point mutation in the gene coding for coagulation factor V, factor V Leiden, has, together with renewed documentation of a link between oral contraceptive use and thrombosis, increased the understanding of the pathophysiology, but also the demands to the prescribers, of the pill. Only with knowledge about hemostasis, thrombophilia, DNA technology, its use and limitations, epidemiology, and absolute risk, can general practitioners perform good clinical practice. This short survey tries to cover some of these aspects and to suggest directions for future research.
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PMID:Plasma resistance to activated protein C: an important link between venous thromboembolism and combined oral contraceptives--a short review. 967 32

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


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