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APC Resistance (apc + resistance)
Selected AbstractsLaboratory findings associated with thrombophilia are not more common in inflammatory bowel diseaseINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2000K. K. Sundaram Summary Thromboembolic disease (TED) has been recognized as a complication of inflammatory bowel disease (IBD) since the 1930s ( Bargen & Barker 1936). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency is unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously, when the disease is in clinical remission ( Talbot et al. 1986 ; Jackson et al. 1997 ). Studies looking at the prevalence of specific thrombophilic states such as Antithrombin III deficiency ( Jackson et al. 1997 ; Lake, Stauffer & Stuart 1978; Cianco et al. 1996 ; Ghosh et al. 1983 ), Factor V Leiden mutation (APC Resistance) ( Jackson et al. 1997 ; Probert et al. 1997 ; Ardizzone et al. 1998 ; Liebman et al. 1998 ), anticardiolipin antibodies ( Ciancio et al. 1996 ), Protein C ( Wyshock, Caldwell & Crowley 1988; Korsten & Reis 1992) and Protein S deficiencies ( Jorens et al. 1990 ; Aadland et al. 1992 ) in IBD have been contradictory or equivocal. We had previously found that IBD patients with a history of TED are not more likely to have a laboratory thrombophilic abnormality than those with uncomplicated disease. We also demonstrated that the prevalence of heterogenous laboratory thrombophilic abnormalities (usually minor) in all IBD patients may be as high as 60%, much higher than the recognized prevalence of TED ( Lim, Jones & Gould 1996). We wondered how this would compare with the healthy non-IBD population. We have therefore explored the prevalence of such thrombophilic abnormalities in a group of IBD patients who had no history of TED and compared them with healthy age and sex matched controls. [source] Increased acquired activated protein C resistance in unselected patients with hematological malignanciesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2008H. F. S. NEGAARD Summary.,Background: We have previously found that activation of coagulation in patients with various hematological malignancies was apparently not initiated by tissue factor (TF). Acquired activated protein C (APC) resistance may be another mechanism responsible for such hypercoagulation, and has been demonstrated in patients with solid tumors, but not in patients with hematological malignancy. Objective: To investigate acquired APC resistance in a hypercoagulable cohort of patients with hematological malignancies. Patients/methods: Blood samples from 93 patients with acute myeloid leukemia (AML), chronic lymphatic leukemia, multiple myeloma, or non-Hodgkin's lymphoma, were analyzed before start and after completion of cancer therapy. APC resistance was measured using calibrated automated thrombography. The APC sensitivity ratio (APC-SR) was calculated as the ratio of the endogenous thrombin potential (ETP) determined in plasma probed with either APC or buffer. Results: Untreated patients were found to have higher APC-SR than healthy controls, and patients with AML had higher APC-SR as compared to the other diagnoses, both findings being consistent with acquired APC resistance. The acquired APC resistance was partly ameliorated with cancer treatment. Decreased levels of protein S and TF pathway inhibitor were inversely correlated to APC resistance. Conclusions: APC resistance may contribute to the hypercoagulable state in hematological malignancies. [source] Activated protein C resistance determined with a thrombin generation-based test is associated with thrombotic events in patients with lupus anticoagulantsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2007S. LIESTØL Summary.,Background:,Several studies suggest that antiphospholipid antibodies interfere with the activity of activated protein C (APC). This acquired form of APC resistance has been proposed as a possible pathogenic mechanism underlying hypercoagulability associated with the antiphospholipid syndrome (APS).Objectives:,We wanted to investigate the inhibitory effect of recombinant APC (rAPC) on ex vivo thrombin generation in plasma and the modification of this effect by the presence of lupus anticoagulants (LA).Patients/Methods:,We analyzed plasmas from 81 patients with LA (52 patients fulfilling the criteria for the APS) and 91 controls. Percent inhibition of the endogenous thrombin potential (ETP) as a parameter of APC sensitivity was determined in plasmas using a thrombin generation-based APC resistance test probed with rAPC. All results were normalized using pooled normal plasma (PNP) as a reference.Results:,Normalized percent inhibition of ETP by APC was lower in patients with LA [61.4%, 95% confidence interval (CI) 45.8,74.5%] compared to controls (107.8%, 95% CI: 107.1,109.3%). In patients with LA and APS, median inhibition was lower than in patients with LA without APS (44.6%, 95% CI: 30.1,55.7% vs. 78.8%, 95% CI: 73.9,95.8%). This difference also persisted when patients on warfarin therapy were excluded from the APS subgroup.Conclusions:,APC resistance can be demonstrated with a thrombin generation-based test in a majority of patients with the LA laboratory phenotype. A history of thrombotic events in patients with LA is associated with a stronger resistance to the anticoagulant effect of APC. [source] Impact of progestagens on activated protein C (APC) resistance among users of oral contraceptivesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2004M. Alhenc-Gelas Summary., Oral contraceptive (OC) use is associated with an increased risk of venous thromboembolism. Previous data reported higher thrombotic risk in women using third-generation combined OC than in those using second generation OC. The difference could be explained by differential effects of progestagens on plasma sensitivity to activated protein C (APC). The main purpose of this cross-sectional study was to assess the influence of a progestagen-only OC (chlormadinone acetate) as well as the effect of several combined OC with different progestagen components on APC resistance. The effect of APC on endogenous thrombin potential (ETP) was investigated in the plasma of healthy women using either combined OC (n = 82) or progestagen-only OC (n = 28), and in non-users (n = 64). Carriers of factor V Leiden were excluded. Compared with non-users, there was no significant change in APC resistance in women using progestagen-only OC. Women who used combined OC were less sensitive to APC than non-users (P < 0.001) and the difference was significantly more pronounced in women using third-generation OC (n = 41) than in those who used second-generation OC containing levonorgestrel (n = 22) (P < 0.05). Compared with OC containing levonorgestrel, use of norethisterone-containing OC (n = 9) was associated with an increased resistance to APC (P < 0.05). Women who used cyproterone-containing OC (n = 10) were less sensitive to APC than those using third-generation OC (P < 0.05) or second-generation OC containing levonorgestrel (P < 0.05). Protein S, factor II and FVIII levels explained in part the OC-related changes in APC sensitivity variations. ETP-based APC resistance may contribute to explain why different brands of OC can be associated with different levels of thrombogenicity. [source] Factor V Leiden and hepatic artery thrombosis after liver transplantationCLINICAL TRANSPLANTATION, Issue 1 2006Ty B Dunn Abstract:, Factor V Leiden (FVL) and other thrombophilias can be acquired during liver transplantation and can have a significant impact on clinical outcomes as well as cost. Standard practice does not include screening deceased donors for heritable thrombophilias, even if they have a personal history of thrombosis. Here we report a case of hepatic artery thrombosis in a liver recipient whose native and donor livers were heterozygous for FVL. The patient subsequently underwent a successful retransplant. FVL and its variants are expressed phenotypically as activated protein C (APC) resistance. We believe that testing liver donors (deceased or living) for APC resistance , a surrogate marker for the most common liver-based thrombophilia , will reduce the incidence of thrombotic events by identifying a need for posttransplant prophylactic anticoagulation in patients at risk. The estimated cost of testing all liver donors in the US for APC resistance is less than the cost of two complications secondary to thrombosis. Testing for APC resistance may further improve outcome and reduce cost after liver transplantation. [source] | ||||||||||