Activated Protein C Resistance (APC Resistance)

A hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). The activated form of Factor V (Factor Va) is more slowly degraded by activated protein C. Factor V Leiden mutation (R506Q) is the most common cause of APC resistance.

Also Known As:

Networked: 1300 relevant articles (15 outcomes, 113 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Thrombosis (Thrombus)
2.	Venous Thromboembolism
3.	Venous Thrombosis (Deep-Vein Thrombosis)
4.	Thrombophilia
5.	Protein S Deficiency (Deficiency, Protein S)

Experts

1.	Rosing, Jan: 29 articles (02/2016 - 03/2002)
2.	Rosing, J: 23 articles (09/2021 - 07/2000)
3.	Favaloro, Emmanuel J: 14 articles (01/2021 - 08/2002)
4.	Van Cott, Elizabeth M: 14 articles (11/2020 - 05/2002)
5.	Tans, Guido: 13 articles (09/2006 - 03/2002)
6.	Castoldi, Elisabetta: 12 articles (08/2014 - 09/2002)
7.	Dahlbäck, Björn: 11 articles (05/2016 - 05/2002)
8.	Douxfils, Jonathan: 10 articles (03/2022 - 12/2012)
9.	Tans, G: 9 articles (02/2009 - 07/2000)
10.	Dogné, Jean-Michel: 8 articles (03/2022 - 12/2012)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Activated Protein C Resistance:

1.	factor V LeidenIBA 02/01/1997 - "Thus the activated protein C resistance assay is not cost-effective in ruling out factor V Leiden in this population." 09/01/2013 - "An improved algorithm for activated protein C resistance and factor V Leiden screening." 05/01/2015 - "Our study emphasizes the presence of other contributory factors towards APC resistance rather than FV Leiden alone. " 01/01/2007 - "In both studies the Pefakit assay showed 100% sensitivity and 100% specificity for detection of the factor V Leiden mutation, compared to 93.1% sensitivity and 93.0% specificity for the COATEST APC Resistance V in the IMCLD study and 93.9% sensitivity and 95.6% specificity in the DUMC study. " 09/01/2005 - "Coagulation studies performed in the neonatal period and at the age of 18 months revealed activated protein C resistance due to factor V Leiden mutation (R506Q). "
2.	Factor V (Coagulation Factor V)IBA 11/01/1997 - "Coatest APC Resistance V and Accélérimat were proven to be the methods most able to discriminate for factor V:Q506, while normalization was not shown to improve the screening performance. " 05/01/1998 - "Predilution of patient plasma with factor V-deficient plasma results in improved sensitivity and specificity of the COATEST APC Resistance Kit, thus offering a simple modification to enhance APC resistance determination in the routine clinical laboratory setting." 11/01/1996 - "Improved characteristics of aPC-resistance assay: Coatest aPC resistance by predilution of samples with factor V deficient plasma." 08/15/1997 - "Moreover, the study of 10 patients with APC resistance in the absence of the factor V R506Q mutation showed a 50-fold higher frequency of HR2 homozygotes. " 09/01/1996 - "Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. "
3.	Prothrombin (Factor II)IBA 01/01/2008 - "In 63 severely or morbidly obese patients and in 65 healthy volunteers, an anthropometric and analytical evaluation (activated protein C resistance and prothrombin fragment F1 + 2) was performed at baseline and after 3 months of diet. " 05/01/2007 - "Activated protein C resistance and prothrombin gene mutation were also determined in three patients. " 04/01/2006 - "The addition of purified prothrombin to normal plasma (final concentration 150%) caused APC resistance in the clotting assay over the whole range of tested APC concentrations (0.125-1.5 microg/ml). " 02/01/2006 - "In reconstituted plasma, APC resistance increased at increasing prothrombin concentration in both assays. " 01/01/2005 - "The heterozygous prothrombin G20210A variant was found together with acquired activated protein C resistance and a reduced activated partial thromboplastin time. "
4.	Protein CIBA 01/01/2003 - "The aim of this study was to test the functionality of the protein C system in normal and complicated pregnancies and APC resistance. " 01/01/2002 - "In every newborn with a thrombotic episode, coagulation studies must be performed, including testing for activated protein C (APC) resistance. " 04/01/2000 - "Among the study subjects, 55 CAD patients and 73 controls were evaluated at random for response to activated protein C (APC) by Coatest APC resistance test. " 09/01/2019 - "We enrolled 97 SLE patients and 38 healthy control volunteers and performed activated protein C (APC) resistance screening test using their plasma samples. " 01/01/2018 - "Both protein C and activated protein C resistance (APC-R) were evaluated. "
5.	Protein SIBA 12/01/2004 - "In both studies, small changes of minor clinical significance were noted in activated protein C resistance and free protein S levels. " 09/01/2008 - "Decreased levels of protein S and TF pathway inhibitor were inversely correlated to APC resistance. " 05/01/2007 - "Outcome of the hematological examination proved the pathological level of activated protein C resistance and lower level of protein S. " 01/01/2007 - "This acquired form of APC resistance was due to proinflammatory changes associated with lower plasma levels of free protein S. " 04/01/2005 - "Among them, in two patients there was also a decreased protein S activity and in one of them there was also APC-resistance. "
6.	AnticoagulantsIBA 07/01/1995 - "Plasma anticoagulant response to exogenous APC as a simple diagnostic assay of APC- resistance shows good sensitivity and specificity as compared to gene analysis, yet standardization of the results needs to be improved. " 02/01/2009 - "It has been shown in most studies that APC resistance was associated with lupus anticoagulants. " 01/01/2020 - "Background Direct oral anticoagulants (DOACs) may cause false results of activated protein C resistance (APC-R) ratio. " 05/01/2016 - "In addition, elucidation of APC resistance resulted in the discovery of the anticoagulant APC cofactor activity of FV. " 09/01/2011 - "Lupus anticoagulants (LA) can cause acquired activated protein C resistance (APC-R), but the clinical significance is unclear. "
7.	AntithrombinsIBA 11/01/2018 - "Assays for antithrombin, activated protein C resistance, lupus anticoagulant (LA) and chromogenic anti-Xa assays were also included. " 11/01/2005 - "antithrombin, activated protein C resistance and antiphospholipid antibodies were assessed. " 03/01/2004 - "Our main inclusion criteria were ejection fraction </= 35% and left ventricular end-diastolic diameter >/= 6.0 cm. These two groups were compared for clinical and hematologic parameters (activated protein C resistance, protein S and antithrombin). " 01/07/2000 - "Laboratory parameters were measured to determine APC resistance, FVL-mutation, antithrombin-, protein C and S deficiency, and were correlated to the results of a detailed, life-time history of thrombembolic events. " 11/01/1999 - "Some women who have pre-existing haemostatic abnormalities such as deficiency in antithrombin or activated protein C resistance with factor V Leiden, may be at a higher risk. "
8.	DNA (Deoxyribonucleic Acid)IBA 09/01/1997 - "In this study we firstly evaluated sensitivity, specificity and diagnostic efficiency of an aPTT-based plasma clotting test (Chromogenix, Sweden) versus DNA analysis; then, since the APC resistance test is invalidated by a basally prolonged aPTT (i.e. " 01/01/2018 - "Activated protein C resistance in FVL-HET patients fell more than 3 SDs below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. " 04/15/2015 - "In Amerindian patients with APC resistance, the promoter region, exon 7 and exon 10 of the F5 gene were screened by PCR-SSCP and DNA sequencing. " 06/05/2002 - "APC resistance was studied by functional and DNA methods. " 04/01/1999 - "APC resistance was studied by functional and DNA methods. "
9.	ThrombinFDA Link 02/01/2003 - "The extent of this so-called acquired APC resistance as determined in a thrombin generation-based assay correlates remarkably well with the risk increases observed in clinical studies. " 01/01/1998 - "Our studies on the effects of APC on thrombin formation in plasma resulted in the development of a new method for the screening of APC resistance that is based on measurement of the effect of APC on the endogenous thrombin potential (the time integral of thrombin generated in clotting plasma). " 06/15/1995 - "In summary, this study shows that purified Gln506-FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC." 01/01/2023 - "Evaluation of Activated Protein C Resistance Using Thrombin Generation Test." 03/01/2022 - "Analytical performance of the endogenous thrombin potential-based activated protein C resistance assay on the automated ST Genesia system."
10.	Lupus Coagulation Inhibitor (Lupus Anticoagulant)IBA 03/01/1997 - "Nevertheless, our results demonstrate that, because of false-positive results such as lupus anticoagulant, genotyping is still indicated for patients with an abnormal ratio determined with the modified APC resistance test. " 01/01/2012 - "Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing. " 11/01/2011 - "Lupus anticoagulant interference in activated protein C resistance testing: in vitro phenomenon or in vivo pathophysiologic effect?" 11/01/2003 - "Tests for estimation of PC, PS, activated protein C resistance (APCR), and lupus anticoagulant (LAC) were performed in all the patients with abnormal Pro C(R) Global and in 10 patients with normal Pro C(R) Global. " 01/01/2003 - "The effect of lupus anticoagulant in the second-generation assay for activated protein C resistance."

Therapies and Procedures

1.	Therapeutics 05/01/2014 - "This is the first study showing acquired APC resistance under TAM therapy. " 10/01/2022 - "Activated protein C resistance impact on Syrian candidates for in vitro fertilisation and the benefit of anticoagulation therapy: a retrospective cohort study." 01/01/2022 - "In these most at-risk patients, a targeted action on NETs could reduce APC resistance and constitute a new therapeutic approach in the treatment of APS patients in addition to antithrombotic therapy." 07/01/2006 - "Compared with oral E2/NETA therapy, intranasal administration of E2/NET had less effect on APC resistance and on a number of other parameters associated with venous thrombosis. " 05/01/1996 - "A modification of the APC resistance test and its application to the study of patients on coumarin therapy."
2.	Hormone Replacement Therapy (Therapy, Hormone Replacement) 11/01/2001 - "The aims of this study were to determine whether hormone replacement therapy (HRT) may also induce acquired APC resistance and to study the effects of APC resistance on the risk of recurrent thrombosis. " 08/01/2004 - "Crucially, oral but not transdermal hormone-replacement therapy increases activated protein C resistance independently of the presence of factor V Leiden. " 08/01/2001 - "Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey." 06/01/1999 - "Higher levels of factor VIII correlated with a marker of coagulation activation, such as prothrombin fragments 1 plus 2. Therefore, to identify women receiving hormone replacement therapy who have a greater risk for deep venous thrombosis, the APC resistance coagulation test should be used instead of the genetic study." 07/01/2002 - "The thrombin generation-based APC resistance test was sensitive for the factor V(Leiden) and prothrombin G20210A mutation, to protein S deficiency, hormone replacement therapy, oral contraceptive use and pregnancy. "
3.	Intrauterine Devices (Intrauterine Device) 04/01/2009 - "It was the objective of this study to evaluate the thrombotic risk by comparing the APC resistance before and after insertion of a levonorgestrel-releasing or a copper-containing intrauterine device. "
4.	Liver Transplantation 01/01/2006 - "Testing for APC resistance may further improve outcome and reduce cost after liver transplantation." 04/01/2005 - "Activated protein C resistance acquired through liver transplantation." 07/15/2003 - "She underwent liver transplantation with subsequent normalization of activated protein C resistance. " 11/01/2000 - "Severe thrombotic complications associated with activated protein C resistance acquired by orthotopic liver transplantation." 04/01/1999 - "In October 1997, elective liver transplantation was performed which led to disappearance of APC resistance. "
5.	Drug Therapy (Chemotherapy) 11/01/2012 - "Retrospective analysis of samples showed the occurrence of an acquired APC resistance during chemotherapy, which was predictive of VTE. " 01/01/2021 - "This acquired aPC resistance may explain the procoagulant phenotype associated with ovarian cancer patients undergoing chemotherapy." 09/01/2013 - "The results obtained showed that age >65 years (p = 0.01), ECOG performance status (p = 0.01), platinum-based (p = 0.035) and fluoropyrimidine-based regimens (p = 0.008) were independent predictors of an acquired APC resistance during the first chemotherapy cycle. " 04/01/2014 - "Antiphopholipid antibodies and functional activated protein C resistance in patients with breast cancer during anthracycline-based chemotherapy administered through an intravenous port-catheter device." 01/01/2007 - "Average basal levels of prothrombin time, partial thromboplastin time, antithrombin, protein C, protein S, folates, vitamin B12, and activated protein-C resistance were normal and remained stable during chemotherapy. "