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: 1122 relevant articles (14 outcomes, 97 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

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

Experts

1.	Rosing, Jan: 27 articles (08/2014 - 03/2002)
2.	Rosing, J: 22 articles (11/2014 - 07/2000)
3.	Tans, Guido: 13 articles (09/2006 - 03/2002)
4.	Castoldi, Elisabetta: 12 articles (08/2014 - 09/2002)
5.	Van Cott, Elizabeth M: 10 articles (12/2014 - 05/2002)
6.	Dahlbäck, Björn: 10 articles (01/2008 - 05/2002)
7.	Favaloro, Emmanuel J: 9 articles (09/2012 - 08/2002)
8.	Tans, G: 9 articles (02/2009 - 07/2000)
9.	Rosendaal, F R: 8 articles (04/2014 - 05/2000)
10.	Simioni, Paolo: 7 articles (08/2014 - 06/2002)

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. " 10/01/2001 - "The evaluation of the study was of the impact of oral contraceptive (OC) use on 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. " 03/01/2014 - "Because of decreased levels of protein C (38.7 %), F II (69.1 %), and activated protein C resistance (1.43), a mutational gene analysis was performed. "
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.	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. " 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. " 04/01/1999 - "APC resistance was studied by functional and DNA methods. " 03/01/1998 - "We report a case where a phenotypic test (an activity assay for activated protein C resistance) correctly indicated that the patient had an abnormality, whereas the initial genetic test (a PCR-based DNA assay used to detect the mutation in the FV gene) incorrectly indicated that the patient did not. " 03/01/1997 - "Eighty frozen coded plasma samples from carriers and non-carriers of the FV:Q506 mutation, diagnosed by DNA analysis, were sent to 8 experienced laboratories that were asked to analyze these samples in blind with their own APC resistance tests. "
7.	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." 05/01/2014 - "APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. " 01/01/2014 - "In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. "
8.	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."
9.	AnticoagulantsIBA 02/01/2009 - "It has been shown in most studies that APC resistance was associated with lupus anticoagulants. " 09/01/2011 - "Lupus anticoagulants (LA) can cause acquired activated protein C resistance (APC-R), but the clinical significance is unclear. " 09/01/2011 - "Acquired activated protein C resistance caused by lupus anticoagulants." 12/17/1994 - "Modified APC resistance assay for patients on oral anticoagulants." 02/15/2001 - "Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus."
10.	A-factor (Streptomyces)IBA 03/01/2006 - "A 2-year retrospective analysis of laboratory testing for activated protein C resistance with a factor V-corrected activated partial thromboplastin time-based method." 08/01/2005 - "Recently, activated protein C resistance (APCR) has been identified as a factor in some cases. " 02/01/2002 - "In 12 cases, an APC resistance caused by a factor V Leiden mutation (11 heterozygous; 1 homozygous) was detected. " 06/01/1997 - "Seventy-three (15%) patients had both APC resistance and the 1691 G to A factor V gene mutation, compared to 6/341 (2%) controls. " 03/01/1997 - "However, one must be aware that APC-resistance ratios obtained with the modified method are likely to be different from those established with the original method, and the source of FV-deficient plasma can be a factor influencing the ratios in the former cases."

Therapies and Procedures

1.	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. "
2.	Transplants (Transplant) 08/01/1999 - "In the study group, smoking at the time of surgery, female gender and the use of prosthetic grafts were significantly associated with graft failure on univariate Cox regression analysis, but activated protein C resistance was not. " 08/01/1999 - "There was a trend for activated protein C resistance to be associated with graft failure. " 08/01/1999 - "Six of the nine patients with activated protein C resistance underwent surgery in the last 10 months of the review period and only three activated protein C resistance patients had a graft patent for more than 8 months. " 08/01/1999 - "After accounting for confounders, there was a trend (P = 0.098) for activated protein C resistance to be associated with graft failure (OR 2.90, 95% CL 0.82-10.3). " 08/01/1999 - "The association of activated protein C resistance with peripheral arterial bypass graft patency was assessed. "
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.	Transplantation (Transplant Recipients) 01/01/1996 - "Follow up testing 2 1/2 years post-transplantation revealed correction of the APC resistance phenotype (normalization of the APCR-R to 2.79). " 05/27/2000 - "A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. " 05/27/2000 - "Allograft loss in renal transplant recipients with Fabry's disease and activated protein C resistance." 01/01/1996 - "Since the presence of activated protein C (APC) resistance has been reported to interfere with PS activity assays resulting in an apparent type II PS deficiency, we retrospectively tested a pre-transplantation frozen plasma sample for APC resistance. " 06/01/2003 - "Analysis of the grafted liver DNA showed that the donor was a heterozygous carrier of the factor V Leiden mutation and that the recipient's activated protein C resistance was acquired through the transplantation. "