Activated protein C resistance (APCR) and combined oral contraceptives: acquired APCR is more pronounced in women receiving desogestrel containing COCs than those containing levonorgestrel and is associated with low protein S levels

2003 ◽  
Vol 1 ◽  
pp. P0883d-P0883d
Author(s):  
C. Gardiner ◽  
I. J. Mackie ◽  
K. Piegsa ◽  
S. A. Furs ◽  
J. Guillebaud ◽  
...  
Keyword(s):  
Oral Contraceptives ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Activated Protein C Resistance ◽  
Combined Oral Contraceptives ◽  
Low Protein

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 844-849 ◽  
Author(s):  
Christoph Male ◽  
Lesley Mitchell ◽  
James Julian ◽  
Patricia Vegh ◽  
Penny Joshua ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Protein C ◽  
Pediatric Patients ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Activated Protein C Resistance ◽  
Systemic Lupus ◽  
Lupus Anticoagulants

Abstract Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs.

scholarly journals Increased Thrombophilic Tendency in Pediatric Cystic Fibrosis Patients

2009 ◽  
Vol 16 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Vaughan Williams ◽  
Adrian B. M. Griffiths ◽  
Zen L. Yap ◽  
James Martin ◽  
Gregory Smith ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
General Population ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Activated Protein C Resistance ◽  
Antithrombin Deficiency ◽  
Indwelling Catheters ◽  
C Protein ◽  
Lupus Anticoagulants

Thrombophilia has recently been reported to be increased in patients with cystic fibrosis (CF). We wanted to determine whether this was applicable to our population with CF and how our patients compared to the previously reported groups. Seventy one pediatric CF patients were assessed for a thrombophilic tendency, using a lupus anticoagulant screen, protein C, protein S, antithrombin assay, and activated protein C resistance (APCR) screen. The incidence of activate protein C resistance (4.2%) was within expected limits for the general population as was the incidence of antithrombin deficiency. However there was a marked increase in the incidence of lupus anticoagulants (18%) and 14% and 19.7% of the patients showed a reduced protein C and protein S, respectively, far in excess of the general population. This increased incidence of thrombophilia was not related to any specific CF phenotype and while perturbed liver function cannot be entirely ruled out, it appeared unlikely to be responsible for all the abnormal coagulation findings. Despite the apparent thrombophilic tendency, no clinically evident thrombotic episodes were noted during the study period. Thrombophilia is of concern because of the increasingly frequent placement of indwelling catheters in CF patients. The precise cause for the thrombophilic tendency in CF patients is unknown at this stage.

Effect of second- and third-generation oral contraceptives on the protein C system in the absence or presence of the factor VLeiden mutation: a randomized trial

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 927-933 ◽  
Author(s):  
Jeanet M. Kemmeren ◽  
Ale Algra ◽  
Joost C. M. Meijers ◽  
Guido Tans ◽  
Bonno N. Bouma ◽  
...  
Keyword(s):  
Oral Contraceptives ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Third Generation ◽  
Double Blind Trial ◽  
Double Blind ◽  
Thrombotic Risk ◽  
Apc Resistance ◽  
Plausible Mechanism

AbstractA plausible mechanism to explain thrombotic risk differences associated with the use of second- and third-generation oral contraceptives (OCs), particularly in carriers of factor VLeiden, is still lacking. In a double-blind trial, 51 women without and 35 women with factor VLeiden were randomized to either a second- (30 μg ethinylestradiol/150 μg levonorgestrel) or third- (30 μg ethinylestradiol/150 μg desogestrel) generation OC. After 2 cycles of use and a wash-out of 2 cycles, the participants continued with the corresponding progestagen-only preparation. Hemostatic variables that probe the activity of the anticoagulant protein C system were determined. Compared with levonorgestrel, desogestrel-containing OCs significantly decreased protein S and increased activated protein C (APC) resistance in both groups. OCs with desogestrel had the most pronounced effects in carriers of factor VLeiden. Progestagen-only preparations caused changes of anticoagulant parameters opposite to those of combined OCs, which in a number of cases were more pronounced with levonorgestrel. Our data show that progestagens in combined OCs counteract the thrombotic effect of the estrogen component. The higher thrombotic risk associated with third-generation OCs compared with second-generation OCs may be explained by the fact that desogestrel appeared less antithrombotic than levonorgestrel, especially in women with factor VLeiden. (Blood. 2004;103:927-933)

scholarly journals Apixaban Does Not Interfere With Protein S or Activated Protein C Resistance (Factor V Leiden) Testing Using aPTT-Based Methods

2020 ◽  
Vol 144 (11) ◽  
pp. 1401-1407 ◽  
Author(s):  
Elena Maryamchik ◽  
Elizabeth M. Van Cott
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Dna Testing ◽  
Activated Protein C Resistance ◽  
S Deficiency ◽  
Free Antigen ◽  
Protein S Activity

Context.— Apixaban causes a false increase in activated protein C resistance (APCR) ratios and possibly protein S activity. Objective.— To investigate whether this increase can mask a diagnosis of factor V Leiden (FVL) or protein S deficiency in an actual population of patients undergoing apixaban treatment and hypercoagulation testing. Design.— During a 4.5-year period involving 58 patients, we compared the following 4 groups: heterozygous for FVL (FVL-HET)/taking apixaban, wild-type/taking apixaban, heterozygous for FVL/no apixaban, and normal APCR/no apixaban. Patients taking apixaban were also tested for protein S functional activity and free antigen (n = 40). Results.— FVL-HET patients taking apixaban had lower APCR ratios than wild-type patients (P < .001). Activated protein C resistance in FVL-HET patients taking apixaban fell more than 3 SD below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite apixaban. In contrast to rivaroxaban, apixaban did not interfere with the assessment of protein S activity (mean activity 93.9 IU/dL, free antigen 93.1 IU/dL, P = .39). A total of 3 of 40 patients (8%) had low free protein S antigen (30, 55, and 57 IU/dL), with correspondingly similar activity results (27, 59, and 52 IU/dL, respectively). Apixaban did not cause a missed diagnosis of protein S deficiency. Conclusions.— Despite apixaban treatment, APCR testing can distinguish FVL-HET from healthy patients, rendering indiscriminate FVL DNA testing of all patients on apixaban unnecessary. Apixaban did not affect protein S activity.

Comparison of Activated Protein C Resistance With Factor V Leiden Testing by Molecular Assay

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S5-S5
Author(s):  
William R Perry ◽  
Steven W Pipe ◽  
Shih-Hon Li
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Protein S ◽  
European Ancestry ◽  
Variant Form ◽  
Factor V ◽  
Low Protein ◽  
Protein C Activity

Abstract Factor V Leiden (FVL) is a variant form of coagulation factor V that is the most common inherited risk factor for venous thromboembolism in people of European ancestry. FVL is associated with the missense mutation, p.R506Q, which encodes a FV protein resistant to cleavage by activated protein C (APC). Laboratory testing for FVL includes both phenotypic assays that assess APC resistance (APCR) and molecular assays that evaluate FVL genotype (FVLM) directly. Although APCR results are typically highly concordant with FVL genotype, discrepancies are known to occur and may result in inference of an incorrect FV genotype if only APCR testing is used. The objective of this study was to compare the results of these two testing methodologies and to identify potential explanations for discrepancies in results. Data were obtained by searching the electronic medical record of a large academic hospital for patients who underwent both APCR and FVLM testing from 2013 to 2018. APCR was evaluated using the ratio between two dilute Russell Viper Venom Time (DRVVT) tests, one preincubated with a protein C activator derived from A contortrix contortrix venom and the other with vehicle; the validated normal APCR ratio is ≥1.7. FVLM was performed by invader analysis utilizing fluorescence resonance energy transfer (FRET). In total, 424 patients underwent testing with both assays. Of 21 patients who had APCR assay clot times that exceeded the measurement range, all were FVLM negative, and 15 were anticoagulated during APCR testing. Of the 403 patients with reportable results for both tests, 385 (95.5%) patients had normal APCR and were FVLM negative. Of the 18 (4.5%) patients with discrepant results, 15 (3.7%) had an abnormally low APCR but were FVLM negative, and 3 (0.8%) had a normal APCR but were FVLM heterozygous. Among the 15 FVLM-negative patients with abnormal APCR <1.7, 11 (73.3%) were on warfarin with/out enoxaparin and had low protein S activity and/or low protein C activity. Of the 3 FVLM heterozygous patients with normal APCR, 1 was on apixaban. Our results demonstrated a high concordance between APCR phenotype and FVLM genotype. The concordance of APCR and FVLM may be limited in patients with low protein S or low protein C activity and those on a range of anticoagulant therapy.

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