Activated Protein C Resistance (APC-R) Analyzed as a Continuous Variable Is Significantly Decreased In Patients with Multiple Myeloma (MM) Compared to Normal Individuals

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4988-4988
Author(s):  
Tamara Berno ◽  
Kenneth Boucher ◽  
Fenghuang Zhan ◽  
Louis M. Fink ◽  
Guido J. Tricot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein C ◽  
Conflicts Of Interest ◽  
Activated Protein C ◽  
Normal Subjects ◽  
Continuous Variable ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Significant Difference

Abstract Abstract 4988 Background: Increased risk of venous thromboembolism (VTE) has been described in multiple myeloma (MM) patients, particularly when exposed to immunomodulatory drugs. Epidemiological studies have showed that monoclonal gammopathy of undetermined significance (MGUS) patients also have an increased risk of VTE compared with normal subjects. Acquired activated protein C resistance (APC-R) is an independent risk factor for VTE in hematologic malignancies. Methods: We reviewed the records of patients with MM and MGUS for APC resistance by PREFAKIT APC-R test. We excluded from the analysis patients with a documented Factor V Leiden mutation. The PREFAKIT APC-R is a plasma-based functional clotting assay based on the ratio of patient clotting time with and without APC which is standardized and reported as normalized ratio (normalized to results obtained on pooled normal plasma which is performed on each run). Results: APC-R results from 33 MGUS and 75 MM patients were compared with 39 normal subjects. The median APC-R for MM, MGUS and normal subjects were 1, 1.05 and 1.1 respectively. MM patients compared to normal subjects, had significantly lower APC-R (P = 0.0016). No significant difference was observed between MGUS and normal subjects (P= 0.11) (Figure 1). Baseline characteristics from the three groups were similar in terms of age, sex, and performance status. Conclusion: APC-R measured as continuous variable shows a statistically significant decrement in patients with paraproteinemias compared to normal subject and correlates to the underline hypercoagulability observed in patients with MGUS and MM. Disclosures: No relevant conflicts of interest to declare.

Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation

2006 ◽  
Vol 95 (04) ◽  
pp. 728-734 ◽  
Author(s):  
Felipe Guerrero ◽  
Catherine Arnaud ◽  
Francoise Nguyen ◽  
Bernard Boneu ◽  
Pierre Sié
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Risk Increase ◽  
Increased Risk

SummaryActivated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC).As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factorV depleted plasma pre-dilution (test B) and a direct factorX activation-based assay with the same pre-dilution (test C).We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95%CI 3.23–12.63; test B OR=2.72; 95%CI 1.50–4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR=3.22; 95%CI 1.47–7.08; test B OR=3.10; 95%CI 1.54–6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.

Activated Protein C Resistance, the Factor V Leiden Mutation, and a Laboratory Testing Algorithm

2002 ◽  
Vol 126 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Elizabeth M. Van Cott ◽  
Britt L. Soderberg ◽  
Michael Laposata
Keyword(s):  
Laboratory Testing ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Testing Algorithm

Abstract Objectives.—To present the current understanding of factor V Leiden and activated protein C resistance, and to propose a laboratory testing algorithm. Data Sources.—Publications on MEDLINE with the terms factor V Leiden or activated protein C resistance through mid 2001, as well as publications in the authors' files, were screened for inclusion in this report. Study Selection.—Original studies that report a novel finding on testing or clinical features of activated protein C resistance or factor V Leiden are included. Data Extraction.—The novel or key findings from the selected studies are analyzed. Data Synthesis.—Protein C and protein S are the integral components of an anticoagulation pathway that limits fibrinogen conversion to fibrin through the degradation of factors Va and VIIIa. When factor Va is resistant to degradation by activated protein C, this anticoagulation pathway does not operate properly, and patients have an increased risk for thrombosis. This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided. Conclusions.—Factor V Leiden is a risk factor for venous thrombosis and it is particularly common in white populations. A laboratory testing algorithm is proposed.

Coagulation Factor V Leiden Mutation Was Detected in the Patients with Activated Protein C Resistance in Thailand

1998 ◽  
Vol 80 (08) ◽  
pp. 344-345 ◽  
Author(s):  
Pasra Arnutti ◽  
Motofumi Hiyoshi ◽  
Wichai Prayoonwiwat ◽  
Oytip Nathalang ◽  
Chamaiporn Suwanasophon ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Coagulation Factor V

scholarly journals Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis

2004 ◽  
Vol 92 (12) ◽  
pp. 1312-1319 ◽  
Author(s):  
Jeannine Kassis ◽  
Carolyn Neville ◽  
Joyce Rauch ◽  
Lambert Busque ◽  
Erika Chang ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Complete Blood Count ◽  
Tertiary Care ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Activated Protein C Resistance ◽  
Increased Risk

SummaryAlthough antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-β2-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.

Contribution of the Cystathionine β-Synthase Gene (844ins68) Polymorphism to the Risk of Early-onset Venous and Arterial Occlusive Disease and of Fasting Hyperhomocysteinemia

2000 ◽  
Vol 84 (10) ◽  
pp. 576-582 ◽  
Author(s):  
Raffaella de Franchis ◽  
Isabella Fermo ◽  
Giuseppina Mazzola ◽  
Gianfranco Sebastio ◽  
Giovanni Di Minno ◽  
...  
Keyword(s):  
Early Onset ◽  
Gene Polymorphisms ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Statistical Significance ◽  
Activated Protein C ◽  
Mthfr Gene ◽  
Occlusive Disease ◽  
Activated Protein C Resistance ◽  
Increased Risk

SummaryThe frequency of the heterozygous 844ins68 mutation of the cystathionine β-synthase (CBS) gene and of its association with the homozygous C677T transition of the methylenetetrahydrofolate reductase (MTHFR) gene, plasma fasting tHcy, folate and vitamin B12 levels were evaluated in 309 consecutive patients with objectively diagnosed early-onset venous (n = 200) or arterial thromboembolic disease (n = 109) recruited over 25 months in Milan (North Italy) and Naples (South Italy). The above gene polymorphisms were also evaluated in a population of 787 unmatched controls, 204 of whom – similar to patients for age- and sex-distribution – had fasting tHcy, vitamins and activated protein C resistance measured in their plasma.Moderate fasting hyperhomocysteinemia was detected in 15.5% of patients and in 5.9% of 204 controls (Mantel-Haenszel OR after stratification for type of occlusive disease and gender: 2.88; 1.48–5.32). The frequencies of the 677TT mutation of the MTHFR gene and of the heterozygous 844ins68 insertion of the CBS gene were not significantly different in the patient (19.4% and 6.9%) and the control population (16.5% and 7.8%), but the association of the two gene polymorphisms – found in 3.9% of patients and in 1.1% of controls – was significantly associated with an increased risk of venous or arterial occlusive diseases (RR = 3.63; 1.48–8.91). The MTHFR 677TT mutation (RR: 6.92; 3.86–12.4) and its association with the 844ins68 insertion (RR: 21.9; 8.35–57.4), but not the isolated insertion (RR: 0.71), were more frequent in patients and controls with fasting hyperhomocysteinemia than in normohomocysteinemic subjects, irrespective of the type of occlusive disease (venous or arterial). When adjusted for determinants of hyperhomocysteinemia in the patient and the control populations (generalized linear model), fasting tHcy levels were significantly higher in subjects with association of the two gene abnormalities (24.2 ± 3.8 µmol/L) than in subjects with the MTHFR 677TT mutation only (14.0 ± 5.8 µmol/L, p = 0.004). Activated protein C resistance was significantly more prevalent in venous patients (9.9%) than in controls (3.9%, OR = 2.69; 1.08–6.88). Six of 21 venous patients with APCresistance also had hyperhomocysteinemia (RR = 5.04; 0.68–37.6), but isolated fasting hyperhomocysteinemia retained statistical significance for the association with venous occlusive disease (RR = 2.84; 1.34–6.01).Heterozygosity for the 844ins68 mutation of the CBS gene is not per se a risk factor for premature arterial and/or venous occlusive diseases. However, when detected in combination with thermolabile MTHFR, it increases by almost 4-fold the risk of occlusive diseases (arterial and/or venous), by increasing the risk and the degree of fasting hyperhomocysteinemia.

scholarly journals Activated Protein C Resistance and Factor V Leiden in Mexico

2007 ◽  
Vol 14 (4) ◽  
pp. 428-437 ◽  
Author(s):  
Abraham Majluf-Cruz ◽  
Manuel Moreno-Hernández ◽  
Adriana Ruiz-de-Chávez-Ochoa ◽  
Rosario Monroy-García ◽  
Karim Majluf-Cruz ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Common Cause ◽  
Factor V Gene ◽  
V Gene ◽  
Low Prevalence

A common cause of hereditary thrombophilia is activated protein C resistance (APCR), and most cases result from factor V Leiden mutation. An APCR phenotype without association with factor V Leiden has been described. This transversal, observational, nonrandomized study evaluated these 2 phenomena in healthy indigenous and mestizo Mexican subjects (n = 4345), including 600 Mexican natives. No indigenous subjects had APCR, but 82 mestizo subjects did. After retesting, 50 subjects had a negative test. The remaining 32 subjects had factor V Leiden, giving a 0.85% prevalence of factor V Leiden in the mestizo Mexican population. Only 31% of APCR carriers had factor V Leiden. These results show a very low prevalence of APCR and factor V Leiden in Mexico. Except for factor V Leiden, there are no other mutations in the factor V gene responsible for the APCR phenotype. Acquired APCR is nearly twice as prevalent as the inherited variant.

Sign in / Sign up

Export Citation Format

Share Document