Activated Protein C Resistance vs Factor V Leiden assay: Which is the most cost effective?

Transcription

1 Activated Protein C Resistance vs Factor V Leiden assay: Which is the most cost effective? Rajiv K. Pruthi, M.B.B.S Co-Director, Special Coagulation Laboratory & Director, Mayo Comprehensive Hemophilia Center Division of Hematology/Internal Medicine Dept of Laboratory Medicine & Pathology Mayo Clinic, Rochester, MN 2017 MFMER slide-1

2 Multifactorial Disease Acquired + inherited Acquired Inherited Thrombosis Acquired + acquired Inherited + inherited 2017 MFMER slide-2

3 Thrombophilia Profile: Reflexive Testing Approach THRMP/Thrombophilia Profile Testing begins with Prothrombin Time (PT), Plasma Activated Partial Thromboplastin Time (APTT), Plasma Dilute Russells Viper Venom Time (DRVVT), Plasma Thrombin Time (Bovine), Plasma Fibrinogen, Plasma D-Dimer, Plasma Soluble Fibrin Monomer Antithrombin Activity, Plasma Protein C Activity, Plasma Protein S Antigen, Free, Plasma Prothrombin G20210A A Mutation, Blood Activated Protein C Resistance V (APCRV), Plasma Special Coagulation Interpretation PT: 14.0 seconds APTT: >36 seconds DRVVT: 1.2 seconds Thrombin Time (Bovine) APCRV: <2.3 OR PT Mix 1:1 APTT Mix 1:1 DRVVT Mix 1:1 Prolonged baseline APTT sec >23 sec Protein C Activity: <70% Protein S. Antigen, Free Males <65% Females <50 years: <50% 50 years: <65% Antithrombin Activity: <80% No evidence of an acquired deficiency 14.0 < > <1.2 Evidence of inhibition* Evidence of coagulation factor deficiency* Evidence of inhibition* Evidence of coagulation factor deficiency* Normal no evidence of heparin or dys/ hypofibrinogenemia Reptilase Time Factor V Leiden (R506Q) Mutation Protein C Antigen Protein S Antigen, Total Antithrombin Antigen, Plasma All initial testing within reference ranges for age and gender: No evidence of thrombotic diathesis No further testing is performed Possible factor inhibitor* No evidence of heparin in sample Does not shorten Platelet neutralization procedure (PNP) Shortens by 4-5 seconds Evidence of lupuslike anticoagulant DRVVT Confirmation 1.2 <1.2 Anticoagulant effect ** No diagnostic of lupuslike anticoagulant sec >23 sec Possible dys/ hypofibrinogenemia* *Additional assays may be performed if further clarification or confirmation is necessary. These may include: Coagulation Factor Assays Staclot Lupus Anticoagulant Protein S Activity **Unfractionated/low-molecular weight heparin or direct thrombin inhibitor (eg, dabigatran, argatroban) An interpretive report is provided that includes all profile tests (always performed) and any reflex tests performed (if appropriate) MFMER slide-3

4 Activated Protein C Resistance and Factor V Leiden Most common congenital hereditary thrombophilia among whites Protein phenotype Normally: Activated protein C (APC) inactivates activated factor V (fva) APC resistance: Mutated factor V resists inactivation by APC Genetic basis Factor V Leiden (R506Q) mutation Testing strategy Initial APC-R assay, FV Leiden only if indicated 2017 MFMER slide-4

5 APC Resistance assay: Normal Baseline aptt (30 sec) aptt after addition of APC (inactivates factor V, prolongs aptt) (90 sec) APCR ratio APC aptt (90) aptt (30) = MFMER slide-5

6 APC Resistance assay: Abnormal (FV Leiden) Baseline aptt (30 sec) aptt after addition of APC (inactivates factor V, prolongs aptt, but not as much as normal) (60 sec) APCR ratio APC aptt (60) aptt (30) = 2.0 V Leiden 2017 MFMER slide-6

7 Factor V Leiden Genetic Basis for activated protein C resistance Direct mutation analysis for presence or absence of FV Leiden Multiple different assay types 2017 MFMER slide-7

8 Approach to testing Screening test first Must be low cost yet requires high sensitivity (Risk false positive) DNA based test first Likely more expensive Low false positive/negative 2017 MFMER slide-8

9 Testing Strategy for APC-R and FV Leiden Taylor et al: Am J Clin Pathol 129:494, 2008 Taylor LJ et al Am J Clin Pathol 2008; 129: MFMER slide-9

10 Testing Strategy for APC-R and FV Leiden Taylor et al: Am J Clin Pathol 129:494, 2008 Taylor LJ et al Am J Clin Pathol 2008; 129: MFMER slide-10

11 Mayo Clinic, Rochester experience vs Optum labs Optum labs data warehouse >100 million enrollees Medical claims data for laboratory testing etc Inpatient and outpatient 2017 MFMER slide-11

12 Mayo APCR/FV Leiden vs Optum Labs database Test description Mayo Sp Coag Lab Optum Labs APC-R ,395 FV Leiden ,129 Ratio: APCR:FVL Cost per evaluated individual (78,525) ~1: 0.2 ~1:15 $36.38 (savings: $47.39) $ Mayo Foundation for Medical Education and Research. All Rights Reserved MFMER slide-12

13 Conclusion Screening with APC Resistance assay Reflexive FV Leiden confirmatory: More cost effective 2017 MFMER slide-13

14 Questions & Discussion 2017 MFMER slide-14