Current Practice of Testing for Hereditary Thrombophilia in the Netherlands.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3288-3288
Author(s):  
Michiel Coppens ◽  
Jan A. van Mourik ◽  
Carel M. Eckmann ◽  
Saskia Middeldorp
Keyword(s):  
Cardiovascular Disease ◽  
The Netherlands ◽  
General Practitioners ◽  
Pregnancy Complications ◽  
Current Practice ◽  
Factor V Leiden ◽  
Factor V ◽  
Test Results ◽  
Therapeutic Consequences ◽  
Thrombophilia Testing

Abstract Inherited thrombophilia is known to increase the risk for venous thromboembolism (VTE). Furthermore, an association between recurrent pregnancy loss and hypertensive pregnancy complications (including preeclampsia and HELLP syndrome) appears present. A relationship between thrombophilia and arterial cardiovascular disease could not be demonstrated in most studies. Since thrombophilia is prevalent in patients with VTE, testing for these abnormalities often reveals positive test results which may lead to widespread testing. This is also the case in patients with various other conditions. However, there is little convincing evidence about effectiveness of testing due to the uncertainty with respect to therapeutic consequences of a positive thrombophilia test results. To assess the current practice of thrombophilia testing in The Netherlands and to get an impression of the therapeutic implications of testing for patients, simple questionnaires were sent out to physicians that ordered tests for protein S, C, or antithrombin activity, factor V Leiden (or APC resistance) or the prothrombin 20210A mutation in 1998 consecutive individuals who were investigated between November 2003 and March 2004. The tests were performed in a laboratory that serves as a diagnostic facility for mainly non-academic hospitals and general practitioners throughout the Netherlands. Of a total of 1265 returned questionnaires, 1130 were suitable for analysis (response rate 63%). Of the tested individuals, 64% were female (median age 38 years, inter-quartile-range [IQR] 30–50) and 35% were male (median age 51, IQR 41–59). Tests were ordered by internists (37%), gynaecologists (20%), neurologists (15%) and general practitioners (13%). Only 42% of the tested individuals had experienced VTE, 23% arterial cardiovascular disease, and 17% had had pregnancy complications. A known carrier or VTE in the family was the reason for testing in 180 asymptomatic individuals (16%). Testing had had no therapeutic consequences in 869 tests (77%). In 32% of these patients, physicians stated that had the test revealed a thrombophilic defect, this would not have altered management of the patient. This study shows that testing for thrombophilia occurs very often in patients with various conditions. In the majority of cases, the results do not change therapeutic management of tested patients. Widespread thrombophilia testing is costly and may cause unnecessary concern in carriers. This study underscores the need to acquire high level evidence about its effectiveness that should include clinical outcomes as well as quality of life and costs.

scholarly journals Clinical Utilization and Cost of Thrombophilia Testing in Patients with Venous Thromboembolism

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e153-e162
Author(s):  
Manila Gaddh ◽  
En Cheng ◽  
Maha A.T. Elsebaie ◽  
Imre Bodó
Keyword(s):  
Venous Thromboembolism ◽  
Patient Management ◽  
Clinical Decision Making ◽  
Factor V Leiden ◽  
Direct Costs ◽  
Cost Of Care ◽  
Factor V ◽  
Test Results ◽  
Thrombophilia Testing ◽  
The Impact

Abstract Introduction Testing for inherited and acquired thrombophilias adds to the cost of care of patients with venous thromboembolism (VTE), though results may not influence patient management. Methods This is a single-center, retrospective study conducted at Emory University Hospitals from January to December 2015 to (1) determine the pattern of thrombophilia testing in patients with VTE, (2) study the impact of results of thrombophilia testing on clinical decision-making, and (3) determine the direct costs of thrombophilia testing in patients with VTE. Results Of the 266 eligible patients, 189 (71%) underwent testing; 51 (26.9%) tested positive and the results impacted management in 32 (16.9%) of tested patients. Patient undergoing testing were more likely to be younger than 40 years (30.9 vs. 18.2%), have had prior pregnancy loss (9.0 vs. 0%), or known family history of hypercoagulability (24.9 vs. 10.4%), and were less likely to have had provoked VTE (37 vs. 79.2%). The most common thrombophilias tested were antiphospholipid syndrome (60.1%), factor V Leiden (59.7%), and prothrombin gene mutation (57.5%). Direct costs of thrombophilia testing were $2,364.32 per patient, $12,331.55 to diagnose 1 positive, and $19,653.41 per patient-management affected. Conclusion We noted significant variability in selection of patients and panel of tests, sparse utilization of test results in patient management, but high cost associated with thrombophilia testing in patients with VTE. With guidelines advocating selective use of thrombophilia testing and attention to potential impact of test results in patient management, we propose the need for measures at institutional levels to improve test-ordering practices.

scholarly journals Risk of placenta-mediated pregnancy complications or pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and heterozygosity for factor V Leiden or G20210 prothrombin mutation

2012 ◽  
Vol 89 (3) ◽  
pp. 250-255 ◽  
Author(s):  
Iris Cordoba ◽  
Carlota Pegenaute ◽  
Tomás José González-López ◽  
Carmen Chillon ◽  
Maria Eugenia Sarasquete ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Factor V Leiden ◽  
Factor V ◽  
Prothrombin Mutation

scholarly journals Utility of Thrombophilia Testing in Portal Vein Thrombosis in a Large Single Institutional Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3646-3646
Author(s):  
Douglas Tremblay ◽  
Leonard Naymagon ◽  
Kevin Troy ◽  
Caroline Cromwell ◽  
Colleen Edwards ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Clinical Management ◽  
Factor V Leiden ◽  
Antiphospholipid Antibody ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
Mthfr Mutation ◽  
Thrombophilia Testing

Introduction: Patients with portal vein thrombosis (PVT) are frequently referred to hematology for hypercoagulable evaluation. The prevalence of identifiable thrombophilic conditions in patients with PVT is not well reported and the clinical impact of thrombophilia testing is unknown. Methods: We conducted a retrospective review of patients at a single tertiary care center. Patients were identified who had a documented PVT with or without concurrent thrombosis in additional splanchnic vessels, followed between 1/1/2000 and 5/1/2019 with at least 3-month follow-up available. Exclusion criteria included liver transplantation within 6 months of PVT and inadequate documentation. Changes in clinical management were determined by chart review and determination of documented change in choice, dose, or duration of anticoagulant, future thromboprophylaxis, or counseling of asymptomatic family members as documented in the medical chart. Results: Baseline characteristics of the entire cohort are summarized in Table 1. Five-hundred and forty-four unique patients were identified. Most patients had an isolated PVT (55.3%). The most common concurrent vessel thrombosed was the superior mesenteric vein (36.9%). Cirrhosis was the most common predisposing provoking condition, followed by recent abdominal surgery and inflammatory bowel disease. Of note, 106 patients (19.4%) had no identifiable underlying provoking factor. Two-hundred ninety-one patients (53.5%) had at least one hypercoagulable laboratory test performed, with a median number of 8 tests (Table 2). PAI-1 polymorphism was the most common positive thrombophilia test, followed by MTHFR mutation and an elevated homocysteine. Of note, these three test abnormalities have not been consistently linked to increased thrombotic potential. Identification of a JAK2 mutation was noted in 16.7% of patients tested and was detected in 37% of patients without a predisposing provoking factor prior to testing. No patients harbored a mutated CALR and MPL. In patients without a predisposing provoking factor who had thrombophilia testing performed (n=98), thrombophilia testing was positive in 59 patients (60.2%). Of note, 39 patients (40.0%) of these patients had a negative thrombophilia evaluation. In patients with thrombophilia testing (n=291), only 41 (14.1%) patients had a test result which impacted management. By far the most common positive-management altering test was JAK2 mutational testing, with 33 patients receiving further workup including a bone marrow biopsy and/or treatment of an underlying MPN as a result of testing. One patient who was diagnosed with paroxysmal nocturnal hemoglobinuria (PNH) received treatment with eculizumab. Two patients with antiphospholipid antibody syndrome were specifically administered coumadin as a result of testing. One patient with Factor V Leiden was anticoagulated for a longer duration, two received thromboprophylaxis during subsequent high-risk situations (which may have been done regardless of Factor V Leiden mutation), and one had screening performed on an asymptomatic family member. One patient with MTHFR mutation and elevated homocysteine received folate supplementation. Conclusions: These results demonstrate that nearly all hypercoagulable laboratory testing in patients with PVT is not of clinical utility. The most notable exception is JAK2 mutational testing, which appears to be an essential component in the workup of PVT without an obvious provoking factor both because of its relatively high frequency of occurrence and its significant impact on clinical management. In addition, while PNH and APLS are rarely positive in thrombophilia evaluation of PVT, they likely merit evaluation in appropriate clinical settings given their potential to meaningfully impact management. Extensive thrombophilia testing does not appear to reliably impact management. Disclosures Kremyanskaya: Incyte, Celgene, Constellation, Protagonist.: Research Funding; La Jolla: Consultancy.

A multi-laboratory assessment of congenital thrombophilia assays performed on the ACL Top 50 family for harmonisation of thrombophilia testing in a large laboratory network

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emmanuel J. Favaloro ◽  
Soma Mohammed ◽  
Ronny Vong ◽  
Kent Chapman ◽  
Priscilla Swanepoel ◽  
...  
Keyword(s):  
Protein C ◽  
Factor V Leiden ◽  
Poor Performance ◽  
Protein S ◽  
Third Party ◽  
Factor V ◽  
Reference Ranges ◽  
Laboratory Assessment ◽  
Study Objective ◽  
Thrombophilia Testing

Abstract Objectives Thrombophilia testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new ‘single platform’ of hemostasis instrumentation. The study objective was to evaluate these instruments and manufacturer reagents for utility of congenital thrombophilia assays. Methods Comparative evaluations of various congenital thrombophilia assays (protein C [PC], protein S [PS], antithrombin [AT], activated protein C resistance [APCR]) using newly installed ACL TOPs 550 and 750 as well as comparative assessments with existing, predominantly STAGO, instrumentation and reagents. Verification of manufacturer assay normal reference ranges (NRRs). Results HemosIL PC and free PS assays showed good comparability with existing Stago methods (R>0.9) and could be considered as verified as fit for purpose. HemosIL AT showed high relative bias with samples from patients on direct anti-Xa agents, compromising utility. Manufacturer NRRs for PC, PS and AT were verified with minor variance. Given the interference with direct anti-Xa agents, an alternate assay (Hyphen) was evaluated for AT, and the NRR also verified. The HemosIL Factor V Leiden (APC Resistance V) evidenced relatively poor performance compared to existing assays, and could not be adopted for use in our network. Conclusions This evaluation of HemosIL reagents on ACL TOP 50 Family instruments identified overall acceptable performance of only two (PC, free PS) of four thrombophilia assays, requiring use of third-party reagents on ACL instruments for the other two assays (AT, APCR).

Thrombophilia Testing Practices: The Mayo Clinic Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Caleb J Scheckel ◽  
Rajiv K. Pruthi ◽  
Ariela L. Marshall ◽  
Aneel A. Ashrani ◽  
Dong Chen ◽  
...  
Keyword(s):  
Mayo Clinic ◽  
Protein C ◽  
Factor V Leiden ◽  
Choosing Wisely ◽  
Prothrombin G20210a ◽  
Reference Laboratory ◽  
Factor V ◽  
Clinic Staff ◽  
G20210a Mutation ◽  
Thrombophilia Testing

Introduction: The 2013 ASH Choosing Wisely campaign recommends against thrombophilia testing in patients with major transient risk factors for venous thromboembolism (VTE). Our Special Coagulation Laboratory (SCL) offers an algorithmic approach to thrombophilia testing which includes assays for lupus anticoagulant, dysfibrinogenemia, anticoagulant proteins (protein C, protein S, antithrombin), activated protein C resistance with reflex to factor v Leiden (if indicated), and prothrombin G20210A mutation. Samples are received through Mayo Clinic Laboratories (MCL), national and international reference laboratory (often with limited or no clinical information) and from internal Mayo Clinic practice. We hypothesized that thrombophilia testing would decline in cases where it was recommended against following the publication of testing guidelines. Methods: We audited the external thrombophilia testing samples between2013-2019 and internal samples between 2014-2019 (periods during which they were available). For the internal samples, complete test volumes were only available 2014-2019. Because external clients may either adopt internal testing or contract with a different reference laboratory, many clients may not have been retained over the entire observed period. To better understand the ordering practices of consistent clients, external clients which did not have thrombophilia testing sent to MCL each year of the observed period were excluded. We separated internal ordering practices by hematology and oncology or thrombophilia clinic staff and trainees contrasted with those of other specialties. Results: MCL received 18,529 external thrombophilia testing samples from 322 external healthcare systems during the observed period. From 37 clients, 5,878 (38.2%) samples met inclusion criteria. Annual volume of samples ranged from 890 in 2013 to 861 in 2019 (861-1046). Special coagulation lab processed 11,639 internal thrombophilia tests during the observed periods. There was a consistent small annual increase in testing with 1,398 performed in 2014 and 2,430 in 2019. Of 11651 tests ordered, only 18.6% (2167) were ordered by people most likely to be familiar with ASH choosing wisely campaign. Annual thrombophilia testing ordered by hematology and oncology or thrombophilia clinic staff increased from 307 in 2014 to 387 in 2019 (307-432). However, the ordering practices of these providers as a proportion of overall practices declined from 22.0% (307/1398) in 2014 to 15.9 % (387/2430) in 2019. Table Discussion: Our preliminary data showed no significant trend in thrombophilia ordering practices among included external clients since publication of the ASH Choosing Wisely guidelines on thrombophilia testing. Internally we found a consistent small rise in numbers of thrombophilia tests ordered since 2014 but this may reflect changes in patient volume. We observed that the majority of internal thrombophilia testing was ordered by non-hematology/oncology or thrombophilia providers who are perhaps less likely to be familiar with ASH Choosing Wisely guidelines. The proportion of testing ordered by hematology & oncology or thrombophilia providers declined during the observed period. Our findings are limited by lacking information on the indication and appropriateness for testing as well as possibility of change in patient population. However the overall trend in test volumes and specialty of ordering providers deserves attention and highlight the value in educating other medical societies on ASH Choosing Wisely recommendations for thrombophilia testing. Future work will focus on appropriateness for thrombophilia testing including the indication and time (remote from anticoagulation and acute thrombotic episode), location of testing (inpatient vs. outpatient), as well as investigating if testing has changed patient management, which may help in creating new Choosing Wisely recommendations for thrombophilia testing. Figure 1. Disclosures Pruthi: HEMA Biologics: Honoraria; Bayer Healthcare: Honoraria; Merck: Honoraria; Instrumentation Laboratory: Honoraria; Genentech Inc.: Honoraria; CSL Behring: Honoraria.

The Risk of Venous Thrombosis in Different Immigrant Groups in the Netherlands

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3393-3393 ◽  
Author(s):  
Suely M Rezende ◽  
Willem M. Lijfering ◽  
Frits R. Rosendaal ◽  
Suzanne C. Cannegieter
Keyword(s):  
Risk Factors ◽  
The Netherlands ◽  
Venous Thrombosis ◽  
Second Generation ◽  
Large Population ◽  
Factor V Leiden ◽  
Population Based ◽  
Factor V ◽  
Southeast Asians ◽  
Second Generation Immigrants

Abstract Abstract 3393 Background: Ethnic differences in the incidence of venous thrombosis have been appreciated for many years. However, with few exceptions, most of the studies on this subject were based on administrative databases from North America and China. The aim of this study was to investigate the risk of venous thrombosis in different first and second generation immigrant groups included in a large population-based case-control study, performed in the Netherlands. Methods: This study was performed using data from the MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis-study), a large, population based case-control study on risk factors for venous thrombosis from the Netherlands. Inclusion criteria consisted of patients and controls whom information were available on the country of birth. For the analysis related to immigration background, patients were compared with random digit dialing (RDD) controls. First generation immigrants were classified as those who were born outside the Netherlands. Second generation immigrants were similarly defined as first generation immigrants, except that second immigrants were born in the Netherlands, while both parents were born in one of aforementioned other countries. In total, 6899 participants were included, of whom 4300 patients and 2599 RDD controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated as estimates of the relative risk, and were adjusted for age, sex, body mass index, smoking, hormonal factors, alcohol consumption, physical activity and malignancy by unconditional logistic regression. Results: The risk of venous thrombosis varied according to the region of birth (Table 1). When compared with the Dutch, Eastern Europeans reached the highest and East/Southeast Asians the lowest risk of venous thrombosis with OR of 2.35, (95% CI, 1.09–4.59) and 0.44 (95% CI, 0.29–0.68), respectively after multivariate adjustments. Caribeans showed an intermediate lower risk of 0.69 (95% CI, 0.36–1.30) after multivariate adjustments (Table 1). We did not observe a major difference on the risk for VT between first and second generation immigrants, although the number of second generation immigrants was small for some groups. Subgroup analysis did not show major differences according to immigration groups, except for Eastern Europeans, who had a higher risk for unprovoked event with OR of 3.79 (95% CI, 1.44–9.97) and East/Southeast Asians with higher risk for pulmonary embolism with OR of 0.60 (95% CI, 0.36–1.0) (Table 2). In comparison with Dutch controls, East/Southeast Asians controls had lower prevalence of factor V Leiden (6% and 1%, respectively) and prothrombin mutation (2% and 1%, respectively) but higher blood group non-O (54% and 62%, respectively). Risk of VT in East/Southeast Asians adjusted for age, sex, factor V Leiden and blood group non-O was 0.53 (95% CI, 0.35–0.80). Analysis of a panel of procoagulant, anticoagulant, profibrinolytic and genetic factors are underway and is expected to be available before the ASH conference of 2012. Conclusions: The risk of VT varies in different populations. The risk of VT in East/Southeast Asians was the lowest and was virtually unchanged after adjustment for several environmental and genetic known risk factors for VT. Disclosures: No relevant conflicts of interest to declare.

Retrospective Cohort of Unprovoked Venous Thromboembolism Patients: What Proportion Have Potent Thrombophilias Necessitating Indefinite Anticoagulants?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2318-2318
Author(s):  
Junghyun Park ◽  
Marc Rodger
Keyword(s):  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Gene Variant ◽  
Anticoagulation Management ◽  
Antithrombin Deficiency ◽  
S Deficiency ◽  
Prothrombin Gene ◽  
Thrombophilia Testing

Introduction Thrombophilia testing in unprovoked venous thromboembolism patients (VTE) is controversial. Common thrombophilias such as Factor V Leiden or prothrombin gene variant appear to not importantly increase the risk of VTE recurrence, and thus are not considered in anticoagulation management decisions. However, patients with potent thrombophilias such as antiphospholipid antibodies (APLA), antithrombin deficiency, protein C and S deficiency, and homozygous genetic thrombophilias or combined defects are at higher risk of recurrence and it is recommended that they receive long-term anticoagulation. If the proportion of patients with "potent" thrombophilia is high then thrombophilia testing should be conducted. We sought to determine the proportion of unprovoked VTE patients with "potent" thrombophilia. Methods All patients with managed in our oral anticoagulation management system in the period from 1998 to 2015 were potentially eligible for the study. Inclusion criteria were: 1) symptomatic, objectively confirmed VTE unprovoked proximal deep vein thrombosis or pulmonary embolism. Exclusion criteria were: 1) cancer or myeloproliferative disease at the time of VTE diagnosis; 2) no cast, surgery, trauma or immobilization (>3 days in bed 90% of waking hours) in the 90 days prior to diagnosis. We selected unprovoked VTE patients diagnosed between 2002 and 2010, as thrombophilia testing was relatively universal and available in our electronic system in that time frame (N=1344). We then selected a convenience sample of N=1165. The primary outcome measure was the proportion of patients with "potent" thrombophilia (potent= homozygous Factor V Leiden, homozygous Prothrombin gene variant, APLA, protein C, protein S or anti-thrombin deficiency or combined deficiencies). Results In 1165 patients with unprovoked VTE, complete screening was done in 470 patients (40.34%) and 976 (83.78%) had at least one thrombophilia test. Complete thrombophilia testing was defined as a screen including testing for factor V Leiden, prothrombin gene defect, APLA, anti-thrombin deficiency, protein C, and protein S. Potent thrombophilias were demonstrated in 103/1165 patients (8.84%; 95% CI, 7.34 to 10.61) (Table 2) in the total study population, and 103/976 (10.55%; 95% CI, 9.62-14.47) in patients with at least one thrombophilia test. Conclusion The proportion of unprovoked VTE patients with "potent" thrombophilia is high. Given a high proportion of "potent' thrombophilia patients who likely benefit from indefinite anticoagulation, complete thrombophilia testing appears warranted in patients with unprovoked VTE in whom anticoagulants maybe discontinued. Thrombophilia testing is warranted for a selected group of patients to detect high-risk thrombophilias that could impact anticoagulation management. Table 1. Thrombophilia screening Complete screening 470 (40.3%) No screening 189 (16.2%) At least one thrombophilia test 976 (83.8%) Table 2. Thrombophilia All patients (n=1165) Tested for individual thrombophilia % 95% CI % 95% CI FVL Heterozygous 162/1165 (13.9%) 12.0-16.0% 162/883 (18.4%) 15.9-21.0% FVL Homozygous 4/1165 (0.3%) 0.1-0.9% 4/883 (0.5%) 0.2-1.2% Prothrombin Heterozygous 63/1165 (5.4%) 4.3-6.9% 63/831 (7.6%) 6.0-9.6% Prothrombin Homozygous 1/1165 (0.0%) 0.0-0.5% 1/831 (0.1%) 0.0-0.7% Antithrombin deficiency 10/1165 (0.9%) 0.5-1.6% 10/815 (1.2%) 0.7-2.2% Protein C deficiency 18/1165 (1.6%) 1.0-2.4% 18/639 (2.8%) 1.8-4.4% Protein S deficiency 13/1165 (1.1%) 0.7-1.9% 13/635 (2.1%) 1.2-3.5% Lupus anticoagulant 24/1165 (2.1%) 1.4-3.1% 24/849 (2.8%) 1.9-4.2% Anticardiolipin IgM 16/1165 (1.4%) 0.9-2.2% 16/886 (1.8%) 1.1-2.9% Anticardiolipin IgG 20/1165 (1.7%) 1.1-2.6% 20/885 (2.2%) 1.5-3.5% β-2 microglobulin IgM 10/1165 (0.9%) 0.5-1.6% 10/333 (3.0%) 1.6-5.4% β-2 microglobulin IgG 8/1165 (0.7%) 0.4-1.4% 8/333 (2.4%) 1.2-4.7% Homocysteine 50/1165 (5.7%) 4.3-7.4% 50/668 (7.5%) 5.7-9.7% Factor VIII elevated 11/1165 (0.9%) 0.5-1.7% 11/646 (1.7%) 1.0-3.0% At least one or more of the above 331/1165 (28.4%) 25.9-31.1% 331/976 (33.9%) 31.0-36.9% Potent thrombophilia 103/1165 (8.8%) 7.34-10.6% 103/976 (10.6%) 9.6-14.5% Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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