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.

Prevalence and Financial Impact of Inappropriate Thrombophilia Testing in the Inpatient Hospital Setting: A Retrospective Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2330-2330 ◽  
Author(s):  
Eric Mou ◽  
Henry Kwang ◽  
Jason Hom ◽  
Lisa Shieh ◽  
Neera Ahuja ◽  
...  
Keyword(s):  
Protein C ◽  
Hospital Setting ◽  
Factor V Leiden ◽  
Protein S ◽  
Financial Impact ◽  
Prothrombin G20210a ◽  
Factor V ◽  
G20210a Mutation ◽  
Thrombophilia Testing ◽  
Test Ordering

Abstract Introduction Thrombophilia diagnostics are frequently ordered in the inpatient hospital setting, but their impact on patient care is often equivocal. Thrombophilia testing is expensive, and many results are subject to confounding when ordered in the context of an acute hospitalization. Furthermore, these tests are frequently lost to follow-up or wastefully repeated after the patient is discharged. In this study, we conducted a retrospective chart review to determine the rate and financial impact of inappropriate thrombophilia test ordering across all inpatient services at Stanford Hospital over one calendar year. Methods Utilizing data from our finance department, we obtained a list of all inpatient thrombophilia testing ordered at Stanford Hospital from June 2014 through June 2015. Thrombophilia testing was defined as ordering any of the following: factor V Leiden, prothrombin G20210A mutation, antithrombin III, lupus anticoagulant, beta-2 glycoprotein 1 IgM/IgG, anticardiolipin IgM/IgG, dilute Russell viper venom time, protein C or protein S levels, and JAK2 V167F mutation. The criteria for defining a test as 'inappropriate' were guided by utilizing major society guidelines and current evidence, placing an emphasis upon the ordered tests' clinical relevance and reliability in the context of the patient's admission diagnosis. The criteria were formulated by a senior hematologist with specific expertise in thrombophilia evaluations. Two internal medicine resident physician data reviewers independently evaluated the ordered tests to determine their appropriateness. To ensure consistency between reviewers, identical test datasets were evaluated and compared, demonstrating satisfactory concordance (>0.85). When the appropriateness of a test was unclear, joint evaluation was performed with the entirety of the study team to arrive at a final conclusion. Each test was linked to the ordering primary service. Charge data for each individual test was obtained through our financial department. Aggregate data were evaluated manually. Results In total, we reviewed 889 individual orders involving 167 patients across 20 ordering specialties. Of the 889 total orders, 331 were deemed inappropriate (37.2%), translating into a cumulative hospital charge of $152,923 (Figure 1). The tests most frequently inappropriately ordered included antithrombin III (94.4%), factor V Leiden (93.2%), protein C (92.7%), protein S (92.2%), and the prothrombin G20210A mutation (89.3%). Ordering individual tests in the setting of clearly provoked thrombotic events, during the acute thrombotic period, while patients were on concurrent anticoagulation, or when results failed to impact management represented the most common reasons testing was deemed inappropriate. Ordering practices were then stratified across the hospital's different primary services. Of services with the highest volume of test ordering, General Medicine (38.1%) and Neurology (34.9%) ordered testing inappropriately at the highest rates, while Rheumatology (12.8%) and Hematology (15.9%) ordered inappropriately at the lowest rates. Notably, the non-teaching services ordered testing inappropriately at one of the highest rates (62.2%), though their volume of ordering was lower in comparison with the aforementioned groups. Discussion Our results illustrate the high prevalence and significant financial impact of inappropriate or unnecessary thrombophilia testing conducted in the inpatient setting at our institution. Factors confounding test validity were frequently present at the time of ordering. Furthermore, stratifying ordering practices by specialty illustrated the differential rates of inappropriate ordering between services. Even when thrombophilia testing results fail to impact short term decision-making, misappropriated labeling of patients as 'thrombophilic' can have a lasting negative impact on future anticoagulation decisions. Combined with the high cost of errant ordering, these serve as a strong impetus to reduce the rate of thrombophilia testing during inpatient hospitalizations. Our baseline data demonstrate a need for institution-wide changes such as implementing electronic best practice advisories or potential ordering restrictions, and of tantamount importance, service-specific educational interventions in order to reduce unnecessary expenditures and improve patient care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1686-1692 ◽  
Author(s):  
Rory R. Koenen ◽  
Guido Tans ◽  
René van Oerle ◽  
Karly Hamulyák ◽  
Jan Rosing ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Healthy Population ◽  
Factor V ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractProtein S exhibits anticoagulant activity independent of activated protein C (APC). An automated factor Xa–based one-stage clotting assay was developed that enables quantification of the APC-independent activity of protein S in plasma from the ratio of clotting times (protein S ratio [pSR]) determined in the absence and presence of neutralizing antibodies against protein S. The pSR was 1.62 ± 0.16 (mean ± SD) in a healthy population (n = 60), independent of plasma levels of factors V, VIII, IX, and X; protein C; and antithrombin, and not affected by the presence of factor V Leiden. The pSR strongly correlates with the plasma level of protein S and is modulated by the plasma prothrombin concentration. In a group of 16 heterozygous protein S–deficient patients, the observed mean pSR (1.31 ± 0.09) was significantly lower than the mean pSR of the healthy population, as was the pSR of plasma from carriers of the prothrombin G20210A mutation (1.47 ± 0.21; n = 46). We propose that the decreased APC-independent anticoagulant activity of protein S in plasma with elevated prothrombin levels may contribute to the thrombotic risk associated with the prothrombin G20210A mutation.

scholarly journals Factor V Leiden, Prothrombin G20210A, and Protein C Mutation Frequency in Turkish Venous Thrombosis Patients

2007 ◽  
Vol 14 (4) ◽  
pp. 415-420 ◽  
Author(s):  
Julide Altinisik ◽  
Omer Ates ◽  
Turgut Ulutin ◽  
Mujgan Cengiz ◽  
Nur Buyru
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Cerebral Vein ◽  
Factor V ◽  
Pulmonary Emboli ◽  
Protein C Deficiency ◽  
Vein Thrombosis ◽  
G20210a Mutation

Several inherited polymorphisms are associated with risk of venous thrombosis, including mutation at codon 506 of the factor V gene, mutation at position 20210 of the prothrombin gene, and mutations in the protein C gene. In this study, genotyping for factor V, prothrombin, and protein C mutations was performed in 50 patients and 25 control subjects by polymerase chain reaction—based analysis. The prevalence of factor V and prothrombin mutations was not significantly different from that in the general population. Nine of the patients had heterozygous protein C mutation. There was a high prevalence of the mutated protein C allele in the pulmonary emboli group (42.8%). Protein C mutation incidence was higher in the pulmonary emboli group than in the deep vein thrombosis (8.33%) and cerebral vein thrombosis (16.1%) groups. These results indicate that patients with protein C deficiency have a greater risk of thrombosis than patients with factor V or prothrombin G20210A mutation.

Abstract 3371: Inherited Thrombophilias In Cryptogenic Stroke Patients Under 55 Years Old

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Patricia Martinez-Sanchez ◽  
Marta Martinez-Martinez ◽  
Blanca Fuentes ◽  
Maria Vicenta Cuesta ◽  
Gerardo Ruiz-Ares ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Protein C ◽  
Brain Infarction ◽  
Cryptogenic Stroke ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation

Background: inherited thrombophilias cause venous thrombotic events, however, their association with brain ischemia in adult patients is controversial. Our objective was to study the association between thrombophilia and cryptogenic stroke in patients under 55 years of age. Methods: prospective observational study of consecutive patients under 55 years of age who had had a brain ischemia (transient ischemic attack of brain infarction). The patients with cryptogenic brain ischemia were compared with the controls patients with brain ischemia of known cause. We examined the presence of thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations; deficiencies in protein S, protein C and antithrombin levels; resistance to activated protein C) and patent foramen ovale (PFO) in all patients. Results: Two hundred fifty-four patients were included, 108 with cryptogenic brain ischemia and 146 controls patients with brain ischemia of known cause. Patients with cryptogenic brain ischemia were younger (mean age 42.4 vs. 45.6 years old, P=0.002). The frequency of thrombophilia was significantly higher among patients with cryptogenic brain ischemia than those with brain ischemia of known cause (22.2% vs. 6.8%, P<0.001). Taking into account each thrombophilic disorder separately, prothrombin G20210A mutation and protein C or S deficiency were significantly higher in the cryptogenic brain ischemia group than in the known cause group (10.2% vs. 2.7% and 8.3% vs. 2.1%, respectively, P<0.05) while Factor V Leiden mutation was similar in both groups (4.6% vs. 2.7%, P NS). The frequency of PFO and PFO plus thrombophilia were higher among patients with cryptogenic brain ischemia (35.2% vs. 12.3% and 8.4% vs. 0%, respectively, P<0.001). The PFO (+) cryptogenic brain ischemia patients showed higher frequency of thrombophilia than the other patients (23.7% vs. 11.6%, P=0.043), in particular prothrombin G20210A mutation (15.8% vs. 4.2%, P=0.014). Multivariate analysis adjusted confounding factors showed than the presence of thrombophilia was independently associated with cryptogenic brain ischemia (OR 3.9; 95% CI, 1.69 - 8.97; P=0.001). Conclusion: there is an association between thrombophilia and cryptogenic brain ichemia in patients under 55 years old. These data suggest that systemic thrombophilic disorders are cause of thromboembolic phenomena in brain arteries

The Association Between Parameters of Erythrocytes Morphology and Thrombophilia-Related Mutations

2021 ◽  
Vol 16 ◽  
Author(s):  
Ozlem Oz ◽  
Ataman Gonel
Keyword(s):  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Cross Sectional ◽  
Factor V Leiden Mutation ◽  
Erythrocyte Morphology ◽  
Mthfr A1298c ◽  
G20210a Mutation ◽  
History Of

Background: Alterations in erythrocyte morphology parameters have been identified and associated with hematological disorders and other chronic and cardiovascular diseases. Erythrocytes are abundant in thrombus content. Their hemoglobin density and differences in the ratio of macrocytic and microcytic cells may be associated with hypercoagulopathy in those with a history of thrombosis. Objective: This cross-sectional study aimed to investigate the relationship between hemogram parameters and thrombophilia genetic parameters. Method: A total of 55 patients whose thrombophilia panel was reviewed due to the diagnosis of thrombosis were included in the study. %MIC, %MAC, %HPO, %HPR and all hemogram parameters were measured using Abbott Alinity HQ. Prothrombin G20210A, MTHFR C677T, MTHFR A1298C, Factor V Leiden G169A and PAI-1 4G/5G mutations were studied using Real Time-PCR. Results: The MTHFR C677T mutation was detected in 58.2% of the patients. The Factor V Leiden mutation was detected in 5.5% of the patients. The MTHFR A1298C mutation was detected in 58.2%, The PAI mutation was detected in 74.5%, and the Factor 13 mutation was detected in 29% of the patients. Prothrombin G20210A mutation was not detected in any of the patients. Red blood cell (RBC) and Hct values were higher in Factor 13 mutant group; the Hgb and Htc values were higher in the MTHFR C677T mutant group. Conclusion: The MTHFR C677T and Factor 13 mutations may be associated with high Hct and RBC, Hgb, and Htc values, respectively and coagulation tendency in patients with a history of thrombosis.

THROMBOPHILIC RISK FACTORS IN PATIENTS WITH CRANIAL AND SPINAL DURAL ARTERIOVENOUS FISTULAE

Neurosurgery ◽  
2008 ◽  
Vol 63 (4) ◽  
pp. 693-699 ◽  
Author(s):  
Rüediger Gerlach ◽  
Martina Boehm-Weigert ◽  
Joachim Berkefeld ◽  
Judith Duis ◽  
Andreas Raabe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Arteriovenous Fistulae ◽  
Factor V Leiden Mutation ◽  
Exact Test ◽  
G20210a Mutation ◽  
Cardiolipin Antibodies ◽  
Prothrombin Gene

ABSTRACT OBJECTIVE Numerous studies have reported the technical aspects and results of surgical and/or endovascular treatment of cranial dural arteriovenous fistulae (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have addressed the question of thrombophilic conditions, which may be relevant as pathogenetic factors or can increase the risk for venous thromboembolic events. Therefore, the objective of this study is to compare thrombophilic risk factors in patients with cDAVF and sDAVF with no history of trauma. METHODS A total of 43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood samples were analyzed for G20210A mutation of the prothrombin gene and factor V Leiden mutation. In all patients, prothrombin time, international normalized ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity, and tissue factor pathway inhibitor were determined. Screening was performed for the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS The prevalence of G20210A mutation of the prothrombin gene was significantly higher in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P &lt; 0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No significant difference was found for other parameters, except for fibrinogen, but decreased protein C activity was more frequent in patients with cDAVF compared with patients with sDAVF (4 versus 1). Decreased protein S activity was encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1 patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION In both groups of patients with dural arteriovenous fistulae, genetic thrombophilic abnormalities occurred in a higher percentage than in the general population. The differences of the genetic abnormalities may be involved in different pathophysiological mechanism(s) in the development of these distinct neurovascular entities.

scholarly journals Utility of current thrombophilia screening in young patients with stroke and TIA

2018 ◽  
Vol 3 (4) ◽  
pp. 231-236 ◽  
Author(s):  
Vafa Alakbarzade ◽  
Alice Taylor ◽  
Marie Scully ◽  
Robert Simister ◽  
Arvind Chandratheva
Keyword(s):  
Protein C ◽  
Young Patients ◽  
Factor V Leiden ◽  
Anticardiolipin Antibody ◽  
Antiphospholipid Antibody ◽  
G20210a Mutation ◽  
Thrombophilia Screening ◽  
Thrombophilia Testing ◽  
Clinical Records ◽  
The Impact

IntroductionApproximately 40% of strokes in young adults are cryptogenic. The diagnostic yield of thrombophilia screening remains controversial. We aimed to determine utility of current thrombophilia testing for young patients with stroke and transient ischaemic attack (TIA).MethodsWe present a retrospective review of all patients with stroke and TIA ≤60 years presenting to University College London Hospital stroke unit and daily TIA clinic from 1 January 2015 to 1 August 2016. Consecutive clinical records and thrombophilia tests, including factor V Leiden (FVL), prothrombin G20210A mutation (PGM), antiphospholipid antibody (APA), and protein S, C and antithrombin (AT) levels, were reviewed.ResultsThe mean age of 628 patients with stroke and TIA was 49.1 years (SD 9.2). Thrombophilia testing was performed in 360 (57%) patients, including 171 with stroke and 189 with TIA. Positive tests were found in 50 (14%) patients, of whom 24 patients were <50 years. Positive results were found in 36 (10%) with acute ischaemic stroke, 4 (1%) with haemorrhagic stroke and 10 (3%) with TIA. Thirteen patients (4%) had homozygous/heterozygous FVL or PGM, and 27 (7.5%) had positive APA (anticardiolipin antibody, anti-β2 glycoprotein antibody or lupus anticoagulant). Of 27 (7.5%) patients with protein C, S or AT deficiency, 10 (2.8%) had primary deficiency, presumed hereditary with other secondary causes excluded. 9% of patients with protein C, S or AT and 27% with APA were followed by confirmatory testing.ConclusionThrombophilia testing was positive in only 14% of cases overall. Thrombophilia mutations and protein C, S or AT abnormalities were found rarely and were very uncommon in patients with TIA. Follow-up of abnormal results was generally poor for all groups, which further limited the impact of the thrombophilia testing policy.

The relationship of a Prothrombin G20210A mutation or a factor V Leiden mutation and on-aspirin platelet (re-)activity

2020 ◽  
Vol 19 ◽  
pp. 127-130
Author(s):  
Jeske J.K. van Diemen ◽  
Jeske M. Bij de Weg ◽  
Arda Arduç ◽  
Olivier Veraart ◽  
David Mager ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Relationship Of ◽  
The Relationship
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