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

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.

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Thrombophilia Testing Practices: The Mayo Clinic Experience

Blood ◽

10.1182/blood-2020-141633 ◽

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.

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Analysis of Ordering Practice of Thrombophilia Testing at a Single Large Teaching Hospital

Blood ◽

10.1182/blood.v116.21.3188.3188 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3188-3188

Author(s):

Judy Peih-Ying Tsai ◽

Evelyn O. Taiwo ◽

Natalie Cervantes ◽

Guadalupe Jasso ◽

Eugene P. Frenkel ◽

...

Keyword(s):

Teaching Hospital ◽

Protein C ◽

Conflicts Of Interest ◽

Thrombotic Event ◽

Young Patients ◽

Factor V Leiden ◽

Repeat Testing ◽

Large Teaching Hospital ◽

Thrombophilia Testing ◽

Abnormal Results

Abstract Abstract 3188 Background: Thrombophilia describes either an inherited or acquired predisposition to thrombosis. There are no well defined guidelines for thrombophilia testing. Thus, testing after a single episode of thrombosis in unselected patients has become a common yet often inappropriate practice. An ideal work-up includes: antithrombin (AT) activity, protein C (PC) activity, protein S (PS) activity and antigen (total and free), activated protein C resistance (APC-R), factor V Leiden (FVL) if the APC-R is abnormal, prothrombin gene mutation (PGM), factor VIII (FVIII) and antiphospholipid antibodies (aPL) (lupus anticoagulant, anti-cardiolipin, and anti-β2 glycoprotein I, IgG, M and A). Objective: The purpose of this retrospective observational study was to characterize the pattern of such thrombophilia testing at a single large teaching hospital. Methods: All laboratory requests for thrombophilia testing in October and November of 2009 were included in this retrospective evaluation. The tests included were PC, PS, AT, FVIII, FVL, PGM, homocysteine and aPL. Clinical information was extracted from electronic medical records and analyzed for indication and timing of testing, completeness of the tests, whether the tests were performed on anticoagulation, and whether an abnormal test result was repeated to confirm the diagnosis. Results: The study consisted of 100 consecutive patients (69 females, 68 less than 50 years of age). 70 patients had a known event prior to thrombophilia testing, 34 had an inappropriate indication [provoked thrombosis, 1–2 pregnancy losses, pre-eclampsia] (Table 1). 88% of the patients who were tested had an incomplete workup for the indication. Of the 70 patients who had an identifiable event prior to testing for thrombophilia, 41 patients were tested at the time of the event (<1 week) when natural anticoagulants could be consumed and results will not alter the management. Of all 100 patients, 30 were tested after anticoagulant therapy was initiated, which is known to affect results of several laboratory tests listed above; 8 of these patients had abnormal results and only 2 had repeat testing to confirm. 53% of all patients in the cohort tested positive; 20 of which underwent repeat testing, with half showing normalization (Table 2). Of the 36 patients tested for the appropriate indications [unprovoked thrombosis, or ≥3 pregnancy losses], only 3 had complete testing; 20 were tested at the time of the acute event, and 13 were tested on anticoagulant. Conclusions: Only 36% of patients had thrombophilia testing done for the appropriate thrombotic or obstetric indications. 10% had confirmed positive tests, while 33% had an abnormal result that remained unconfirmed. Thrombophilia testing at our center deviates markedly from what would be considered appropriate in terms of indication, completeness, timing from thrombotic event, testing off anticoagulation and necessity of repeat testing. Ideally testing should be performed on young patients with unprovoked events, off anticoagulation to allow factor levels to return to baseline, and repeated for all abnormal results. Building on these observations, this study aims to devise standards of practice to minimize cost and prevent misdiagnosis in thrombophilic patients. Disclosures: No relevant conflicts of interest to declare.

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Acquired and Inherited Thrombophilia Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension: Value of Testing in an Academic Health Center

Blood ◽

10.1182/blood-2021-148655 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4256-4256

Author(s):

Bharath Ram S ◽

Monisha Harimadhavan ◽

Shilpa Prabhu ◽

Karthick R G ◽

Devi Prasad Shetty ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Protein C ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Factor V Leiden ◽

Anticardiolipin Antibody ◽

Mthfr Gene ◽

Factor V ◽

Inherited Thrombophilia ◽

Glycoprotein I ◽

Thrombophilia Testing

Abstract Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is classed as group 4 in the present classification of pulmonary hypertension. The pathophysiology of CTEPH is complex, mainly is a consequence of prior acute pulmonary embolism with failure of thrombi to resolve and the recent recognition of added small vessel changes which impacts long-term outcomes even after surgical management. The role of thrombophilia testing in this condition has been debated. Hence, we here analyzed the utility of thrombophilia testing in CTEPH from a center in a developing country. Methods This is a single institution (Narayana Health City, Bangalore); retrospective study including patients ≥ 18 years of age who underwent thrombophilia workup in a diagnosis of CTEPH from January 2019 till July 2021. Tests done to evaluate thrombophilia included factor V Leiden; prothrombin F20210A mutation; MTHFR gene mutation; Protein C, S, and antithrombin deficiency; lupus anticoagulant, anti-beta2 glycoprotein I (IgM and IgG) and anticardiolipin antibody (IgM and IgG); hyperhomocysteinemia and anti-nuclear antibody testing (ANA-IF). The study was approved by the ethics committee of the institute and was carried out in accordance with the principles of the declaration of Helsinki. Results and discussion The study included 56 patients with a median age of 37 years (range 23-50), and 36 (64%) were males. Patients with recurrent venous thrombosis included 37 (66%), with the majority having thrombosis at 2 sites (53%; 22 patients with associated deep vein thrombosis). A family history of thrombosis was present in 4 patients. The majority of patients received vitamin K antagonists (76%), with the rest receiving direct oral anticoagulants (DOAC). Among the tests sent for acquired thrombophilia, ANA-IF and antiphospholipid antibody (APLA) were most frequently evaluated (94%). ANA-IF and APLA tests were positive in 5.6% and 30.1%, respectively. Among the APLA tests, Anti-beta2 glycoprotein I (IgM or IgG) was the most commonly detected antibody (13/46), followed by anticardiolipin antibody (IgG or IgM) (9/43) and lupus anticoagulant (7/40). Double and triple positive APLA were present in 3 and 4 patients, respectively. Homocysteine levels were high in 93.7% though only 16 patients were tested in this cohort. Among the tests for inherited thrombophilia, genetic tests (factor V Leiden, prothrombin F20210A mutation, and MTHFR gene mutation) were tested in only ~50%. Twenty-three percent were positive for heterozygous MTHFR followed by MTHFR compound heterozygous (10%) and heterozygous factor V Leiden heterozygous (10%). Antithrombin III, protein C, and S were tested in ~30% of patients. Antithrombin III was low in only 1 patient, with protein C and S assays being normal in all the patients. The cost analysis was calculated, showed a median of $364 (₹ 27,055) was spent per person on thrombophilia workup. The median cost incurred per patient for inherited thrombophilia workup was $232 (₹ 17,300) and for acquired thrombophilia was $132 (₹ 9814), respectively. Conclusion This single-institution study on thrombophilia workup in CTEPH patients reveals that APLA was the most commonly performed test with high positivity rates of 30.1%. Among the inherited thrombophilia, the positivity rate of MTHFR mutation was highest (33.3%), with other tests having a low positivity rate (0-10%). Hence, we would recommend APLA testing in all patients with CTEPH considering its high positivity and clinical utility. Testing for other thrombophilias should be pursued judiciously especially in economically restrictive settings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v128.22.2330.2330 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2330-2330 ◽

Cited By ~ 1

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.

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Heritable and Acquired Thrombophilias in Clinical Practice

10.2310/im.1649 ◽

2019 ◽

Author(s):

Hanny Al-Samkari ◽

Nathan T. Connell

Keyword(s):

Clinical Practice ◽

Venous Thromboembolism ◽

Gene Mutation ◽

Protein C ◽

Factor V Leiden ◽

Protein S ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Factor V ◽

Thrombophilia Testing

Thrombosis is common in clinical practice. Venous thromboembolism in particular raises questions of a possible underlying hereditary or acquired thrombophilic state. Despite considerable data describing the impact of various thrombophilic states on risks of initial and recurrent thromboembolic events, thrombophilia testing is not standardized. An understanding of the utility and pitfalls of clinical thrombophilia testing is necessary to employ this testing properly. When utilized appropriately, thrombophilia testing can be vital in informing an individual patient’s thrombosis risk and pursuing optimal anticoagulant management. Hereditary thrombophilia testing involves investigation for factor V Leiden, the prothrombin G202010A gene mutation, and deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. Assessment for acquired thrombophilias is perhaps even more important, recognizing the possibility for myeloproliferative neoplasms, antiphospholipid antibody syndrome, occult malignancy and other important acquired thrombotic predispositions. Timing of thrombophilia testing in relation to anticoagulation, acute thrombosis, and use of hormonal agents or pregnancy is critical to ensure accurate diagnosis. This review describes each of the most important hereditary and acquired thrombophilias, explains their relationship to venous and arterial thrombosis, delineates evidence-based indications for thrombophilia testing, identifies potential testing pitfalls, and synthesizes the key points in outlining algorithms for thrombophilia testing in clinical practice. This review contains 4 figures, 4 tables, and 48 references. Key words: thrombophilia, venous thromboembolism, pulmonary embolus, deep vein thrombosis, factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome, hypercoagulability of malignancy

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Heritable and Acquired Thrombophilias in Clinical Practice

10.2310/fm.1649 ◽

2019 ◽

Author(s):

Hanny Al-Samkari ◽

Nathan T. Connell

Keyword(s):

Clinical Practice ◽

Venous Thromboembolism ◽

Gene Mutation ◽

Protein C ◽

Factor V Leiden ◽

Protein S ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Factor V ◽

Thrombophilia Testing

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Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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

Blood ◽

10.1182/blood-2003-02-0620 ◽

2003 ◽

Vol 102 (5) ◽

pp. 1686-1692 ◽

Cited By ~ 16

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.

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

TH Open ◽

10.1055/s-0040-1714334 ◽

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.

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

Neurosurgery ◽

10.1227/01.neu.0000325730.77263.7e ◽

2008 ◽

Vol 63 (4) ◽

pp. 693-699 ◽

Cited By ~ 18

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 < 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.

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