Testing For Inherited Thrombophilia Research Articles

Contribution of anti-β2 glycoprotein1 IgA testing in the diagnosis of seronegative-APS for patients with cerebral thrombosis

Seronegative antiphospholipid syndrome has been suggested for patients with clinical manifestations highly suggestive of APS but persistently negative criteria-aPLs. Evidence gathered over the last years of research in thrombosis reported the pathogenic significance of non-criteria aPLs, among them IgA isotype. However, their role in the occurrence of neurological thrombosis, has not yet been studied. In this article, we aim to: (1) determine the prevalence of aβ2GP1 IgA in cerebral thrombosis, (2) study the association and (3) assess the diagnostic value of aβ2GP1. This study enrolled 70 patients with cerebral thrombosis without underlying autoimmune disease referred for thrombophilia assessment and 165 healthy controls. In addition to a coagulation screen and inherited thrombophilia testing, patients and controls were tested for criteria (LA; aβ2GP1; aCL IgM/IgG) and non-criteria aPLs (aβ2GP1 IgA; aCL IgA; aPS-PT; IgM/IgG). The overall aβ2GP1 IgA prevalence in patients was 61.4 % (43/70) mostly isolated in 50 % (35/70) while 50 % were positive for criteria-aPLs. aβ2GP1 IgA were the most prevalent aPLs in cerebral venous thrombosis compared with stroke (92.3 % vs 54.4 %). A significative relationship between aβ2GP1 IgA and the occurrence of CVT and stroke has been established (x2 = 6.9, p = 0.008; x2 = 4.03, p = 0.045). There was a high specificity of aβ2GP1 IgA testing for stroke (79 %) and CVT (100 %) despite a lower sensitivity (73 %; 52 %, respectively). The aβ2GP1 IgA testing improved considerably (50 %) the diagnosis of patients with cerebral thrombosis and negative criteria-aPLs, who may benefit from an adapted therapeutic care. Laboratory consensus criteria might consider aβ2GP1 IgA and set up a sequential approach improving APS diagnosis.

Low value of inherited thrombophilia testing among patients with stroke or transient ischemic attack: A three-year retrospective study

Background/PurposeInherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and rarely changes clinical management. We evaluated ordering patterns and results of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism. MethodsWe retrospectively analyzed patients admitted for acute ischemic stroke or TIA between January 1st, 2019 and December 31st, 2021 at Thomas Jefferson University Hospitals in Philadelphia, PA and who underwent inherited thrombophilia testing during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management. ResultsAmong 2108 patients admitted for acute ischemic stroke or TIA (including branch and central retinal artery occlusions) during the study period, the study included 249 patients (median age 49.0 years, 50.2% female) who underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 42.2% of patients had at least one abnormal test, and among the 1035 tests ordered, 14.3% resulted abnormal. However, 28% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. There was no significant difference in the likelihood of a positive test among patients without stroke risk factors vs those with risk factors (47.1% vs 40.9%, P = .428), nor any significant difference between those under vs over age 50 years (45.7% vs 38.3%, P = .237). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $468,588 USD. ConclusionsInherited thrombophilia testing in the hospital immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of likely false positive results and was expensive. Positive results did not change clinical management in a single case.

A Multidisciplinary Quality Improvement Project to Improve Appropriate Inherited Thrombophilia Testing at VA Connecticut

Background Many guidelines and expert opinions do not recommend inherited thrombophilia testing in unselected patients with venous thromboembolism (VTE), and per American Society of Hematology Choosing Wisely Recommendations, inherited thrombophilia testing is not recommended in patients with venous thromboembolism occurring in the setting of major transient risk factors. Furthermore, non-hematologists may lack knowledge on the effect of direct oral anticoagulants on these assays. From 2019 to 2021, 75% of inherited thrombophilia testing (protein C, S and antithrombin deficiencies and Factor V Leiden and prothrombin mutations) at VA Connecticut were ordered by non-hematologists. Of these orders, 55% of tests were ordered by primary care clinicians, 29% by inpatient teams, and the remainder by non-hematology specialists. Approximately 10% of testing by non-hematologists had abnormal results, generating further hematology consults and workup. Given that testing has limited clinical utility and can result in unnecessary downstream healthcare use, there is a need to improve guideline concordant and appropriate thrombophilia testing by non-hematologists. Methods The aim of this multidisciplinary quality improvement project was to decrease the number of inherited thrombophilia tests ordered by non-hematologists at VA Connecticut by 25% six months after our intervention implementation. Quality Improvement (QI) principles were used to identify root causes, which included complexity of and confusion over appropriate patient selection for testing, a lack of awareness of potential false positives with active anticoagulant use, limitations of our electronic medical record system (EMR) to provide clinical decision support tools to triage testing or provide education, and more. After multidisciplinary stakeholder engagement and feedback from hematology, internal medicine, laboratory medicine, and clinical informatics, we established a best practice alert (BPA) for inpatient and outpatient inherited thrombophilia testing at the time of order entry. Our BPA notified the ordering clinician that inherited thrombophilia testing rarely impacts the choice or duration of anticoagulation and is not recommended for most patients. The BPA recommended that as an alternative, clinicians can consider a hematology electronic consult (e-consult) for guidance and education regarding appropriate patient selection for testing. Data was collected from our EMR seven months after intervention initiation and analyzed via Excel 365. A control chart was used to assess the outcome measure, which was the number of orders for inherited thrombophilia testing by non-hematology clinicians per month. Our balancing measure was the number of hematology e-consults for inherited thrombophilia per month. Institutional pricing was used to determine costs associated with testing and potential cost savings. Results After our BPA implementation in January 2022, the mean number of monthly inherited thrombophilia tests from January to July 2022 decreased to 7.6 tests from 13.3 tests in 2021. All 7 monthly test order numbers post-implementation were below the mean, consistent with a potential trend towards a special cause variation shift. Inpatient testing decreased from 40 total tests in 2021 to 7 tests since implementation. The average cost of testing per month decreased from $653 to $366 with an estimated $2004 saved after intervention implementation. The mean number of hematology e-consults for inherited thrombophilia related questions increased to 3.4 consults per month during the first five months of the intervention period from 2.5 consults per month in 2021. Conclusion A best practice alert in the EMR reminding clinicians about the limited role of inherited thrombophilia testing in unselected patients and the option for hematology e-consult for further specialist guidance was associated with a trend towards reduced inherited thrombophilia testing. Furthermore, there were decreased costs associated with testing without any substantial increase in workload for the hematology service. The BPA remains in place, and data collection and analysis are ongoing. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Value of Inpatient Inherited Thrombophilia Testing Following Acute VTE: A 3-Year Retrospective Study

BACKGROUND: Inherited thrombophilia testing following venous thromboembolism (VTE) is of limited utility and, performed in the setting of an acute thrombotic episode, is especially unreliable. Studies suggest that inpatient thrombophilia workups, often performed in the context of acute VTE or stroke, lead to high rates of false positives and can result in inappropriate long-term management decisions. Therefore, various professional societies advise against such testing, especially in acute care settings. These include Choosing Wisely recommendations from the American Society of Hematology, who recommend against routine testing following first episode of provoked VTE, and the American Society for Clinical Pathology, who advise against ordering these tests during an active clotting event. However, these studies continue to be ordered regularly, increasing the overall cost of health care with limited clinical benefit. METHODS: We carried out a retrospective chart review of all inpatient inherited thrombophilia tests ordered between January 1st, 2019 and December 31st, 2021 at Thomas Jefferson University Hospitals, including its 3 primary hospitals in Philadelphia, PA. The goal was to determine indications for testing, rate of positivity, and whether positive results changed patients’ clinical management. Tests included in the study were for the following conditions: Factor V Leiden (FVL); prothrombin G20210A variant (PTG20210A); Protein C, S, and antithrombin deficiency; hyperhomocysteinemia; and plasminogen activator inhibitor-1 (PAI-1) elevation. The study included 152 patients, among whom 574 unique tests were ordered. Tests sent for non-thrombotic indications or in patients with a known factor deficiency were excluded. RESULTS: Patient demographics, clinical presentations, and VTE risk factors are summarized in Table 1. Median age of the patients was 49 years (IQR 34-62) and 53.9% were under age 50. 93 patients (61.2%) were female. VTE was associated with a major transient risk factor or cancer in 44.7% of patients. Conditions for which testing was ordered included FVL (24.7%), PTG20210A (20.4%) Protein S deficiency (16.5%), Protein C deficiency (14.8%), antithrombin deficiency (13.0%), hyperhomocysteinemia (10.3%), and PAI-1 elevation (0.2%). Overall, 81.9% of tests were normal. Among unique tests, MTHFR analysis was most frequently abnormal (71.4% of ordered tests), followed by antithrombin (44.0%), Protein C antigen (27.3%), total Protein S (26.7%), Protein C function (25.7%), and free protein S (20.0%). Certain tests, including antithrombin activity, Protein C antigen and function, and total Protein S, have reference ranges in our lab that start well above 50%, so results that fell below normal but >60% were termed "borderline positive” and considered to be likely false positives. Among individual patients, 62/152 (40.8%) had at least one abnormal result and 47/152 (30.9%) had at least one positive result not considered borderline. There was no significant difference in rate of having at least one non-borderline positive result between patients with unprovoked VTE (27/84, 32.1%) and those with a major transient risk factor, estrogen use/pregnancy, or cancer (20/68, 29.4%; χ2, P=.717). There was also no difference in positive test rate between patients age < 50 years (24/82, 29.3%) and those ≥ 50 years (23/70, 32.9%; P=.633) (Figure 1). All charts were reviewed for inpatient and outpatient documentation to determine short- and long-term clinical decision-making. In 2/152 (1.3%) patients, documentation supported a definitive change in management because of a positive thrombophilia test result. These included a 20-year-old woman with large PE while on a combined oral contraceptive and a 33-year-old man with provoked DVT following severe spinal cord injury (resulting in tetraplegia) who were continued on long-term anticoagulation for Protein S deficiency and double heterozygosity for FVL and PTG20210A, respectively. Based on query of the hospital chargemaster, all tests during the study period totaled $264,913 in charges. CONCLUSION: Our single-institution study found that following acute VTE, inpatient testing for inherited thrombophilias was frequently done in patients with provoked events and resulted in many abnormal tests likely comprising false positives, rarely changed clinical management, and was associated with high costs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract TMP59: Low Value Of Inherited Thrombophilia Testing Among Patients With Stroke Or Transient Ischemic Attack: A Single-institution Study

Background/Purpose: Inherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and in many cases does not change clinical management. We sought to determine the value of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism. Methods: We retrospectively analyzed a database comprising patients who were admitted for acute ischemic stroke or TIA in 2019 at Thomas Jefferson University Hospitals in Philadelphia, PA and had inherited thrombophilia testing performed during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management. Results: The study included 102 patients (median age 49.0 years, 53.9% female) who presented with acute ischemic stroke or TIA (including branch and central retinal artery occlusions) and underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 406 tests were ordered, among which 14.0% resulted abnormal, and 41.2% of patients had at least one abnormal test. Patients without stroke risk factors were more likely to have an abnormal result (60.0% vs 35.1%, P = .028). However, 40% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. Considering only definitively positive results, there was no significant difference in the likelihood of a positive test in patients with vs without stroke risk factors (32.0% vs 26.0%, P = .557) or those under vs over age 50 years (30.2% vs 24.5%, P = .519). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $182,994 USD. Conclusions: Inpatient inherited thrombophilia testing immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of false positive results and was expensive. Positive results did not change clinical management in a single case.

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

IntroductionChronic 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.MethodsThis 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 discussionThe 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.ConclusionThis 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. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Referral for Thrombophilia Testing in an Obstetric Patient Population: A Tertiary Centre Experience

Introduction:Thrombophilias augment the risk of pregnancy related morbidity, increasing the likelihood of adverse events such as fetal loss [1,2]. Current guidelines recommend women be tested for antiphospholipid antibodies when they present with recurrent miscarriage (3 or more consecutive pregnancy losses before 24 weeks) or with a late miscarriage (loss between 12-24 weeks) [1]. Inherited thrombophilia testing (including factor V Leiden, prothrombin gene mutation and protein S) is also recommended for women with 2nd trimester miscarriage [1]. Controversy exists around the benefit of universal thrombophilia screening given the low relative increase in risk of pregnancy events and the lack of evidence surrounding interventions such as low molecular weight heparin (LMWH) and aspirin in most thrombophilias [2,3].Our aim was to evaluate our own testing for thrombophilia in pregnancy related events. We aimed to assess the frequency of positive results and evaluate whether testing resulted in a change in management for our cohort of women.Methods:Data was collected retrospectively on 151 thrombophilia screens requested for obstetric reasons from July 2016 to July 2017 at Waikato Hospital. The tests comprised antiphospholipid antibodies (APL) including lupus anticoagulant (LA), factor V Leiden (FVL), protein C and S levels, antithrombin III (ATIII) and prothrombin (PT) gene mutations. Data pertaining to request information, outcome of current and previous results were included. Cost analysis was done using NZ $300 (US $223) for a full thrombophilia screen and NZ $30 (US $22) for protein S alone. GraphPad Prism 7 software was used for all data interpretation.Results:The mean patient age was 31 years (range 18-48 years). The commonest reason for referral for testing was recurrent miscarriage (49/151) (Figure 1) and the majority of requests were from the obstetrics department (79/151) (Figure 2).83% (126/151) of tests requested were for a full thrombophilia screen; the remainder (25/151) were for single tests or a combination. The majority were being tested for the first time; 16.5% (25/151) had previous testing done. Of those with previous tests 52% (13/25) had no abnormality found; the others had low protein S levels or ATIII deficiency, or both.With the current test, almost two thirds of patients (62%, 94/151) had no abnormality found. Of the others, low protein S levels made up the majority of positive tests (26/57) (Figure 3). Of these 4/26 tests were repeated with 1 ongoing low result representing a likely true protein S deficiency. The laboratory cost of negative tests was estimated to be NZ $28,200 (US $20,992); while the cost of testing for protein S, including repeat testing due to low levels likely associated with pregnancy, was estimated at NZ $879 (US $648).Results that could potentially change management (APL antibodies, presence of VTE with positive inherited thrombophilia result) were few (6/151).Conclusion:In our tertiary centre, the majority of thrombophilia testing done for obstetric reasons over a 12 month period was negative. Most positive results (low protein S) were likely attributable to recent pregnancy, with a lack of repeat testing undertaken. There was a potential change in management for only 6 patients. Our results are in line with the literature which shows a scarcity of evidence supporting thrombophilia screens in pregnancy related morbidity. These tests are not only costly but for the majority provide no clinical benefit. Our next step is to disseminate these results locally and we aim to educate our colleagues on the utility of thrombophilia testing in pregnancy related events and when it is clinically helpful. We await with interest the results of ongoing randomised controlled trials assessing the role of LMWH and aspirin in thrombophilia in pregnancy.[1] Royal College of Obstetricians and Gynaecologists (RCOG) Green-top guideline No 7. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. April 2011.[2] Baglin T, Gray E, Graves M, et al . Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010; 149(2): 209-20[3] de Jong PG, Kaandorp S, Di NM, et al . Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev . 2014;7:CD004734 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Predicting Thrombosis Recurrence in Children: The Role of Thrombophilia Testing

Background: The role of inherited thrombophilia testing in predicting a recurrence of deep vein thrombosis (DVT) after an incident of the first DVT in children remains unclear Objectives: To investigate the association between inherited thrombophilia and DVT recurrence. Design/Method: We conducted a retrospective regional study of all consecutive ICD10 codes of venous thromboembolism (VTE) in children over 15 years (January 1, 2000, to December 31, 2015) in a regional catchment area of southern Sweden using an electronic diagnosis registry. Eligible subjects were children aged 1-18 years presenting with DVT diagnosed with imaging and having undergone complete inherited thrombophilia workup after the first DVT event. Of the 174 patients diagnosed with DVTs, 139 were eligible for inclusion. Data regarding subject demographics and medical history, location of DVT and imaging method, coagulation studies at primary investigation including at least plasma concentrations of protein C, protein S, antithrombin, resistance to activated protein C, and the genotypes FVG1691A and FIIG20210A. Also, plasma values for coagulation factors, VIII and XI, D-dimer, INR, and cardiolipin antibodies, were analyzed. Results: A total of 139 patients had inherited thrombophilia workup after the incident of the first DVT. Inherited thrombophilia was found in 30 % of patients, the prevalence of minor thrombophilia among these 139 patients was 23 % (n = 32), whereas major thrombophilia accounted for 7 % (n = 10) of abnormal results. Anticoagulants as treatment were administered in 92 % of the first DVT. The majority of the cohort treated with anticoagulation therapy for 12 weeks. Patients with minor inherited thrombophilia treated for at least 24 weeks, whereas the patients with major inherited thrombophilia were continued on anticoagulation therapy for the long term. The incidence rate of recurrent thromboembolic events was 6.5 % (n = 9) of patients after their incident of the first thrombotic event. Recurrent thrombosis in patients with spontaneous DVT and proven inherited thrombophilia found in only 1 %. Conclusion: Inherited thrombophilia was not predictive of recurrent DVT among our cohort patients. Our findings suggest that Inherited thrombophilia testing may not predict risk for the recurrence of DVT, although it may help for adjustment of the duration of the anticoagulation therapy. Figure Disclosures No relevant conflicts of interest to declare.

Inpatient Inherited Thrombophilia Testing at an Academic Health Center: High Cost, Low Value

Testing for inherited thrombophilias following venous and arterial thrombotic events remains controversial. These conditions are associated with an increased risk of initial and recurrent venous thromboembolism (VTE) and, in some cases, arterial events such as strokes and myocardial infarctions. However, testing for them in unselected patients with thrombotic events is not associated with lower recurrence rates, and other risk factors may be more clinically useful for determining whether and for how long to anticoagulate. Further, these tests are expensive and in the setting of an acute thrombosis, many may result in false positives. As such, the American Society of Hematology and American Society for Clinical Pathology recommended in their Choosing Wisely campaigns to not test for inherited thrombophilias after a provoked VTE or in the acute setting, respectively. The AHA/ASA determined that the utility of thrombophilia screening in stroke patients was unknown in its 2014 guidelines. This single institution, retrospective study reviewed all instances of inpatient inherited thrombophilia testing in 2019 at Thomas Jefferson University Hospitals, including its 3 primary hospitals in Philadelphia, PA. Tests included those to evaluate the following conditions: Factor V Leiden (FVL); prothrombin G20210A mutation; Protein C, S, and antithrombin deficiency; hyperhomocysteinemia; and plasminogen activator inhibitor-1 (PAI-1) elevation. The study included 231 patients, among whom a total of 872 tests were sent. Tests sent for non-thrombotic indications, such as homocysteine for B12 or folate deficiency, or in patients with a known deficiency were excluded. Median age of the patients was 50.8 years (IQR 38-63) and 129 (55.8%) were female. Diagnoses for which testing was sent and predisposing risk factors are summarized in Table 1. Arterial events were most common (54.5%), followed by VTE (26.0%). 14.7% of patients had no documented thrombosis, ischemic event, or pregnancy complication. Arterial events primarily included stroke/TIA (74.6%), and 76.7% of patients had at least one documented risk factor for these conditions. VTE was associated with a major transient risk factor or cancer in 32.8% of patients. Among all inherited thrombophilia tests sent, the most common were for the evaluation of FVL (20.9%), hyperhomocysteinemia (17.0%), Protein S deficiency (16.5%), prothrombin G20210A mutation (15.1%), Protein C deficiency (14.8%), and antithrombin deficiency (14.3%) (Table 2). Overall, 83.3% of tests were normal. Tests that were most frequently abnormal included MTHFR mutation (76.0%), antithrombin (36.0%), Protein C antigen (40.0%), PAI-1 (33.3%), and total Protein S (22.2%). Given our lab's references ranges, values for antithrombin, and Protein C antigen and function, and total Protein S that fell below normal but &amp;gt;60% were deemed "borderline positive." The likelihood of an abnormal result was not significantly different in cases of unprovoked VTE or arterial event without a risk factor, compared to those with risk factors. All charts were reviewed, including both inpatient and outpatient notes, to determine short- and long-term clinical decision-making. Importantly, among all positive tests, clinical management was not definitively changed in response to the test result in a single case. In two patients, it was unclear whether anticoagulation was continued based upon the test result. Both patients had heterozygous FVL mutations. Most positive results were deemed by the treating clinicians to be due to the acute thrombotic episode. Last, the hospital's chargemaster was queried, showing that these tests were associated with $398,912 in total charges. This single-institution retrospective study of inpatient inherited thrombophilia tests reveals the limited benefit of thrombophilia testing in the acute setting. Arterial ischemic/thrombotic events were the most common indication for testing, yet over 3/4 of patients had at least one risk factor. Nearly a third of patients with VTE had a major provoking factor, patients in whom thrombophilia testing is not recommended. While nearly 17% of tests returned abnormal, not one was associated with a clear change in clinical management. Despite limited clinical utility, costs of these tests are high. These data justify education and pathway implementation aimed at decreasing inpatient utilization of thrombophilia tests. Disclosures No relevant conflicts of interest to declare.

Assessment and Reduction of Unnecessary Thrombophilia Testing in Patients 18-60 Years with Acute Cryptogenic Ischemic Stroke

Patients &lt; 60 years with acute ischemic stroke (AIS) are commonly tested for thrombophilia. Underlying this practice is the perception that the stroke may be the result of a hypercoagulable state, especially when an alternative cause is not evident. Although certain conditions, such as antiphospholipid antibody syndrome (APS), can be associated with AIS and require anticoagulation, inherited thrombophilia, largely, is not a risk factor for AIS even in young adults with cryptogenic stroke, as supported by case-control and prospective observational studies. Moreover, testing in the acute phase of AIS may give erroneous results (i.e., increase of Factor 8 as an acute phase reactant), and increase health care costs. To assess our institutional performance on this matter, we conducted a retrospective chart review of 104 patients, age 18-60 years, who were admitted for AIS to Memorial Hermann Hospitals at the Texas Medical Center between 11/2016 and 7/2018, and whose stroke was considered cryptogenic or of undetermined origin (i.e., more than one possible causes) after initial diagnostic evaluation. Mean age at the time of event was 43 (range 20-58) years. There were 61 (59%) males. Fifty nine (57%) patients were White, 42 (40%) Black, 18 (17%) Hispanic, 2 (2%) Asian, and one (1%) of unknown race. Risk factors for AIS were: hypertension in 64 (61%) patients, diabetes in 26 (25%), smoking in 27 (26%), dyslipidemia in 32 (31%), prior AIS in 17 (16%), coronary artery disease in 4 (4%), and obesity in 10 (10%). None had known atrial fibrillation or other cardiac arrhythmia. Thrombophilia testing (at least one test) was performed in 82 (79%) of the patients. In the vast majority (70 patients, 85%) of cases, such testing was done within 1-3 days of admission as part of the initial stroke evaluation. A total of 752 tests were performed on the 82 patients, 56 (7%) of which were positive. Increased Factor 8 (F8) activity (i.e., ≥200%) was the commonest abnormality observed (31/58 patients tested, or 53%), followed by low protein S (PS) activity (13/77, 17%), Factor V Leiden (FVL) mutation (3/71, 4%), low antithrombin (AT) activity (3/73, 4%), elevated homocysteine (2/79, 3%), low protein C (PC) activity (1/76, 1%), and positive APL (1/251, 1%), while no prothrombin gene mutation was seen. All but one of F8, PS, and AT tests were performed in the acute phase of the stroke. The estimated annual cost for testing was $65000. Forty-two (51%) of the 82 patients tested had at least one abnormal test. In 2/42 (5%) of these patients, repeat testing (i.e., PS activity, F8) was done at least a month later, which, however, did not confirm the abnormality. Forty-seven (45%) patients were seen in the Outpatient Neurology Clinic after their stroke, for a median follow up of 5 (0.2 - 24) months. In 54 (52%) patients the cause of stroke remained undetermined even after thorough evaluation. Sixteen (15%) patients had a patent foramen ovale (PFO). Of all patients tested, thrombophilia was confirmed in three, i.e., two patients with heterozygous FVL mutation and one with known homozygous FVL mutation and a significant personal history of venous thromboses. Only in one patient (1/82, 1%) management was changed taking into account the thrombophilia testing results: a 57 year old male with low PS activity (tested 3 months after the stroke) and a PFO not amenable to closure, for whom anticoagulation was started despite the lack of venous thromboembolism. Based on these results, and due to concerns of indiscriminate testing, we created a practice guideline supported by current literature, as a reference for clinicians (see Figure). Briefly, we eliminated inherited thrombophilia testing in the acute phase, and rendered it optional in the chronic phase at the discretion of the treating physician, when anticoagulation is considered (i.e., some cases of PFO or recurrent stroke). Accordingly, we removed these tests from the admission order panel in the Electronic Medical Record. After internal audit and feedback from health care providers across disciplines, we submitted the new guideline for multidisciplinary review and system-wide adoption (i.e., multiple hospitals). We conclude that routine thrombophilia testing is not an effective tool for secondary stroke prevention even in young patients with cryptogenic AIS. Institutional practice guidelines are helpful in tailoring such testing, hence avoiding misdiagnosis of a thrombophilic state and unnecessary costs. Figure Disclosures No relevant conflicts of interest to declare.

Inherited Thrombophilia and Pregnancy Complications: Should We Test?

Recurrent miscarriages and pregnancy-related complications cause significant stress to couples looking for successful pregnancy outcome as well as to health care professionals. There is conflicting evidence with respect to the presence and the strength of associations between inherited thrombophilia and these complications. A complete thrombophilia screen is expensive, and no proven effective treatment for women with recurrent miscarriage and inherited thrombophilia is currently available. Based on the concept of microvascular thrombosis of the placenta, women with recurrent miscarriage and placenta-related complications frequently get treated with antithrombotic therapy. In this narrative review, the authors explore the evolving understanding and evidence of inherited thrombophilia in recurrent miscarriages and other pregnancy complications, and whether antithrombotic treatment would modify pregnancy outcome in women with inherited thrombophilia. Finally, they provide some personal recommendations based on available evidence for clinical practice. In summary, inherited thrombophilia testing is not required outside a clinical trial for women with recurrent pregnancy losses or late pregnancy complications. The presence of thrombophilia markers does not generally indicate additional therapy during pregnancy, even if a heritable thrombophilic defect is found in women with recurrent miscarriages or late pregnancy complications.

Inpatient inherited thrombophilia testing.

Inpatient inherited thrombophilia testing.