Equivalent thrombotic risk with Warfarin, Dabigatran, or Enoxaparin after failure of initial direct oral anticoagulation (DOAC) therapy.

BACKGROUND: The direct oral anticoagulants (DOACs) are now commonly regarded as first line anticoagulants in most cases of venous thromboembolism (VTE). However, the optimal choice of subsequent anticoagulant in instances of first line DOAC failure is unclear. OBJECTIVES: To describe and compare outcomes with second line anticoagulants used after DOAC failure. METHODS: Patients seen at an urban hospital system for an episode of acute VTE initially treated with either apixaban or rivaroxaban who experienced a subsequent recurrent thrombosis while on anticoagulation (1st recurrent thrombosis) were included. RESULTS: In total, 166 patients after apixaban or rivaroxaban failure were included. Following DOAC failure (1st recurrent thrombosis), the subsequent anticoagulant was warfarin in 60 patients (36%), dabigatran in 42 patients (25%), and enoxaparin in 64 patients (39%). Enoxaparin was preferentially prescribed in patients with a malignancy-associated etiology for 1st recurrent thrombosis (p < 0.01). The median follow-up time in our cohort was 16 months. There was no difference in 2nd recurrent thrombosis-free survival (p = 0.72) or risk for major bleeding event (p = 0.30) among patients treated with dabigatran, warfarin, or enoxaparin. CONCLUSIONS: In this retrospective analysis of patients failing first line DOAC therapy, rates of 2nd recurrent thrombosis and bleeding did not differ among subsequently chosen anticoagulants. Our study provides evidence that the optimal 2nd anticoagulant is not clear, and the choice of 2nd anticoagulant should continue to balance patient preference, cost, and provider experience.

The Role of Hereditary Thrombophilia Testing in Management of First-Time Pulmonary Embolism.

AIM: Hereditary thrombophilia (HT) testing is frequently conducted during the evaluation of patients with pulmonary embolism (PE). However, the utility of routine HT testing in this setting is unclear. We sought to assess the association of HT with risk of recurrent venous thromboembolism (VTE) following first-time PE. METHODS: We conducted a multi-hospital retrospective study. Two hundred and ninety (290) patients with a first-time PE, who had been tested for HT, completed at least 3 months of therapeutic anticoagulation (AC), subsequently discontinued AC, and were followed for at least 36 months thereafter, were included. RESULTS: HT was present in 48 of the 290 included patients (17%). Median follow-up after discontinuing AC was 61 months (interquartile range, 43-79 months). The overall recurrence rate of VTE during follow-up was 58 per 290 (20%). A total of 47 of 242 patients (19%) in the HT-absent group had a recurrent VTE, compared with 11 of 48 (22%) in the HT-present group. There was no significant difference in VTE-free survival between groups on Kaplan-Meier analysis; the hazard ratio (HR) for VTE recurrence for those with HT compared to those without (HR HT-present: HT-absent) was 1.240 (95% confidence interval [CI] 0.614-2.502; p=0.548). On multivariable analysis, HT was not associated with risk of recurrent VTE (HR 1.262; 95% CI 0.640-2.488), and the only variable associated with VTE recurrence was unprovoked PE (HR 2.954; 95% CI 1.64-5.314). CONCLUSIONS: These findings demonstrate that the presence of HT is not associated with the risk of recurrent VTE following first PE, and support limiting the use of HT testing among patients with first PE.

Direct oral anticoagulants versus warfarin in patients with single antibody-positive anti-phospholipid syndrome.

BACKGROUND: The role of direct oral anticoagulants (DOACs) among patients with antiphospholipid syndrome (APLS) remains unclear. Warfarin has been shown to be superior to DOACs among high-risk APLS patients (particularly those with triple-positive APLS). However, it remains unknown whether DOACs may be appropriate for lower-risk patients such as those with single-positive APLS. METHODS: We conducted a retrospective study comparing the risk of recurrent thrombosis among single-positive APLS patients treated with DOACs (apixaban or rivaroxaban), and those treated with warfarin. RESULTS: One-hundred-forty-three single-positive APLS patients, newly started on anticoagulation following a first thrombotic event, were included. Median follow-up was 54 months (IQR 29-73 months). Ninety-one patients (64%) received warfarin and 52 patients (36%) received a DOAC. Six patients (6.6%) who received warfarin experienced a recurrent thrombotic event compared with 3 of 52 (5.8%) patients who received a DOAC (p = .845). There was no difference in event-free survival between groups (HR DOAC:Warfarin = 0.952, 95% CI 0.232 - 3.908). Major bleeding was similar in both groups. CONCLUSIONS: These findings suggest that DOACs may be a safe and effective option for patients with single-positive APLS. Prospective studies are needed to confirm these findings.

Risk factors and outcomes of COVID-19 in New York City; a retrospective cohort study.

Coronavirus disease 2019 (COVID-19) is a global pandemic and information on risk factors for worse prognosis is needed to accurately identify patients at risk and potentially provide insight into therapeutic options. In this retrospective cohort study, including 3703 patients with laboratory confirmed COVID-19, we identified risk factors associated with all-cause mortality, need for hospitalization and mechanical ventilation. Male gender was independently associated with increased risk of hospitalization (adjusted odds ratio [ORadj ]: 1.62; 95% confidence interval [95% CI]: 1.38-1.91)), mechanical ventilation (ORadj : 1.35; 95% CI: 1.08-1.69) and death (ORadj : 1.46; 95% CI: 1.17-1.82). Patients > 60 years had higher risk of hospitalization (ORadj : 5.47; 95% CI: 4.29-6.96), mechanical ventilation (ORadj : 3.26; 95% CI: 2.08-5.11) and death (ORadj : 13.04; 95% CI: 6.25-27.24). Congestive heart failure (ORadj: 1.47; 95% CI: 1.06-2.02) and dementia (ORadj : 2.03; 95% CI: 1.46-2.83) were associated with increased odds of death, as well as the presence of more than two comorbidities (ORadj : 1.90; 95% CI: 1.35-2.68). Patients with COVID-19 of older age, male gender, or having more than two comorbidities are at higher risk of hospitalization, mechanical ventilation and death, and should therefore be closely monitored.

The utility of thrombophilia and hematologic screening in live liver donation.

BACKGROUND: Most centers perform some degree of hematologic screening, including thrombophilia testing, on prospective live liver donors. The nature and extent of such screens are not standardized, and there is limited evidence regarding hematologic risk stratification. METHODS AND RESULTS: We present an experience of hematologic screening among prospective liver donors. Five-hundred-eightyfour patients were screened for liver donation between 1/2013 and 1/2020, of whom 156 (27%) proceeded to donor hepatectomy. Thirty-three of 428 (8%) declined patients were excluded for hematologic indications. Hematologic indications were the 2nd most frequent medical indications for exclusion (trailing only hepatologic indications). The most common reason for hematologic exclusion was concern regarding thrombophilia. Nevertheless, 21 patients with evidence of possible thrombophilia proceeded to donor hepatectomy, and none incurred hematologic complications. Similarly, seven patients with screening findings concerning for increased bleeding risk (most often thrombocytopenia) underwent donor hepatectomy without hematologic complication. Three of 156 (2%) of patients who underwent donor hepatectomy incurred a hematologic complication (all thrombotic, none fatal). None of these patients had any evident hematologic risk factor on screening. CONCLUSION: This study underscores the difficulty of hematologic risk stratification among prospective living donors, however, suggests that some patients with relatively mild risk factors may be safe for donation.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis.

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank p = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633-1.799, p = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

Safety, Efficacy, and Long-Term Outcomes of Anticoagulation in Cirrhotic Portal Vein Thrombosis.

BACKGROUND: The role of anticoagulation (AC) in the management of cirrhotic patients with portal vein thrombosis (PVT) remains unclear. AIMS: We conducted a retrospective study of cirrhotic patients diagnosed with PVT from 1/1/2000 through 2/1/2019, comparing those who received AC to those who did not. METHODS: Outcomes included rate of complete radiographic resolution (CRR) of PVT, recanalization of occlusive PVT (RCO), PVT extension, major bleeding, and overall survival (OS). The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox-proportional-hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: A total of 214 patients were followed for a median 27 months (IQR 12-48). Eighty-six patients (39%) received AC. AC was associated with significantly greater CRR (48% vs. 27%, p = 0.0007), (multivariable HR for CRR with AC; 2.49 (1.54-4.04, p = 0.0002)). AC was also associated with significantly greater RCO (69% vs. 28%, p = 0.0013), (multivariable HR for RCO with AC; 4.86 (1.91-12.37, p = 0.0009)). Rates of major bleeding were similar with and without AC (20% vs. 17%, p = 0.5207), multivariable HR for major bleeding with AC; 1.29 (0.68-2.46, p = 0.4423)). OS rates in the AC and no-AC groups were 83% and 70%, respectively (p = 0.1362), (HR for death with AC; 0.69 (0.38-1.28, p = 0.2441)). Among 75 patients who had CRR, 10 (13%) experienced recurrent PVT during follow-up (none were receiving AC at the time of recurrence). CONCLUSIONS: AC appears safe and effective for the treatment of cirrhotic PVT; however, prospective studies to confirm these findings and evaluate additional outcomes are needed.

The Impact of Socioeconomic Status on the Clinical Outcomes of COVID-19; a Retrospective Cohort Study.

There have been limited data assessing the influence of disadvantaged socioeconomic status (SES) on the incidence and clinical outcomes of COVID-19 patients within the diverse communities of the United States. Here, we aim to investigate the association between poverty level, as an indicator of SES, and COVID-19 related clinical outcomes including hospitalization and all-cause mortality. This retrospective cohort study included 3528 patients with laboratory confirmed COVID-19 seen at a large New York City health system between March 1, 2020 and April 1, 2020. Data for neighborhood level poverty was acquired from the American Community Survey 2014-2018 and defined as the percent of residents in each ZIP code whose household income was below the federal poverty threshold (FPT): 0% to < 20% below FPT (low poverty) and > 20% below FPT (high poverty). COVID-19 positive patients who resided in high poverty areas were significantly younger, had a higher prevalence of comorbidities and were more likely to be of female gender or a racial minority when compared to individuals living in low poverty areas. Residence in a high poverty area was not associated with an increased risk of COVID-19 related hospitalization and was found to be associated with a decreased risk of in-hospital mortality. This study suggests the existence of an unequal socioeconomic gradient in the demographic and clinical presentation of COVID-19 patients including differences in age, gender and race between poverty groups. Further studies are needed to fully assess the intersectionality of SES with the COVID-19 pandemic.

Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: The standard diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) include hyperferritinemia to >500 ng/mL. This ferritin threshold is based on pediatric data, and evidence for its application among adults with secondary HLH is lacking. OBJECTIVE AND METHODS: We conducted a retrospective study assessing the relationship between extreme hyperferritinemia and adult secondary HLH at our institution. All adult inpatients seen over a 10-year period, with serum ferritin >5000 ng/mL, were included. RESULTS: Among 1055 patients with serum ferritin >5000 ng/mL, there were 69 cases of HLH (HLH prevalence of 6.5%). Mean ferritin among HLH patients was 70 398 ng/mL (SD 122 908), median 40 019 ng/mL (IQR 16 051-68 326). The prevalence of HLH only reached 50% as serum ferritin approached 90 000 ng/mL. A variety of conditions were contributory to hyperferritinemia, most commonly bacterial sepsis (33%), hematologic malignancy (29%), renal failure (24%), and liver injury (18%). The optimal cutoff ferritin for diagnosis of HLH was 16 000 ng/mL (sensitivity 79.4%, specificity 79.2%, PPV 20.9%, and NPV 98.2%). CONCLUSIONS: The threshold ferritin levels used in diagnostic criteria for adult secondary HLH are too low to be clinically relevant, and efforts should be undertaken to revise them upward. Similar reappraisals should be taken of the other criteria used to diagnose adult HLH.

Soluble interleukin-2 receptor (sIL-2r) level is a limited test for the diagnosis of adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: Soluble interleukin-2 receptor (sIL-2r) level is used as a diagnostic tool in hemophagocytic lymphohistiocytosis (HLH). However, evidence supporting its use among adults is inadequate. OBJECTIVE AND METHODS: We conducted a retrospective study to assess the performance characteristics of sIL-2r for the diagnosis of adult HLH. RESULTS: One hundred thirty-two adults with sIL-2r levels sent for evaluation of HLH over a ten-year period were included. Sixty-five (49%) met criteria for HLH. Mean sIL-2r was significantly higher among patients with HLH relative to all patients without HLH (12942U/ml vs. 6308 U/mL, P = .00311). However, when comparing mean sIL-2r in the HLH group to those in the non-HLH group with primary diagnoses of hematologic malignancy (8911 U/mL), sepsis (7127 U/mL), and rheumatologic disease (4624 U/mL), no significant differences were found (P = .241, P = .178, and P = .0607, respectively). There was only weak correlation between sIL-2r and diagnosis of HLH (r = .253). The standard cutoff sIL-2r > 2400 U/ml yielded a sensitivity of 89.2% and specificity of 38.8%. The area under the curve for the corresponding receiver-operator curve was 0.691, consistent with a poor discriminating ability for the diagnosis of HLH. CONCLUSIONS: sIL-2r is a limited test for the diagnosis of adult secondary HLH, and its role in this setting should be reevaluated.

Portal vein thrombosis patients harboring JAK2V617F have poor long-term outcomes despite anticoagulation.

Non-cirrhotic portal vein thrombosis (ncPVT) most often occurs in the setting of intraabdominal proinflammatory processes. Less often, ncPVT may result from primary hematologic thrombophilia (most commonly JAK2V617F). Although these etiologic categories are pathophysiologically distinct, they are treated similarly using anticoagulation. We conducted a retrospective assessment of outcomes among ncPVT patients harboring JAK2V617F, and compared them to outcomes among patients with other etiologies for ncPVT, to determine whether anticoagulation alone is adequate therapy for JAK2V617F associated PVT. Outcomes were complete radiographic resolution (CRR) of PVT, recanalization (RC) of occlusive PVT, and development of significant portal hypertension (SPH). Three-hundred-thirty ncPVT patients seen between 1/2000 and 1/2019, including 37 harboring JAK2V617F (JAK2), 203 with other evident etiology (OE) for PVT, and 90 with no evident etiology (NE) for PVT followed for a median 29 months (53, 21, and 32 months respectively). Outcomes among the JAK2 cohort were dismal relative to the other groups. CRR rates were 8%, 31%, and 55% for the JAK2, NE, and OE cohorts respectively (multivariable HR JAK2:OE = 0.15 (0.05, 0.49), p = 0.0016). RC rates were 16%, 33%, and 49% for the JAK2, NE, and OE cohorts respectively (multivariable HR for RC JAK2:OE = 0.24 (0.09, 0.63), p = 0.0036). SPH rates were 49%, 32%, and 17% for the JAK2, NE, and OE cohorts respectively (multivariable HR for SPH JAK2:OE = 1.23 (0.62, 2.42), p = 0.5492). Given the strikingly poor outcomes among patients harboring JAK2V617F, anticoagulation alone does not appear to be adequate therapy for this cohort. Further investigation into thrombolysis and/or thrombectomy as an adjunct to anticoagulation is merited in this high-risk group.

The role of anticoagulation in pylephlebitis: a retrospective examination of characteristics and outcomes.

Pylephlebitis, or suppurative thrombophlebitis of the portal vein, typically occurs in the context of an intraabdominal infection or abdominal sepsis. Antibiotics are the mainstay of treatment. The role of anticoagulation in the management of pylephlebitis is controversial, and data regarding its impact on outcomes is limited. The records of 67 consecutive patients with pylephlebitis treated at our institution over a 19 year period were retrospectively reviewed. Data was gathered regarding their baseline characteristics, presentations, management, and outcomes. Patients who did and did not receive anticoagulation were compared. Outcomes of interest included survival, portal vein thrombosis (PVT) resolution, development of chronic symptomatic portal hypertension, and major bleeding. Forty-seven patients received anticoagulation and 20 did not. The anticoagulated and non-anticoagulated groups did not differ significantly with respect to potential covariates or confounders. Anticoagulated patients had significantly higher rates of PVT resolution than non-anticoagulated patients (58% vs. 21%, p = 0.0201). This translated to lower rates of future chronic portal hypertensive symptoms among anticoagulated patients (11% vs. 47%, p = 0.0034). Anticoagulated patients had a trend toward improved survival however this improvement was not significant on multivariable analysis. There was no significant difference in rates of major bleeding between groups. Thrombophilia testing was common in this cohort however the occurrence of meaningful positive results was exceedingly low. Anticoagulation significantly improves the rate of PVT resolution, and significantly reduces the rate of chronic symptomatic portal hypertension, among patients with pylephlebitis. Treatment of pylephlebitis should incorporate the use of systemic anticoagulation whenever possible.

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases.

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients' charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Inflamed-HLH, MAS, or something else?

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive and maladaptive inflammation. Primary HLH is most frequently encountered in young children, and, without timely recognition and therapy, can lead to multiorgan failure and death. It is most often diagnosed using the HLH-2004 criteria and by identifying pathological mutations. However, the HLH-2004 criteria are not specific for HLH, and patients can easily fulfill these diagnostic criteria in other proinflammatory states in which HLH-therapy would not be indicated, including hematologic malignancies, infections, and rheumatologic disease. Therefore, great care must be taken to ensure that the specific disease associated with features of HLH is accurately recognized, as consequences of improper treatment can be catastrophic. We propose a diagnostic pathway for patients for whom HLH is on the differential (visual abstract). Importantly, in situations in which the initial diagnostic workup is equivocal or unrevealing, reevaluation for occult malignancy, infection, or rheumatologic disease would be prudent, as occult presentations may be missed on primary evaluation. Temporizing medications can be used in critically ill patients while awaiting secondary evaluation. By using this framework, clinicians will be able to more reliably discern primary HLH from other pro-inflammatory states and thus provide timely, appropriate disease-specific therapy.

Plasmodium falciparum-Induced Autoimmune Hemolytic Anemia in a Pregnant Patient with Sickle Cell Disease.

BACKGROUND Sickle cell disease (SCD) is an autosomal recessive hereditary condition characterized by chronic hemolytic anemia and painful vaso-occlusive episodes. Homozygous sickle cell patients are at increased risk of morbidity and mortality from malaria. Autoimmune hemolytic anemia (AIHA) secondary to, or in the setting of, malarial infection is rare. In our case, the concurrence of Plasmodium falciparum malarial parasitemia and AIHA led to severe hemolytic anemia with an extensive packed red blood cell transfusion requirement. The patient's underlying SCD also contributed to the severity of the anemia and persistence of the malarial infection. CASE REPORT We report the case of a 29-year-old woman in the second trimester of pregnancy, with a history of SCD, who presented with severe anemia beyond her typical baseline in the setting of P. falciparum malaria. Hemolysis markers, including lactate dehydrogenase and bilirubin, were elevated. Direct Coombs testing was positive for IgG and C3 antibodies. Treatment with antimalarial agents and steroids led to clinical improvement and eventual clearance of the parasitemia. CONCLUSIONS Our patient's clinical course was most compatible with P. falciparum malaria-induced AIHA. Although she received a short course of steroids, it was treatment and clearance of the parasitemia that led to resolution of the hemolysis and a return to baseline hemoglobin levels. While the exact mechanism of AIHA in malaria is not well characterized, several unique mechanisms have been proposed and should be considered in cases of P. falciparum malaria manifesting with particularly severe hemolytic anemia.

Anakinra for the treatment of adult secondary HLH: a retrospective experience.

Anti-cytokine therapies have been gaining attention as a means of improving outcomes in adult secondary HLH (asHLH), which currently has poor outcomes when treated with standard etoposide-based therapies. Anakinra is an interleukin-1 antagonist that is increasingly being used in the management of asHLH. Here is described a multi-hospital series of 16 adult patients with secondary HLH treated with anakinra. Provoking factors of secondary HLH included hematologic malignancy (n = 7, 44%), bacterial infection (n = 7, 44%), viral infection (n = 5, 31%), rheumatologic disorder (n = 4, 25%), and unknown (n = 1, 6%). Five patients remained alive at time of last follow-up (OS = 31%). Median OS was 1.7 months from initiation of anakinra (range 0.2-59). OS among patients with rheumatologic causes of secondary HLH was 75%, whereas only 17% of patients with other provoking factors survived (p = 0.0293). Anakinra was well tolerated, with only 1 patient experiencing associated toxicity (grade 3 liver injury). Anakinra may be useful in the management of asHLH provoked by rheumatologic conditions, although its benefit in asHLH provoked by other factors may be limited.

The utility of hereditary thrombophilia testing among patients with unprovoked venous thromboembolism.

INTRODUCTION: Hereditary-thrombophilia (HT) testing is often sent during the evaluation of patients with unprovoked venous thromboembolism (VTE). This remains a frequent practice even though the results of such testing are often of unclear practical significance. METHODS: We conducted a multicenter retrospective study to assess whether HT is associated with risk of recurrent VTE among patients who discontinue anticoagulation (AC) following an unprovoked VTE. RESULTS: A total of 528 adult patients were included, 28% of whom (N = 110) tested positive for HT. Median follow-up was 55 months (IQR 40-66 months) following AC discontinuation. One hundred and twenty-four patients (23%) had a recurrent VTE during follow-up, including 29/110 with HT (26%) and 95/418 without HT (23%). Risk of recurrent VTE over time was similar between the two groups (logrank P = .47). The HR for recurrence among patients with HT was 1.17 (95% CI 0.76 to 1.81). On multivariable analysis, HT was not associated with recurrence of VTE (HR with HT = 1.07 (95% CI 0.69-1.65), P = .74). The only factor significantly associated with risk of VTE recurrence on multivariable analysis was presence of PE (as opposed to DVT alone) (HR = 1.54, 95% CI 1.02-2.30, P = .035). CONCLUSION: The presence of HT was not associated with risk of recurrent VTE in this cohort of patients. These findings underscore the questionable clinical utility of routine thrombophilia testing among patient with unprovoked VTE and suggest that such testing should not be routinely pursued.