Publications by authors named "Aneel Ashrani"

78 Publications

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2021 10 15;19(10):1181-1201. Epub 2021 Oct 15.

National Comprehensive Cancer Network.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.
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http://dx.doi.org/10.6004/jnccn.2021.0047DOI Listing
October 2021

Timing of venous thromboembolism diagnosis in hospitalized and non-hospitalized patients with COVID-19.

Thromb Res 2021 Oct 7;207:150-157. Epub 2021 Oct 7.

Department of Cardiovascular Diseases, Division of Vascular Medicine, Rochester, MN, United States of America; Department of Internal Medicine, Division of Hematology/Oncology, Mayo Clinic, MN, United States of America. Electronic address:

Background: The reported incidence of venous thromboembolism (VTE) in COVID-19 patients varies widely depending on patient populations sampled and has been predominately studied in hospitalized patients. The goal of this study was to assess the evolving burden of COVID-19 and the timing of associated VTE events in a systems-wide cohort.

Methods: COVID-19 PCR positive hospitalized and non-hospitalized patients ≥18 years of age tested between 1/1/2020 through 12/31/2020 were retrospectively analyzed using electronic medical records from multiple states across the Mayo Clinic enterprise. Radiology reports within 90 days before and after confirmed COVID-19 diagnosis were examined for VTE outcomes using validated Natural Language Processing (NLP) algorithms.

Results: A 29-fold increased rate of VTE compared to the pre-COVID-19 period was noted during the first week following the first positive COVID-19 test (RR: 29.39; 95% CI 21.77-40.03). The rate of VTE steadily decreased and returned to baseline by the 6th week. Among 366 VTE events, most occurred during (n = 243, 66.3%) or after (n = 111, 30.3%) initial hospitalization. Only 11 VTE events were identified in patients who did not require hospitalization (3.0% of total VTE events). VTE and mortality increased with advancing age with a pronounced increased each decade in older patients.

Conclusion: We observed a profoundly increased risk of VTE within the first week after positive testing for COVID-19 that returned to baseline levels after 6 weeks. VTE events occurred almost exclusively in patients who were hospitalized, with the majority of VTE events identified within the first days of hospitalization.
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http://dx.doi.org/10.1016/j.thromres.2021.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495042PMC
October 2021

Reduced calf muscle pump function is a risk factor for venous thromboembolism: a population-based cohort study.

Blood 2021 06;137(23):3284-3290

Division of Vascular Medicine, Department of Cardiovascular Diseases.

The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P < .001) and unilateral (P < .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.
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http://dx.doi.org/10.1182/blood.2020010231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351902PMC
June 2021

Thrombin Generation Kinetics are Predictive of Rapid Transfusion in Trauma Patients Meeting Critical Administration Threshold.

Shock 2021 03;55(3):321-325

Department of Surgery, Mayo Clinic, Rochester, Minnesota.

Introduction: We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR).

Methods: In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CAT+, CAT- but receiving some pRBC Tx, receiving no Tx within the first 24 h. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR.

Results: A total of 484 trauma pts were analyzed: injury severity score = 13 [7,22], age = 48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT-, and 370 received no Tx. Risk factors for meeting CAT+: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2.27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type.

Conclusions: Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.
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http://dx.doi.org/10.1097/SHK.0000000000001633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970628PMC
March 2021

An In Silico Exploration of the Factors That Affect the Precision of the Bethesda Assay.

Am J Clin Pathol 2020 10;154(5):671-682

Special Coagulation Laboratory, Mayo Clinic, Rochester, MN.

Objectives: Despite more than 40 years of experience performing the Bethesda assay (BA), poor intra- and interlaboratory precision remains the biggest laboratory challenge to date.

Methods: The BA procedure was modeled using stochastic simulation techniques to determine the precision of the BA up to dilutions of 1:4,096, to estimate the minimum significant relative change at various inhibitor titers, and to understand the laboratory procedural variables that could significantly affect the performance of the BA at high dilutions.

Results: Selecting the lowest dilution tube with a residual activity closest to 25% for calculating the reported Bethesda titer (BT), using a factor activity assay with a coefficient of variation less than or equal to 7.5% in the range of 15% to 50% factor activity level, performing the factor activity measurement in replicates, and minimizing pipette volumetric error resulted in the lowest imprecision in the reported BT. The factor neutralization kinetics of the inhibitor appear to have little impact on the precision of the assay if the incubation time is greater than 90 minutes.

Conclusions: This in silico model will assist future laboratory efforts in standardizing the quantification of specific coagulation factor inhibitors and improving the precision of the reported results.
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http://dx.doi.org/10.1093/ajcp/aqaa085DOI Listing
October 2020

Leukocytosis and Tobacco Use: An Observational Study of Asymptomatic Leukocytosis.

Am J Med 2021 01 16;134(1):e31-e35. Epub 2020 Jul 16.

Division of Hematology.

Purpose: This study aimed to characterize the white blood cell differential of tobacco smoking-induced leukocytosis and describe the longitudinal impact of smoking cessation on this peripheral blood abnormality.

Methods: Medical records of patients undergoing evaluation by hematologists for persistent leukocytosis were reviewed. Patients in whom leukocytosis was determined to be secondary to tobacco use after exclusion of other causes were identified. Demographic and laboratory data were collected at time of diagnosis. Patients were longitudinally followed and information regarding smoking cessation and follow-up white blood cell values were recorded.

Results: Forty patients were determined to have smoking-induced leukocytosis. The median age was 49.5 years (range: 28-75 years), 24 patients were female, and the mean body mass index (BMI) was 31.5 kg/m. The mean white blood cell count was 13.3 × 10/L (range: 9.8-20.9 × 10/L); 39 patients had absolute neutrophilia (98%), 21 had lymphocytosis (53%), 20 had monocytosis (50%), and 19 had basophilia (48%). During follow-up, 11 patients either quit (n = 9) or reduced (n = 2) tobacco use. Reduction in tobacco smoking led to a significant decrease in mean white blood cell count (13.2 × 10/L vs 11.1 × 10/L, P = 0.02). The median time to decrease in white blood cell count following reduction in tobacco use was 8 weeks (range: 2-49 weeks).

Conclusions: Tobacco-induced leukocytosis was characterized by a mild elevation in total white blood cell count and was most commonly associated with neutrophilia, lymphocytosis, monocytosis, and basophilia. Cessation of smoking led to improvement in leukocytosis. Tobacco history should be elicited from all patients presenting with leukocytosis to limit unnecessary diagnostic testing, and counseling regarding smoking cessation should be offered.
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http://dx.doi.org/10.1016/j.amjmed.2020.06.014DOI Listing
January 2021

A study of dedicated haemophilia carrier clinics in the United States: Prevalence, services offered and barriers to development.

Haemophilia 2020 Sep 14;26(5):e253-e255. Epub 2020 Jun 14.

Division of Hematology, Department of Internal Medicine, Comprehensive Hemophilia Center, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1111/hae.14071DOI Listing
September 2020

Clinical outcomes of adults with hemophagocytic lymphohistiocytosis treated with the HLH-04 protocol: a retrospective analysis.

Leuk Lymphoma 2020 07 11;61(7):1592-1600. Epub 2020 Mar 11.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation in children that is increasingly being recognized in adults. Efficacy data for the HLH-04 protocol in adults is lacking. This study retrospectively analyzed 31 adult patients, median age 46 years, who received HLH-04 from 1/1/2004 to 5/1/2018. HLH etiology included malignancy ( = 9), autoimmune ( = 8), infection ( = 8), and idiopathic ( = 6). Eighteen patients were evaluable for response at week 4 with 7 having no response, 11 reaching partial response, and 0 reaching complete response (CR). Six patients eventually achieved CR at a median 195 days. The 1-year overall survival (OS) was 35% and median OS was 3.2 months. Univariate analysis showed shorter survival for hemoglobin <9 g/dL (HR 4.29,  = 0.003), platelets <100 × 10/L (HR 4.06,  = 0.027), ANC <1 × 10/L (HR 5.24,  = 0.001), and total bilirubin >1.2 mg/dL (HR 3.30,  = 0.022). Outcomes of adults treated with HLH-04 remain dismal and newer treatment modalities are needed.
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http://dx.doi.org/10.1080/10428194.2020.1737684DOI Listing
July 2020

Hemostatic prophylaxis and colonoscopy outcomes for patients with bleeding disorders: A retrospective cohort study and review of the literature.

Haemophilia 2020 Mar 6;26(2):257-268. Epub 2020 Mar 6.

Comprehensive Hemophilia Center, Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States.

Introduction: Hemostatic prophylaxis (HP) is recommended for patients with bleeding disorders (PWBD) before invasive procedures. However, evidence-based guidelines are needed to determine optimal HP strategies.

Aim: To determine outcomes of HP for PWBD undergoing colonoscopy.

Methods: We undertook a retrospective cohort study of HP and outcomes of colonoscopy procedures performed between 9 November 1993 and 13 February 2018 for PWBD who received care in the Mayo Clinic Comprehensive Hemophilia Treatment Center.

Results: During the study period, 73 PWBD (58 with milder phenotypes: haemophilia, von Willebrand disease [subtypes 1 and 2; II, VII and XI deficiency]) underwent 141 procedures. Preprocedural HP was given to 61%, and interventions were performed in 47%. Of the 39% without preprocedural HP, postprocedural HP was given for 11%. One major (0.7%; 6 days postprocedure despite HP) and 10 minor (7%) bleeding complications occurred, which tended to be in patients with severe disease and/or after excision of larger polyps. There was no significant difference in the rate of bleeding complications with or without preprocedural HP (8.1% vs 5.5%, respectively; P = .74, Fisher's exact test).

Conclusion: The low bleeding rates in our cohort suggest that preprocedure HP may be withheld for patients with mild bleeding disorders who undergo colonoscopy with a low likelihood of requiring an intervention or who require only low-risk intervention. This strategy may be best used in experienced centres, provided optimal local hemostasis measures are undertaken and postprocedural HP is rapidly available if high-risk intervention is required. Further studies are needed to determine optimal evidence-based HP strategies for PWBD undergoing colonoscopy.
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http://dx.doi.org/10.1111/hae.13954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154734PMC
March 2020

Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial.

J Thromb Haemost 2020 02 28;18(2):411-421. Epub 2019 Nov 28.

Medical Oncology Department, Mayo Clinic, Rochester, Minnesota.

Background: Low-molecular-weight heparin is the guideline-endorsed treatment for cancer-associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, limited data support its use in cancer patients.

Objectives: The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding (CRNMB).

Patients/methods: Patients with cancer-associated VTE were randomly assigned to receive either apixaban 10 mg twice daily for seven days followed by 5 mg twice daily for six months or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg once daily).

Results: Of 300 patients randomized, 287 were included in the primary analysis. Metastatic disease was present in 66% of subjects; 74% were receiving concurrent chemotherapy. Major bleeding occurred in 0% of 145 patients receiving apixaban, compared with 1.4% of 142 patients receiving dalteparin [P = .138; hazard ratio (HR) not estimable because of 0 bleeding event in apixaban group]. Recurrent VTE occurred in 0.7% of apixaban, compared to 6.3% of dalteparin patients [HR 0.099, 95% confidence interval [CI], 0.013-0.780, P = .0281). Major bleeding or CRNMB rates were 6% for both groups.

Conclusions: Oral apixaban was associated with low major bleeding and VTE recurrence rates for the treatment of VTE in cancer patients.
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http://dx.doi.org/10.1111/jth.14662DOI Listing
February 2020

Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE trial.

Eur J Haematol 2020 Feb 11;104(2):88-96. Epub 2019 Nov 11.

Vascular Medicine Division, Gonda Vascular Center, Mayo Clinic, Rochester, Minnesota.

Background: Cancer-associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA-approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double-blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883).

Methods/design: The primary study objective is to estimate differences in the combined rate of major plus clinically relevant non-major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium.

Conclusion: We anticipate these trial results to provide evidence supporting low-dose apixaban as a safe agent for secondary prevention of cancer-associated VTE for patients who have already completed 6-12 months of anticoagulation.
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http://dx.doi.org/10.1111/ejh.13338DOI Listing
February 2020

Etiologies of Extreme Thrombocytosis: A Contemporary Series.

Mayo Clin Proc 2019 08;94(8):1542-1550

Division of Hematology, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To describe the multifactorial etiologies of extreme thrombocytosis (EXT) in different care settings and the frequency of finding an occult malignancy.

Patients And Methods: We conducted a retrospective chart review at Mayo Clinic from January 1, 2011, through December 31, 2016. Adult patients who had at least 2 readings of platelet counts greater than 1000×10/L within 30 days of each other were included. We determined the causes of EXT on the basis of preset definitions of precipitating factors and identified the dominant causes on the basis of the trend of platelet counts.

Results: A total of 44,490 patients had thrombocytosis, and 305 patients (0.7%) had EXT. In 242 patients (79.3%), EXT was multifactorial. Surgical complications (54.1%) and hematologic malignancies (27.9%) were the 2 most dominant causes. Thirty-eight patients (12.5%) had new diagnoses of malignancies, mostly myeloproliferative neoplasms. In inpatients, surgical complications (71.9%), concurrent/previous splenectomy (50.5%), and infections (44.9%) were the most common causes, whereas hematologic malignancies (56.9%), iron deficiency (36.7%), and previous splenectomy (28.4%) were the most common causes in outpatients. Hematologic malignancy was 3.4 times more likely to be the cause of EXT in outpatients than in inpatients (56.9% vs 16.8%), and a new diagnosis of hematologic malignancy was 1.9 times more likely to be made in outpatients (15.6% vs 8.2%). Eighty-four percent of patients had resolution of EXT within 30 days. One patient died during the period of EXT. Nonsurgical patients with hematologic malignancies had the most prolonged period of EXT.

Conclusion: Extreme thrombocytosis is a multifactorial hematologic condition, and its etiology differs substantially between inpatients and outpatients. Occult hematologic malignancies are uncommon in EXT when other major causes are present.
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http://dx.doi.org/10.1016/j.mayocp.2019.01.041DOI Listing
August 2019

47-Year-Old Man With Pancytopenia and Fever.

Mayo Clin Proc 2019 06;94(6):1073-1078

Advisor to residents and Consultant in Hematology, Mayo Clinic, Rochester, MN. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2018.10.030DOI Listing
June 2019

Patterns and utility of vitamin B12 and folate testing in patients with isolated thrombocytopenia.

Ann Hematol 2019 Aug 15;98(8):1993-1994. Epub 2019 Mar 15.

Division of Hematology, Department of Medicine, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.

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http://dx.doi.org/10.1007/s00277-019-03666-2DOI Listing
August 2019

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism.

Mayo Clin Proc 2019 07 6;94(7):1242-1252. Epub 2019 Feb 6.

Department of Cardiovascular Diseases, Thrombophilia Clinic, Gonda Vascular Center, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE).

Patients And Methods: Consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB.

Results: Within the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer.

Conclusion: In the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable.
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http://dx.doi.org/10.1016/j.mayocp.2018.09.022DOI Listing
July 2019

NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018.

J Natl Compr Canc Netw 2018 11;16(11):1289-1303

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.
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http://dx.doi.org/10.6004/jnccn.2018.0084DOI Listing
November 2018

Clinical and laboratory diagnosis of autoimmune factor V inhibitors: A single institutional experience.

Thromb Res 2018 11 5;171:14-21. Epub 2018 Sep 5.

Division of Hematology, Department of Internal Medicine, and the Division of Hematopathology and Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, MN, United States of America. Electronic address:

Background: Coagulation factor V inhibitors (FV-i) may occur in patients with congenital FV deficiency or previously hemostatically normal patients (autoimmune (AI)-FV-i). Most of the published literature is confined to case reports.

Objective: Describe clinical and laboratory features of AI-FV-i identified through the Special Coagulation Laboratory at Mayo Clinic, Rochester, Minnesota.

Methods: In this retrospective study individuals with FV-i screens performed from January 1999 to February 2017 were identified through the special coagulation laboratory database. Clinical presentation, management, and outcomes were collected for our institutional patients while detailed laboratory data was collected for all tested patients.

Results: Of patients with FV-i managed at our institution, 2/8 (25%) patients experienced no bleeding. There was no correlation between inhibitor titers and/or FV activity (FV:C) levels and clinical bleeding. Hemostatic management included fresh frozen plasma, platelet transfusion, activated prothrombin complex concentrates, and recombinant factor VIIa. Only 2 patients received immunomodulatory treatment. FV-i mixing studies with normal pooled plasma (n = 26) demonstrated inhibition on immediate mix but progressive inhibition after 1 h of incubation could not be demonstrated. 71% of platelet neutralization procedures were falsely positive while 59% of DRVVT assays were indeterminate.

Conclusion: FV-i demonstrates immediate inhibition on mixing studies; however our limited data does not support a time dependent inhibition. Our clinical cohort confirms the variable clinical phenotype for individuals with FV-i and supports the notion that management of FV-i should be guided by clinical symptoms and not FV:C or FV-i titer.
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http://dx.doi.org/10.1016/j.thromres.2018.09.044DOI Listing
November 2018

Early thrombotic events and preemptive systemic anticoagulation following splenectomy for myelofibrosis.

Am J Hematol 2018 09 31;93(9):E235-E238. Epub 2018 Aug 31.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1002/ajh.25203DOI Listing
September 2018

Venous Thromboembolism (VTE) Incidence and VTE-Associated Survival among Olmsted County Residents of Local Nursing Homes.

Thromb Haemost 2018 Jul 2;118(7):1316-1328. Epub 2018 Jul 2.

Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, United States.

Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources. We tested associations between NHVTE and age, sex and time since each NH admission using Poisson modelling. Additionally, we tested incident NHVTE as a potential predictor of survival using Cox proportional hazards, adjusting for age, sex and NH residency. Between 1 October 1998 and 31 December 2005, 3,465 Olmsted County residents with ≥1 admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residents, 111 experienced incident NHVTE (2.3% of all eligible stays), for an overall rate of 3,653/100,000 NH person-years (NH-PY). VTE incidence was inversely associated with time since each NH admission, and was highest in the first 7 days after each NH admission (18,764/100,000 NH-PY). The adjusted hazard of death for incident NHVTE was 1.90 (95% confidence interval [CI]: 1.38-2.62). In conclusion, VTE incidence among NH residents was nearly 30-fold higher than published incidence rates for the general Olmsted County population. VTE incidence was highest within 7 days after NH admission, and NHVTE was associated with significantly reduced survival. These data can inform future research and construction of clinical trials regarding short-term prophylaxis.
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http://dx.doi.org/10.1055/s-0038-1660436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206861PMC
July 2018

Thrombotic and hemorrhagic complications in children and young adult recipients of Hematopoietic Stem Cell Transplant (HSCT).

Thromb Res 2018 07 26;167:44-49. Epub 2018 Apr 26.

Department of Pediatric and Adolescent Medicine, Mayo Clinic Children's Center, Mayo Clinic, Rochester, MN, USA; Division of Pediatric Hematology Oncology, Mayo Clinic, Rochester, MN, USA.

Background: Overall incidence of hemostatic complications in pediatric recipients of Hematopoietic Stem Cell Transplant (HSCT) is scarcely studied. This retrospective review explored the incidence and underlying risk factors of bleeding and thrombotic complications in children.

Procedure: Clinical characteristics, hemorrhagic events (HE), thrombotic events (TE) and follow up data were abstracted from medical records on patients aged <21 years undergoing HSCT during January 2000-June 2015.

Results: From start of conditioning until last follow up, 238 pediatric patients were reviewed during this study. There were 16 symptomatic thrombotic complications in 15 patients, along with 13 major bleeding events. Incidence of HE or TE was higher in allogeneic HSCT compared to autologous HSCT (p = 0.02). Severe thrombocytopenia could not be identified as a major contributor to bleeding. All patients with HE had platelets between 20,000-50,000 × 10/L, except one patient, who had platelets <20,000 × 10/L. All patients with hemorrhagic cystitis (n = 7) had received cyclophosphamide (Cy). For patients with sinusoidal obstruction syndrome, conditioning included either busulfan (Bu)/Cy (n = 5), Cy with total body irradiation (n = 4), or thiotepa (n = 2). Among allogeneic HSCT recipients, 60% of HE and 92% with TE had underlying myeloid neoplasms. Graft versus Host disease contributed to both types of complications (p = 0.07), although not reaching statistical significance.

Conclusions: Allogeneic pediatric HSCT patients had higher overall risk of hemorrhagic or thrombotic complications compared to autologous recipients in this study. HSCT for myeloid malignancies was a risk factor for higher complications.
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http://dx.doi.org/10.1016/j.thromres.2018.04.023DOI Listing
July 2018

Treatment approaches and outcomes in plasmacytomas: analysis using a national dataset.

Leukemia 2018 06 21;32(6):1414-1420. Epub 2018 Mar 21.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Solitary plasmacytomas are uncommon plasma cell disorders, which may present as a single bone lesion (P-bone) or extramedullary plasmacytoma (P-EM). There is a paucity of large studies analyzing prognostic factors and outcomes of plasmacytomas. While the treatment of choice is radiation therapy (RT), there is a lack of data evaluating optimal RT dose. In this study, we sought to answer these questions by utilizing the National Cancer Database plasmacytoma data from 2000 to 2011. A total of 5056 patients were included in the study (median age 62 years; range 52-72). To obtain a pure plasmacytoma cohort, potential multiple myeloma patients were excluded from the study (bone marrow involvement, systemic chemotherapy use). P-bone constituted 70% of the patients. The median overall survival (OS) of P-EM was significantly longer than P-bone (132 vs. 85 months), and for soft/connective tissue it was worse than remainder of P-EM (82 vs. 148 months). On multivariable analysis, factors associated with worse OS included older age (≥65), presence of P-bone, and treatment with a radiation dose <40 Gy.
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http://dx.doi.org/10.1038/s41375-018-0099-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522261PMC
June 2018

Prevalence and survival of smouldering Waldenström macroglobulinaemia in the United States.

Br J Haematol 2019 03 13;184(6):1014-1017. Epub 2018 Mar 13.

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1111/bjh.15201DOI Listing
March 2019

Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population-Based, Case-Control Study.

Am J Med 2018 03 4;131(3):307-316.e2. Epub 2017 Oct 4.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minn; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minn.

Background: The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors.

Methods: By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum.

Results: A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism.

Conclusions: Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis.
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http://dx.doi.org/10.1016/j.amjmed.2017.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817009PMC
March 2018

The Impact of Antithrombin Deficiency on Women's Reproductive Health Experiences and Healthcare Decision-Making.

J Womens Health (Larchmt) 2017 12 21;26(12):1350-1355. Epub 2017 Sep 21.

1 Division of Hematology, Department of Internal Medicine, Mayo Clinic , Rochester, Minnesota.

Background: Women with inherited antithrombin (AT) deficiency are at high risk for venous thromboembolism (VTE), especially during times of estrogen exposure, but little is known about patient-oriented reproductive decision-making in this population.

Materials And Methods: Provider-administered survey of women with AT deficiency. Participants were asked to discuss their diagnosis of AT deficiency and questioned about (1) contraception, (2) pregnancies, and (3) menorrhagia, and the impact of their AT deficiency on each reproductive health experience.

Results: Of 31 women with inherited AT deficiency, 18 (58%) were surveyed, 8 (26%) were unreachable, and 5 (16%) were deceased. Twelve (67%) had a VTE, including two which occurred during pregnancy and five during oral contraceptive (OCP) use. Women reported using OCPs, intrauterine device (IUD), and condoms for contraception. Of five women diagnosed with AT deficiency while taking OCPs, three switched to an IUD, one to condoms, and one used no alternative method. Eighteen women reported 42 total pregnancies, with 33 (79%) resulting in live term birth, 3 (7%) in live preterm birth, and 6 (14%) in spontaneous abortion at a median of 12 weeks. Four (22%) women reported the use of anticoagulation during pregnancy. Eleven (61%) women reported menorrhagia and 4 (36%), while on anticoagulation for VTE events. Ten of 18 women (56%) reported that the diagnosis of AT had affected their reproductive health in some way.

Conclusion: Women with AT deficiency require careful multidisciplinary management to avoid complications in the setting of contraception and pregnancy. AT deficiency impacts women's reproductive health experiences and patient-oriented reproductive decision-making is key.
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http://dx.doi.org/10.1089/jwh.2017.6333DOI Listing
December 2017

Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial.

Thromb Haemost 2017 10 24;117(10):1952-1961. Epub 2017 Aug 24.

Robert D. McBane II, MD, Gonda Vascular Center, Mayo Clinic, 200 First Street SW, Rochester, MN, USA, Tel.: +1 507 266 3964, Fax: +1 507 266 1617, E-mail:

Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). The main aim of the ADAM-VTE trial is to test the hypothesis that apixaban is associated with a significantly lower rate of major bleeding compared to dalteparin in the treatment of cancer patients with acute VTE. The primary safety outcome is rate of major bleeding. Secondary efficacy objective is to assess the rates of recurrent VTE or arterial thromboembolism. Cancer patients with acute VTE (n=300) are randomized to receive apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) or dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg daily thereafter) for 6 months. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.
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http://dx.doi.org/10.1160/TH17-03-0193DOI Listing
October 2017
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