Publications by authors named "Damon E Houghton"

30 Publications

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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

Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

J Am Heart Assoc 2021 09 13;10(18):e020809. Epub 2021 Sep 13.

Division of Biomedical Informatics and Personalized Medicine Department of Medicine, Anschutz Medical Campus, University of Colorado Aurora CO.

Background Individual blood cell count abnormalities have been associated with cardiovascular disease and increased mortality. In this study, we defined a "cytopenia phenotype," reflecting bone marrow hypoproliferation, to determine if peripheral blood cytopenia is associated with increased cardiovascular disease and mortality risk. Methods and Results Study participants were derived from a biracial observational cohort study, REGARDS (Reasons for Geographic and Racial Differences in Stroke), that enrolled 30 239 Black and White participants aged ≥45 years between 2003 and 2007. Median follow up was ≈9 years. The current study included 19 864 participants from REGARDS study (37.9% men, 40% Black participants) who have complete blood count available at study enrollment. We defined a cytopenia phenotype based on age-, sex-, and race-adjusted lowest fifth percentile of blood counts. Multivariable Cox proportional hazards models estimated the hazard ratios (HR) and 95% CI of cytopenia for mortality and incident cardiovascular disease in adjusted models. Mean age of the study participants was 64 years (SD:9.7). The prevalence of cytopenia was 1.9% (n=378). Cytopenia was associated with increased risk of all-cause mortality (HR, 1.73; 95% CI, 1.34-2.22) and cardiovascular disease mortality (HR, 1.56; 95% CI, 1.11-2.29). Cytopenia was associated with stroke risk in Black but not White participants (HR, 1.96 versus 0.86; -interaction for race=0.08) and was not associated with coronary heart disease risk. Conclusions We defined a cytopenia phenotype with clinical implications for mortality and stroke risk in a large biracial and geographically diverse population. Whether generated through somatic mutations or decreased organ function, cytopenia was associated with mortality risk and was a race-specific risk factor for stroke.
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http://dx.doi.org/10.1161/JAHA.121.020809DOI Listing
September 2021

Evaluation of Changing Vena Cava Filter Use and Inpatient Hospital Mortality from 2016-2019: A Single-Institution Quality Improvement Project.

Mayo Clin Proc Innov Qual Outcomes 2021 Oct 3;5(5):851-858. Epub 2021 Sep 3.

Cardiovascular Diseases, Mayo Clinic, Rochester, MN.

Objective: To evaluate the changing trends of vena cava filter (VCF) insertion and determine whether changes in VCF use affected inpatient mortality.

Patients And Methods: A quality improvement project at Mayo Clinic, Rochester, Minnesota, tracks the type and reason for VCF insertions from January 1, 2016, through December 31, 2019, to facilitate appropriate retrieval. The rate of VCF insertions was compared with inpatient mortality rates, normalized for patient volumes using the number of hospital inpatient discharges.

Results: A total of 698 VCFs were placed in 695 patients: 2016 (n=243), 2017 (n=156), 2018 (n=156), and 2019 (n=120). The rate of VCF insertions (per 1000 inpatient discharges) was 4.02 in 2016, 2.91 in 2017, 2.54 in 2018, and 1.93 in 2019. Mean ± SD age at placement was 62±16.4 years and 59.2% (413/698) were men. Most VCFs were retrievable (85.1%; 594/698) and were placed for treatment (78.4%; 547/698) indications (acute venous thromboembolism within 3 months). The rate of VCF insertions was compared with the inpatient mortality rate (per 100 inpatient discharges) and remained stable (1.83 in 2016, 1.79 in 2017, 1.83 in 2018, and 1.76 in 2019) despite the significant decline in VCF use.

Conclusion: Data from this quality improvement study demonstrate a reduction of more than 50% in the use of VCFs from 2016 through 2019 at a large academic hospital. These changes are difficult to attribute to any single change in clinical use and there was no appreciable increase in the inpatient hospital mortality rate associated with this decrease in VCF filter use.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424125PMC
October 2021

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban, Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism.

Mayo Clin Proc 2021 Nov 20;96(11):2793-2805. Epub 2021 Aug 20.

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

Objective: To compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE).

Patients And Methods: Consecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB).

Results: In the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37).

Conclusion: Apixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer.

Trial Registration: ClinicalTrials.gov identifier: NCT03504007.
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http://dx.doi.org/10.1016/j.mayocp.2021.04.026DOI Listing
November 2021

Risk of pulmonary emboli after removal of an upper extremity central catheter associated with a deep vein thrombosis.

Blood Adv 2021 07;5(14):2807-2812

Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.

Standard treatment of catheter-associated upper extremity deep vein thrombosis (UE-DVT) is anticoagulation, although catheters are often removed for this indication. The optimal time for catheter removal and whether the act and/or timing of catheter removal is associated with pulmonary embolism (PE) remain unknown. A retrospective cohort study was performed at 8 participating institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies and central venous catheter (CVC)-associated UE-DVT were included from 1 January 2010 through 31 December 2016. The primary outcome was objectively confirmed PE within 7 days of UE-DVT diagnosis in anticoagulated patients comparing early (≤48 hours) vs delayed (>48 hours) catheter removal. A total of 626 patients were included, among whom 480 were treated with anticoagulation. Among anticoagulated patients, 255 underwent early CVC removal, while 225 had delayed or no CVC removal; 146 patients received no anticoagulation, among whom 116 underwent CVC removal alone. PE within 7 days occurred in 2 patients (0.78%) with early removal compared with 1 patient (0.44%) with delayed or no CVC removal (P > .9). PE or any cause of death within 7 days occurred in 3 patients in both the early removal (1.18%) and delayed/no removal (1.33%) groups (P > .9). In patients treated with CVC removal only (no anticoagulation), there were no PEs but 3 deaths within 7 days. In patients with hematological malignancy and CVC-associated UE-DVT, early removal of CVCs was not associated with an increased risk of PE compared with delayed or no removal.
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http://dx.doi.org/10.1182/bloodadvances.2021004698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341352PMC
July 2021

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19-Positive Compared With COVID-19-Negative Patients.

Mayo Clin Proc 2021 07 4;96(7):1718-1726. Epub 2021 May 4.

Division of Hematology/Oncology, Mayo Clinic, Rochester, MN; Division of Vascular Medicine, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.

Objective: To determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)-positive compared with COVID-19-negative patients.

Patients And Methods: Adult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list.

Results: We identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive-patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death.

Conclusion: Early experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.
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http://dx.doi.org/10.1016/j.mayocp.2021.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096191PMC
July 2021

Delayed anticoagulation in venous thromboembolism: Reasons and associated outcomes.

Res Pract Thromb Haemost 2021 May 7;5(4):e12500. Epub 2021 Apr 7.

Department of Cardiovascular Medicine Division of Vascular Medicine Gonda Vascular Center Mayo Clinic Rochester MN USA.

Objective: We assessed the number of cases with delayed anticoagulation initiation, explored the reasons for the delay, and its impact on outcome in patients with acute venous thromboembolism (VTE) treated in an organized setting of treatment initiation and continuous, prospective follow-up.

Methods: Patients with anticoagulation initiation delay >24 hours were identified within the cohort of patients with acute VTE enrolled in the Mayo Clinic Venous Thromboembolism Registry between 2013 and 2020. The reasons for treatment delay were explored by reviewing the electronic database. VTE recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared to those with no anticoagulation delay.

Results: Of 2378 patients with acute VTE, 100 (4.2%) experienced an anticoagulation delay. We identified seven reasons for treatment delays: deferring anticoagulation initiation to specialists (n = 38, thrombocytopenia (n = 10), planned or recent procedure (n = 16), active or recent bleeding (n = 12), missed diagnosis (n = 7), logistics (n = 6), and patient decision (n = 4). In seven cases, no reason was identified. We identified modifiable reasons for anticoagulation delay in 55%. At 90-day follow-up, patients with anticoagulation delay had a higher rate of mortality and major bleeding. VTE recurrence and CRNMB were not statistically different compared to those without anticoagulation delay. After adjustment for age, weight, and cancer, hazard ratios (HRs) for VTE recurrence and major bleeding remained elevated but not to a statistically significant level.

Conclusion: In the setting of a highly organized system of anticoagulation initiation, the incidence of treatment delay is low. Yet most delays could be avoided. A low number of cases provide insufficient power to evaluate the clinical consequences of anticoagulation initiation delay; however, elevated HR for VTE recurrence and major bleeding suggest association and need for further investigation.
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http://dx.doi.org/10.1002/rth2.12500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117818PMC
May 2021

Treatment of catheter-related thrombosis in patients with hematologic malignancies: A Venous thromboEmbolism Network U.S. retrospective cohort study.

Thromb Res 2021 06 6;202:155-161. Epub 2021 Apr 6.

Albert Einstein College of Medicine, Bronx, NY, USA; Montefiore Medical Center, New York City, NY, USA.

Introduction: Optimal treatment of catheter-related thrombosis (CRT) is uncertain in patients with hematologic malignancy. We aimed to evaluate the treatment strategies, outcomes, and predictors of recurrent venous thromboembolism (VTE) associated with catheter-related thrombosis (CRT) in patients with hematologic malignancy.

Methods: We performed a multicenter retrospective cohort study of eight institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies with documented CRT were identified using ICD-9 and ICD-10 diagnostic codes. Semi-competing risks proportional hazard regression models were created.

Results And Conclusions: Of the 663 patients in the cohort, 124 (19%) were treated with anticoagulation alone, 388 (58%) were treated with anticoagulation and catheter removal, 119 (18%) treated with catheter removal only, and 32 (5%) had neither catheter removal nor anticoagulation. 100 (15%) patients experienced a recurrent VTE event. In the 579 patients who had catheter removal, the most common reason for catheter removal was the CRT [392 (68%)]. For subjects who received any anticoagulation (n = 512), total anticoagulation duration was not associated with VTE recurrence [1.000 (0.999-1.002)]. After adjustment patients treated with catheter removal only had an increased risk of VTE recurrence [2.50 (1.24-5.07)] and death [4.96 (2.47-9.97)]. Patients with no treatment had increased risk of death [16.81 (6.22-45.38)] and death after VTE recurrence [27.29 (3.13-238.13)]. In this large, multicenter retrospective cohort, we found significant variability in the treatment of CRT in patients with hematologic malignancy. Treatment without anticoagulation was associated with recurrent VTE.
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http://dx.doi.org/10.1016/j.thromres.2021.03.021DOI Listing
June 2021

Prophylactic placement of inferior vena cava filters and the risk of death or venous thromboembolism in severe trauma patients: a retrospective study comparing two hospitals with different approaches.

Acta Radiol Open 2021 Mar 9;10(3):2058460121999345. Epub 2021 Mar 9.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: Prophylactic use of inferior vena cava filters to prevent pulmonary embolism in trauma is controversial. The practice varies between hospitals and countries, in part due to conflicting evidence and guidelines.

Purpose: To compare the effects of pulmonary embolism, deep venous thrombosis and mortality in two hospitals using prophylactic inferior vena cava filter placement or prophylactic anticoagulation alone.

Material And Methods: Patients presenting with severe trauma were recruited from two level-1 trauma centres between January 2008 and December 2013. Recruited patients from an US hospital having prophylactic inferior vena cava filter inserted were compared to a Scandinavian hospital using prophylactic anticoagulation alone. Inclusion criteria were age >15 years, Injury Severity Score >15 and survival >24 h after hospital admission. Patients with venous thromboembolism diagnosed prior to inferior vena cava filter placement were excluded. A Cox proportional hazard regression model was used with adjustment for immortal time bias and predictor variables.

Results: In total, 951 patients were reviewed, 282 from an US hospital having inferior vena cava filters placed and 669 from a Scandinavian hospital without inferior vena cava filters. The mean age was 45.9 vs. 47.4 years and the mean Injury Severity Score was 29.8 vs. 25.9, respectively. Inferior vena cava filter placement was not associated with the hazard of pulmonary embolism (Hazard ratio=0.43; 95% confidence interval (CI) 0.12, 1.45; P=0.17) or mortality (Hazard ratio=1.16; 95% CI 0.70, 1.95; P=0.56). However, an increased rate of deep venous thrombosis was observed with inferior vena cava filters in place (Hazard ratio=3.75; 95% CI 1.68, 8.36; P=0.001).

Conclusion: In severely injured trauma patients, prophylactic inferior vena cava filter placement was not associated with pulmonary embolism or mortality. However, inferior vena cava filters were associated with increased rate of deep venous thrombosis.
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http://dx.doi.org/10.1177/2058460121999345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952846PMC
March 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

Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 8;5(2):388-402. Epub 2021 Feb 8.

Division of Vascular Medicine, Mayo Clinic, Rochester, MN.

Objective: To evaluate differences in thromboinflammatory biomarkers between patients with severe coronavirus disease 2019 (COVID-19) infection/death and mild infection.

Patients And Methods: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched for studies comparing thromboinflammatory biomarkers in COVID-19 among patients with severe COVID-19 disease or death (severe/nonsurvivors) and those with nonsevere disease or survivors (nonsevere/survivors) from January 1, 2020, through July 11, 2020. Inclusion criteria were (1) hospitalized patients 18 years or older comparing severe/nonsurvivors vs nonsevere/survivors and (2) biomarkers of inflammation and/or thrombosis. A random-effects model was used to estimate the weighted mean difference (WMD) between the 2 groups of COVID-19 severity.

Results: We included 75 studies with 17,052 patients. The severe/nonsurvivor group was older, had a greater proportion of men, and had a higher prevalence of hypertension, diabetes, cardiac or cerebrovascular disease, chronic kidney disease, malignancy, and chronic obstructive pulmonary disease. Thromboinflammatory biomarkers were significantly higher in patients with severe disease, including D-dimer (WMD, 0.60; 95% CI, 0.49 to 0.71; =83.85%), fibrinogen (WMD, 0.42; 95% CI, 0.18 to 0.67; =61.88%; <.001), C-reactive protein (CRP) (WMD, 35.74; 95% CI, 30.16 to 41.31; =85.27%), high-sensitivity CRP (WMD, 62.68; 95% CI, 45.27 to 80.09; =0%), interleukin 6 (WMD, 22.81; 95% CI, 17.90 to 27.72; =90.42%), and ferritin (WMD, 506.15; 95% CI, 356.24 to 656.06; =52.02%). Moderate to significant heterogeneity was observed for all parameters ( > 25%). Subanalysis based on disease severity, mortality, and geographic region of the studies revealed similar inferences.

Conclusion: Thromboinflammatory biomarkers (D-dimer, fibrinogen, CRP, high-sensitivity CRP, ferritin, and interleukin 6) and marker of end-organ damage (high-sensitivity troponin I) are associated with increased severity and mortality in COVID-19 infection.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869679PMC
April 2021

Does prophylactic inferior vena cava filter reduce the hazard of pulmonary embolism and mortality in severe trauma? A single center retrospective comparative study.

Eur J Radiol Open 2021 10;8:100299. Epub 2020 Dec 10.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.

Objectives: Use of inferior vena cava (IVC) filters in patients following severe trauma without recent history of venous thromboembolism (VTE) is controversial. Our objective was to determine if IVC filter placement in the setting of severe trauma effects the hazard of in-hospital pulmonary embolism (PE), deep venous thrombosis (DVT) and mortality.

Methods: This retrospective study recruited patients from a single Level I Trauma Center between 1/2008 and 12/2013. Inclusion criteria were age>15 years, Injury Severity Score (ISS)>15 and survival>24 h after hospital admission. Patients with VTE diagnosed prior to IVC filter placement were excluded. A Cox proportional hazards regression model was used, adjusting for immortal time bias with landmark analysis at predefined time after injury. Differences between IVC filter and non-IVC filter groups were adjusted using propensity score.

Results: In total 1451 patients were reviewed; 282 patients received an IVC filter and 1169 patients had no IVC filter placed. The mean age was 45.9 vs. 56.9 years and the mean ISS was 29.8 vs. 22.6 in the IVC filter and the non-IVC filter group, respectively. IVC filter placement was not associated with the hazard of PE (HR = 0.46; 95 % CI, 0.12,1.70; P = 0.24) or mortality (HR = 1.02; 95 % CI 0.60,1.75; P = 0.93). However, IVC filter placement was associated with the hazard of DVT (HR = 2.73; 95 % CI, 1.28,5.85; P = 0.01).

Conclusions: In patients with severe trauma, those with prophylactic IVC filter placement did not have a reduced hazard of PE or mortality, but an increased hazard of DVT was observed.
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http://dx.doi.org/10.1016/j.ejro.2020.100299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734225PMC
December 2020

Anticoagulation in COVID-19: A Systematic Review, Meta-analysis, and Rapid Guidance From Mayo Clinic.

Mayo Clin Proc 2020 11 31;95(11):2467-2486. Epub 2020 Aug 31.

Evidence-based Practice Center and Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN. Electronic address:

A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve.
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http://dx.doi.org/10.1016/j.mayocp.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458092PMC
November 2020

Calf muscle pump function as a predictor of all-cause mortality.

Vasc Med 2020 12 25;25(6):519-526. Epub 2020 Sep 25.

Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 - December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( < 0.001), predominantly female ( = 0.01) and had higher mean Charlson scores ( < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.
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http://dx.doi.org/10.1177/1358863X20953212DOI Listing
December 2020

Calf Vein Thrombosis Comparison of Outcomes for Axial and Muscular Venous Thrombosis.

Thromb Haemost 2021 Feb 22;121(2):216-223. Epub 2020 Aug 22.

Gonda Vascular Center, Mayo Clinic, Rochester, Minnesota, United States.

Background:  The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins.

Methods:  Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016-August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared.

Results:  Over the study period, there were 647 patients with calf DVT equally distributed between axial ( = 321) and muscular ( = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%;  = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%,  = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%;  = 0.0017) and PE (3.4% vs. 0.6%;  = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%;  = 0.029).

Conclusion:  Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.
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http://dx.doi.org/10.1055/s-0040-1715646DOI Listing
February 2021

Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC).

Elife 2020 08 17;9. Epub 2020 Aug 17.

nference, inc, Cambridge, United States.

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVID) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVID) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVID patients at the time of diagnostic testing, COVID patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVID patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVID patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.
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http://dx.doi.org/10.7554/eLife.59209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473767PMC
August 2020

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

Eur J Haematol 2020 Oct 27;105(4):484-494. Epub 2020 Jul 27.

Gonda Vascular Center, Thrombophilia Clinic, Division of Vascular Medicine, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.

Objectives: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg.

Methods: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview.

Results: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01).

Conclusions: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.
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http://dx.doi.org/10.1111/ejh.13471DOI Listing
October 2020

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism.

Mayo Clin Proc Innov Qual Outcomes 2020 Jun 5;4(3):249-258. Epub 2020 Jun 5.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.

Objective: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome.

Methods: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories.

Results: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; =.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; =.02); when adjusted for cancer, the relationship was no longer significant (=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; =.66). Similar cumulative rates for CRNMB were observed (=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category.

Conclusion: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes.

Trial Registration: clinicaltrials.gov Identifier: NCT03504007.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283932PMC
June 2020

Venous Thromboembolism Prophylaxis: Need for Continuous Assessment Due to Changes in Risk During the Same Hospitalization.

Mayo Clin Proc Innov Qual Outcomes 2020 Apr 18;4(2):170-175. Epub 2020 Mar 18.

Division of Vascular Medicine, Mayo Clinic, Rochester, MN.

Objective: To explore the role of venous thromboembolism (VTE) risk reassessment in hospitalized medically ill patients without a change in level of care.

Patients And Methods: In this exploratory retrospective study, the medical records of 171 consecutive adult patients (≥18 years) hospitalized under the medicine service for more than 3 days without a change in the level of care from January 1, 2015, to March 1, 2015, were reviewed. The primary outcome was a change in the risk score between day 1 and day 3 of hospital stay (using the Padua Prediction Score). The secondary outcomes were changes in risk stratification class (low vs high) and cost-benefit analysis.

Results: The risk score was significantly different between day 1 and day 3 (4.7±1.7 vs 4.2±1.8; =.008). All the patients with low risk on day 1 remained at low risk on day 3. However, 25 of 136 patients (18.4%) with high risk on day 1 were reclassified as low risk on day 3 (<.001). No patients changed from low risk to high risk at day 3. The reclassification could have saved $35 per patient-day of inappropriate pharmacological prophylaxis in addition to patient discomfort, bleeding risk, and heparin-induced thrombocytopenia.

Conclusion: This is the first study to suggest the need for regular assessment for VTE risk on medicine wards because of changing patient risk. Regular reassessment could reduce health care waste and patient discomfort.
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http://dx.doi.org/10.1016/j.mayocpiqo.2019.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140011PMC
April 2020

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban.

Am J Hematol 2020 07 20;95(7):817-823. Epub 2020 Apr 20.

Gonda Vascular Center, Thrombophilia Clinic, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.
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http://dx.doi.org/10.1002/ajh.25820DOI Listing
July 2020

Hemoglobin levels and coronary heart disease risk by age, race, and sex in the reasons for geographic and racial differences in stroke study (REGARDS).

Am J Hematol 2020 03 22;95(3):258-266. Epub 2019 Dec 22.

Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont.

Higher and lower hemoglobin concentrations are associated with coronary heart disease (CHD), but whether this risk is consistent across age, sex, and race is unclear. The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study is an observational cohort study of 30 239 black, and white, adults aged 45 and older recruited 2003-7. Participants were included if they had hemoglobin measures, were CHD-free at baseline, and had all baseline variables. The primary outcome was incident CHD. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident CHD by hemoglobin concentration. This was expressed as a continuous variable and divided into age-, sex-, and race-specific quintiles. The 16 332 participants were included, contributing 114 362 person-years of follow-up and 915 incident CHD events. The mean age was 63 years, 35% were male, 41% were black, and the mean baseline hemoglobin was 13.6 g/dL (SD 1.4). A significant non-linear association between hemoglobin and CHD was identified (P < .001). This association differed significantly by race (P = .025) but not by sex or age. In whites, the risk for incident CHD was higher in the lowest (HR 2.28, 95% CI 1.61, 3.33) and highest (HR 1.94, 95% CI 1.35, 2.79) hemoglobin quintiles relative to the third quintile. For blacks, only those in the lowest hemoglobin quintile had an increased risk for incident CHD events (HR 1.70, 95% CI 1.20, 2.41). Hemoglobin is an independent risk factor for CHD in whites and blacks but with different hemoglobin concentrations conferring different risks.
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http://dx.doi.org/10.1002/ajh.25703DOI Listing
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

Resolution of acute lower extremity deep vein thrombosis with rivaroxaban compared to warfarin.

J Thromb Thrombolysis 2020 Feb;49(2):199-205

Department of Cardiovascular Diseases, Gonda Vascular Center, Thrombophilia Clinic, Mayo Clinic, 200 First Street, Rochester, MN, 55905, USA.

Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown whether rivaroxaban contributes to a higher degree of thrombus resolution compared to conventional anticoagulation with warfarin. Our objective was to compare thrombus resolution for rivaroxaban versus warfarin treated patients with acute lower extremity DVT. Consecutive patients treated for proximal or distal lower extremity DVT with rivaroxaban were identified from the Mayo Thrombophilia Clinic Anticoagulants Registry (November 2015-June 2016) and compared to patients treated with warfarin. Ultrasonography/Doppler images were analyzed by two independent radiologists blinded to anticoagulant and using a standardized assessment algorithm. A total of 111 patients with DVT were studied. Sixty-three rivaroxaban treated patients were compared to 48 warfarin treated patients over a median follow up of 92 and 97 days, respectively. Percentage of patients with total or partial resolution of thrombosis was similar in rivaroxaban and warfarin treated groups (95.2% vs. 91.7%, p = 0.46, respectively); also the proportion of patients with total thrombus resolution was not significantly different (38.1% vs. 29.2%, p = 0.42, respectively). There was no significant difference in the proportion of patients with no thrombus resolution between rivaroxaban and warfarin treated groups either (4.8% vs. 2.1%, p = 0.63). Thrombus propagation with warfarin therapy was observed in 6.3% of patients treated with warfarin and in none of the patients from the rivaroxaban group (p = 0.08). Resolution of acute lower extremity DVT in patients treated with rivaroxaban is similar to those treated with warfarin.
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http://dx.doi.org/10.1007/s11239-019-01932-8DOI Listing
February 2020

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.

Am J Hematol 2019 11 19;94(11):1185-1192. Epub 2019 Aug 19.

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

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.
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http://dx.doi.org/10.1002/ajh.25604DOI Listing
November 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

Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis.

Thromb Res 2018 12 28;172:94-103. Epub 2018 Oct 28.

University of North Carolina School of Medicine, Department of Medicine, Division of Hematology/Oncology, Chapel Hill, NC, USA.

Background: Testosterone prescribing for men has dramatically increased, and there have been concerns about inappropriate use and adverse events. While regulatory bodies have warned about increased risk of venous thromboembolism (VTE), published clinical data supporting an increased risk for VTE are limited.

Objective: To conduct a systematic review of studies examining the association between testosterone therapy in men and VTE.

Methods: Comprehensive searches of multiple databases were performed from inception through October 3rd, 2018. Randomized control trials (RCTs) and observational studies examining the association between exogenous testosterone (any route) and VTE. Study selection and data extraction were performed by two independent investigators. Random-effect model meta-analyses were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CIs). Heterogeneity among studies was evaluated using the I statistic. Risk of bias was assessed using the Cochrane and Newcastle-Ottawa tools.

Results: Six RCTs (n = 2236) and 5 observational studies (n = 1,249,640) were included. Five RCTs were performed in men with documented hypogonadism. The observational studies included: 2 case-control studies, 2 retrospective cohorts, and 1 retrospective cohort with a nested case-control study. There was no evidence of a statistically significant association between VTE and testosterone (OR 1.41, 95%CI 0.96-2.07). Heterogeneity was high (I-squared = 84.4%). The association remained nonsignificant when the analysis was stratified by study design: RCTs (2.05, 95% CI 0.78-5.39); cohort (1.06, 95% CI 0.85-1.33); and case-control (1.34, 95% CI 0.78-2.28). The overall risk of bias was moderate.

Conclusions: The current evidence is of low certainty but does not support an association between testosterone use and VTE in men.
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http://dx.doi.org/10.1016/j.thromres.2018.10.023DOI Listing
December 2018

Thrombosis of atypical location: how to treat patients in the era of direct oral anticoagulants?

Pol Arch Intern Med 2018 10 20;128(10):604-608. Epub 2018 Sep 20.

In 4% of cases, venous thromboembolism (VTE) involves organ‑related venous territories such as splanchnic, renal, gonadal, and cerebral venous segments, and is often called venous thromboembolism of atypical location (VTE‑AL). Recommendations regarding the method, intensity, and duration of anticoagulant therapy for VTE‑AL are not well established. Direct oral anticoagulants (DOACs) have been a promising alternative to vitamin K antagonists in the treatment of acute VTE. However, all major clinical trials on DOACs excluded patients with VTE‑AL. Therefore, data on the use of DOACs in patients with VTE‑AL are still limited to case reports and small clinical series, with a relative predominance of publications on splanchnic vein thrombosis including mesenteric, splenic, portal, and hepatic vein thrombosis. The only randomized clinical trial comparing a clinical outcome of patients with acute portal vein thrombosis randomized to either rivaroxaban or warfarin treatment yielded significantly impaired results due to the use of an atypical rivaroxaban dose. A prospective registration of clinical outcome for DOACs used in patients with VTE‑AL, in those with VTE of typical location, and in those with VTE‑AL treated with enoxaparin showed similar VTE recurrence and major bleeding rates in all 3 groups. High cancer prevalence, typical for VTE‑AL, significantly impacted survival as well as VTE recurrence rates and major bleeding outcomes in this study. In general, although still limited, the results for DOAC use in VTE‑AL are encouraging and we do not hesitate to use DOACs, particularly rivaroxaban or apixaban, in selected patients with VTE‑AL.
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http://dx.doi.org/10.20452/pamw.4333DOI Listing
October 2018

Antiphospholipid antibodies.

Vasc Med 2017 12 5;22(6):545-550. Epub 2017 Nov 5.

Department of Medicine, Division of Hematology-Oncology, The University of North Carolina, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1177/1358863X17737374DOI Listing
December 2017

Perils in the thrombophilia workup: Frequency and circumstances of erroneously ordered factor V activity tests for thrombophilia.

Vasc Med 2017 12 30;22(6):527-528. Epub 2017 Sep 30.

3 University of North Carolina, Department of Pathology and Laboratory Medicine, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1177/1358863X17728122DOI Listing
December 2017

Analysis of anticoagulation strategies for venous thromboembolism during severe thrombocytopenia in patients with hematologic malignancies: a retrospective cohort.

Leuk Lymphoma 2017 11 9;58(11):2573-2581. Epub 2017 Apr 9.

a Department of Medicine, Division of Hematology/Oncology , University of North Carolina , Chapel Hill , NC , USA.

The safety and efficacy of anticoagulation for venous thromboembolism (VTE) at times of severe thrombocytopenia is unclear. In this retrospective study, we evaluated patients with hematologic malignancy and either (1) acute or chronic VTE on anticoagulation before platelet count dropped below 50 × 10/L or (2) acute VTE occurring while platelets were <50 × 10/L. In 78 eligible patients, the primary outcomes of time to recurrent VTE or clinically significant bleeding within 100 d were compared by management strategy. Bleeding occurred in 27% of patients receiving anticoagulation versus 3% when anticoagulation was held (IRR 10.1, 95% CI 1.5-432.6). Recurrent VTE occurred in 2% of patients receiving anticoagulation versus 15% when anticoagulation was held (IRR 0.17, 95% CI 0.0-1.51). Most bleeding occurred before day 31(11/13), but recurrent VTE mostly occurred after day 40 (5/6). Our findings suggest that temporarily withholding anticoagulation for VTE during severe thrombocytopenia in patients with hematologic malignancies might reduce adverse outcomes.
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http://dx.doi.org/10.1080/10428194.2017.1306644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211440PMC
November 2017
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