Biomarker derived risk scores predict venous thromboembolism and major bleeding among patients with COVID-19

Scott C Woller, Scott M Stevens, Joseph R Bledsoe, Masarret Fazili, James F Lloyd, Greg L Snow, Benjamin D Horne, Scott C Woller, Scott M Stevens, Joseph R Bledsoe, Masarret Fazili, James F Lloyd, Greg L Snow, Benjamin D Horne

Abstract

Background: Venous thromboembolism (VTE) risk is increased in patients with COVID-19 infection. Understanding which patients are likely to develop VTE may inform pharmacologic VTE prophylaxis decision making. The hospital-associated venous thromboembolism-Intermountain Risk Score (HA-VTE IMRS) and the hospital-associated major bleeding-Intermountain Risk Score (HA-MB IMRS) are risk scores predictive of VTE and bleeding that were derived from only patient age and data found in the complete blood count (CBC) and basic metabolic panel (BMP).

Objectives: We assessed the HA-VTE IMRS and HA-MB IMRS for predictiveness of 90-day VTE and major bleeding, respectively, among patients diagnosed with COVID-19, and further investigated if adding D-dimer improved these predictions. We also reported 30-day outcomes.

Patients/methods: We identified 5047 sequential patients with a laboratory confirmed diagnosis of COVID-19 and a CBC and BMP between 2 days before and 7 days following the diagnosis of COVID-19 from March 12, 2020, to February 28, 2021. We calculated the HA-VTE IMRS and the HA-MB IMRS for all patients. We assessed the added predictiveness of D-dimer obtained within 48 hours of the COVID test.

Results: The HA-VTE IMRS yielded a c-statistic of 0.70 for predicting 90-day VTE and adding D-dimer improved the c-statistic to 0.764 with the corollary sensitivity/specificity/positive/negative predictive values of 49.4%/75.7%/6.7%/97.7% and 58.8%/76.2%/10.9%/97.4%, respectively. Among hospitalized and ambulatory patients separately, the HA-VTE IMRS performed similarly. The HA-MB IMRS predictiveness for 90-day major bleeding yielded a c-statistic of 0.64.

Conclusion: The HA-VTE IMRS and HA-MB IMRS predict 90- and 30-day VTE and major bleeding among COVID-19 patients. Adding D-dimer improved the predictiveness of the HA-VTE IMRS for VTE.

Keywords: biomarker; bleeding; risk score; thrombosis; venous thromboembolism.

© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier survival curve for 90‐day VTE based on the HA‐VTE IMRS using the threshold of ≥7 for high risk and p < 0.001). Abbreviations: HA‐VTE IMRS, hospital‐associated venous thromboembolism–Intermountain Risk Score; VTE, venous thromboembolism
FIGURE 2
FIGURE 2
Kaplan–Meier survival curves for 90‐day VTE using HA‐VTE IMRS ≥7 versus p = 0.47), (B) 0.5–2.0 (p = 0.003), (C) >2.0 (p = 0.75). Abbreviations: HA‐VTE IMRS, hospital‐associated venous thromboembolism–Intermountain Risk Score; VTE, venous thromboembolism
FIGURE 3
FIGURE 3
Kaplan–Meier survival curve for 90‐day major bleeding based on the HA‐MB IMRS using the threshold of ≥9 for high risk and p < 0.001). Abbreviations: HA‐MB IMRS, hospital‐associated major bleeding–Intermountain Risk Score
FIGURE 4
FIGURE 4
Receiver operating characteristic curves show the predictiveness of the HA‐VTE IMRS (green), and HA‐VTE IMRS + D‐dimer (blue) for 90‐day VTE; and the HA‐MB IMRS (red) for major bleeding. Abbreviations: HA‐MB IMRS, hospital‐associated major bleeding–Intermountain Risk Score; HA‐VTE IMRS, hospital‐associated venous thromboembolism–Intermountain Risk Score; VTE, venous thromboembolism

References

    1. Chan KW, Wong VT, Tang SCW. COVID‐19: an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese‐Western medicine for the management of 2019 novel coronavirus disease. Am J Chin Med. 2020;48(3):737‐762.
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497‐506.
    1. Porfidia A, Pola R. Venous thromboembolism in COVID‐19 patients. J Thromb Haemost. 2020;18(6):1516‐1517.
    1. Le Berre A, Marteau V, Emmerich J, Zins M. Concomitant acute aortic thrombosis and pulmonary embolism complicating COVID‐19 pneumonia. Diagn Interv Imaging. 2020;101(5):321‐322.
    1. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus‐infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061‐1069.
    1. Klok FA, Kruip M, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID‐19. Thromb Res. 2020;191:145‐147.
    1. Middeldorp S, Coppens M, van Haaps TF, et al. Incidence of venous thromboembolism in hospitalized patients with COVID‐19. J Thromb Haemost. 2020;18(8):1995‐2002.
    1. Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID‐19: a systematic review and meta‐analysis. Res Pract Thromb Haemost. 2020;4(7):1178‐1191.
    1. ATTACC Investigators , ACTIV‐4a Investigators , REMAP‐CAP Investigators , et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid‐19. N Engl J Med. 2021;385(9):790‐802.
    1. ATTACC Investigators , ACTIV‐4a Investigators , REMAP‐CAP Investigators , et al. Therapeutic anticoagulation with heparin in critically ill patients with Covid‐19. N Engl J Med. 2021;385(9):777‐789.
    1. Marone EM, Rinaldi LF. Upsurge of deep venous thrombosis in patients affected by COVID‐19: preliminary data and possible explanations. J Vasc Surg Venous Lymphat Disord. 2020;8(4):694‐695.
    1. Barnes BJ, Adrover JM, Baxter‐Stoltzfus A, et al. Targeting potential drivers of COVID‐19: neutrophil extracellular traps. J Exp Med. 2020;217(6):1‐7.
    1. Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID‐19. JCI Insight. 2020;5(11):e138999. doi:10.1172/jci.insight.138999
    1. Harzallah I, Debliquis A, Drenou B. Lupus anticoagulant is frequent in patients with Covid‐19. J Thromb Haemost. 2020;18(8):2064‐2065.
    1. Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and antiphospholipid antibodies in patients with Covid‐19. N Engl J Med. 2020;382(17):e38.
    1. Obi AT, Tignanelli CJ, Jacobs BN, et al. Empirical systemic anticoagulation is associated with decreased venous thromboembolism in critically ill influenza a H1N1 acute respiratory distress syndrome patients. J Vasc Surg Venous Lymphat Disord. 2019;7(3):317‐324.
    1. Webb BJ, Peltan ID, Jensen P, et al. Clinical criteria for COVID‐19‐associated hyperinflammatory syndrome: a cohort study. Lancet Rheumatol. 2020;2(12):e754‐e763.
    1. Artifoni M, Danic G, Gautier G, et al. Systematic assessment of venous thromboembolism in COVID‐19 patients receiving thromboprophylaxis: incidence and role of D‐dimer as predictive factors. J Thromb Thrombolysis. 2020;50(1):211‐216.
    1. Nauka PC, Baron SW, Assa A, et al. Utility of D‐dimer in predicting venous thromboembolism in non‐mechanically ventilated COVID‐19 survivors. Thromb Res. 2021;199:82‐84.
    1. Dujardin RWG, Hilderink BN, Haksteen WE, et al. Biomarkers for the prediction of venous thromboembolism in critically ill COVID‐19 patients. Thromb Res. 2020;196:308‐312.
    1. Demelo‐Rodriguez P, Farfan‐Sedano AI, Pedrajas JM, et al. Bleeding risk in hospitalized patients with COVID‐19 receiving intermediate‐ or therapeutic doses of thromboprophylaxis. J Thromb Haemost. 2021;19(8):1981‐1989.
    1. Flumignan RL, Tinoco JDS, Pascoal PI, et al. Prophylactic anticoagulants for people hospitalised with COVID‐19. Cochrane Database Syst Rev. 2020;10:CD013739.
    1. Woller SC, Stevens SM, Fazili M, et al. Post‐discharge thrombosis and bleeding in medical patients: a novel risk score derived from ubiquitous biomarkers. Res Pract Thromb Haemost. 2021;5(5):e12560.
    1. Woller SC, De Wit K, Hansen JB, et al. Predictive and diagnostic variables scientific standardization committee podium presentation: biomarkers predictive for VTE in hospitalized COVID‐19 patients: a systematic review. Paper presented at: International Society of Thrombosis and Haemostasis (ISTH2021); 17 July 2021, 2021; Virtual in Philedelphia.
    1. Evans RS, Lloyd JF, Aston VT, et al. Computer surveillance of patients at high risk for and with venous thromboembolism. AMIA Annu Symp Proc. 2010;2010:217‐221.
    1. Woller B, Daw A, Aston V, et al. Natural language processing performance for the identification of venous thromboembolism in an integrated healthcare system. Clin Appl Thromb Hemost. 2021;27:10760296211013108.
    1. Woller SC, Stevens SM, Evans RS, et al. Electronic alerts, comparative practitioner metrics, and education improve thromboprophylaxis and reduce venous thrombosis in community hospitals. Res Pract Thromb Haemost. 2018;2(3):481‐489.
    1. Woller SC, Stevens SM, Evans RS, et al. Electronic alerts, comparative practitioner metrics, and education improves thromboprophylaxis and reduces thrombosis. Am J Med. 2016;129(10):1124‐1126.
    1. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients. J Thromb Haemost. 2005;3(4):692‐694.
    1. Therneau TM, Grambsch PM. Modeling Survival Data: Extending the Cox Model. Springer; 2000.
    1. R Core Team . R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. 2021.
    1. Therneau TM. A package for survival analysis in R_. R package version 3.3‐1. 2022.
    1. Connors JM, Brooks MM, Sciurba FC, et al. Effect of antithrombotic therapy on clinical outcomes in outpatients with clinically stable symptomatic COVID‐19: the ACTIV‐4B randomized clinical trial. JAMA. 2021;326(17):1703‐1712.
    1. Ramacciotti E, Agati LB, Calderaro D, et al. Medically ill hospitalized patients for COVID‐19 THrombosis extended ProphyLaxis with rivaroxaban ThErapy: rationale and design of the MICHELLE trial. Am Heart J. 2021;242:115‐122.
    1. Schulman S. ISTH Draft Guidelines for Antithrombotic Treatment in COVID‐19. ISTH: International Society of Thrombosis and Haemostasis; 2022:1‐20.
    1. Lopes R. Dr. Renato Lopes and Dr. C. Michael Gibson Discuss: The MICHELLE trial: Medically Ill hospitalized Patients for COVID‐19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy. European Society of Cardiology. August 30, 2021 ed. Virtual2021. .
    1. Darzi AJ, Karam SG, Charide R, et al. Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta‐analysis. Blood. 2020;135(20):1788‐1810.
    1. Darzi AJ, Karam SG, Spencer FA, et al. Risk models for VTE and bleeding in medical inpatients: systematic identification and expert assessment. Blood Adv. 2020;4(12):2557‐2566.
    1. Spyropoulos AC, Lipardi C, Xu J, et al. Improved benefit risk profile of rivaroxaban in a subpopulation of the MAGELLAN study. Clin Appl Thromb Hemost. 2019;25(1076029619886022).
    1. Spyropoulos AC, Lipardi C, Xu J, et al. Modified IMPROVE VTE risk score and elevated D‐dimer identify a high venous thromboembolism risk in acutely ill medical population for extended thromboprophylaxis. TH Open. 2020;4(1):e59‐e65.
    1. Gibson CM, Spyropoulos AC, Cohen AT, et al. The IMPROVEDD VTE risk score: incorporation of D‐dimer into the IMPROVE score to improve venous thromboembolism risk stratification. TH Open. 2017;1(1):e56‐e65.
    1. Goldin M, Lin SK, Kohn N, et al. External validation of the IMPROVE‐DD risk assessment model for venous thromboembolism among inpatients with COVID‐19. J Thromb Thrombolysis. 2021;52(4):1032‐1035.
    1. Burles K, Innes G, Senior K, Lang E, McRae A. Limitations of pulmonary embolism ICD‐10 codes in emergency department administrative data: let the buyer beware. BMC Med Res Methodol. 2017;17(1):89.
    1. White RH, Garcia M, Sadeghi B, et al. Evaluation of the predictive value of ICD‐9‐CM coded administrative data for venous thromboembolism in the United States. Thromb Res. 2010;126(1):61‐67.
    1. Spyropoulos AC, McGinn T, Khorana AA. The use of weighted and scored risk assessment models for venous thromboembolism. Thromb Haemost. 2012;108(6):1072‐1076.
    1. McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS. Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence‐Based Medicine Working Group. JAMA. 2000;284(1):79‐84.

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