Utility of D-dimer as a Prognostic Factor in SARS CoV2 Infection: A Review

Pramod Theetha Kariyanna¹, Lyudmila Aurora¹, Apoorva Jayarangaiah², Vivek Yadav³, Naseem. A. Hossain¹, Nasrin Akter¹, Moro O. Salifu¹ and Isabel M. McFarlane^1,

¹Department of Internal Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, New York, U.S.A

²Department of Internal Medicine, Albert Einstein College of Medicine, NYC Health and Hospitals/Jacobi Medical Center, Bronx, New York-10461, U.S.A

³Department of Internal Medicine, Brookdale University Hospitals and Medical Center, 1 Brookdale Plaza, Brooklyn, New York- 11212, USA

Cite this paper

Pramod Theetha Kariyanna, Lyudmila Aurora, Apoorva Jayarangaiah, Vivek Yadav, Naseem. A. Hossain, Nasrin Akter, Moro O. Salifu and Isabel M. McFarlane. Utility of D-dimer as a Prognostic Factor in SARS CoV2 Infection: A Review. American Journal of Medical Case Reports. 2020; 8(10):337-340. doi: 10.12691/AJMCR-8-10-5

Abstract

Coronavirus Disease-2019 (COVID-19) is currently a public health emergency and has been listed by the World Health Organization (WHO) as a pandemic. It has commonly been associated with pulmonary manifestations and there is a growing body of evidence of multisystem involvement of the virus. As evidenced by various case reports and cohort studies, COVID-19-associated coagulopathy has been a common manifestation amongst the critically ill and has been associated with increased mortality. The presence of venous thromboembolic events in patients who are critically ill due to COVID-19 has prompted the adoption of anticoagulation regimens aimed at preventing thromboembolic phenomena. Coagulation abnormalities have also been implicated in the progression and the severity of COVID-19 related acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). There is strong evidence that D-dimer levels help predict which patients are at risk of thromboembolic events, progression to ARDS, DIC, immune dysregulation and mortality. We will review the utility of D-dimer as screening tool and in the risk stratification of COVID-19 patients prone to developing thromboembolic events, DIC, immune dysregulation and death. To date, the studies that have been published show the presence of elevated D-dimer levels in both the adult and pediatric populations and the measured level correlates with disease severity. Studies have also shown the relative increase of D-dimer levels in non-survivors compared to survivors. The elevation of D-dimer levels has shown to guide clinical decision making, namely the initiation of therapeutic anticoagulation and mortality benefit in patients with severe COVID-19 pneumonia compared to severe non COVID-19 pneumonia. Although the current body of literature suggested the use of D-dimer as a risk stratification tool and as a test to augment clinical judgement regarding the initiation of anticoagulation, randomized control trials are needed to fully understand the relationship between COVID-19 infection and the efficacy of D-dimer assays in clinical decision making.

Keywords

COVID-19, Corona Virus, D-dimer, microvascular thrombosis and macrovascular thrombosis

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References

[1]	WHO. Novel coronavirus-China. Jan 12, 2020. Available online: http: //www.who. int/csr/don/12-january-2020- novel-coronavirus-china/en/ (accessed Jan 19, 2020).
[2]	Bulut C, Kato Y. Epidemiology of COVID-19. Turkish journal of medical sciences. 2020 Apr 21; 50(SI-1): 563-70.
[3]	Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD. A pneumonia outbreak associated with a new coronavirus of probable bat origin. nature. 2020 Mar; 579(7798): 270-3.
[4]	Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P. A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine. 2020 Jan 24.
[5]	Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 2020 Feb 15; 395(10223): 514-23.
[6]	Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020 Feb 15; 395(10223): 497-506.
[7]	Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, Qin R, Wang H, Shen Y, Du K, Zhao L. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes/metabolism research and reviews. 2020 Mar 31.
[8]	Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Yu T. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020 Feb 15; 395(10223): 507-13.
[9]	Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nature medicine. 2005 Aug; 11(8): 875-9.
[10]	Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circulation research. 2016 Apr 15; 118(8): 1313-26.
[11]	Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme cloning and functional expression as a captopril-insensitive carboxypeptidase. Journal of Biological Chemistry. 2000 Oct 27; 275(43): 33238-43.
[12]	Zhang H, Li HB, Lyu JR, Lei XM, Li W, Wu G, Lyu J, Dai ZM. Specific ACE2 Expression in Small Intestinal Enterocytes may Cause Gastrointestinal Symptoms and Injury after 2019-nCoV Infection. International Journal of Infectious Diseases. 2020 Apr 18.
[13]	Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020 Apr 1.
[14]	Kollias A, Kyriakoulis KG, Dimakakos E, Poulakou G, Stergiou GS, Syrigos K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: Emerging evidence and call for action. British journal of haematology. 2020 Apr 18.
[15]	Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, Pesenti A, Peyvandi F, Tripodi A. Hypercoagulability of COVID-19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis. Journal of Thrombosis and Haemostasis. 2020 Apr 17.
[16]	Wang J, Hajizadeh N, Moore EE, McIntyre RC, Moore PK, Veress LA, Yaffe MB, Moore HB, Barrett CD. Tissue plasminogen activator (tpa) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series. Journal of thrombosis and haemostasis. 2020 Apr 8.
[17]	Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, Ferraz da Silva LF, Pierre de Oliveira E, Nascimento Saldiva PH, Mauad T, Marcia Negri E. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. Journal of Thrombosis and Haemostasis. 2020 Apr 15.
[18]	Kariyanna PT, Hossain NA, jayarangaiah A, Hossain NA, Uppin V, Hegde S, Capric V, Salifu MO, McFarlane SI. Thrombus in transit and impending pulmonary embolism detected on POCUS in a a patient with COVID-19 pneumonia. American Journal of medical Case Reports. 2020 May 05.
[19]	Kariyanna PT, Hossain NA, Jayarangaiah A, Hossain NA, Francois JC, Marmur JD, Salifu MO, McFarlane SI. Pharmaco-invasive Therapy for STEMI in a Patient with COVID-19: A Case Report. American Journal of medical Case Reports. 2020 April 22.
[20]	Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020 Apr 9.
[21]	Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clinical Chemistry and Laboratory Medicine (CCLM). 2020 Mar 16; 1(ahead-of-print).
[22]	Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama. 2020 Mar 17; 323(11): 1061-9.
[23]	Yang X, Yu Y, Xu J, Shu H, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020 Feb 24.
[24]	Li T, Lu H, Zhang W. Clinical observation and management of COVID-19 patients. Emerging Microbes & Infections. 2020 Jan 1; 9(1): 687-90.
[25]	Xu JF, Wang L, Zhao L, Li F, Liu J, Zhang L, Li Q, Gu J, Liang S, Zhao Q, Liu J. Risk assessment of venous thromboembolism and bleeding in COVID-19 patients. Respiratory Research. 2020 Mar 24.
[26]	Luo W, Yu H, Gou J, Li X, Sun Y, Li J, Liu L. Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19). Preprints. 2020 Feb 27; 2020: 2020020407.
[27]	Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C. Covid-19 Cases: Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. The New England Journal of Medicine.
[28]	Minet C, Potton L, Bonadona A, Hamidfar-Roy R, Somohano CA, Lugosi M, Cartier JC, Ferretti G, Schwebel C, Timsit JF. Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis. Critical Care. 2015 Dec; 19(1): 287.
[29]	Malato A, Dentali F, Siragusa S, Fabbiano F, Kagoma Y, Boddi M, Gensini GF, Peris A, Crowther M, Napolitano M. The impact of deep vein thrombosis in critically ill patients: a meta-analysis of major clinical outcomes. Blood Transfusion. 2015 Oct; 13(4): 559.
[30]	Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiology: Cardiothoracic Imaging. 2020 Mar 16; 2(2): e200067.
[31]	Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M, Falco M, Albano G, Menicanti L. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. Journal of Thrombosis and Haemostasis. 2020 Apr 17.
[32]	Long B, Brady WJ, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. The American Journal of Emergency Medicine. 2020 Apr 18.
[33]	Ji HL, Zhao R, Matalon S, Matthay MA. Elevated plasmin (ogen) as a common risk factor for COVID-19 susceptibility. Physiological Reviews. 2020 Jul 1; 100(3): 1065-75.
[34]	Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, Zhu H, Hu K, Liu J, Liu Z, Wang S. Clinical characteristics of 82 death cases with COVID-19. medRxiv. 2020 Jan 1.
[35]	Thachil J. The versatile heparin in COVID-19. Journal of Thrombosis and Haemostasis. 2020 Apr 2.
[36]	Liu Y, Sun W, Li J, Chen L, Wang Y, Zhang L, Yu L. Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019. medRxiv.
[37]	Li X, Wang L, Yan S, Yang F, Xiang L, Zhu J, Shen B, Gong Z. Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China. International Journal of Infectious Diseases. 2020 Apr 3.
[38]	Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, Caricchio R, Mahmud S, Hazen MM, Halyabar O, Hoyt KJ. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis & Rheumatology. 2020 Apr 15.
[39]	Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X. Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of clinical investigation. 2020 Apr 13; 130(5).
[40]	Zhang G, Zhang J, Wang B, Zhu X, Wang Q, Qiu S. Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis. Respiratory research. 2020 Dec; 21(1): 1-0.
[41]	Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, Lang C, Huang D, Sun Q, Xiong Y, Huang X. Clinical features and treatment of COVID-19 patients in northeast Chongqing. Journal of medical virology. 2020 Mar 21.
[42]	Gao Y, Li T, Han M, Li X, Wu D, Xu Y, Zhu Y, Liu Y, Wang X, Wang L. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. Journal of Medical Virology. 2020 Mar 17.
[43]	Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020 Mar 11.
[44]	Wu C, Chen X, Cai Y, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA internal medicine. 2020 Mar 13.
[45]	Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Feb 19.
[46]	Yin S, Huang M, Li D, Tang N. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. Journal of Thrombosis and Thrombolysis. 2020 Apr 3: 1.
[47]	Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DS, Du B. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine. 2020 Apr 30; 382(18): 1708-20.
[48]	Zheng Y, Xu H, Yang M, Zeng Y, Chen H, Liu R, Li Q, Zhang N, Wang D. Epidemiological characteristics and clinical features of 32 critical and 67 noncritical cases of COVID-19 in Chengdu. Journal of Clinical Virology. 2020 Apr 10: 104366.
[49]	Porfidia A, Pola R. Venous thromboembolism in COVID-19 patients. Journal of Thrombosis and Haemostasis. 2020 Apr 15.
[50]	Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. The Lancet Infectious Diseases. 2020 Mar 25.
[51]	Zhang Y, Cao W, Xiao M, Li YJ, Yang Y, Zhao J, Zhou X, Jiang W, Zhao YQ, Zhang SY, Li TS. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua xue ye xue za zhi= Zhonghua Xueyexue Zazhi. 2020 Mar 28; 41: E006.
[52]	Zhu J, Ji P, Pang J, Zhong Z, Li H, He C, Zhang J, Zhao C. Clinical characteristics of 3,062 COVID-19 patients: a meta-analysis. Journal of Medical Virology. 2020 Apr 15.
[53]	Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. Bmj. 2020 Mar 26; 368.
[54]	Zhou Y, Zhang Z, Tian J, Xiong S. Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Annals of Palliative Medicine. 2020 Mar 17; 9(2): 428-36.
[55]	Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. Journal of Thrombosis and Haemostasis. 2020 May; 18(5): 1094-9.
[56]	Li J, Li Y, Yang B, Wang H, Li L. Low-molecular-weight heparin treatment for acute lung injury/acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2018 Jan 1; 11(2): 414-22.
[57]	Hanify JM, Dupree LH, Johnson DW, Ferreira JA. Failure of chemical thromboprophylaxis in critically ill medical and surgical patients with sepsis. Journal of critical care. 2017 Feb 1; 37: 206-10.