Impact on coagulation due to coronavirus

Viral infections caused by SARS-CoV-2, SARS-CoV-1 or MERS-CoV may lead to coagulation disturbances and thromboembolic complications. It is important to understand the impact of the infection on blood coagulation both for treatment and prophylaxis.

Question

What scientific studies are there on (1) the impact on coagulation, (2) treatment of thromboembolic complications and (3) treatment of patients with an ongoing anticoagulantic drug treatment, during infection with SARS-CoV 2, Sars-CoV-1 or Mers-CoV?

Method

SBU’s Enquiry Service identifies and summarizes systematic reviews or scientific studies which answer specific questions posed by decision makers and health care personnel. For this response, PubMed, Embase, and Cinahl were systematically searched on May 4th 2020. Records relevant to the question posed were identified and assessed for risk of bias by two independent persons. Systematic reviews were assessed for risk of bias using AMSTAR [1] and the identified primary studies were assessed for risk of bias using  translations of ROBINS-I [2,3]. This response does not attempt to weigh together or grade the reliability of the results presented.

Identified literature

We identified two relevant systematic reviews [4,5]  and eleven primary studies [6-16]. One relevant systematic [17] review was assessed as having a high risk of bias and its results are not presented.

Table 1. Systematic reviews with low/medium risk of bias

Included studies Population Outcome
Violi et al. 2020 [5]
9 cohort studies from China Patients with covid-19,  severely ill and non-severe patients, total n=2 109 D-dimer, platelet count, prothrombin time, activated partial thromboplastin time, alanine aminotransferase, aspartate aminotransferase
Authors' conclusion:
“The data so far reported are suggestive of low-grade intravascular clotting activation, which is evident overall in patients with severe disease. The finding more consistent in support of this hypothesis is the increase of D-dimer”
Henry et al, 2020 [4]
21 cohort studies from Asia Laboratory confirmed covid-19 patients, total n=3 377 Hematologic (count of WBC, neutrophil, lymphocyte, monocyte, platelet and eosinophil, CD4, CD8, hemoglobin); Biochemical (albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, creatine kinase, lactate dehydrogenase, myoglobin, creatine kinase-MB, cardiac troponin); Coagulation (prothrombin, APTIT, D-dimer); Inflammatory biomarkers (erythrocyte sedimentation rate, CRP, serum ferritin, PCT, IL1, IL-2R, IL-6,IL-8, IL-10, TNF)
Authors' conclusion:
“Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal covid-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.”

 

Table for included primary studies – Question 1: What scientific studies are there on the impact on coagulation during infection with SARS-CoV 2, Sars-CoV-1 or Mers-CoV?

Table for included primary studies – Question 2: What scientific studies are there on treatment of thromboembolic complications during infection with SARS-CoV 2, Sars-CoV-1 or Mers-CoV?

References

  1. Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, Grimshaw J, et al. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol 2009;62:1013-20.
  2. SBU. Bedömning av randomiserad studie. Stockholm: Statens beredning för medicinsk och social utvärdering (SBU); 2020. [cited 2020 June 15]. Available from: https://www.sbu.se
  3. SBU. Bedömning av icke randomiserad studie (retrospektiv och prospektiv ITT). Stockholm: Statens beredning för medicinsk och social utvärdering (SBU); 2020. [cited 2020 June 15]. Available from: https://www.sbu.se
  4. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020.
  5. Violi F, Pastori D, Cangemi R, Pignatelli P, Loffredo L. Hypercoagulation and Antithrombotic Treatment in Coronavirus 2019: A New Challenge. Thromb Haemost 2020;120:949-956.
  6. Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020;191:9-14.
  7. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020;18:1324-9.
  8. Zou Y, Guo H, Zhang Y, Zhang Z, Liu Y, Wang J, et al. Analysis of coagulation parameters in patients with COVID-19 in Shanghai, China. Biosci Trends 2020.
  9. Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol 2020;92:791-6.
  10. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020;368:m1091.
  11. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020;46:1089-1098.
  12. Spiezia L, Boscolo A, Poletto F, Cerruti L, Tiberio I, Campello E, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost 2020;120:998-1000.
  13. Chen RF, Chang JC, Yeh WT, Lee CH, Liu JW, Eng HL, et al. Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS). Microbes Infect 2006;8:122-7.
  14. 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. J Thromb Haemost 2020;18:1094-9.
  15. Yin S, Huang M, Li D, Tang N. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J Thromb Thrombolysis 2020:1-4.
  16. Liu X, Li Z, Liu S, Sun J, Chen Z, Jiang M, et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020.
  17. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta 2020;506:145-148.

SBU Enquiry Service Consists of structured literature searches to highlight studies that can address questions received by the SBU Enquiry Service from Swedish healthcare or social service providers. We assess the risk of bias in systematic reviews and when needed also quality and transferability of results in health economic studies. Relevant references are compiled by an SBU staff member, in consultation with an external expert when needed.

Published: 6/24/2020
Contact SBU: registrator@sbu.se
Report no: ut202026
Registration no: SBU 2020/460