Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients

K Stattin, M Lipcsey, H Andersson, E Pontén, S Bülow Anderberg, A Gradin, A Larsson, N Lubenow, M von Seth, S Rubertsson, M Hultström, R Frithiof, K Stattin, M Lipcsey, H Andersson, E Pontén, S Bülow Anderberg, A Gradin, A Larsson, N Lubenow, M von Seth, S Rubertsson, M Hultström, R Frithiof

Abstract

Purpose: The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients.

Material and methods: We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously).

Results: Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity.

Conclusions: Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.

Keywords: COVID-19; Intensive care; Low-molecular-weight heparin; Thrombelastography; Thromboembolism.

Conflict of interest statement

Declaration of Competing Interest None.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
The association between dalteparin dose and anti-factor Xa in the cohort with corresponding Spearman rank correlation coefficient.

References

    1. Klok F.A., Kruip M., van der Meer N.J.M., Arbous M.S., Gommers D., Kant K.M., et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145–147. (10.1016)
    1. Daniel E.L., Clifford S.D., Matthieu L. Facing COVID-19 in ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020;46(6):1105–1108. (10.1007)
    1. Bikdeli B., Wang Y., Jimenez D., Ross J., Desai M., Parikh S., et al. Pulmonary embolism hospitalizations and use of inferior vena caval filters in older adults: national study of medicare beneficiaries. J Am Coll Cardiol. 2019;73:9. (10.1016)
    1. Xie Y., Wang X., Yang P., Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiol Cardiothorac Imaging. 2020;2(2)
    1. Wu Y., Xu X., Chen Z., Duan J., Hashimoto K., Yang L., et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18–22. (10.1016)
    1. Du Y., Tu L., Zhu P., Mu M., Wang R., Yang P., et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational study. Am J Respir Crit Care Med. 2020;201(11):1372–1379. (10.1164)
    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
    1. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–1720. (10.1056)
    1. 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(5):1094–1099. (10.1111)
    1. Wei M.Y., Ward S.M. The anti-factor Xa range for low molecular weight heparin Thromboprophylaxis. Hematol Rep. 2015;7(4):5844. (10.4081)
    1. Moreno R.P., Metnitz P.G., Almeida E., Jordan B., Bauer P., Campos R.A., et al. SAPS 3--from evaluation of the patient to evaluation of the intensive care unit. Part 2: development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med. 2005;31(10):1345–1355.
    1. Dias J.D., Haney E.I., Mathew B.A., Lopez-Espina C.G., Orr A.W., Popovsky M.A. New-generation thromboelastography: comprehensive evaluation of citrated and heparinized blood sample storage effect on clot-forming variables. Arch Pathol Lab Med. 2017;141(4):569–577.
    1. Ranucci M., Ballotta A., Di Dedda U., Bayshnikova E., Dei Poli M., Resta M., et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020;18:1747–1751. (10.1111)
    1. 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(6):998–1000. (10.1055)
    1. Panigada M., Bottino N., Tagliabue P., Grasselli G., Novembrino C., Chantarangkul V., et al. Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020;18(7):1738–1742. (10.1111)
    1. Brown W., Lunati M., Maceroli M., Ernst A., Staley C., Johnson R., et al. The ability of thromboelastography to detect hypercoagulability. J Orthop Trauma. 2019;34(6):278–286. (10.1097)
    1. Gary J., Schneider P., Galpin M., Radwan Z., Munz J., Achor T., et al. Can Thrombelastography predict venous thromboembolic events in patients with severe extremity trauma? J Orthop Trauma. 2016;30:294–298.
    1. Cook D., Meade M., Guyatt G., Walter S., Heels-Ansdell D., Warkentin T.E., et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011;364(14):1305–1314.
    1. Thachil J., Tang N., Gando S., Falanga A., Cattaneo M., Levi M., et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18(5):1023–1026. (10.1111)
    1. Garcia D.A., Baglin T.P., Weitz J.I., Samama M.M. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S–e43S.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere