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      Heparin resistance in COVID-19 patients in the intensive care unit

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          Abstract

          Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.

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          Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

          Ning Tang, Dengju Li, Xiong Wang … (2020)
          Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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            Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia

            Songping Cui, Shuo Chen, Xiunan Li … (2020)
            Abstract Background Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world. Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned. Objectives To determine the incidence of VTE in patients with severe NCP. Methods In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled. The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed. Results The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died. The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc. If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%. Conclusions The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis. The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.
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              Hypercoagulability of COVID‐19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis

              Mauro Panigada, Nicola Bottino, Paola Tagliabue … (2020)
              Background The severe inflammatory state secondary to COVID‐19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D‐dimer, as well as low fibrinogen. Aims Whole blood from 24 patients admitted at the intensive care unit because of COVID‐19 was collected and evaluated with thromboelastography by the TEG point‐of‐care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis. Results TEG parameters are consistent with a state of hypercoagulability as shown by decreased values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D‐dimer was dramatically increased. C‐reactive protein was increased. Factor VIII and von Willebrand factor (n = 11) were increased. Antithrombin (n = 11) was marginally decreased and protein C (n = 11) was increased. Conclusion The results of this cohort of patients with COVID‐19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage, and optimal duration of prophylaxis.
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                Author and article information

                Contributors
                W. Thomas:
                ORCID: http://orcid.org/0000-0001-6969-3173
                william.thomas@addenbrookes.nhs.uk
                Journal
                Journal ID (nlm-ta): J Thromb Thrombolysis
                Journal ID (iso-abbrev): J. Thromb. Thrombolysis
                Title: Journal of Thrombosis and Thrombolysis
                Publisher: Springer US (New York )
                ISSN (Print): 0929-5305
                ISSN (Electronic): 1573-742X
                Publication date (Electronic): 22 May 2020
                Pages: 1-5
                Affiliations
                [1 ]GRID grid.24029.3d, ISNI 0000 0004 0383 8386, Department of Haematology, , Cambridge University Hospitals NHS Foundation Trust, ; Cambridge, UK
                [2 ]GRID grid.24029.3d, ISNI 0000 0004 0383 8386, Pharmacy Department, , Cambridge University Hospitals NHS Foundation Trust, ; Cambridge, UK
                [3 ]GRID grid.24029.3d, ISNI 0000 0004 0383 8386, Department of Intensive Care Medicine, , Cambridge University Hospitals NHS Foundation Trust, ; Cambridge, UK
                Author information
                http://orcid.org/0000-0001-6969-3173
                Article
                Publisher ID: 2145
                DOI: 10.1007/s11239-020-02145-0
                PMC ID: 7242778
                PubMed ID: 32445064
                SO-VID: d64d98a4-19c2-4df2-a6b9-6ad89a1a72ef
                Copyright © © Springer Science+Business Media, LLC, part of Springer Nature 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                Subject: Article

                ScienceOpen disciplines: Hematology
                Keywords: thrombosis,intensive care,covid-19,heparin
                Data availability:
                ScienceOpen disciplines: Hematology
                Keywords: thrombosis, intensive care, covid-19, heparin

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