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Anticoagulation in COVID – 19: An Update Cover

Figures & Tables

Table 1

Summary of important studies looking at haematological parameters in COVID – 19 patients. (aPTT - Activated Partial Thromboplastin time, FDP – Fibrin degradation products, PT – Prothrombin Time)

AuthorsSample Size (n)Haematological
Abnormalities (%)
Key Features
Chen et al. [29]99Elevated D-dimer - 36 (36%)
Thrombocytopenia – 12 (12%)
Prolonged aPTT – 6 (6%)
Prolonged PT – 5 (5%)
The first study to report both the clinical and laboratory features of COVID-19 related illness.
Wang et al. [30]138
(ICU – 36, Non-ICU – 102)
Prolonged PT – 80 (58%)
Elevated D-dimer - (26% of the patients from ICU)
1 – The levels of D-dimer were significantly higher in ICU patients than non-ICU patients. (p<0.001)
2 – The levels of D-dimer were significantly higher in non-survivors than survivors. (p<0.05)
3 – D-dimer levels showed an increasing trend in patients who succumbed to the illness.
Zhou et al. [31]191
(Survivors -137, Non-survivors – 54)
Elevated D-dimer
Survivors – 67 (57%)
Non-survivors – 50 (92%)
1 – A D-dimer level of >1.0 μg/mL at admission was associated with higher odds of mortality. OR=18.42 (p=0.0033)
2 – D-dimer levels were significantly higher in non-survivors than in survivors. (5.2 vs. 0.6, p<0.0001)
Huang et al. [32]41
(ICU – 13, Non-ICU – 28)
-1- Median D-dimer levels were significantly higher in ICU patients as compared to the non-ICU patients.
(2.4 vs. 0.5, p=0.0042)
2 – Median prothrombin time was significantly higher in ICU patients as compared to the non-ICU patients.
(12.2sec vs. 10.7sec, p=0.012)
Chen et al. [33]21
(Severe cases – 11, Moderate cases – 10)
-Compared to moderate cases, severe cases had significantly elevated levels of D-dimer.
(2.6 vs. 0.3, p=0.029)
Guan et al. [9]1099Elevated D-dimer
260/560 (46.4%)
D-dimer levels were significantly elevated in a higher proportion of patients with severe illness than those with non-severe illness.
(59.6 % vs. 43.2 %, p = 0.0021)
Han et al. [34]94 patients
40 healthy controls
-1- D-dimer levels were significantly higher in the patient group than the healthy control group.
(10.36 vs. 0.26, p<0.001)
2 – FDP levels were significantly higher in patients than in controls.
(33.83 vs. 1.55mg/L, p<0.001)
3- Higher D-dimer and FDP levels were found to be predictive of severe disease.
Li et al [35]279
(Ordinary - 136
Improved - 23
Poor- 120)
-The D-dimer levels on admission were significantly higher in the improved and poor group of patients than ordinary patients.
(p<0.01)
Ordinary – Mild disease, subsidedImproved – First deteriorated, then improved gradually with treatment Poor – Deteriorated or died
Tang et al. [12]183
(Survivors – 162, Non-survivors – 21)
-Abnormal coagulation tests (Elevated D-dimer, FDPs and decreased fibrinogen) were associated with a poorer prognosis, i.e. these parameters were significantly deranged in non-survivors than the survivors.
Table 2

Summary of the interim guidelines published by some of the societies and forums. (aPTT – Activated Partial Thromboplastin Time, DOAC – Direct Oral Anticoagulant, ESC – European Society of Cardiology, ISTH – International Society on Thrombosis and Haemostasis, LMWH – Low Molecular Weight Heparin, VTE – Venous Thromboembolism)

Society/ForumRecommendations
European Society of Cardiology
(ESC) [25]
1 – All admitted patients with COVID-19 related illnesses should get, at the least, prophylactic dose of enoxaparin (40mg daily).
2 - Depending on the clinical features, a patient at a high risk of thromboembolism should receive therapeutic dose anticoagulation. It can be in the form of a heparin drip (per parenteral protocol) or enoxaparin (1mg/kg twice a day) based on whether the patient is in the intensive care unit or not.
3 - Patients at low risk of thromboembolism are further classified based on the D-dimer levels.
A) D-dimer <0.5 μg/mL = Prophylactic dose anticoagulation (Enoxaparin 40mg/day)
B) D-dimer 0.5 to 3.0 μg/mL = Enoxaparin 40mg twice a day
C) D-dimer >3.0 μg/mL = Enoxaparin 1mg/kg twice a day
4 - The patients at high risk of thromboembolism and having markedly elevated D-dimer (>3.0 μg/mL) should undergo a point-of-care ultrasound. Based on its results, a call should be on whether to continue therapeutic dose or switch to prophylactic dose anticoagulation.
International society of thrombosis and haemostasis (ISTH) on the management of coagulopathy [26]1 - Patients having one/more of the following should be admitted to the hospital.
A) Markedly raised D-dimer (>3-4 times of the normal)
B) Prolonged prothrombin time
C) Platelet count of <100 × 109/L
D) Fibrinogen concentration <2.0 g/L
2 - All admitted patients, in the absence of contraindications - should receive prophylactic dose anticoagulation (LMWH).
Scientific and standardization committee by ISTH - guidance on prevention and treatment of VTE [27]1 - Universal routine thromboprophylaxis should be given in all admitted patients of COVID-19 related illnesses.
(LMWH as preferred agent)
2 - Dose should be modified appropriately in patients with renal failure and obesity as required.
3 - Intermediate dose anticoagulation can be a reasonable option in patients admitted to ICU with COVID-19 related illnesses.
4 - Extended post-discharge thromboprophylaxis should be considered in patients that are a high risk of thromboembolism. The duration can be up to 30 days post-discharge.
Interim clinical guidance from the anticoagulation forum [28]1 - All hospitalized patients, with COVID-19 related illnesses, should receive prophylactic anticoagulation.
2 - Escalated dose anticoagulation should be considered in critically ill (ICU) patients.
3 - To monitor the anticoagulant activity of heparin, an anti-factor-Xa assay should be used in place of aPTT as the baseline aPTT may be abnormal in some COVID-19 patients.
4 – Post-discharge VTE prophylaxis may be considered on a case-to-case basis in COVID -19 patients that have one/more of the following-
A) Prolonged ICU stay
B) Paralyzed for a long time
C) Risk factor for VTE at the time of discharge (Decreased mobility, severe weakness)
5 – All pregnant patients of COVID-19 should receive prophylactic dose anticoagulation for the prevention of VTE.
6 – Patients on vitamin K antagonists (warfarin) should be transitioned to directly acting oral anticoagulants (DOACs), except for indications like mechanical heart valves, antiphospholipid antibody syndrome.
DOI: https://doi.org/10.2478/jccm-2020-0033 | Journal eISSN: 2393-1817 | Journal ISSN: 2393-1809
Language: English
Page range: 217 - 223
Submitted on: Jul 14, 2020
Accepted on: Sep 16, 2020
Published on: Nov 7, 2020
Published by: University of Medicine, Pharmacy, Science and Technology of Targu Mures
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2020 Nishant R Tiwari, Khalid I Khatib, Subhal B Dixit, Prajay K Rathore, Sameer Melinkeri, Abhijeet Ganapule, Kapil S Borawake, Ujwala Mhatre, published by University of Medicine, Pharmacy, Science and Technology of Targu Mures
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