Abstract Number: PB0244
Meeting: ISTH 2021 Congress
Theme: COVID and Coagulation » COVID and Coagulation, Clinical
Background: Critically-ill COVID-19 patients demonstrate a hypercoagulable state, hence necessitating thromboprophylaxis. However, in non-critically ill COVID-19 patients, the haemostatic profile is unknown.
Aims: A prospective, observational study was performed to evaluate coagulation parameters, and thrombotic outcomes in critically and non-critically ill COVID-19 patients.
Methods: Informed consent was obtained from 10 critically ill (oxygen dependent, PaO2/FiO2 ratio<300) PCR positive COVID-19 patients matched for age and gender with 10 non-critically ill patients (non-oxygen dependent). On recruitment, laboratory (FBC/LDH/CRP/procalcitonin) and coagulation tests (PT/APTT/D-Dimer/Fibrinogen/TCT/Factors II,V,VII,VIII,IX,X,XI/vWF/anti-thrombinIII/ProteinC/ProteinS/antiphospholipid antibodies), Thromboelastography(TEG), Clot Waveform Analysis(CWA) were performed, with repeat TEG/CWA every 3 days, till 21 days of admission or discharge. This study was DSRB approved and supported by an NHG-NCID grant.
Results: The median age was 60 years(49.5,64.5) with 16 males and 4 females. Median Padua score of critically ill patients was 5 with PaO2/FiO2 ratio 194.5(174,241). Hypercoagulability was present in critically ill patients with elevated median levels of Fibrinogen 5.6g/L(4.9,6.6), D-dimer 1.0ug/ml(0.6,1.4), Factor VIII 206%(171,230), von Willebrand Factor 265%(206,321) as compared with lower levels in non-critically ill patients. Hypercoagulability was shown in TEG with increased CRT Angle 78.9˚(78.3,80.0), CFF MA 34.6mm(27.4,38.6) and CFF A10 30.9sec(25.5, 34.0); and CWA had increased clot velocity, aPTT Min1 7.7%/s(6.4,8.3). CK K, CK Angle, CK MA, CRT MA were higher in critically ill patients (Table 1). In non-critically ill patients, D-dimer levels were normal, 0.3ug/mL(0.3,0.4) while Factor VIII levels of 176%(157,192) and vWF levels of 225%(158,237) were mildly elevated, with TEG and CWA demonstrating no hypercoagulability. 2 critically-ill patients developed thromboembolism(stroke, DVT) while no non-critically ill patients (not on thromboprophylaxis) had thrombosis.
Tests (Reference Range) | Overall | Non critically ill patients (n=10) |
Critically ill patients (n=10) |
p-value |
Thromoboelastography (TEG†) CK K (TEG) (0.8-2.1 min) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
1.3 (0.9, 1.6) 0.8 (0.8, 1.3) 0.8 (0.8, 1.1) 1.0 (0.8, 1.2) 1.1 (1.0, 1.3) 1.2 (1.0, 1.8) 1.1 (1.1, 1.1) 0.8 (0.8, 0.8) |
1.6 (1.3, 2.1) – – – – – – – |
1.1 (0.9, 1.2) 0.8 (0.8, 1.3) 0.8 (0.8, 1.1) 1.0 (0.8, 1.2) 1.1 (1.0, 1.3) 1.2 (1.0, 1.8) 1.1 (1.1, 1.1) 0.8 (0.8, 0.8) |
0.008 – – – – – – – |
CK Angle (TEG) (63-78 degrees) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
73.9 (69.1, 76.0) 76.8 (71.5, 78.2) 77.6 (74.6, 80.5) 75.7 (73.8, 78.1) 73.0 (64.5, 74.6) 74.4 (68.6, 77.8) 74.8 (74.8, 74.8) 78.8 (78.8, 78.8) |
69.1 (64.6, 74.5) – – – – – – – |
75.3 (73.4, 77.2) 76.8 (71.5, 78.2) 77.6 (74.6, 80.5) 75.7 (73.8, 78.1) 73.0 (64.5, 74.6) 74.4 (68.6, 77.8) 74.8 (74.8, 74.8) 78.8 (78.8, 78.8) |
0.01 – – – – – – – |
CK MA (TEG) (52-69 mm) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
62.4 (58.7, 67.8) 68.2 (65.6, 69.3) 67.8 (65.2, 70.5) 68.5 (65.5, 69.9) 67.2 (64.6, 71.3) 64.6 (63.3, 67.8) 69.3 (69.3, 69.3) 70.2 (70.2, 70.2) |
58.8 (57.2, 59.9) – – – – – – – |
66.6 (64.2, 69.6) 68.2 (65.6, 69.3) 67.8 (65.2, 70.5) 68.5 (65.5, 69.9) 67.2 (64.6, 71.3) 64.6 (63.3, 67.8) 69.3 (69.3, 69.3) 70.2 (70.2, 70.2) |
0.009 – – – – – – – |
CRT Angle(TEG) (60-78 degrees) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
77.7 (73.2, 79.2) 78.4 (77.6, 81.0) 79.5 (77.9, 81.6) 79.8 (77.7, 81.2) 79.7 (78.1, 80.0) 77.5 (76.8, 79.6) 81.0 (81.0, 81.0) 80.5 (80.5, 80.5) |
74.1 (72.0, 75.2) – – – – – – – |
78.9 (78.3, 80.0) 78.4 (77.6, 81.0) 79.5 (77.9, 81.6) 79.8 (77.7, 81.2) 79.7 (78.1, 80.0) 77.5 (76.8, 79.6) 81.0 (81.0, 81.0) 80.5 (80.5, 80.5) |
0.002 – – – – – – – |
CRT MA (TEG) (52-70 mm) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
66.1 (61.0, 69.2) 69.0 (68.2, 72.5) 69.8 (67.3, 73.1) 69.5 (67.7, 72.6) 69.2 (67.8, 71.5) 67.7 (66.1, 70.6) 71.2 (71.2, 71.2) 71.0 (71.0, 71.0) |
61.7 (60.0, 65.2) – – – – – – – |
69.0 (68.1, 70.6) 69.0 (68.2, 72.5) 69.8 (67.3, 73.1) 69.5 (67.7, 72.6) 69.2 (67.8, 71.5) 67.7 (66.1, 70.6) 71.2 (71.2, 71.2) 71.0 (71.0, 71.0) |
0.009 – – – – – – – |
CFF MA (TEG) (15-32mm) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
25.5 (19.2, 36.8) 35.1 (27.5, 43.8) 37.3 (26.5, 46.0) 37.6 (29.3, 40.3) 35.4 (31.2, 40.6) 27.7 (25.8, 36.7) 40.2 (40.2, 40.2) 41.3 (41.3, 41.3) |
19.6 (18.9, 21.4) – – – – – – – |
34.6 (27.4, 38.6) 35.1 (27.5, 43.8) 37.3 (26.5, 46.0) 37.6 (29.3, 40.3) 35.4 (31.2, 40.6) 27.7 (25.8, 36.7) 40.2 (40.2, 40.2) 41.3 (41.3, 41.3) |
0.003 – – – – – – – |
CFF A10 (TEG) (15-30mm) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18* Day 21* |
24.2 (18.1, 32.5) 32.6 (25.1, 38.5) 32.0 (24.8, 42.3) 34.6 (27.0, 35.8) 31.1 (29.5, 36.7) 25.0 (23.8, 34.0) 70.8 (70.8, 70.8) 37.4 (37.4, 37.4) |
18.9 (-1.0, 20.8) – – – – – – – |
30.9 (25.5, 34.0) 32.6 (25.1, 38.5) 32.0 (24.8, 42.3) 34.6 (27.0, 35.8) 31.1 (29.5, 36.7) 25.0 (23.8, 34.0) 70.8 (70.8, 70.8) 37.4 (37.4, 37.4) |
0.004 – – – – – – – |
Clot Waveform Analysis# (CWA) Min 1 (aPTT ) (Clot Velocity) (2.86-6.78%/s) Baseline Day 3 Day 6 Day 9 Day 12 Day 15 Day 18 Day 21 |
6.4 (5.5, 7.7) 6.3 (5.6, 7.2) 6.8 (6.5, 7.9) 6.6 (5.3, 7.5) 6.6 (6.4, 7.8) 6.4 (5.6, 7.0) 6.4 (4.4, 8.5) 8.3 (8.3, 8.3) |
6.0 (5.0, 6.3) 6.1 (5.5, 6.8) 6.6 (6.5, 8.8) 6.1 (6.1, 6.1) 6.1 (6.1, 6.1) 4.4 (4.4, 4.4) 4.4 (4.4, 4.4) – |
7.7 (6.4, 8.3) 6.8 (5.9, 8.1) 7.0 (6.5, 7.7) 7.2 (4.7, 7.5) 7.2 (6.5, 7.8) 6.7 (6.0, 7.9) 8.5 (8.5, 8.5) 8.3 (8.3, 8.3) |
0.02 0.33 0.94 0.99 0.29 0.40 0.99 – |
*Day 18 and Day 21 had only 2 critically ill patients remaining on study, these had stroke and lower limb deep vein thrombosis, this hypercoagulable state was still persistent in parameters on TEG and CWA. †TEG 6s Hemostasis Analyzer, Haemonetics, USA #CN-6000 Coagulation Analyser, Sysmex Corporation, Japan |
Table 1: Comparison of statistically significant results (Thromboelastography and Clot Waveform Analysis) between critically ill and non-critically ill COVID-19 patients
Conclusions: Critically ill COVID-19 patients demonstrate a hypercoagulable state with raised fibrinogen and Factor VIII levels correlating with raised CK, CRT, CFF maximal amplitude and increased CWA clot velocity(min1), while non-critical patients showed an absence of hypercoagulability in global tests of haemostasis.
To cite this abstract in AMA style:
Fan BE, Sum CLL, Lee RM, Lim JY, Bok CF, Young BE, Lye CB, Chia YW, Ong KH. Global Haemostatic Tests Demonstrate the Absence of Hypercoagulability in Non-supplemental Oxygen Dependent COVID-19 Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/global-haemostatic-tests-demonstrate-the-absence-of-hypercoagulability-in-non-supplemental-oxygen-dependent-covid-19-patients/. Accessed September 29, 2023.« Back to ISTH 2021 Congress
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