Elevated activated partial thromboplastin time-based clot waveform analysis markers have strong positive association with acute venous thromboembolism

Tan, Chuen Wen; Cheen, McVin Hua Heng; Wong, Wan Hui; Wu, Ian Qianhuang; Chua, Brian Lee Wei; Ahamedulla, Sahul Hameed; Lee, Lai Heng; Ng, Heng Joo

doi:10.11613/bm.2019.020710

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…The higher min1 value could possibly suggest an overall elevated prothrombotic state in COVID-19 infection given our previous finding that min1, in comparison to min2 and max2, is more strongly associated with thrombotic events. 5 Consistent with published reports, 4 all the patients expressed high CRP levels even on initial assessment during hospitalization, while procalcitonin remained unremarkable (data not shown). We did not observe a definitive pattern of association between CRP and ICU admission -patient 3 had a CRP upon ICU admission that was lower than that of patient 1 upon initial hospitalization.…”

Section: O R R E S P O N D E N C Esupporting

confidence: 91%

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Critically ill COVID‐19 infected patients exhibit increased clot waveform analysis parameters consistent with hypercoagulability

et al. 2020

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developed thrombosis, our patients' CWA parameters remained remarkably high despite the use of thromboprophylaxis during their ICU stay. It is possible that CWA and other thrombin generation assays might not be sensitive enough to detect the haemostatic changes caused by the standard prophylactic dose of low molecular weight heparin.All three patients recovered from COVID-19 infection.Thatour findings of markedly raised CWA parameters in critically ill infected cases are possibly consistent with hypercoagulability is not unexpected. Such patients exhibit hyperinflammation and cytokine overdrive, and extensive crosstalk is known to exist in the cytokines, the inflammatory system, and coagulation. 6 Critically ill COVID-19 patients have been shown to have increased proinflammatory cytokines including IL-2 and TNF-α, 4 and these factors could upregulate the coagulation system. 6 We speculate that this could partially account for the CWA changes observed.Although our findings are limited by the relatively few patients and data points and by the lack of other correlation studies with other coagulation assays, we believe there are still valuable points to take away. Many of the specialized and research haemostatic assays cannot be safely and easily performed on samples collected from COVID-19 patients in view of laboratory biosafety concerns. As COVID-19 infection is spreading relentlessly worldwide, there is an urgent need for rapid and readily accessible biomarkers that can aid clinical stratification and management. So, CWA represents a simple, automated and rapid test, which fulfills these biosafety criteria. Whenever an aPTT is performed, an aPTT waveform is generated automatically by commonly used optical analysers worldwide.In conclusion, the rise of CWA parameters precedes and coincides with ICU admission and warrant further study to confirm its utility in the routine management of COVID-19 patients.

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Section: O R R E S P O N D E N C Esupporting

confidence: 91%

“…Many of the levels were at least as high as what we noted in acute venous thromboembolism, which had an odds ratio of four or greater for thrombotic events. 5 Of note, although none of our cases…”

Section: O R R E S P O N D E N C Ementioning

confidence: 54%

Critically ill COVID‐19 infected patients exhibit increased clot waveform analysis parameters consistent with hypercoagulability

et al. 2020

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“…To further evaluate the thrombotic potential in COVID-19, we analysed available CWA parameters as a global haemostatic assessment. It has been reported that CWA parameters differ in various types of infections 34 and increased CWA is associated with hypercoagulability 35 , 36 . Our findings suggest that there were no significant changes in the overall haemostatic functions in mild COVID-19 but severe COVID-19 was associated with a prothrombotic state and this hypercoagulability gradually normalizes during the convalescent phase.…”

Section: Discussionmentioning

confidence: 99%

Clinical and laboratory features of hypercoagulability in COVID-19 and other respiratory viral infections amongst predominantly younger adults with few comorbidities

Tan

Jinquan

Wong

et al. 2021

Sci Rep

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COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P < 0.001; min2: 0.92%/s2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.

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“…Our study further supports the available evidence that severe SARS-CoV-2 infection is associated with hypercoagulability [ 7 , 21 ]. Clot waveform analysis (CWA) has not been well described as a tool to evaluate a hypercoagulable state, although emerging literature shows promising evidence that this may be useful in predicting for VTE [ 22 ] and also in several procoagulable states [ 23 , 24 ]. CWA showed a hypercoagulable state with increased parameters of clot maximum velocity (min1), clot maximum acceleration (min2), clot maximum deceleration (max2) and delta change (decreased light transmission reflective of increased clot thickness) characterizing a hypercoagulable state in 10 patients (with corresponding raised Factor VIII, vWF antigen, D-dimer and fibrinogen levels), with no evidence of concurrent bacterial infection at the time of assessment.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis

Fan

Chan

et al. 2020

J Thromb Thrombolysis

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Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1–9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1–11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s 2 (IQR 1.0–1.6%/s 2 ), elevated PT median Min2 5.2%/s 2 (3.6–5.7%/s 2 ), elevated aPTT median Max2 (clot deceleration) 1.3%/s 2 (IQR 0.8–1.4%/s 2 ) elevated PT median Max2 3.8%/s 2 (IQR 2.6–4.2%/s 2 ), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2–91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 μg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.

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Elevated activated partial thromboplastin time-based clot waveform analysis markers have strong positive association with acute venous thromboembolism

Cited by 16 publications

References 31 publications

Critically ill COVID‐19 infected patients exhibit increased clot waveform analysis parameters consistent with hypercoagulability

Critically ill COVID‐19 infected patients exhibit increased clot waveform analysis parameters consistent with hypercoagulability

Clinical and laboratory features of hypercoagulability in COVID-19 and other respiratory viral infections amongst predominantly younger adults with few comorbidities

COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis

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