Hypercoagulability in COVID19 Patients pt. 1

Critically Ill COVID-19 Infected Patients Exhibit Increased Clot Waveform Analysis Parameters Consistent with Hypercoagulability.

Tan CW, Low JGH, Wong WH, Chua YY, Goh SL, Ng HJ

DOI: 10.1002/ajh.25822

Disclaimer: This is a summary of the highlights of this article, I do not own any or endorse any of the findings within this article. This is for educational purposes only and a full link for further review is included.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process at the time of this summary blog post. This may lead to differences between this version and the Version of Record. 

I personally felt it important to get the information out and the DOI is included for further and future review.

Key Highlights

• In this article, the authors hypothesized that the COVID19 (+) patients that needed ICU support would have hemodynamic disturbances and monitored the patient’s activated partial thromboplastin time (aPTT) based clot waveform analysis (CWA) to assess for hemodynamic functions.

  • aPTT-based CWA: is a form of global hemostatic assay where the lower CWA parameters are associated with bleeding while the higher CWA parameters are associated with hyper coagulability.

• Prothrombotic mechanisms in viral ARIs might be exacerbated in patients with severe viral ARIs.

  • This might be because there is a lot of crosstalk between inflammation and coagulation.

• Rise of CWA parameters seems to precede and coincides with ICU admission.

• Critically ill COVID19 patients have been seen to have increased proinflammatory cytokines including IL-2 and TNF-alpha.

  • These factors could up regulate the coagulation system.

  • This might partly explain the CWA changes seen.

Key Points

• Viral acute respiratory infections (ARI) are associated with thrombotic events.

  • Pathophysiology is multifactorial.

• Most ARIs are mild but some people can progress to severe disease –> excessive proinflammatory response and downstream uncontrolled cytokine storm.

• Prothrombotic mechanisms in viral ARIs might be exacerbated in patients with severe viral ARIs.

  • This might be because there is a lot of crosstalk between inflammation and coagulation.

• 1/5 of COVID19 (+) patients develop severe to critical disease and require ICU care and these patients often have elevation of pro inflammatory cytokines and CRP –> this is pretty consistent with hyperinflammation.

• In this article, the authors hypothesized that the patients that needed ICU support would have hemodynamic disturbances and monitored the patient’s activated partial thromboplastin time (aPTT) based clot waveform analysis (CWA) to assess for hemodynamic functions.

  • aPTT-based CWA: is a form of global hemostatic assay where the lower CWA parameters are associated with bleeding while the higher CWA parameters are associated with hyper coagulability.

• Feb 2020: Three COVID19 patients were admitted to the ICU at Singapore General Hospital

  • APTT tests were performed in addition to routine clinical management and associated CWA data was retrieved from CS2100i and CS2500 automated coagulation analysers:

    • Maximum velocity (min1)

    • Maximum acceleration (min2)

    • Maximum deceleration (max2)

• None of the patients had any:

  • Pre-existing malignancies

  • Bleeding or thrombotic conditions

  • Antithrombotic medications

  • Superimposed infection

  • Overt disseminated intravascular coagulation (DIC)

• 1 patient had underlying HTN and hyperlipidemia

• Refer to article by clicking the DOI for details on each patient clinical and laboratory features

Summary of key results:

• All 3 patients had elevated min1 when their clinical conditions deteriorated to the point of requiring ICU support.

• All CWA parameters became super elevated as ICU stay progressed

• Seems to suggest a positive association between the rise in CWA parameters and worsening severity of COVID19 infection.

• Findings of markedly raised CWA parameters in critically ill infected cases is expected.

  • Patients exhibit state of hyperinflammation and cytokines go into overdrive

  • Extensive crosstalk is known to exist in the cytokine + inflammatory system and coagulation.

  • Critically ill COVID19 patients have been seen to have increased proinflammatory cytokines including IL-2 and TNF-alpha.

    • These factors could up regulate the coagulation system.

    • This might partly explain the CWA changes seen.

Study Limitations:

• Relatively few patients, data points, and lack of other correlation studies with other coagulation assays.

• Many of the specialized and research hemostatic assay can’t be safely and easily performed on samples taken from COVID19 patients because of their laboratory biosafety concern.