PURPOSE:

• Coagulation disorders and thrombosis are recognized COVID-19 complications, particularly for patients with severe disease
• Maier et al. (Lancet, 2020) found evidence for multiple anticoagulation failures at their institution among patients with severe COVID-19
• Therefore, the authors sought to identify other mechanisms to explain ‘refractory hypercoagulability’ (i.e. when prophylactic/ therapeutic dosing of medications such as heparin do not prevent significant VTE)

METHODS:

• Case series
• Participants
  • COVID-19 pneumonia, critically ill and admitted to the ICU
• Testing
  • Capillary viscometry which tests for plasma viscosity

RESULTS:

• 15 patients included
  • Intubation for ARDS: 14 patients
  • Shock requiring vasopressors: 12 patients
  • Renal failure (on renal replacement therapy): 11 patients

Anticoagulation

• D-dimer ≥3 μg/mL
  • Clinical concern for thrombotic event: 5 patients received therapeutic anticoagulation | 2 patients received IV heparin and 3 patients received direct thrombin inhibitor (argatroban or bivalirudin)
  • No clinical concern for thrombotic event: 6 patients received intermediate dosing (subtherapeutic) of LMWH or IV heparin
• D-dimer <3 μg/mL: 4 patients received low dose thromboprophylaxis with LMWH or subcutaneous heparin

Viscosity Testing Results

• All patients had plasma viscosity measurements >95% normal
  • 1.9 to 4.2 centipoise | Normal range 1.4 to 1.8
• 4 patients >3.5 centipoise had thrombotic events
  • PE | limb ischemia and PE | Renal treatment related clotting (2 patients)
• Centipoise levels were highly correlated with disease severity (p<0.001)

Fibrinogen Levels

• Fibrinogen results significantly elevated
  • Median fibrinogen: 708 mg/dL (range 459 to 1188) | Normal reference range 200 to 393

CONCLUSION:

• Hyperviscous plasma can damage endothelium and lead to thrombosis
• Patients with severe COVID-19 had significantly increased plasma viscosity compared to normal range
  • Plasma viscosity was highly correlated with disease severity
• Cellular components associated with inflammation (e.g. fibrinogen or immunoglobulin) can lead to increased viscosity
• The authors conclude that

Our novel observation might provide an important link between inflammation and coagulopathy in critically ill patients with COVID-19

We are actively exploring any beneficial role of therapeutic plasma exchange, a highly effective treatment for symptomatic hyperviscosity in other conditions such as hypergammaglobulinaemia, in the clinical management of these patients

Learn More – Primary Sources:

COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?

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