NOTE: Information and guidelines may change rapidly. Check in with listed references in ‘Learn More – Primary Sources’ to best keep up to date

SUMMARY:

The ISTH released guidance on the recognition and management of coagulopathy in the setting of COVID-19. The ISTH emphasizes the term ‘interim’ as the medical community continues to learn more about the clinical course of those infected with SARS-CoV-2. The stated goal of this guidance is

…to provide a risk stratification at admission for a COVID‐19 patient and management of coagulopathy which may develop in some of these patients, based on easily available laboratory parameters

Recommended Labs at Admission (decreasing order of importance)

D-dimers

• Consider hospital admission for patients with markedly raised D-dimers even in absence of other severity symptoms
  • “Arbitrarily defined as three-four fold increase”
  • High levels indicate increased thrombin generation

Note: This guidance does not address pregnancy specifically | D-dimer is elevated in normal pregnancy (see ‘Learn More – Primary Sources’ below)

Prothrombin time (PT)

• Current literature is demonstrating mild prolongation of PT at admission in ICU vs non-ICU cohorts (e.g., 12·2 s vs 10·7 s; Huang et al. Lancet, 2020)
• Caution: Such “subtle changes” will not be as readily identified if PT is reported as INR

Thrombocytopenia

• Unlike typical sepsis, thrombocytopenia at admission for COVID-19 was not as strong an indicator of sepsis mortality
• The authors state that “thrombocytopenia at presentation may be but not consistent prognosticator”

Monitoring Coagulation Markers

• Monitor D-dimers, platelet count, PT and fibrinogen to identify worsening coagulopathy
  • Worsening parameters: “More aggressive critical care support is warranted” including consideration of ‘experimental’ therapies and blood product support
  • Stable or improving parameters: Provides “added confidence for stepdown of treatment if corroborating with the clinical condition”

DIC

• Importance of regular laboratory monitoring
  • Day 4: In one study (Tang et al. J Thromb Haemost, 2020), DIC was much more likely to develop on day 4 among nonsurvivors vs survivors (71.4% vs 0.6%)
• Days 10 and 14: Statistically significant increase in D-dimer levels, and PT, and decrease in fibrinogen levels were likewise seen in nonsurvivors

KEY POINTS:

Management Points

• Inhibition of thrombin generation may reduce risk for multi-organ failure in the setting of sepsis

Prophylactic LMWH

• “Should be considered in ALL patients (including non-critically ill) who require hospital admission for COVID-19 infection, in the absence of any contraindications (active bleeding and platelet count less than 25 x 109 /L)”
• Monitor closely if severe renal impairment is present
• “Abnormal PT or APTT is not a contraindication”
• Additional benefits of LMWH include
  • VTE prevention
  • Anti-inflammatory properties

Parameter Thresholds

• Non-bleeding patients: Maintain
  • Platelet count >20 x 109/L
  • Fibrinogen >2.0 g/L
• Bleeding patients (rare in setting of COVID-19): Maintain
  • Platelet count >50 x 109/L
  • Fibrinogen >2.0 g/L
  • PT ratio <1.5 (note: not the same as INR)

Other therapies to manage coagulopathy

• Should be considered experimental, for example
  • Antithrombin supplementation | Recombinant thrombomodulin | Hydroxychloroquine

Lancet Haematology – Expert Opinion

Hospitalized Patients (Severe COVID-19)

• Closely monitor patient for coagulopathy: Repeat every 2–3 days
  • D-dimer
  • PT
  • Platelet counts
• Administer subcutaneous LMWH for all hospitalized patients
  • Evidence to support this practice in severe COVID-19 | “In view of the hypercoagulable state of patients with severe COVID-19, and the potential increased risk of thrombosis, we suggest that all patients with COVID-19 that are admitted to hospital should receive this prophylactic treatment in the absence of medical contraindications”
• Be on alert for VTE
  • Consider VTE in the setting of rapid respiratory deterioration and/or high D-dimer concentrations
  • CT angiography or ultrasound of the venous system of the lower extremities

Note: If diagnostic testing is not possible and there are no bleeding risk factors, consider therapeutic anticoagulation | Experimental therapies such as plasma exchange, or administration of other anticoagulants or anti-inflammatory drugs should only be undertaken via clinical trials

Learn More – Primary Sources:

ISTH interim guidance on recognition and management of coagulopathy in COVID‐19

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China (Huang et al. Lancet 2020)

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia (Tang et al. J Thromb Haemost, 2020)

D-dimer During Pregnancy: Establishing Trimester-Specific Reference Intervals

Coagulation abnormalities and thrombosis in patients with COVID-19 (Lancet Haematology Expert Comment)

Critical Care Medicine: Coagulopathy of Coronavirus Disease 2019

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