COVID-19 and Coagulopathy: ISTH Issues Guidance on Diagnosis and Management
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
D-dimer During Pregnancy: Establishing Trimester-Specific Reference Intervals
Critical Care Medicine: Coagulopathy of Coronavirus Disease 2019

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