Hypercoagulation in COVID19 Patients pt. 3

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.

Tang N, Li D, Wang X, Sun Z.

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.

Key Highlights

• Study has findings that suggest that existence of DIC is common in deaths with NCP and that elevated D-Dimer and Fibrin Degradation Product (FDP) might be able to guide therapy and evaluate prognosis

Key Points

• Complete coagulation parameters of novel coronavirus pneumonia (NCP) may have prognostic values and might be important therapeutic targets.

• In this study, the coagulation parameters of consecutive NCP cases showed differences between survivors and non-survivors

Methods:

• Patients with confirmed NCP from Jan 1 – Feb 3, 2020 to Tongji Hospital of Huazhong University of Science and Technology were enrolled.

• NCP criteria was based on World Health Organization (WHO) and confirmed with RNA detection of 2019-nCov in the Tongji Hospital clinical laboratory.

• Clinical outcomes were monitored until Feb 13, 2020.

• Coagulation test samples were collected on admission and during hospital stay and detected using a STA-R MAX coagulation analyzed and original reagents (Diagnostica Stago, Saint-Denis, France):

  • Prothrombin time (PT)

  • Activated Partial Thromboplastin Time (aPTT)

  • Antithrombin Activity (AT)

  • Fibrinogen

  • Fibrin Degradation Product (FDP)

  • D-Dimer

Statistical methods:

• Survivor vs non-survivor, normally and abnormally distributed quantitative variables were compared during Student’s T-Tbest and Mann-Whitney U Test

• Categorical variables compared using chi-squared test

• A P-value of < 0.05 is statistically significant

• Data analyzed using SPSS 21.0 for Windows

Results and Discussion:

• There are a total of 183 patients (85 female and 98 males) with NCP enrolled into the study.

  • Mean disease onset was 54.1 years

  • 75 patients (41%) had chronic diseases (including cardiovascular and cerebrovascular disease, respiratory system disease, malignant tumors, chronic liver and kidney disease, and others)

• All patients received antiviral and supportive therapies after diagnosis

• By Feb 13, 2020: 78 patients were discharged (42.6%), 21 died (11.5%), and 84 (45.9) were still hospitalized in stable condition

• Coagulation parameters on admission were compared between survivor and non-survivor.

• Refer to article using the DOI for full details of data collected.

• Dynamic change in coagulation parameters were tracked from day 1 to day 14 after admission at 3 days intervals.

• Diagnostic criteria for DIC was taken from the International Society of Thrombosis and Hemostatic (ISTH)

  • 15 (71.4%) of non-survivors matched the grade of overt DIC in the later stages of the NCP

  • 1 (0.6%) of survivors matched the DIC criteria

  • Median time from admission to DIC was 4 days (range: 1-12 days)

• D-Dimer and FDP levels:

  • Non-survivors had significantly higher D-Dimers, FDP levels and longer PT compared to survivors on admission.

  • By late hospitalization: the fibrinogen and AT levels were lower in non-survivors

  • Suggests that conventional coagulation parameters during the course of NCP were significantly associated with prognosis.

• DIC appeared in most of the deaths.

  • Sepsis is established as one of the most common causes of DIC.

  • Patients that presented with viral infection might develop into sepsis associated with organ dysfunction.

  • DIC results when monocytes and endothelial cells are activated to the point of cytokine release after injury with expression of tissue factor and secretion of vWF. Circulation of free thrombin that is uncontrolled by natural anticoagulants can activate platelets and stimulates fibrinolysis.

• Late States of NCP: levels of D-dimer and FDP were moderately – markedly elevated in all deaths

  • Suggestive of: common coagulation activation and secondary hyperfibrinolysis condition

• Gralinski et al: investigated viral pathogenesis and identified a novel host pathway involved in severe acute SARS disease progression

  • Data suggested that dysregulation of urokinase pathway during SARS contributed to more severe lung pathology and plasminogen activator inhibitor-1 plays protective role after infection.

• Fatma Berri et al: plasminogen contributes to inflammation caused by influenza through fibrinolysis and 6-aminocaproic acid can protect against influenza

  • Fibrinolysis might be induced after COVID19 infection.

Limitations:

• Relatively small, single-center study

• Morality and characteristics of enrolled patients might not be representative.

• Findings should be confirmed in adequately powered clinical study

• Some of the patients were still hospitalized at the time of manuscript submission.