Abnormal Coagulation Parameters Associated With Mortality in Severe Coronavirus Pneumonia

Disseminated intravascular coagulation (DIC), marked by elevated D-dimer and fibrin degradation products (FDP), is associated with a higher risk of mortality in patients with severe novel coronavirus pneumonia (NCP), according to a recent study from Wuhan, China. The study authors, led by Ning Tang, MD, of the Huazhong University of Science and Technology in Wuhan, found that abnormal anticoagulation results may help guide therapy and assess prognosis in patients with NCP.

The study analyzed 183 consecutive patients with RNA-confirmed NCP from Tongji Hospital in Wuhan. Patients were admitted to the hospital between January 1 and February 3, 2020, and investigators assessed clinical outcomes to February 13. All patients were treated with antiviral and supportive therapies following diagnosis of NCP.

Coagulation tests were performed on admission (see TABLE 1) and during the hospital stay. The samples assessed the following coagulation parameters:

  • prothrombin time
  • activated partial thromboplastin time
  • antithrombin activity
  • fibrinogen
  • FDP
  • D-dimer

Changes in coagulation parameters of NCP were monitored at 3-day intervals. Assessments started at day 1 and continued to day 14 following admission.

As of February 13, patients were classified as survivors (n=162) or nonsurvivors (n=21). Survivors were either discharged (n=78) or remained hospitalized (n=84) by the end of the study period.

In the overall cohort, the mean age at onset of NCP was 54.1 years (range = 14-94). Approximately 41% of patients (n=75) had a chronic disease, including cardiovascular and cerebrovascular diseases, respiratory system diseases, malignant tumors, chronic liver and kidney diseases, and others.

Among nonsurvivors, 72% (n=15) met the International Society on Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC (≥5 points). The median time from hospital admission to the onset of DIC was 4 days (range = 1-12 days). Only 1 survivor met the ISTH criteria for DIC during hospitalization (TABLE 2).

Nonsurvivors were significantly older than those who were alive on February 13 (median 64.0 vs. 52.4 years, respectively; p<0.001). In addition, nonsurvivors had a higher prothrombin time at the time of hospital admission (15.5 vs. 13.6 seconds; p<0.001).

DIC is associated with a higher risk of mortality in patients with novel coronavirus.

Nonsurvivors also had significantly higher D-dimer on admission compared with survivors (normal range = <0.50; 2.12 vs. 0.61 μg/mL, respectively; p<0.001). Patients who had died by February 13 also had significantly higher FDP on admission (normal range = <5.0; 7.6 vs. 4.0 μg/mL; p<0.001). The researchers suggest that the elevated D-dimer and FDP, both markers of fibrinolysis and DIC, could indicate that nonsurvivors share a common coagulation activation and secondary hyperfibrinolysis condition.

No differences were found between survivors and non-survivors in terms of initial values for activated partial thromboplastin time (41.2 vs. 44.8 seconds, respectively; p=0.096), fibrinogen (4.51 vs. 5.16 g/L; p=0.149), or antithrombin activity (91% vs. 84%; p=0.096). The investigators reported that nonsurviving patients had significantly lower fibrinogen and antithrombin activity by late hospitalization compared with survivors, indicating that conventional coagulation variables during NCP directly correlate with prognosis.

The study consisted of a very small subset of patients with the 2019 novel coronavirus from a single center in a single geographic region in China, which may limit the generalizability of the findings. An adequately powered study is needed to confirm the results of the study, the authors noted.

However, the findings from this analysis demonstrate a high prevalence of coagulopathy in NCP and of DIC in deaths associated with NCP, which should be considered an important finding during a pandemic when data from specific subpopulations are only now emerging.

The authors report no relevant conflicts of interest.

Reference

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-47.