COVID-19 y Parametros de Coagulacion

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Received: 13 February 2020    Accepted: 18 February 2020

DOI: 10.1111/jth.14768

BRIEF REPORT

Abnormal coagulation parameters are associated with poor


prognosis in patients with novel coronavirus pneumonia

Ning Tang1 | Dengju Li2 | Xiong Wang1 | Ziyong Sun1

1
Department of Clinical Laboratory, Tongji
Hospital, Tongji Medical College, Huazhong Abstract
University of Science and Technology, Background: In the recent outbreak of novel coronavirus infection in Wuhan, China,
Wuhan, China
2 significantly abnormal coagulation parameters in severe novel coronavirus pneumo-
Department of Hematology, Tongji
Hospital, Tongji Medical College, Huazhong nia (NCP) cases were a concern.
University of Science and Technology,
Objectives: To describe the coagulation feature of patients with NCP.
Wuhan, China
Methods: Conventional coagulation results and outcomes of 183 consecutive pa-
Correspondence
tients with confirmed NCP in Tongji hospital were retrospectively analyzed.
Ziyong Sun, Department of Clinical
Laboratory, Tongji Hospital, Tongji Medical Results: The overall mortality was 11.5%, the non-survivors revealed significantly
College, Huazhong University of Science and
higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin
Technology, Wuhan, Hubei, China.
Email: [email protected] time and activated partial thromboplastin time compared to survivors on admission
(P < .05); 71.4% of non-survivors and 0.6% survivors met the criteria of disseminated
intravascular coagulation during their hospital stay.
Conclusions: The present study shows that abnormal coagulation results, especially
markedly elevated D-dimer and FDP are common in deaths with NCP.

KEYWORDS

coagulation parameter, D-dimer, disseminated intravascular coagulation, fibrin degradation


product, novel coronavirus pneumonia

1 | I NTRO D U C TI O N and the differences between survivors and non-survivors were
investigated.
Since December 2019, novel coronavirus pneumonia (NCP) cases
have emerged in Wuhan, China, and the 2019 novel coronavirus
(2019-nCoV) was confirmed as the cause of the NCP.1 The number 2 | M E TH O DS
of infected patients in China has increased rapidly and exceeded
60 000 in mid-February 2020. In previous reports, 2-4 the clinical Consecutive patients with confirmed NCP admitted to Tongji
characteristics of NCP patients have been investigated, the re- Hospital of Huazhong University of Science and Technology in
ported mortalities were 4.3%, 11.0%, and 14.6%, respectively; Wuhan from January 1 to February 3, 2020, were enrolled. This
organ dysfunction and coagulopathy were associated with high study was approved by the Ethics Committee of Tongji Hospital
mortality. However, the complete coagulation parameters of NCP (Wuhan, China). The diagnosis of NCP was according to World Health
cases were not fully reported, which may have prognostic values Organization interim guidance5 and confirmed by RNA detection of
and be important therapeutic targets. In this study, the coagulation the 2019-nCoV in the clinical laboratory of Tongji Hospital. The clini-
parameters of consecutive NCP cases in our hospital were shown cal outcomes were monitored up to February 13, 2020.
The samples for coagulation tests were collected on admission
Manuscript handled by: David Lillicrap
and during the hospital stay: prothrombin time (PT), activated partial
Final decision: David Lillicrap, 18 February 2020

© 2020 International Society on Thrombosis and Haemostasis

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844     
wileyonlinelibrary.com/journal/jth J Thromb Haemost. 2020;18:844–847.
TANG et al. |
      845

thromboplastin time (APTT), antithrombin activity (AT), fibrinogen,


fibrin degradation product (FDP), and D-dimer were detected using a Essentials
STA-R MAX coagulation analyzer and original reagents (Diagnostica
Stago, Saint-Denis, France). • The role of coagulopathy in severe novel coronavirus

Between survivors and non-survivors, normally and abnormally pneumonia (NCP) remains to be clarified.

distributed quantitative variables were compared using the Student's • Conventional coagulation parameters of consecutive

t test and the Mann-Whitney U test, respectively. Categorical vari- patients with NCP were retrospectively analyzed.

ables were compared using the chi-squared test. The results were • Abnormal coagulation results, are associated with poor

given as the mean ± standard deviation, median (interquartile range), prognosis.

or number (percentage), wherever appropriate. A P-value of < .05 • Existence of disseminated intravascular coagulation is

was considered statistically significant. Data were analyzed using common in deaths with NCP.

SPSS 21.0 for Windows (SPSS Inc.).

3 |  R E S U LT S A N D D I S CU S S I O N grade of overt-DIC (≥5 points) in later stages of NCP (Table 2), the
median time from admission to DIC was 4 days (range, 1-12 days).
There were 183 patients (85 females and 98 males) with NCP en- On the contrary, only one (0.6%) survivor matched the DIC criteria
rolled into the study, and these patients had complete clinical infor- during hospital stay.
mation and the laboratory data required for this study. The mean In our enrolled patients with NCP, the non-survivors revealed
age at disease onset was 54.1 years (range, 14-94 years). Seventy- significantly higher D-dimer and FDP levels, and longer PT compared
five (41.0%) patients had chronic diseases, including cardiovascular to survivors on admission. By the late hospitalization, the fibrinogen
and cerebrovascular diseases, respiratory system disease, malignant and AT levels were also significantly lower in non-survivors; this sug-
tumor, chronic liver and kidney disease, and others. All patients re- gested that conventional coagulation parameters during the course
ceived antiviral and supportive therapies after diagnosis. By the end of NCP were significantly associated with prognosis.
of February 13, 78 (42.6%) patients had been discharged and 21 DIC appeared in most of the deaths. Patients presenting with
(11.5%) patients had died, the rest 84 (45.9%) of the patients remain a virus infection may develop into sepsis associated with organ
hospitalized in stable condition. dysfunction. Sepsis is well established as one of the most common
The coagulation parameters on admission between survivors and causes of DIC; development of DIC results when monocytes and
non-survivors were compared (Table 1). Based on our detection sys- endothelial cells are activated to the point of cytokine release fol-
tem, the reportable range of D-dimer and FDP were 0.22-21.00 µg/mL lowing injury, with expression of tissue factor and secretion of von
and 4.0-150.0 µg/mL, respectively. The dynamic changes in coagulation Willebrand factor. Circulation of free thrombin, uncontrolled by nat-
parameters were tracked from day 1 to day 14 after admission at three- ural anticoagulants, can activate platelets and stimulate fibrinolysis.8
day intervals (Figure 1). At the late stages of NCP, levels of fibrin-related markers (D-dimer
According to the International Society on Thrombosis and and FDP) moderately or markedly elevated in all deaths, which sug-
Haemostasis (ISTH) diagnostic criteria for disseminated intravascu- gested a common coagulation activation and secondary hyperfibri-
lar coagulation (DIC),6 15 (71.4%) of the non-survivors matched the nolysis condition in these patients.

TA B L E 1   Coagulation parameters of NCP patients on admission

Parameters Normal range Total (n = 183) Survivors (n = 162) Non-survivors (n = 21) P values

Age (years) 54.1 ± 16.2 52.4 ± 15.6 64.0 ± 20.7 <.001


Sex (male/female) 98/85 82/80 16/5 .035
With underlying diseases 75 (41.0%) 63 (38.9%) 12 (57.1%) .156
On admission
PT (sec) 11.5-14.5 13.7 (13.1-14.6) 13.6 (13.0-14.3) 15.5 (14.4-16.3) <.001
APTT (sec) 29.0-42.0 41.6 (36.9-44.5) 41.2 (36.9-44.0) 44.8 (40.2-51.0) .096
Fibrinogen (g/L) 2.0-4.0 4.55 (3.66-5.17) 4.51 (3.65-5.09) 5.16 (3.74-5.69) .149
D-dimer (µg/mL) <0.50 0.66 (0.38-1.50) 0.61 (0.35-1.29) 2.12 (0.77-5.27) <.001
FDP (µg/mL) <5.0 4.0 (4.0-4.9) 4.0 (4.0-4.3) 7.6 (4.0-23.4) <.001
AT (%) 80-120 91 (83-97) 91 (84-97) 84 (78-90) .096

Abbreviations: APTT, activated partial thromboplastin time; AT, antithrombin activity; FDP, fibrin degradation product; NCP, novel coronavirus
pneumonia; PT, prothrombin time (PT).
846       | TANG et al.

Survivors
Non-survivors

22.0 55.0

50.0
20.0

45.0

APTT (s)
18.0
PT (s)

42.0

40.0

16.0
35.0
14.5

14.0
30.0

12.0 a a a 25.0 a a
1 4 7 10 14 1 4 7 10 14
Day after admission Day after admission

25.00
140.0

20.00 120.0

100.0
D-dimer (µg/mL)

15.00

FDP (µg/mL)
80.0

10.00 60.0

40.0
5.00
20.0

0.5 5.0
0.00 0.0
a a a a a a a
1 4 7 10 14 1 4 7 10 14
Day after admission Day after admission
6.00 110

5.00
100
4.00
Fibrinogen (g/L)

AT (%)

3.00 90

2.00 2.0

80 80.0

1.00

0.00 a a 70 a a a

1 4 7 10 14 1 4 7 10 14
Day after admission Day after admission

F I G U R E 1   Dynamic profile of coagulation parameters in patients with novel coronavirus pneumonia (NCP). Timeline charts illustrate
the changes of coagulation parameters in 183 patients with NCP (21 non-survivors and 162 survivors) after admission. The error bars
show medians and 25% and 75% percentiles. The horizontal lines show the upper normal limits of prothrombin time, activated partial
thromboplastin time, D-dimer and fibrin degradation product, and the lower normal limits of fibrinogen and antithrombin activity,
respectively. aP < 0.05 for survivors versus non-survivors

In a previous study,9 Gralinski et al investigated viral pathogen- influenza. Presumably, fibrinolysis may also be induced following se-
esis and identified a novel host pathway involved in severe acute vere 2019-nCoV infection.
respiratory syndrome (SARS)-coronavirus disease progression. Their The limitations of this report included that, as a relatively small,
data suggest that dysregulation of the urokinase pathway during single-center study, the mortality and characteristics of enrolled pa-
SARS-coronavirus infection contributes to more severe lung pa- tients may not be representative; our findings should be confirmed in
thology and that plasminogen activator inhibitor-1 plays a protec- an adequately powered clinical study. In addition, some patients are
tive role following infection. In addition, Fatma Berri et al10 reported still hospitalized at the time of manuscript submission. Nonetheless,
that plasminogen contributes to inflammation caused by influenza the present study has shown that existence of DIC is common in
through fibrinolysis, and 6-aminocaproic acid can protect against deaths with NCP; abnormal coagulation results, especially markedly
TANG et al. |
      847

TA B L E 2   The grade of DIC in non-survivors with NCP (n = 21) REFERENCES


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We thank all patients involved in the study.
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AU T H O R C O N T R I B U T I O N S
N. Tang and X. Wang collected the clinical data and processed sta- How to cite this article: Tang N, Li D, Wang X, Sun Z. Abnormal
tistical data. N. Tang and D. Li drafted and revised the manuscript. Z. coagulation parameters are associated with poor prognosis in
Sun designed and guided the study. patients with novel coronavirus pneumonia. J Thromb Haemost.
2020;18:844–847. https://doi.org/10.1111/jth.14768
C O N FL I C T S O F I N T E R E S T
The authors declare that they have no conflicts of interest.

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