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

Authors:

Abstract

Background: In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives: To describe the coagulation feature of patients with NCP. Methods: Conventional coagulation results and outcomes of consecutive 183 patients with confirmed NCP in Tongji hospital were retrospectively analysed. Results: The overall mortality was 11.5%, the non-survivors revealed significantly higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P<0.05). 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.
J Thromb Haemost. 2020;00:1–4.
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  1wileyonlinelibrary.com/journal/jth
1 | INTRODUCTION
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
of infected patients in China has increased rapidly and exceeded
60 000 in mid-February 2020. In previous reports,2-4 the clinical
characteristics of NCP patients have been investigated, the re-
ported mortalities were 4.3%, 11.0%, and 14.6%, respectively;
organ dysfunction and coagulopathy were associated with high
mortality. However, the complete coagulation parameters of NCP
cases were not fully reported, which may have prognostic values
and be important therapeutic targets. In this study, the coagulation
parameters of consecutive NCP cases in our hospital were shown
and the differences between survivors and non-survivors were
investigated.
2 | METHODS
Consecutive patients with confirmed NCP admitted to Tongji
Hospital of Huazhong University of Science and Technolog y in
Wuhan from January 1 to Februar y 3, 2020, were enrolled. This
study was approved by the Ethics Committee of Tongji Hospital
(Wuhan, C hina). The diagnosis of N CP was according to World He alth
Organization interim guidance5 and confirmed by RNA detection of
the 2019-nCoV in the clinical laboratory of Tongji Hospit al. The clini-
cal outcomes were monitored up to February 13, 2020.
The samples for coagulation tests were collected on admission
and during the hospital stay: prothrombin time (PT), activated partial
Received: 13 February 2020 
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  Accepted: 18 Feb ruar y 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
© 2020 Internation al Society on Thr ombosis a nd Haemostasis
Manuscript handled by: David Lillicrap
Final de cision: David Li llicra p, 18 February 20 20
1Department of Clinical Laboratory, Tongji
Hospital, Tongji Medical College, Huazhong
University of Science and Technology,
Wuhan, China
2Department of Hematology, Tongji
Hospital, Tongji Medical College, Huazhong
University of Science and Technology,
Wuhan, China
Correspondence
Ziyong Sun, Depa rtment of Clinic al
Labor atory, Tongji Hospit al, Tongji Medical
College , Huazhong Univer sity of Science and
Technology, Wuhan, Hubei, China.
Email: 499388475@qq.com
Abstract
Background: In the recent outbreak of novel coronavirus infection in Wuhan, China,
significantly abnormal coagulation parameters in severe novel coronavirus pneumo-
nia (NCP) cases were a concern.
Objectives: To describe the coagulation feature of patients with NCP.
Methods: Conventional coagulation results and outcomes of 183 consecutive pa-
tients with confirmed NCP in Tongji hospital were retrospectively analyzed.
Results: The overall mortality was 11.5%, the non-survivors revealed significantly
higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin
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
2 
|
   TANG eT Al.
thromboplastin time (APTT), antithrombin activity (AT), fibrinogen,
fibrin degradation product (FDP), and D -dimer were detected using a
STA-R MAX coagulation analyzer and original reagents (Diagnostica
Stago, Saint-Denis, France).
Between survivors and non-survivors, normally and abnormally
distributed quantitative variables were compared using the Student's
t test and the Mann-Whitney U test, respectively. Categorical vari-
ables were compared using the chi-squared test. The results were
given as the mean ± standard deviation, median (interquartile range),
or number (percentage), wherever appropriate. A P-value of < .05
was considered statistically significant. Data were analyzed using
SPSS 21.0 for Windows (SPSS Inc.).
3 | RESULTS AND DISCUSSION
There were 183 patients (85 females and 98 males) with NCP en-
rolled into the study, and these patients had complete clinical infor-
mation and the laboratory data required for this study. The mean
age at disease onset was 54.1 years (range, 14-94 years). Seventy-
five (41.0%) patients had chronic diseases, including cardiovascular
and cerebrovascular diseases, respiratory system disease, malignant
tumor, chronic liver and kidney disease, and others. All patients re-
ceived antiviral and supportive therapies after diagnosis. By the end
of February 13, 78 (42.6%) patient s had been discharged and 21
(11.5%) patients had died, the rest 84 (45.9%) of the patients remain
hospitalized in stable condition.
The coagulation parameters on admission between survivors and
non-survivors were compared (Table 1). Based on our detection sys-
tem, the reportable range of D-dimer and FDP were 0.22-21.00 µg/mL
and 4.0-150.0 µg/mL, respectively. The dynam ic changes in coagulat ion
parameters were tracked from day 1 to day 14 after admission at three-
day intervals (Figure 1).
According to the International Society on Thrombosis and
Haemostasis (ISTH) diagnostic criteria for disseminated intravascu-
lar coagulation (DIC),6 15 (71.4%) of the non-survivors matched the
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).
On the contrary, only one (0.6%) sur vivor matched the DIC criteria
during hospital stay.
In our enrolled patients with NCP, the non-survivors revealed
significantly higher D-dimer and FDP levels, and longer PT compared
to survivors on admission. By the late hospitalization, the fibrinogen
and AT levels were also significantly lower in non-sur vivors; this sug-
gested that conventional coagulation parameters during the course
of NCP were significantly associated with prognosis.
DIC appeared in most of the deaths. Patients presenting with
a virus infection may develop into sepsis associated with organ
dysfunction. Sepsis is well established as one of the most common
causes of DIC; development of DIC results when monocytes and
endothelial cells are activated to the point of cytokine release fol-
lowing injury, with expression of tissue factor and secretion of von
Willebrand factor. Circulation of free thrombin, uncontrolled by nat-
ural anticoagulants, can activate platelets and stimulate fibrinolysis.8
At the late stages of NCP, levels of fibrin-related markers (D-dimer
and FDP) moderately or markedly elevated in all deaths, which sug-
gested a common coagulation activation and secondary hyperfibri-
nolysis condition in these patients.
Essentials
The role of coagulopathy in severe novel coronavirus
pneumonia (NCP) remains to be clarified.
• Conventional coagulation parameters of consecutive
patients with NCP were retrospectively analyzed.
Abnormal coagulation results, are associated with poor
prognosis.
• Existence of disseminated intravascular coagulation is
common in deaths with NCP.
TABLE 1 Coagulation parameters of NCP patients on admission
Parameters Normal range Total (n = 183) Survivors (n = 162) Non-sur vivors (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 .4-1 6.3 ) <.001
APTT (sec) 29.0-42.0 41.6 (36.9-4 4.5) 41.2 (36.9-44.0) 4 4.8 (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) <.0 01
FDP (µg/mL) <5.0 4.0 (4.0-4.9) 4.0 (4.0-4.3) 7.6 ( 4 .0-2 3.4 ) <.001
AT (%) 80-1 2 0 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).
  
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 3
TANG eT Al.
In a previous study,9 Gralinski et al investigated viral pathogen-
esis and identified a novel host pathway involved in severe acute
respiratory syndrome (SARS)-coronavirus disease progression. Their
data suggest that dysregulation of the urokinase pathway during
SARS-coronavirus infection contributes to more severe lung pa-
thology and that plasminogen activator inhibitor-1 plays a protec-
tive role following infection. In addition, Fatma Berri et al10 reported
that plasminogen contributes to inflammation caused by influenza
through fibrinolysis, and 6-aminocaproic acid can protect against
influenza. Presumably, fibrinolysis may also be induced following se-
vere 2019-nCoV infection.
The limitations of this report included that, as a relatively small,
single-center study, the mortality and characteristics of enrolled pa-
tients may not be representative; our findings sho uld be confirmed in
an adequately powered clinic al study. In addition, some patients are
still hospitalized at the time of manuscript submission. Nonetheless,
the present study has shown that existence of DIC is common in
deaths with NCP; abnormal coagulation results, especially markedly
FIGURE 1 Dynamic profile of coagulation parameters in patient s with novel coronavirus pneumonia (NCP). Timeline charts illustrate
the changes of coagulation parameters in 183 patients with NCP (21 non-survivors and 162 sur vivors) af ter 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
22.0
20.0
18.0
16.0
14.0
12.0
PT (s)
Survivors
Non-survivors
1 4 71014
Day after admission
1 4 71
01
4
Day after admission
147 10 14
Day after admission
14710 14
Day after admission
1471014
Day after admission
1471014
Day after admission
55.0
50.0
45.0
40.0
35.0
30.0
25.0
APTT (s)
aa
aaa
aaa
14.5
140.0
120.0
100.0
80.0
60.0
40.0
20.0
0.0
FDP (µg/mL)
25.00
20.00
15.00
10.00
5.00
0.00
D-dimer (µg/mL)
110
100
90
80
70
AT (%)
6.00
5.00
4.00
3.00
2.00
1.00
0.00
Fibrinogen (g/L)
aa
2.0
aa a
80.0
0.5 5.0
aa
aa
42.0
4 
|
   TANG eT Al.
elevated D-dimer and FDP, may have the potential to guide therapy
and evaluate prognosis.
ACKNOWLEDGMENTS
We thank all patients involved in the study.
AUTHOR CONTRIBUTIONS
N. Tang and X. Wang collected the clinical data and processed sta-
tistical data. N. Tang and D. Li drafted and revised the manuscript. Z.
Sun designed and guided the study.
CONFLICTS OF INTEREST
The authors declare that they have no conflic ts of interest.
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How to cite this article: 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;00:1–4. https://doi .org/10.1111/
jth.14768
TABLE 2 The grade of DIC in non-survivors with NCP (n = 21)
Number of
patients (%)
Platelet counts (×109/L)
50-100 (1 point) 7 (33.3)
<50 (2 points) 5 (23.8)
D-dimer (µg/mL)
1.0-3.0 (2 points) 3 (14. 3)
>3.0 (3 points) 18 (85.7)
Fibrinogen (g/L)
<1.0 (1 point) 6 (28.6)
Prolongation of PT (sec)
3-6 (1 point) 5 (23.8)
>6 (2 points) 10 (47. 6)
Meeting the ISTH criteria of DIC (Total points ≥5) 15 (71.4)
Note: D-dimer cutoff levels were defined according to a previous report
derived from more than 1000 samples in intensive care.7
Abbreviations: DIC, disseminated intravascular coagulation; ISTH,
International Society on Thrombosis and Haemostasis; NCP, novel
coronavirus pneumonia
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... The infection principally causes respiratory symptoms, ranging from intermittent coughing, via dyspnea, to life threatening acute respiratory distress syndrome [1]. Additionally, coagulopathy is a common and dangerous complication, in particular among severe cases of COVID-19 in SARS-CoV-2-infected patients [2,3]. In critically ill COVID-19 patients, the incidence of thrombotic complications, including pulmonary embolism, is reported to be over 30% [2,4]. ...
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To test the main hypothesis that anticoagulation reduces risk of hospitalization, intensive care unit (ICU) admission and death in COVID-19. Nested case–control study among patients with atrial fibrillation (AF) in Stockholm. COVID-19 cases were matched to five disease-free controls with same sex, born within ± 1 years. Source population was individuals in Stockholm with AF 1997–2020. Swedish regional and national registers are used. National registers cover hospitals and outpatient clinics, local registers cover primary care. Records were linked through the personal identity number assigned to each Swedish resident. Cases were individuals with COVID-19 (diagnosis, ICU admission, or death). The AF source population consisted of 179,381 individuals from which 7548 cases were identified together with 37,145 controls. The number of cases (controls) identified from hospitalization, ICU admission or death were 5916 (29,035), 160 (750) and 1472 (7,360). The proportion of women was 40% for hospitalization and death, but 20% and 30% for admission to ICU in wave one and two, respectively. Primary outcome was mortality, secondary outcome was hospitalization, tertiary outcome was ICU admission, all with COVID-19. Odds ratios (95% confidence interval) for antithrombotics were 0.79 (0.66–0.95) for the first wave and 0.80 (0.64–1.01) for the second wave. Use of anticoagulation among patients with arrythmias infected with COVID-19 is associated with lower risk of hospitalization and death. If further COVID-variants emerge, or other infections with prothrombotic properties, this emphasize need for physicians to ensure compliance among vulnerable patients.
... Such associations are supported by a number of pathophysiological mechanisms. SARS-CoV-2 activates the coagulation pathway (including over expression of fibrinogen, thrombin, factor V and VIII) and D-dimer levels have been shown to be markedly elevated and associated with an increased mortality rate [4][5][6]. Immunothrombosis is also an important component, with the involvement of systemic inflammation, including neutrophils and cytokines, such as interleukin-6 [7,8]. In addition, there is evidence that SARS-CoV-2 provokes a diffuse alveolar and endothelial damage with marked inflammation around thrombotic microangiopathy limited to pulmonary small vessels [9,10]. ...
... 6 High levels of D-dimer, fibrinogen and fibrinogen depravity amount are associated with worse outcomes. 7 Previous studies on the incidence of venous thromboembolism in COVID19 have proved contradictory results. A meta-analysis concluded that occurrence of venous thromboembolism in COVID19 is about 13%. 8 Incidence of PE in patients with COVID19 was 21% in another study. ...
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Introduction Preliminary data suggest that the prevalence of pulmonary hypertension (PH) in patients with COVID-19 is around 13%, but its prognostic role remains unclear. Approximately 3% of patients develop chronic thrombo-embolic pulmonary hypertension (CTEPH) following diagnosis of acute pulmonary embolism (PE). It is recommended that patients are screened for CTEPH if they remain symptomatic 3 months following diagnosis of PE. Aims The primary aim of the study was to assess the chances of persistent PH following PE secondary to COVID-19. Methods We conducted a retrospective cohort study at a District General Hospital (DGH) in the United Kingdom. All patients diagnosed with COVID-19 and PE between April 2020 and October 2021 were examined. Patients were divided into two groups:·COVID-19 and PE with comorbidities (excluding pre-existing PH) and·COVID-19 and PE without comorbidities. We compared the ECHO features suggestive of PH between the two groups at the time of diagnosis of PE and at 3 months following treatment. Results 80 patients were included in the study (49 with comorbidities and 31 with no comorbidities). Average age of comorbidities and no comorbidities groups were 73 years and 70 years, respectively. Average PaO 2 /FiO 2 ratio for comorbidities and no comorbidities groups were 170 and 195, respectively. Fourteen patients (13 with comorbidities and 1 with no comorbidities) died in total. Results showed that risk of persistent PH and subsequent mortality following PE in COVID19 is 4.17 times and 1.32 times more in comorbidity group as compared to no comorbidity group, respectively ( p < 0.001). Conclusion Patients with comorbidities are at high risk of persistent PH and mortality due to PE secondary to COVID19.
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Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
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In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
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Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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Detrimental inflammation of the lungs is a hallmark of severe influenza virus infections. Endothelial cells are the source of cytokine amplification, although mechanisms underlying this process are unknown. Here, using combined pharmacological and gene-deletion approaches, we show that plasminogen controls lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication was not responsible for the observed effect. However, pharmacological depletion of fibrinogen, the main target of plasminogen reversed disease resistance of plasminogen-deficient mice or mice treated with an inhibitor of plasminogen-mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious inflammation of the lungs and local fibrin clot formation may be implicated in host defense against influenza virus infections. Our studies suggest that the hemostatic system might be explored for novel treatments against influenza.
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Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.
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Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.
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The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.