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



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.
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
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 
  Accepted: 18 Feb ruar y 2020
DOI: 10.1111/jth.14768
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
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.
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.
coagulation parameter, D-dimer, disseminated intravascular coagulation, fibrin degradation
product, novel coronavirus pneumonia
   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.).
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.
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
• 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).
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
PT (s)
1 4 71014
Day after admission
1 4 71
Day after admission
147 10 14
Day after admission
14710 14
Day after admission
Day after admission
Day after admission
APTT (s)
FDP (µg/mL)
D-dimer (µg/mL)
AT (%)
Fibrinogen (g/L)
aa a
0.5 5.0
   TANG eT Al.
elevated D-dimer and FDP, may have the potential to guide therapy
and evaluate prognosis.
We thank all patients involved in the study.
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.
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/
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
... Although, there is no published case series until our present time, it was reported that there may be an increased risk for venous thromboembolism in COVID-19 patients, and abnormal clotting parameters are detected in severe COVID-19 cases. It was reported in a multicenter study that was conducted in China that especially elevated D-dimer levels and fibrin destruction products were associated with mortality, and 71.4% of patients who died because of COVID-19 showed common intravenous clotting criteria during the disease [4]. ...
... They emphasized that patients infected with COVID-19 are at high risk for venous thromboembolism [20]. It was found that D-dimer and FDP levels were significantly higher, PT(s) values were longer, and coagulation parameters were significantly associated with prognosis in patients who died from COVID-19 [4]. In a study investigating the relationship between coagulation and disease severity in COVID-19 patients, the PT, INR, APTT, and D-dimer levels of deceased patients were found to be significantly higher than those of surviving patients [25]. ...
... In our study, the rate of those who died and who had high D-dimer levels and those who had high INR levels was higher than in patients with normal values. Previous studies [4,20,25,26] support our study results and it was observed that high INR level is associated with mortality in COVID-19 patients. It is important to detect fatal complications early, improve patient outcomes, and reduce mortality rates in infected patients in COVID-19. ...
Objective: Our aim is to determine the levels of troponin-I and some coagulation markers (D-dimer, fibrinogen and International Normalized Ratio (INR)) in coronavirus disease 2019 (COVID-19) patients and to investigate the effects of these markers on mortality. Patients and Methods: It is planned as a descriptive, cross-sectional and analytical study. The study was conducted by retrospectively scanning the files of COVID-19 patients who applied to Inonu University Turgut Ozal Medical Center between 01.03.2020 and 31.12.2020. Levels of cardiac troponin I markers and coagulation parameters (D-dimer, fibrinogen and INR) were detected. Results: The results of a total of 1858 patients were obtained. One thousand, three hundred and twenty-six patients with only troponin I and D-dimer results (Group 1), 606 patients with only troponin I and fibrinogen results (Group 2), and 1308 patients with only troponin I and INR results (Group 3) were included. Troponin I levels were significantly higher in all patients who died. 96.6% of the patients with high D-dimer levels died in Group 1, 85.5% of the patients with high fibrinogen levels died in Group 2 and 77.3 % of the patients with high INR levels died in Group 3. Conclusion: Measurements of troponin-I and coagulation markers such as D-dimer, fibrinogen and INR can help predict clinical severity and mortality in COVID-19 patients.
... In October 2021, the cumulative number of global cases had exceeded 240 million with nearly 5 million deaths. In addition to the interactions of the SARS-CoV-2 virus with human cells, severe COVID-19 disease was associated with a provoked hypercoagulable state that resulted in microvascular angiopathy and thromboembolic complications [1,2]. Likewise, marked elevations in coagulation markers such as D-dimer were associated with severe COVID-19 disease states and increased mortality [3]. ...
... In a meta-analysis of 91 studies evaluating 35,017 COVID-19 patients, Mansory et al. found the overall incidence of VTE events in all hospitalized and ICU patients was 12.8 and 24.1% respectively [22]. Reports showed hyper-thrombotic laboratory changes (e.g., d-dimer) in COVID-19 patients, and these changes are observed to be negative independent predictors of end-organdamage and death [1,[23][24][25]. In addition, critically-ill COVID-19 patients manifest with a wide range of clinical symptoms that include interstitial pulmonary edema, ST elevation myocardial infarction, brainstem infarcts, gastro-intestinal mucosal bleeding, acute kidney failure, liver dysfunction, and skin petechial rashes [7,[26][27][28][29][30]. ...
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Background Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States. Methods A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). Results We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. Conclusion AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.
... With an odds ratio of 3.37 and a mortality rate of 29%, arterial thrombosis is an emerging diagnosis in the COVID-19 pandemic (5,6). In this study, we present a case of right acute limb ischemia (ALI) due to acute arterial thrombosis in a 37-yearold man diagnosed with COVID- 19 and treated with open thromboembolectomy. ...
... COVID-19 induces an increase in cytokine levels, including tumor necrosis factor, interleukin-1, interleukin-6, procalcitonin, and interferon (16)(17)(18). Patients with COVID-19 are more likely to have thrombotic dysfunction, and those with severe symptoms had increased C-reactive protein levels and higher thrombotic risk (19). ...
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Introduction The spread of severe acute respiratory syndrome coronavirus 2 has resulted in coronavirus disease 2019 (COVID-19) pandemic, raising significant concerns. COVID-19 can lead to thrombotic complications such as acute limb ischemia (ALI). In patients with COVID-19, thrombotic complications may increase the risk of morbidity and mortality. Presentation of case We report the case of a 37-year-old man who presented with a 2 weeks history of right foot pain, toes blackish discoloration, and numbness. He tested positive for COVID-19 10 days prior to his presentation. Computed tomography angiography (CTA) of the lower limbs revealed near-complete occlusion of the right popliteal artery with single-vessel posterior tibial artery runoff. The patient was brought to a hybrid operating room, and diagnostic angiography confirmed the diagnosis. He underwent popliteal artery thromboembolectomy and intraoperative thrombolysis through a posterior approach. A completion angiography demonstrated a patent popliteal artery with a 2-vessels patency to the foot. His postoperative recovery was uneventful. After surgery, the popliteal, anterior tibial, and posterior tibial arteries were all palpable. The patient was discharged home on antiplatelet therapy with frequent postoperative follow-ups during the last 1 year in our outpatient clinic. Discussion The frequency of ALI has reduced worldwide, and the hypercoagulable condition remains an infrequent cause of limb ischemia. Patients with COVID-19 have a 35%–45% thromboembolic complication rate. In many studies, the virus launches a second attack between 7 and 14 days after symptom onset, possibly causing hypercoagulability. If conservative treatment fails, various surgical methods, including thromboembolectomy, thrombolysis, and thrombosuction, can be performed to treat ALI. Conclusion In mild ALI symptoms, unfractionated heparin can be used with vigilant follow-up. Open and endovascular procedures are currently used to treat patients with acute limb ischemia, and technological advancements continue to make interventions easier and safer.
... COVID-19 mortality is mainly due to ARDS and life-threatening cardiovascular complications. 1 Cardiovascular involvements in COVID-19 can be due to direct damage from the virus (such as myocarditis, heart failure, and arrhythmia) and indirect damage (such as thromboembolism and metabolic disorder) due to the release of cytokines (interleukin 6), coagulopathy, and insulin resistance. 2,3 Given the direct anatomical connection of the lungs with the right ventricle (RV); intuitively, it is likely to be affected leading to RV pressure overload. RV dysfunction is frequently associated with moderate to severe ARDS and is one of the major determinants of mortality. ...
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... The lipid-soluble vitamin is currently a choice of supplement to maintain body functions. The main concern about vitamin K is its effectiveness in COVID-19 patients as hospitalized patients are diagnosed with multiple blood clots in the lungs (at the site of SARS-CoV-2 infection) (Ackermann et al., 2020;Guan et al., 2020;Tang et al., 2020). The infection progressively affects the endothelial cells, which play a crucial role in coagulation, resulting in imbalance of the coagulation factors after infection and thrombosis in the lungs (Kudelko et al., 2021). ...
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... В ретроспективном анализе наличия связи между параметрами коагуляции и внутрибольничной летальностью при 14-дневном наблюдении среди 183 пациентов с подтвержденным COVID-19 N. Tang и соавт. [48] показали, что уровень D-димера при поступлении был более высоким у умерших пациентов по сравнению с выжившими: 2,12 (0,77-5,27) и 0,61 (0,35-1,29) мкг/мл соответственно (р < 0,001). ...
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Investigations into the causes of adverse outcomes of the novel coronavirus infection (COVID-19) have been ongoing since the beginning of the pandemic. There is evidence that coronavirus-induced cardiovascular injury is as important to a risk of adverse outcome as respiratory injury. Many studies have shown that concomitant cardiovascular disease aggravates the course of COVID-19. However, in some patients who did not have cardiovascular diseases before COVID-19, they are detected during hospitalization or after discharge from the hospital. The review examines data on the effect of serum biomarkers of cardiovascular disease determined during COVID-19 on the risk of adverse outcomes in the near and long-term follow-up periods. Among such biomarkers are considered: troponins, N-terminal pro B-type natriuretic peptide, creatine phosphokinase-MB, lactate dehydrogenase, myoglobin, growth stimulation expressed gene 2, pentraxin 3, angiotensin II, as well as D-dimer and homocysteine. Threshold values have been set for some of these biomarkers, which allow predicting the risk of an unfavorable outcome. At the same time, in most prognostic models, these markers are considered in association with cytokine storm indicators and other risk factors.
... 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.
Aim: COVID-19 progresses rapidly and severely and often causes death in people with underlying health problems or co-morbidities. This study aimed to investigate the effect of clinical and some specific laboratory parameters on the prognosis and mortality of critically ill COVID-19 patients who need to be followed in the intensive care unit (ICU). Subjects and methods: This is a retrospective cohort study. A total of 180 patients treated in the ICU were included in the study. The data of clinical and levels of D-dimer, cardiac troponin I (cTnI), Ferritin, and CK-MB were researched. The multivariate and univariate logistic regression models were employed to investigate the risk factors affiliated with in-hospital death. Results: There was a significant difference in mortality between women and men (p=0.002). Hypertension was the most common comorbid disease, mortality was detected to be significantly greater in patients over 65 years of age. The serum D-dimer, cTnI, CK-MB, and ferritin levels were found to be higher in patients at risk. In the multivariate logistic regression model, we detected that ferritin above 300 μg/l (p=0.05) alongside cancer was associated with mortality. Conclusions: This study showed that advanced age is an important risk factor as well as the mortality of patients with cancer –especially those with a ferritin value above 300 μg/l and patients with a high cTnI value. Mortality was significantly higher in patients with increased serum D-dimer, cTnI, CK-MB, and ferritin levels.
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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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Unlabelled: Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. Importance: Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI.
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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.
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.
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.
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.