• Users Online: 270
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 2  |  Page : 139-144

Coagulopathy in hospitalized COVID-19 patients: A single-center experience


1 Department of Haematology, Baghdad Teaching Hospital, Medical City, Baghdad, Iraq
2 Department of Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq

Date of Submission25-Jun-2022
Date of Acceptance11-Aug-2022
Date of Web Publication25-Oct-2022

Correspondence Address:
Dr. Marwa Kasim Ahmed
Department of Haematology, Baghdad Teaching Hospital Medical City, Baghdad
Iraq
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijh.ijh_33_22

Rights and Permissions
  Abstract 


BACKGROUND: The coronavirus disease pandemic had spread across all countries. SARS-COV-2 infected up to date millions of people and the threat remains there for others. A lot of SARS-19-infected people with critically ill symptoms admitted to intensive care facilities had developed respiratory failure, coagulopathy, and organ failure.
AIMS: The aims of this study were to investigate the prevalence and risk factors associated with coagulopathy in COVID-19 patients who were admitted to the Private Nursing Home Hospital in Baghdad/Iraq.
PATIENTS AND METHODS: A case series study was conducted in the Nursing Home Hospital in Baghdad, Iraq, from October 2020 to December 2021. A total of 150 cases were included in this study with confirmed COVID-19 infection by polymerase chain reaction of throat or nose swab. These patients were admitted to two isolation wards (isolation intensive care unit for critical cases and medical ward isolation unit for moderately severe cases). Baseline and follow-up characteristics and laboratory parameters of coagulopathy (blood counts, prothrombin time [PT], partial thromboplastin time, D-dimers, and plasma fibrinogen) were obtained for each patient. The ISARIC 4C has been used for risk stratification (4C Mortality Score is a prognostic model for clinical deterioration among hospitalized adults with community-acquired or hospital-acquired COVID-19, it is used for stratifying and predicting mortality in COVID-19 patients on arrival in hospital).
RESULTS: The mean age across patients was 56.6 ± 15.7 years (range: 14–90 years). Males were representing the majority of cases (63.3%) with a male-to-female ratio of 2:1. The mean 4C score of patients was 10.3 ± 4.9 (range: 0–20 points). The risk group stratification showed that many patients had high risk (42.7%), and only 10.7% of patients had low scores. There were 86 (57.3%) patients who developed coagulopathy during the follow-up period and 46.7% of total patients died. There was a significant association between developing coagulopathy with higher risk group and death in COVID-19 patients (P < 0.05), while age and gender did not demonstrate a significant association. Furthermore, there was a significant association between respiratory failure, patients with cancer, patients with stroke, higher computed tomography lung involvement, lower SPO2, the presence of shock, and pulmonary embolism with the development of coagulopathy (P < 0.05). There were significant higher baseline levels of the neutrophil count, PT, D-dimer, and ferritin among patients who developed coagulopathy, while there were significant lower baseline levels of platelet count and serum albumin among patients who developed coagulopathy.
CONCLUSIONS: The development of coagulopathy in the course of severe SARS-COV-2 infection is associated with different severity biomarkers and is associated with excessive mortality.

Keywords: Coagulopathy, COVID-19, respiratory failure


How to cite this article:
Ahmed MK, Almothaffar AM. Coagulopathy in hospitalized COVID-19 patients: A single-center experience. Iraqi J Hematol 2022;11:139-44

How to cite this URL:
Ahmed MK, Almothaffar AM. Coagulopathy in hospitalized COVID-19 patients: A single-center experience. Iraqi J Hematol [serial online] 2022 [cited 2023 May 30];11:139-44. Available from: https://www.ijhonline.org/text.asp?2022/11/2/139/359640




  Introduction Top


COVID-19 virus is number seventh member of the coronavirus family. This family is divided into four generations, of which the alpha and beta subfamilies contain those relevant in human disease.[1],[2] SARS-COV-2 virus has high contagiousness and unusual potential lethality.[3],[4]

The pathogenesis of the COVID-19-induced coagulopathy has not yet been fully elucidated, but the mechanisms may overlap in some parts to those including[2],[3],[4],[5]

  1. Bacteria-induced septic coagulopathy/disseminated intravascular coagulation (DIC)
  2. The excess production of pro-inflammatory cytokines
  3. Increased levels of damage-associated molecular patterns (DAMPs)
  4. The stimulation of cell death mechanisms and vascular endothelial damage are the major causes of coagulation disorder in any severe infection
  5. Activation of fibrinolysis and elevated levels of fibrin-related biomarkers, prolonged prothrombin time (PT), and partial thromboplastin time (PTT) are often recognized in COVID-19, but the degree is less prominent compared to the bacterial sepsis-induced coagulopathy/DIC
  6. Viral pathogenesis and viral virulence with host reaction determine the clinical symptoms and outcomes both direct virus-induced cytotoxic effect and indirect injury mediated by host responses collaboratively damage the host and consumptive coagulopathy further worsens the condition
  7. Complement-mediated microangiopathy, dysregulated complement system activation may be a major contributor to cytokine storm, particularly through the pro-inflammatory effects of anaphylatoxins C3a and C5a, these effects are likely to become more detrimental in patients with a genetic predisposition for decreased complement regulation and may contributed to findings of thrombotic microangiopathy and subsequent organ dysfunction
  8. Dysregulated renin–angiotensin system.


The ISARIC 4C has been used for risk stratification (4C Mortality Score is a prognostic model for clinical deterioration among hospitalized adults with community-acquired or hospital-acquired COVID-19, it is used for stratifying and predicting mortality in COVID-19 patients on arrival in hospital).[6]

Hence, the aim of this study was to investigate the prevalence and risk factors associated with coagulopathy in COVID-19 patients who were admitted to the Private Nursing Home Hospital in Baghdad/Iraq.


  Patients and Methods Top


A case series study was conducted in Baghdad, Iraq, from October 2020 to December 2021. With 150 cases were included in this study confirmed infected by COVID-19. These patients were admitted to two isolation wards (isolation intensive care unit [ICU] for critical cases and medical ward/isolation unit) in Private Nursing Home Hospital in Medical City Complex, then each admitted patient was assessed clinically, and full laboratory reading including complete blood count, PT, PTT, fibrinogen level, renal function test, liver function test, ferritin, D-dimer, C-reactive protein, and albumin were tested at admission then on weekly basis till discharge or death.

The diagnostic criteria are proposed as follows:[4],[5]

  1. Confirmed COVID-19 patients
  2. Two or more of the following criteria:
    1. Low platelet count (<150 × 109/L)
    2. High D-dimer (>2 times the of normal limit)
    3. Prolonged PTT or INR.
    4. Low in fibrinogen level
    5. The presence of thrombosis.
This study was approved by the Ethical Committee of Iraqi Ministry of Health, and written informed consent was waived because of the nature of the study. The privacy was protected to all patients.

Statistical analysis

The Statistical Package for Social Sciences (SPSS) software (version 23) (IBM SPSS Statistics 23, USA) had been used for data entry and analysis. In the descriptive statistics for sociodemographic characteristics, the means, standard deviations, min, and max values were used for continuous data. Numbers and percentage values were used for countable data. In analyzing the differences between the groups, the Chi-square test was used for categorical variables and the independent sample t-test for continuous variables. Independent t-test and paired sample t-test were used for continuous variable comparison. Pearson correlation has been used to assess the correlation between continuous variables. P < 0.05 was used as the threshold for statistical significance.


  Results Top


The mean age across patients was 56.6 ± 15.7 years (range: 14–90 years). Males were representing the majority of cases (63.3%) with a male-to-female ratio of 2:1. Majority of patients were presented with cough (87.3%), followed by fever (75.3%). The most common comorbidities were hypertension (50%), followed by diabetes mellitus (37%), and there were 32 (21.3%) patients smokers [Table 1]. The mean 4C score of patients was 10.3 ± 4.9 (range: 0–20 points). The risk group stratification showed that the majority of patients had high risk (42.7%) and only 10.7% of patients had low scores [Table 2]. There were 65 (43.3%) patients who developed respiratory failure and 10 (6.7%) patients who developed cytokine storm. There were 86 (57.3%) patients who developed coagulopathy during follow-up and 70 (46.7% of total) patients died [Table 3].
Table 1: Demographic characteristics of patients

Click here to view
Table 2: 4C Mortality Score stratification

Click here to view
Table 3: Serious events

Click here to view


Factors associated with coagulopathy

There was a significant association between developing coagulopathy with higher risk group and death in COVID-19 patients (P < 0.05), while age and gender did not demonstrate significant difference. Furthermore, there was a significant association between respiratory failures, patients with cancer, patients with cerebrovascular accident (CVA), higher computed tomography (CT) scan involvement, lower SPO2, the presence of shock, and PE with the development of coagulopathy (P < 0.05) [Table 4].
Table 4: Factors associated with developing coagulopathy

Click here to view


There were significantly higher baseline levels of neutrophil, PT, D-dimer, and ferritin among patients who developed coagulopathy, while there were significantly lower baseline levels of platelet and albumin among patients who developed coagulopathy [Table 5].
Table 5: Initial laboratory results association with developing coagulopathy

Click here to view



  Discussion Top


Coagulopathy and COVID-19

The prevalence of coagulopathy in COVID-19 Iraqi patients with moderate-to-severe symptoms was 57%. Other studies showed lower prevalence, the prevalence of systemic coagulopathy was 7.1% in a large meta-analysis study.[7] Another three studies reported the prevalence of DIC ranging from 4% to 8%.[8],[9],[10] While two studies reported the prevalence of sepsis-induced coagulopathy ranging from 1% to 14%.[11] The difference was due to the nature of the patients sample in this study which included patients with moderate and severe cases mainly.

Factors associated with coagulopathy

In this study, age did not show a significant association with the development of coagulopathy, this was against Yuan's et al.'s[10] study which demonstrated a significant higher rate of coagulopathy among elderly patients (>65 years).[12] Furthermore, it has been shown by previous studies that elderly is being a risk factor in the development of venous thromboembolism (VTE).[13],[14]

There was a significant association between developing coagulopathy with higher risk group in COVID-19 patients. This was in line with Klok FA et al.'s[13] study which reported the rate of VTE was 27% in patients with severe COVID-19 infection.[15] Furthermore, another study reported that coagulopathy results from severe cases of COVID-19 infection.[16]

Llitjos et al.[15] reported an overall rate of 69% VTE in severe COVID-19 patients admitted to ICU. In this study, VTE incidence was found to be significantly higher in patients treated with prophylactic anticoagulation compared with those treated with therapeutic anticoagulation.[17] Thus, COVID patients with severe disease status need special attention to overcome coagulopathy development. Furthermore, Tang et al. interestingly found that more than 70% of dead patients met the criteria for DIC, with only <1% of survivals had DIC.[5]

There was a significant association between respiratory failure and the development of coagulopathy and this was in line with another study that showed thrombotic dysregulation in COVID-19 is associated with respiratory failure and coagulopathy and severe acute respiratory syndrome coronavirus 2 pneumonia is linked to both acute respiratory distress syndrome and development of systemic hypercoagulability.[18]

A variety of disorders, including infectious conditions or malignant disease, can lead to activation of coagulation.[19] Moreover, in this study, there was a significant association between the development of coagulopathy and cancer in patients with COVID-19 infection. This might relate to the synergistic effect of cancer and COVID-19 to increase the incidence of coagulopathy. However, a study by Patell et al.[18] showed that similarly high incidence of thrombosis and bleeding among patients admitted with COVID-19 with or without active cancer.[20]

In this study, there was a significant association between coagulopathy and CVA, in which COVID-19 is also associated with inflammatory coagulopathy that causes disseminated vascular obstructions, including but not limited to CVA.[21]

Both CT involvement and Spo2 saturation showed a significant association in developing coagulopathy in this study and this relates to the fact that both CT involvement and Spo2 saturation have been associated with increased severity of COVID-19 infection and the severity by turn is associated significantly with coagulopathy development.

Furthermore, pulmonary embolism during illness showed to be associated significantly with coagulopathy. In a study showed that acute pulmonary embolism was observed in 81% of all acute thrombotic complications in patients with COVID-19 infection.[22] Out of 12 autopsies, 4 of them were found that PE is the cause of death.[23]

Laboratory results and development of coagulopathy

In hospitalized patients for suspected or confirmed COVID-19, a coagulation profile should be performed, including D-dimer, PT, PTT, platelet count, and fibrinogen, repeating these coagulopathy parameters are recommended in patients with severe COVID-19, at least every 2–3 days.[24]

In this study, a higher neutrophil count showed to be associated with coagulopathy. This is related to the fact that DIC releases DAMPs and neutrophil extracellular traps that promote thrombosis, which lead to increase neutrophil count.[25]

Furthermore, there was a significant lower platelet level among patients who developed coagulopathy. Although thrombocytopenia is considered the most sensitive indicator in sepsis-induced coagulopathy/DIC, the platelet was significantly lower among patients who developed coagulopathy; however, the mean was above 200 × 109/L.

Lippi et al.[24] showed in a meta-analysis study that increased risk of disease severity and mortality was associated with low platelet in a patient with COVID-19.

Huang et al.[26] showed that admission in ICU patients had higher D-dimers and prolonged PT at the time of admission. Similarly, Wang et al.[27] reported elevated PT in ICU patients, as well as for D-dimers.

Furthermore, Han et al.[12] compared COVID-19 patients with healthy controls reported lower antithrombin and higher D-dimers, fibrinogen degradation product, and fibrinogen.

Overall, apart from elevated PT, increased D-dimer and fibrinogen levels, and thrombocytopenia in COVID-19 patients, bleeding events requiring therapeutic intervention are not reported.

Several other studies have shown D-dimer levels and fibrinogen levels as good indices for identifying patients at high risk for VTE and in predicting disease severity.[28],[29]

Albumin levels showed to be significantly lower in patients who develop coagulopathy and this was in line with Ronit et al.[28] showed that hypoalbuminemia enhanced the risk of artery and venous thrombosis.[30] Furthermore, many studies demonstrate the role of low albumin in bad prognosis of COVID-19 patients.[31],[32] However, data regarding coagulopathy and vascular disease in COVID-19 are unknown.

In this study, the ferritin level showed a significant association with the development of coagulopathy, in which a higher ferritin level was associated with the development of coagulopathy. This was in line with Long et al.'s[31] study that showed higher ferritin levels associated with the development of coagulopathy, and interestingly, they reported that serum ferritin is closely related to the coagulopathy severity of patients with COVID-19.[32]


  Conclusions Top


There is a high incidence of hypercoagulability in critically ill patients with COVID-19 infection and a significant higher mortality rate in patients with hypercoagulability. There is a significant association between coagulopathy and higher 4 CM score, development of respiratory failure, lower SPO2, the presence of cancer, higher CT involvement, higher neutrophil count, lower platelet count, higher serum ferritin, higher D-dimer, and lower serum albumin.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med 2020;26:450-2.  Back to cited text no. 1
    
2.
Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 2016;3:237-61.  Back to cited text no. 2
    
3.
Taylor D, Lindsay AC, Halcox JP. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2010;382:1564-7.  Back to cited text no. 3
    
4.
Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost 2020;18:2103-9.  Back to cited text no. 4
    
5.
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;18:844-7.  Back to cited text no. 5
    
6.
Gupta RK, Harrison EM, Ho A, Docherty AB, Knight SR, van Smeden M, et al. Development and validation of the ISARIC 4C deterioration model for adults hospitalised with COVID-19: A prospective cohort study. Lancet Respir Med 2021;9:349-59.  Back to cited text no. 6
    
7.
Uaprasert N, Moonla C, Sosothikul D, Rojnuckarin P, Chiasakul T. Systemic coagulopathy in hospitalized patients with coronavirus disease 2019: A systematic review and meta-analysis. Clin Appl Thromb Hemost 2021;27:1076029620987629.  Back to cited text no. 7
    
8.
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: A multicenter prospective cohort study. Intensive Care Med 2020;46:1089-98.  Back to cited text no. 8
    
9.
Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020;191:9-14.  Back to cited text no. 9
    
10.
Yuan X, Tong X, Wang Y, Wang H, Wang L, Xu X. Coagulopathy in elderly patients with coronavirus disease 2019. Aging Med (Milton) 2020;3:260-5.  Back to cited text no. 10
    
11.
Rosendaal FR, VAN Hylckama Vlieg A, Doggen CJ. Venous thrombosis in the elderly. J Thromb Haemost 2007;5 Suppl 1:310-7.  Back to cited text no. 11
    
12.
Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med 2020;58:1116-20.  Back to cited text no. 12
    
13.
Klok FA, Kruip MJ, van der Meer NJ, Arbous MS, Gommers DA, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145-7.  Back to cited text no. 13
    
14.
Katneni UK, Alexaki A, Hunt RC, Schiller T, DiCuccio M, Buehler PW, et al. Coagulopathy and thrombosis as a result of severe COVID-19 infection: A microvascular focus. Thromb Haemost 2020;120:1668-79.  Back to cited text no. 14
    
15.
Llitjos JF, Leclerc M, Chochois C, Monsallier JM, Ramakers M, Auvray M, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 2020;18:1743-6.  Back to cited text no. 15
    
16.
Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, et al. Immunothrombotic dysregulation in COVID-19 pneumonia is associated with respiratory failure and coagulopathy. Circulation 2020;142:1176-89.  Back to cited text no. 16
    
17.
Levi M. Pathophysiology of coagulopathy in hematological malignancies and in COVID-19. Hemasphere 2021;5:e571.  Back to cited text no. 17
    
18.
Patell R, Bogue T, Bindal P, Koshy A, Merrill M, Aird WC, et al. Incidence of thrombosis and hemorrhage in hospitalized cancer patients with COVID-19. J Thromb Haemost 2020;18:2349-57.  Back to cited text no. 18
    
19.
Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, Parra-Virto A, Toledano-Macías M, Toledo-Samaniego N, et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res 2020;192:23-6.  Back to cited text no. 19
    
20.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8.  Back to cited text no. 20
    
21.
Cattaneo M, Bertinato EM, Birocchi S, Brizio C, Malavolta D, Manzoni M, et al. Pulmonary embolism or pulmonary thrombosis in COVID-19? Is the recommendation to use high-dose heparin for thromboprophylaxis justified? Thromb Haemost 2020;120:1230-2.  Back to cited text no. 21
    
22.
Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: A meta-analysis. JAMA 2014;311:2414-21.  Back to cited text no. 22
    
23.
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020;135:2033-40.  Back to cited text no. 23
    
24.
Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta 2020;506:145-8.  Back to cited text no. 24
    
25.
Qu R, Ling Y, Zhang YH, Wei LY, Chen X, Li XM, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J Med Virol 2020;92:1533-41.  Back to cited text no. 25
    
26.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 26
    
27.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.  Back to cited text no. 27
    
28.
Ronit A, Kirkegaard-Klitbo DM, Dohlmann TL, Lundgren J, Sabin CA, Phillips AN, et al. Plasma albumin and incident cardiovascular disease: Results from the CGPS and an updated meta-analysis. Arterioscler Thromb Vasc Biol 2020;40:473-82.  Back to cited text no. 28
    
29.
Huang W, Li C, Wang Z, Wang H, Zhou N, Jiang J, et al. Decreased serum albumin level indicates poor prognosis of COVID-19 patients: Hepatic injury analysis from 2,623 hospitalized cases. Sci China Life Sci 2020;63:1678-87.  Back to cited text no. 29
    
30.
Popadic V, Klasnja S, Milic N, Rajovic N, Aleksic A, Milenkovic M, et al. Predictors of mortality in critically Ill COVID-19 patients demanding high oxygen flow: A thin line between inflammation, cytokine storm, and coagulopathy. Oxid Med Cell Longev 2021;2021:6648199.  Back to cited text no. 30
    
31.
Long X, Zhang Z, Zou W, Ling J, Li D, Jing L, et al. Coagulopathy of patients with COVID-19 is associated with infectious and inflammatory markers. Risk Manag Healthc Policy 2020;13:1965-75.  Back to cited text no. 31
    
32.
Iba T, Warkentin TE, Thachil J, Levi M, Levy JH. Proposal of the definition for COVID-19-associated coagulopathy. J Clin Med 2021;10:191.  Back to cited text no. 32
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and Methods
Results
Discussion
Conclusions
References
Article Tables

 Article Access Statistics
    Viewed1168    
    Printed50    
    Emailed0    
    PDF Downloaded75    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]