May17, Unitedkingdom  2021 

Worldwide Corona Cases -159,232,645 *WearMask,KeepSanitizeYourHands*

Abstract Volume: 1 Issue: 2 (World Lung Day) ISSN:

Pulmonary Thromboembolism  Complicated COVID-19

Attapon Cheepsattayakorn*, Ruangrong Cheepsattayakorn1

1.Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

*Corresponding Author: Dr. Attapon Cheepsattayakorn, 10th Zonal Tuberculosis and Chest Disease Center, 143 Sridornchai Road Changklan Muang Chiang Mai 50100 Thailand.

Received Date: September 18, 2020

Publication Date: October 01, 2020



Recent studies demonstrated that most severe COVID-19  patients with intensive-care-unit (ICU) admission for respiratory failure presented possible arterial and thromboembolisms.  Infection and hypoxia in severe pneumonia can cause increased thrombin generation and reduced fibrinolysis confirmed by the presence of occlusive microthrombi in pulmonary blood vessels in lung dissection of critical  COVID-19  patients.  In conclusion, COVID-19-related  hypercoagulopathy can be evaluated by another interesting test, called “ thromboelastometry ”.  This test is also used for screening COVID-19-related hypercoagulopathy to allow identifying patients at the greatest risk of thrombosis, including thromboprophylaxis.

Keywords: COVID-19, embolism, hypercoagulopathy, pulmonary, thromboembolism, thrombosis.

Pulmonary Thromboembolism Complicated COVID-19


COVID-19: Coronavirus Disease 2019,

ICU: Intensive Care Unit,

LMWH: Low Molecular Weight Heparin,

SARS: Severe Acute Respiratory Syndrome,

SOFA: Sequential Organ Failure Assessment,

UFH: Ultra-Fine heparin,

vs: versus,

p: probability 



Recent studies demonstrated that most severe  COVID-19 patients with intensive-care-unit (ICU)  admission for respiratory failure presented possible arterial and thromboembolisms (1).  Infection (2)  and hypoxia in severe pneumonia (3)  can cause increased thrombin generation and reduced fibrinolys is confirmed  by  presence of  occlusive  microthrombi in  pulmonary  blood vessels  in  lung dissection  of  critical COVID-19  patients (4).  The final step of the coagulative cascade  in  COVID-19 nary alveolar and interstitial  spaces  may lead  to  acute  respiratory  failure (5), supported  by a  Chinese  expert consensus  of  the implementation  of  thromboprophylaxis  in severe  COVID-19  patients (5). Other known  risk factors  for  thromboembolism  in COVID-19  patients  are  corticosteroid  treatment, hospitalization, bed  rest, etc. It is  reasonable to  hypothesize  that thromboembolism  in  COVID-19 patients  could  mirror previously  reported  data in  SARS  patients, such  as 11.4 %  of  pulmonary embolism  and  20.5 % of  deep  vein thrombosis, whereas  there  is currently limited  data on venous thromboembolism  in COVID-19  patients (6, 7, 8).  Nevertheless,this  complication may  be  associated with  host-pathogen  interaction immune  mechanisms (7, 8).  A previous  study  demonstrated that  D-dimer  levels > 1 µg/ml, higher  SOFA score, and  older  age  on  hospital admission  were  associated with  higher  hospital death (9).      

Tacking COVID-19 Coagulopathy

Several reports from Wuhan, China demonstrated that  low-molecular  weight heparin (LMWH)  or  ultra-fine heparin (UFH)  uses  at prophylactic  doses  decreased 28-day  mortality  in COVID-19  patients  with severe  pneumonia  and either  D-dimer  levels > 6 folds the  upper limit of normal (mortality rate 32.8 % vs  52.4 %, p = 0.017), or  an SIC  score  at least  4 (mortality  rate 40.0 %  vs  64.2 %, p = 0.029) (10).  In vitro  and  in vivo  studies  have demonstrated  that  human coronavirus  utilize  heparin sulfate  proteoglycans  for target  cell  attachment (11), indicating  a potential  role  of heparin  against  COVID-19. Fondapariux, an  attractive  drug has  been  proposed as  a  COVID-19 treatment (12)  due  to its  anti-viral    and anti-inflammatory  properties (13, 14)  and as  it  is not  associated  with heparin-induced  thrombocytopenia (15).     



COVID-19  patients presenting  with  rapidly worsening  respiratory  symptoms or  sudden  hypoxic respiratory  failure  could be  from  worsening pneumonia, but  could  be due  to  an undiagnosed  pulmonary embolism.  Evaluation  of the  pre-test  probability of  pulmonary  embolism via  scores, such  as Wells  score  is difficult  in  these COVID-19  patients, as  the score  may  already be  high  at the  time  of hospital admission.  COVID-19 patients  frequently  demonstrate right  ventricular  dysfunction on  the  echocardiography  that whether  they  may  be pulmonary  embolism  or not.  This observation raise  the  importantly initiating  an  adequate and  timely  anticoagulant prophylaxis  or  therapy in  COVID-19  patients, either  with LMWH  or  fondaparinux or  mechanical  methods in  high  bleeding risk patients (16).       



COVID-19-related  hypercoagulopathy  can be  evaluated  by  another  interesting test,  called “thromboelastometry”. This test is also  used  for screening  COVID-19-related  hypercoagulopathy  to allow  identifying  patients at  greatest  risk of  thrombosis, including thromboprophylaxis.


Authors Contributions

Dr. Attapon  Cheepsattayakorn  conducted the  study  framework and  wrote  the manuscript.  Associate  Professor Dr. Ruangrong Cheepsattayakorn  contributed  to scientific  content  and assistance  in  manuscript writing.  Both  authors read  and  approved the  final  version of  the  manuscript.


Competing Interests

The authors declare that they  have  no actual  or  potential competing  financial  interests.


Funding  Sources

The  authors  disclose no  funding  sources.  



1. Spiezia  L, Boscolo  A, Poletto  F, Cerruti  L, Tiberio  I, Campello  E, et  al.  “COVID-19-related  severe  hypercoagulability  in  patients  admitted  to  intensive  care  unit  for  acute  respiratory  failure”.  Throm  Haemost  2020. DOI : 

2.Levi  M, van  der  Poll  T.  “Coagulation  and  sepsis”.  Thromb  Res  149 : 38-44.

3. Gupta  N, Zhao  YY, Evans  CE.  “The  stimulation  of  thrombosis  by  hypoxia”.  Thromb  Res  2019.  181 : 77-83.

4. Luo  W, Yu  H, Gou  J, Li  X, Sun  Y, Li  J, et  al.  “Clinical  pathology  of  critical  patient  with  novel  coronavirus  pneumonia (COVID-19)”.  Preprints, p  2020020407

5. Shanghai  Clinical  Treatment  Expert  Group  for  COVID-19.  “Comprehensive  treatment  and  management  of  coronavirus  disease  2019 : expert  consensus  statement  from  Shanghai”.  Chin  J  Infect, p 38 (in  Chinese).  

6. Chong  PY, Chui  P, Ling  AE, Franks  TJ, Tai  DY, Leo  YS, et  al.  “Analysis  of  death  during  the  severe  acute  respiratory  syndrome (SARS)  epidemic  in  Singapore : challenges  in  determining  a  SARS  diagnosis”.  Arch  Pathol  Lab  Med  2004; 128 : 195-204

7. Cao  X. “ COVID-19 : immunopathology  and  its  implications  for  therapy”.  Nat  Rev  Immunol  2020; 20 (5) : 269-270.  DOI : 

8.Moon  C.  “Fighting  COVID-19  exhausts  T  cells”.  Nat Rev Immunol  2020. DOI : 

9. Zhou  F, Yu  T, Du  R, Fan  G, Liu  Y, Liu  Z, et  al.  “Clinical  course  and  risk  factors  for  mortality  of  adult  inpatients  with  COVID-19  in  Wuhan, China : a  retrospective  cohort  study”.  Lancet  2020; 395 : 1054-1062

10. Tang  N, Bai  H, Chen  X, Gong  J, Li  D, Sun  Z.  “Anticoagulant  treatment  is  associated  with  decreased  mortality  in  severe  coronavirus  disease  2019  patients  with  coagulopathy”.  J  Thromb  Haemost  2020.  DOI : 

11. Milewska  A, Zarebski  M, Nowak  P, Stozek  K, Potempa  J, Pyrc  K.  “Human  coronavirus  NL63  utilizes  heparin  sulfate  proteoglycans  for  attachment  to  target  cells”.  J  Virol  2014; 88 : 13221-13230. DOI : 

12. Marongiu  F, Grandone  E, Barcellona  D.  “Pulmonary  thrombosis  in  2019-nCoV  pneumonia  ?”  J  Thromb  Haemost  2020; 18 : 151-1513. DOI :

13. Keshari  RS, Silasi  R, Popescu  NI, Georgescu  C, Chaaban  H, Lupu  C, et  al. “ Fondaparinux  pentasaccharide  reduces  sepsis  coagulopathy  and  promotes  survival  in  the  baboon  model  of  Escherichia  coli  sepsis”.  J  Thromb  Haemost  2020; 18 : 180-190.  DOI : 

14. Xie  Q, Spear  JM, Noble  AJ, Sousa  DR, Meyer  NL, Davulcu  O, et  al.  “The  2.8  Ao   electron  microscopy  structure  of  adeno-associated  virus-DJ  bound  by  a  heparinoid pentasaccharide”.  Mol  Ther  Methods  Clin  Dev  2017; 5 : 1-12. DOI :

15. Liu  X, Zhang  X, Xiao  Y, Gao  T, Wang  G, Wang  Z, et  al.  “Heparin-induced  thrombocytopenia  is  associated  with  a  high  risk  of  mortality  in  critical  COVID-19  patients  receiving  heparin-involved  treatment”.  MedRxiv. DOI : 

16. Bikdeli  B, Madhavan  MV, Jimenez  D, Chuich  T, Dreyfus  I, Driggin  E, et  al.  “COVID-19  and  thrombolic  or  thromboembolic  disease : implications  for  prevention, antithrombotic  therapy, and  follow-up”.  J  Am  Coll  Cardiol  2020. DOI : 



Volume 1 Issue 2 October 2020

©All rights reserved by Dr. Attapon Cheepsattayakorn.