Carli G, Nichele I, Ruggeri M, Barra S, Tosetto A. Deep vein thrombosis (DVT) occurring shortly after the second dose of mRNA SARS-CoV-2 vaccine. Intern Emerg Med. 2021 Mar 9:1–2. doi: 10.1007/s11739-021-02685-0
Source :
https://link.springer.com/article/10.1007/s11739-021-02685-0
One of the first reported and investigated case of DVT in a patient having received mRNA COVID-19 vaccine (BNT162b2, Comirnaty, Pfizer/BioNTech).
Nazy I, Jevtic SD, Moore JC, Huynh A, Smith JW, Kelton JG, Arnold DM. Platelet-activating immune complexes identified in critically ill COVID-19 patients suspected of heparin-induced thrombocytopenia. J Thromb Haemost. 2021 Feb 27. doi: 10.1111/jth.15283.
Source :https://onlinelibrary.wiley.com/doi/10.1111/jth.15283
While learning societies keep their eyes on patients receiving COVID19 patients; the team from Hamilton in the Canada reports here the development of some HIT-like antibodies in critically ill COVID-19 patients, which could explain some thrombotic developments.
INSPIRATION Investigators, Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, Farrokhpour M, Sezavar SH, Payandemehr P, Dabbagh A, Moghadam KG, Jamalkhani S, Khalili H, Yadollahzadeh M, Riahi T, Rezaeifar P, Tahamtan O, Matin S, Abedini A, Lookzadeh S, Rahmani H, Zoghi E, Mohammadi K, Sadeghipour P, Abri H, Tabrizi S, Mousavian SM, Shahmirzaei S, Bakhshandeh H, Amin A, Rafiee F, Baghizadeh E, Mohebbi B, Parhizgar SE, Aliannejad R, Eslami V, Kashefizadeh A, Kakavand H, Hosseini SH, Shafaghi S, Ghazi SF, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Piazza G, Kirtane AJ, Van Tassell BW, Dobesh PP, Stone GW, Lip GYH, Krumholz HM, Goldhaber SZ, Bikdeli B. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Mar 18. doi: 10.1001/jama.2021.4152.
Source :https://jamanetwork.com/journals/jama/fullarticle/2777829
Et Al-Samkari H. Finding the Optimal Thromboprophylaxis Dose in Patients With COVID-19. JAMA. 2021 Mar 18. doi: 10.1001/jama.2021.4295.
Source :https://jamanetwork.com/journals/jama/fullarticle/2777828
The multicentric INSPIRATION randomized trial compared primary outcomes at 30 days for COVID 19 patients under ECMO when receiving intermediate (therapeutic) dose of heparin or standard (prophylactic) one. Surprisingly, not difference was found, which deserved an editorial comment too.
2021 Jan 7. Iba T, Warkentin TE, Thachil J, Levi M, Levy JH. Proposal of the Definition for COVID-19-Associated Coagulopathy. J Clin Med.;10(2):E191. doi: 10.3390/jcm10020191. PMID: 33430431
Source:JCM | Free Full-Text | Proposal of the Definition for COVID-19-Associated Coagulopathy (mdpi.com)
This review summarizes the current knowledge about COVID-19- associated coagulopathy including differences and similarities with sepsis-associated disseminated intravascular coagulopathy.
2021 Jan 7. Barbosa LC, Lopes T, de Araujo LP, de Oliveira Rosario LV, Ferrer VP. Endothelial cells and SARS-CoV-2: An intimate relationship. Vascul Pharmacol.:106829. doi: 10.1016/j.vph.2021.106829. Online ahead of print. PMID: 33422689
Source:https://doi.org/10.1016/j.vph.2021.106829
Endothelial cells have a critical role in the inflammatory and disseminate coagulation process reported in COVID-19 patients, which culminate in a higher risk of thromboembolic, cardiovascular, and cerebrovascular complications in these patients. This paper reviews how endothelial cell injury contributes to COVID-19 coagulopathy and how endothelial cells can be a target for therapies.
2021 Jan 5. Bongiovanni D, Klug M, Lazareva O, Weidlich S, Biasi M, Ursu S, Warth S, Buske C, Lukas M, Spinner CD, Scheidt MV, Condorelli G, Baumbach J, Laugwitz KL, List M, Bernlochner I.
SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype. Cell Death Dis.;12(1):50. doi: 10.1038/s41419-020-03333-9. PMID: 33414384
In this paper, the authors detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients.
2021 Jan 15. Philippe A, Chocron R, Gendron N, Bory O, Beauvais A, Peron N, Khider L, Guerin CL, Goudot G, Levasseur F, Peronino C, Duchemin J, Brichet J, Sourdeau E, Desvard F, Bertil S, Pene F, Cheurfa C, Szwebel TA, Planquette B, Rivet N, Jourdi G, Hauw-Berlemont C, Hermann B, Gaussem P, Mirault T, Terrier B, Sanchez O, Diehl JL, Fontenay M, Smadja DM. Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality. Angiogenesis; 1-13. doi: 10.1007/s10456-020-09762-6.
Source:SpringerLink
This study looked at the endothelial dysfunction in COVID-19 patients. VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. The authors hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.
2020 Dec 24. Delrue M, Siguret V, Neuwirth M, Joly B, Beranger N, Sène D, Chousterman BG, Voicu S, Bonnin P, Mégarbane B, Stépanian A. von Willebrand factor/ADAMTS13 axis and venous thromboembolism in moderate-to-severe COVID-19 patients.Br J Haematol. Doi:10.1111/bjh.17216
Source:von Willebrand factor/ADAMTS13 axis and venous thromboembolism in moderate‐to‐severe COVID‐19 patients - Delrue - - British Journal of Haematology - Wiley Online Library
The authors conducted an exploratory study in moderate‐to‐severe COVID‐19 patients managed in hospital to analyse the implication of the VWF/ADAMTS13 axis in VTE (i.e., deep venous thrombosis or pulmonary embolisms. Their data highlights the role of the VWF/ADAMTS13 axis at the crossroads between lung system microthrombosis and venous macrothrombosis in COVID‐19.
Dec, 2020. Stefely JA, Christensen BB, Gogakos T, Cone Sullivan JK et al. Marked factor V activity elevation in severe COVID-19 is associated with venous thromboembolism. Am J Hematol. doi: 10.1002/ajh.25979.
Source:onlinelibrary.wiley.com
In this series of 102 with COVID-19 infection, patients with factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49,33%) compared to those with factor V activity <150 IU/dL (7/53,13%) (P = .03). Within this severe COVID-19 cohort, factor V activity associated with SARS-CoV-2 load in a sex-dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality.
Nov 12, 2020. Goudot G, Chocron R, Augy JL et al. Predictive Factor for COVID-19 Worsening: Insights for High-Sensitivity Troponin and D-Dimer and Correlation with Right Ventricular Afterload. Front Med (Lausanne). doi: 10.3389/fmed.2020.586307
Source:www.frontiersin.org
Hs-cTnl appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with right ventricular dilatation probably reflects a myocardial injury due to an increased right ventricular wall tension.
Sep 22, 2020. Gerotziafas GT, Sergentanis TN, Voiriot G et al. Derivation and Validation of a predictive score for disease Worsening in patients with COVID-19. Thromb Haemost. doi: 10.1055/s-0040-1716544
Source:www.thieme-connect.de
The COMPASS-COVID-19 score derived from a prospective study is composed of easily assessable clinical and hematological predictors. The score has high sensitivity (81%) for the identification of hospitalized patients at high risk of disease worsening.
Aug 19, 2929. Chatterjee S, Sengupta T, Majumder S et al. COVID-19: a probable role of the anticoagulant Protein S in managing COVID-19-associated coagulopathy. Aging (Albany NY). 12(16):15954-15961. doi: 10.18632/aging.103869
Source:https://pubmed.ncbi.nlm.nih.gov/32826388/
Most severely ill COVID-19 patients manifest a hyperactivated immune response, instigated by interleukin 6 (IL6) that triggers a so called "cytokine storm" and coagulopathy. Hypoxia is also associated with COVID-19. So far overlooked is the fact that both IL6 and hypoxia depress the abundance of a key anticoagulant, Protein S. The authors highlight a mechanism by which the IL6-hypoxia curse causes a deadly hypercoagulable state in COVID-19 patients, and suggest a path to therapy.
Oct. 12, 2020. Anti-Xa Monitoring improves low-molecular-weight heparin effectiveness in patients with SARS-CoV-2 infection.
Source:Trunfio M, Salvador E, Cabodj D, Marinaro L, Alcantarini C, Gaviraghi A, Trentalange A, Lipani F, Sciascia S, Roccatello D, Bonora S, Di Perri G, Calcagno A, for the e-COVID Study group - trhomb Res 2020.
This research paper suggests that close anti-Xa monitoring of COVID-19 patients administered LMWH treatment along with dose-adjustment based on the result of the anti-Xa activity assay could be beneficial in terms of outcome.
Oct. 12, 2020. D-Dimer cut-off points and risk of venous thromboembolism in adult hospitalized patients with COVID-19.
Source:Choi JJ, Wehmeyer GT, Li HA, Alshak MN, Nahid M, Rajan M, Liu B, Schatoff EM, Elahjji Rn Abdelghany Y, D'Angelo D, Crossman D, Evans AT, Steel P, Pinheiro LC, Goyal P, Safford MM, Mints G, DeSancho MT - Thromb Res 2020.
This paper confirms the importance of Dimer testing for prognosis evaluation in COVID-19 patients.
Oct. 12, 2020. Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.
Source:Voicu S, Delrue M, Chousterman BG, Stépanian A, Bonnin P, Malissin I, Deye N, Neuwirth M, Ketfi C, Mebazaa A, Siguret V, Mégarbane B - Eur Rev Med Pharmacol Sci 2020; 24:9161-8
This paper shows that mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway and that D-dimer may be a useful biomarker at the bedside for suspicion of VTE.
Sep. 15, 2020. Pulmonary embolism, pulmonary microvascular thrombosis, or both in COVID-19?
Source:Paramo JA. Clin Appl Thromb Hemost. Jan-Dec; 26:1076029620933953. doi: 10.1177/1076029620933953
Focusing on COVID-19 pathophysiology and the results of post-mortem examinations, the author differentiates pulmonary lesions between pulmonary embolism and intrapulmonary acute microvascular thrombosis and proposes to include the term "primary pulmonary thrombi" which develop directly in the lungs without traveling from DVT to refer to the most common thrombotic manifestations in patients with COVID-19 infection.
Sep. 15, 2020. Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory.
Source:Hardy M, Lecompte T, Douxfils J, Lessire S, Dogné JM, Chatelain B, Testa S, Gouin-Thibault I, Gruel Y, Medcalf RL, Ten Cate H, Lippi G, Mullier F. Thromb J. 2020 Sep 7; 18:17. doi: 10.1186/s12959-020-00230-1. eCollection 2020.
This paper is a comprehensive review of the literature and provides a detailed focus on coagulation laboratory alteractions observed in COVID-19 patients, including routine, specialized and global assays, as well as on anticoagulation in COVID-19 patients and its monitoring.
Sep. 15, 2020. Evaluation of COVID-19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays.
Source:White D, MacDonald S, Edwards T, Bridgeman C, Hayman M, Sharp M, Cox-Morton S, Duff E, Mahajan S, Moore C, Kirk M, Williams R, Besser M, Thomas W. Int J Lab Hematol. 2020 Sep 5. doi: 10.1111/ijlh.13329.
The authors looked at COVID-19-induced coagulation alteractions using thrombin generation and esoteric lab testing. This helps better understand COVID-19 infection physiopathology.
Sep. 15, 2020. Rotational thromboelastometry to assess hypercoagulability in COVID-19 patients.
Source:van Veenendaal N, Scheeren TWL, Meijer K, van der Voort PHJ. Thrombosis Research (2020).
In this study, the authors looked at COVID-19-induced hypercoagulability using rotational thromboelastography. They confirmed the hypercoagulable state of COVID-19 patients admitted to the ICU. However, the study results do not support the use of ROTEM in identifying COVID-19 patients at risk for developing thromboembolic complications.
Sep. 15, 2020. In vitro hypercoagulability and ongoing in vitro activation of coagulation and fibrinolysis in COVID-19 patients on anticoagulation.
Source:Blasi A, von Meijenfeldt FA, Adlmeijer J, Calvo A, Ibañez C, Perdomo J, Reverter JC, Lisman T. J Thromb Haemost. 2020 Aug 6:10.1111/jth.15043. doi: 10.1111/jth.15043.
In this paper, the authors confirm a hypercoagulable status of enhanced thrombin generating capacity, enhanced ex vivo clot formation likely related to hyperfibrinogenemia, and a decreased ex vivo fibrinolytic capacity in patients with COVID-19.
Sep. 15, 2020. COVID-19: a collision of complement, coagulation and inflammatory pathways.
Source:Chauhan AJ, Wiffen LJ, Brown TP. J Thromb Haemost. 2020 Jun 30:10.1111/jth.14981. doi: 10.1111/jth.14981.
This paper focuses on interactions among the complement, coagulation and inflammatory pathways following COVID-19 infection. More specifically, this review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID-19 infection.
July 31, 2020. Are antiphospholipid antibodies associated with thrombotic complication in critically ill COVID-19 patients?
Source:Singuret V, Voicu S, Neuwirth M, Delrue M, Gayat E, Stépanian A, Mégarbane B. Thromb Res. 2020 Jul 8;195:74-76. doi: 10.1016/j.thromres.2020.07.016.
The presence of antiphospholipid antibodies in COVID-19 patients has been widely reported in the literature as well as the high prevalence of thrombotic manifestations. This paper raises the question of the contribution of antiphospholipid antibodies to thrombosis and points out some limitations of lupus anticoagulant testing in these patients.
July 31, 2020. Hematological Manifestations of COVID-19: from Cytopenia to Coagulopathy.
Source:Agbuduwe C, Basu S. Eur J Haematol. 2020 Jul 14. doi: 10.1111/ejh.13491.
In this paper, authors provide a comprehensive overview of all haemotological alterations observed in COVID-19 infection with a specific focus on the importance inflammation biomarkers. D-dimer and absolute lymphocyte count for patient's stratification and for monitoring response to therapy.
July 31, 2020. D-dimer level is associated with the severity of COVID-19.
Source:Yu HH, Qin C, Chen M, Wang W, Tian DS. Thromb Res 2020, High levels of D-dimer have been reported in COVID-19 patients.
The study reported in this paper confirms the high level of D-dimer in patients with a poor outcome and a meta-analysis is on poor prognosis and elevated D-dimer is presented.
July 20, 2020. Thrombosis and coagulopathy in COVID-19: an illustrated review.
Source:Levi M, Hunt BJ. Res Pract Thromb Haemost. 2020 Jul 11;4(5):744-751. doi: 10.1002/rth2.12400. eCollection 2020 Jul. PMID: 32685883.
This paper depicts as a cartoon the up-to-date knowledge on pathologysiology of COVID-19 infection coagulopathy and indicates the mos relevant parameters for severe patients' monitoring.
July 20, 2020. Antiphospholipid antibodies in patients with COVID-19: a relevant observation?
Source:Devreese KMJ, Linskens EA, Benoit D, Peperstraete H. J Thromb Haemost. 2020 Jul 3:10.1111/jth.14994. doi: 10.1111/jth.14994. Online ahead of print. PMID: 32619328.
In this paper the potential contribution of frequently observed antiphospholipd antibodies in patients with severe COVID-19 infection presentation to the pathophysiology of thrombotic manifestations is discussed based on a literature review and personal authors' observation.
July 10, 2020. High prevalence of deep vein thrombosis in mechanically ventilated COVID-19 patients.
Source:Voicu S, Bonnin P, Stépanian A, Chousterman BG, Le Gall A, Malissin I, Deye N, Siguret V, Mebazaa A, Mégarbane B. J Am Coll Cardiol. 2020 May 29:S0737-1097(20)35462-0. doi: 10.1016/j.jaac.2020.05.053. Online ahead of print. PMID: 32479784.
This study shows the high prevalence of DVT in mechanically ventilated COVID-19 patients. Furthermore, the potential of D-dimer for DVT diagnosis in these patients is underlined.
July 10, 2020. Incidence of Deep Vein Thrombosis among non-ICU Patients Hospitalized for COVID-19 despite pharmacological Thromboprophylaxis.
Source:Santoliquido A, Porfidia A, Nesci A, De Matteis G, Marrone G, Porceddu E, Cammà G, Giarretta I, Fantoni M, Landi F, Gasbarrini A, Pola R; GEMELLI AGAINST COVID-19 Group. J Thromb Haemost. 2020 Jul 6. doi: 10.1111/jth.14992.
This paper shows the incidence of DVT in non-ICU COVID-19 patients despite prophylactic anticoagulation. Furthermore, the article highlights the potential role of D-dimer for DVT diagnosis.
June 22, 2020. Systemic Inflammatory response syndrome is a major contributor to COVID-19-Associated Coagulopathy: insights from a prospective SingleCenter Cohort study.
Source:Paul Masi, Guillaume Hékimian, Manon Lejeune et al. Circulation. 2020.
This recent paper, published in Circulation, helps better understand the Covid-19 infection pathophysiology from a haemostasis perspective in patients with acute respiratory distress syndrome (ARDS), in comparison with non-Covid-19 ARDS patients. The test panel comprises core lab parameters along with data generated with the Quantra point of care viscoelastic analyser. This study confirms the ability of Quantra to show Covid-19-associated coagulopathy, as previously described by Ranucci et al. (please see article below), and to differentiate Covid-19 from non-Covid-19 ARDS coagulopathy.
May 29, 2020. Undestanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19.
Source:Joly BS, Siguret V, Veyradier A. Intensive Care Med. 2020 May 15;1-4. doi: 10.1007/s00134-020-06088-1.
This short review uses easy-to-understand illustrations to summarize the complex mechanisms behind the haemostasis disorders observed in critically ill COVID-19 patients.
May 29, 2020. Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS-CoV-2.
Source:Huisman A et al. Int J Lab Hematol. 2020;00:1-2. doi: 10.1111/ijlh.13244
As thrombotic microangiopathy (TMA) is one of the consequences of sepsis, authors measured ADAMTS13 and vWF levels in 12 patients with SARS-CoV-2 infection with a clinical suspicion of TMA. The combination of low ADAMTS13 activity and high vWF levels might contribute to the microangiopathic state observed in these patients.
Authors therefore suggest including ADAMTS13 and vWF in the diagnostic workup of patients infected with SARS-CoV-2 when a microangiopathic state is suspected.
May 29, 2020. COVID-19 and hypercoagulability in the outpatient setting.
Source:Emert R, Shah P, Zampella JG. Thromb Res. 2020 Aug; 192: 122-123. doi: 10.1016/j.thromres.2020.05.031
This article raises the issue of hypercoagulability in outpatients with COVID-19 infection. Caution should be taken not to omit exploring the development of VTE in COVID-19 outpatients. Some of the issues raised inT. Akel's article, which reported on outpatients who developed PE, are raised again here.
The authors suggest that risk stratification and anticoagulation could also be requested for outpatients.
May 29, 2020. Fibrinolysis Shutdown correlates to thromboembolic events in severe COVID-19 infection.
Source:Wright FL, Vogler TO, Moore EE et al. J Am Coll Surgeons.
In this paper, the authors highlight that the reduction of fibrinolysis, evidenced by an increased D-dimer level (proposed threshold 2600 ng/mL) and a complete failure in TEG clot lysis after 30minutes, is correlated with thromboembolic events and renal failure requiring hemodialysis. These results would therefore suggest the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.
May 20, 2020. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis.
Source:Klok FA, Kruip MJHA, van der Meer NJM, et al. Thromb Res. 2020 Apr 10. doi: 10.1016/j.thromres.2020.04.013.
May 20, 2020. Incidence of venous thromboembolism in hospitalized patients with COVID-19.
Source:Middeldorp S, Coppens M, van Haaps TF, et al. J Thromb Haemost. 2020 May 5. doi: 10.1111/jth.14888.
These two articles confirm the elevated incidence of thromboembolic events in ICU COVID-19 patients: 49% (95% CI: 41-57) at 14 days in Klok's study and 59% (95% CI: 42-72) at 21 days in Middeldorp's study. Chronic anticoagulation therapy at admission is recommended in both articles to improve survival.
May 20, 2020. Autopsy Findings and Venous Thromboembolism in patients with COVID-19.
Source:Wichmann D, Sperhake JP, Lügehetmann M et al. Ann Intern Med. 2020 May 6. doi: 10.7326/M20-2003.
Complete autopsy was performed on 12 patients with confirmed COVID-19 infection. Atopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.
These findings underline the significant role of COVID-19-induced coagulopathy.
May 20, 2020. A proposal for staging COVID-19 coagulopathy.
Source:Thachil J, Cushman M, Srivastava A. Res Pract Thromb Haemost. 2020 May . Doi: 10.1002/rth2.12372
COVID-19 is associated with thrombotic complications. This forum discusses the lungs as the epicenter for the haemostatic issues, puts forward a proposal for staging COVID-19 coagulopathy based on available diagnostic markers, and suggests current and future treatment options be considered based on these different stages.
High risk of thrombosis in patients with severe SARS CoV 2 infection: a multicenter prospective cohort study
Source:Helms J, Tacquard C, Severac F et al. Intensive Care Med. 2020 May 4. doi: 10.1007/s00134-020-06062-x.
This study aims at evaluating the thrombotic risk in ARDS COVID-19 patients. Over 150 patients, 64 clinically relevant thrombotic complications were diagnosed (mainly pulmonary embolism, 17%). Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. 50/57 tested patients (87.7%) had positive lupus anticoagulant.
These results show that life-threatening thrombotic complications are frequent and that higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.
COVID-19 and its implications for thrombosis and anticoagulation
Source:Connors JM, Levy JH. Blood. 2020 Apr 27. doi: 10.1182/blood.2020006000.
This paper reviews the coagulation abnormalities that occur in association with COVID-19, and clinical management questions likely to arise. Authors thus suggest to perform coagulation test screening, including the measurement of D-dimer and fibrinogen levels, and to manage coagulopathy as it would be for any critically ill patient. However, they do not suggest the use of full intensity anticoagulation doses unless otherwise clinically indicated.
Lupus Anticoaulant and Abnormal Coagulation Tests in Patients with Covid-19
Source:Bowles L, Platton S, Yartey N et al. N Engl J Med. 2020 May 5. doi: 10.1056/NEJMc2013656.
In this study, aPTT prolongation has been investigated in 35 patients and 31 of them were positive lupus anticoagulant (91%) and often had an associated factor XII deficiency.
In general cases, a prolonged aPTT could be seen as a reason to avoid the use of anticoagulation at both therapeutic and prophylactic doses. However no factor deficiency, nor bleeding tendency were reported. Authors suggest that a prolonged aPTT should not be a barrier to the use of anticoagulation therapies in the prevention and treatment of venous thrombosis in patients with Covid-19.
Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia
Source:Rovina N, Akinosoglou K, Eugen-Olsen J et al. Crit Care. 2020 Apr 30;24(1):187. doi: 10.1186/s13054-020-02897-4.
In this letter, authors suggest that the soluble urokinase plasminogen activator receptor (suPAR) may reflect the endothelial activation in patients with COVID-19 infection, and may thus be an early predictor of severe respiratory failure (SRF). Receiver operator characteristics curve analysis identified levels ≥ 6 ng/ml as the best predictor for SRF. At that cutoff point, the sensitivity, specificity, positive predictive value, and negative predictive value for the prediction of SRF was 85.7%, 91.7%, 85.7%, and 91.7%, respectively.
COVID-19 cytokine storm: the interplay between inflammation and coagulation.
Source:Jose RJ, Manuel A. Lancet Respir Med. 2020 Apr 27. doi: 10.1016/S2213-2600(20)30216-2.
This letter reviews the interaction between coagulation and inflammatory systems in COVID-19 patients. The cytokine storm observed in patients enhances thrombin generation, and the thrombin generated may further augment inflammation via proteinase activated receptors (PARs). Authors thus suggest that targeting thrombin, coagulation factor Xa or PAR-1, might therefore be an attractive approach to reduce SARS-CoV-2 microthrombosis, lung injury, and associated poor outcomes.
Direct oral anticoagulant plasma levels striking increase in severe COVID-19 respiratory.
Syndrome patients treated with antiviral agents. The Cremona experience.
Source:Testa S, Prandoni P, Paoletti O et al. J Thromb Haemost. 2020 Apr 23. doi: 10.1111/jth.14871.
The authors showed in this paper that DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels, with C‐trough levels 6.14 times higher during hospitalization than in pre‐hospitalization period. They recommend to replace DOAC with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.
COVID‐19 Coagulopathy in Caucasian patients.
Source:Fogarty H, Townsend L, Ni Cheallaigh C. Br J Haematol 2020 Apr 24. doi: 10.1111/bjh.16749.
This paper shows haemostasis parameters depicting the coagulopathy in Caucasian patients (until now, most of reports reports were from Chinese patients).
Authors conclude that the marked increase in D-dimer levels is consistent with progressive coagulation activation, along with concurrent activation of fibrinolysis within the lungs. They also suggest that the pulmonary inflammation observed in COVID-19 is associated with a novel pulmonary-specific vasculopathy which they termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC.
Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19
Source:Whyte CS, Morrow GB, Mitchell JL et al. J Thromb Haemost. 2020 Apr 23. doi: 10.1111/jth.14872.
It appears that in addition to high-dose anticoagulation, fibrinolytic therapy may be necessary to degrade microthrombi present in the pulmonary alveoli of COVID-19 patients with ARDS. This review presents the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated with ARDS. Nebulizer plasminogen activators, currently in Phase II clinical trial, may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.
Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2
Source:Beun R, Kusadasi N,Sikma M, et al. Int J Lab Hematol. 20 April 2020. Doi: 10.1111/ijlh.13230
The high risk for arterial or venous thrombosis lead clinician to set up anticoagulant therapy in COVID-19 patients. As they observed heparin resistance in some patients, the authors suggest to monitor the heparin activity of UFH treatment based on anti-Xa levels with a target value of 0.3 - 0.7 U/L in all patients with SARS-CoV-2 instead of treatment based on aPTT levels.
Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID-19): a Meta-Analysis
Source:Xiong M, Liang X, Wei YD. Br J Haematol. 2020 Apr 18. doi: 10.1111/bjh.16725.
In this article, authors pooled data from 9 studies performed in China evaluating coagulation abnormalities in COVID-19 patients, between severe and mild patients.
Pooled results revealed that prothrombin time and D-dimer levels were significantly higher in patients with severe COVID-19. However, no significant difference in PLT and APTT values between severe and mild patients were observed
The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome
Source:Ranucci M, Ballotta A, Di Dedda U, et al. J THromb Haemost, 17 April 2020. Doi: 10.1111/jth.14854
Sixteen patients with COVID-19 ARDS were followed with haemostasis assays (aPTT, PT, platelet count, fibrinogen,D-dimer and antithrombin activity) and the Quantra® analyzer (Haemosonics, Charlottesville), a viscoelastic POC testing. The authors confirmed the pro‐coagulant pattern of these patients that may justify the thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.
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Tissue Plasminogen Activator (tPA) Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Case Series
Source:Wang J, Hajizadeh N, Moore EE et al. J Thromb Haemost. 2020 Apr 8. doi: 10.1111/jth.14828.
As thrombosis and DIC are frequently observed in patients who die from COVID-19, an American team has reported the off-label use of tPA (Alteplase®) in 3 critically-ill patients. They report clinical improvement in these patients with a decrease in hypoxemia as long as the tPA infusion lasted. These preliminary data, subject to confirmation in independent study, provide insights for improving the anticoagulant and fibrinolytic strategy in critically ill COVID-19 patients. The risk of catastrophic bleeding from use of tPA must be considered in the context of patient treatment.
Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
Source:Tang N, Li D, Wang X, Sun Z. J Thromb Haemost. 2020 Apr;18(4):844–7.
Available from: In this paper, the coagulation features of patients with COVID-19 infection is described, by use of datacomparing survivors (n=162) and non-survivors (n=21). The non-survivors revealed significantly higher D-dimer and FDP levels, longer PT results (expressed in seconds) and significantly lower antithrombin levels compared with survivors on admission. A decrease in fibrinogen levels in non-survivors was found on days 10 and 14. DIC, mostly due to virus sepsis, appeared in most of the non-survivors.
Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
Source:Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. J Thromb Haemost [Internet]. 2020 Mar 27
A paper retrospectively investigating the effect of anticoagulation on COVID-19 outcomes included 449 patients, 22% received treatment with UFH or LMWH. Use of anticoagulant treatment was associated with better prognosis in severe COVID‐19 patients meeting sepsis-induced coagulopathy criteria (SIC score) >4 or with markedly elevated D‐dimer (> 3 μg/L).
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https://link.springer.com/article/10.1007/s11739-021-02685-0One of the first reported and investigated case of DVT in a patient having received mRNA COVID-19 vaccine (BNT162b2, Comirnaty, Pfizer/BioNTech).
Nazy I, Jevtic SD, Moore JC, Huynh A, Smith JW, Kelton JG, Arnold DM. Platelet-activating immune complexes identified in critically ill COVID-19 patients suspected of heparin-induced thrombocytopenia. J Thromb Haemost. 2021 Feb 27. doi: 10.1111/jth.15283.
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https://onlinelibrary.wiley.com/doi/10.1111/jth.15283While learning societies keep their eyes on patients receiving COVID19 patients; the team from Hamilton in the Canada reports here the development of some HIT-like antibodies in critically ill COVID-19 patients, which could explain some thrombotic developments.
INSPIRATION Investigators, Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, Farrokhpour M, Sezavar SH, Payandemehr P, Dabbagh A, Moghadam KG, Jamalkhani S, Khalili H, Yadollahzadeh M, Riahi T, Rezaeifar P, Tahamtan O, Matin S, Abedini A, Lookzadeh S, Rahmani H, Zoghi E, Mohammadi K, Sadeghipour P, Abri H, Tabrizi S, Mousavian SM, Shahmirzaei S, Bakhshandeh H, Amin A, Rafiee F, Baghizadeh E, Mohebbi B, Parhizgar SE, Aliannejad R, Eslami V, Kashefizadeh A, Kakavand H, Hosseini SH, Shafaghi S, Ghazi SF, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Piazza G, Kirtane AJ, Van Tassell BW, Dobesh PP, Stone GW, Lip GYH, Krumholz HM, Goldhaber SZ, Bikdeli B. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Mar 18. doi: 10.1001/jama.2021.4152.
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https://jamanetwork.com/journals/jama/fullarticle/2777829Et Al-Samkari H. Finding the Optimal Thromboprophylaxis Dose in Patients With COVID-19. JAMA. 2021 Mar 18. doi: 10.1001/jama.2021.4295.
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https://jamanetwork.com/journals/jama/fullarticle/2777828The multicentric INSPIRATION randomized trial compared primary outcomes at 30 days for COVID 19 patients under ECMO when receiving intermediate (therapeutic) dose of heparin or standard (prophylactic) one. Surprisingly, not difference was found, which deserved an editorial comment too.
2021 Jan 7. Iba T, Warkentin TE, Thachil J, Levi M, Levy JH. Proposal of the Definition for COVID-19-Associated Coagulopathy. J Clin Med.;10(2):E191. doi: 10.3390/jcm10020191. PMID: 33430431
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JCM | Free Full-Text | Proposal of the Definition for COVID-19-Associated Coagulopathy (mdpi.com)This review summarizes the current knowledge about COVID-19- associated coagulopathy including differences and similarities with sepsis-associated disseminated intravascular coagulopathy.
2021 Jan 7. Barbosa LC, Lopes T, de Araujo LP, de Oliveira Rosario LV, Ferrer VP. Endothelial cells and SARS-CoV-2: An intimate relationship. Vascul Pharmacol.:106829. doi: 10.1016/j.vph.2021.106829. Online ahead of print. PMID: 33422689
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https://doi.org/10.1016/j.vph.2021.106829Endothelial cells have a critical role in the inflammatory and disseminate coagulation process reported in COVID-19 patients, which culminate in a higher risk of thromboembolic, cardiovascular, and cerebrovascular complications in these patients. This paper reviews how endothelial cell injury contributes to COVID-19 coagulopathy and how endothelial cells can be a target for therapies.
2021 Jan 5. Bongiovanni D, Klug M, Lazareva O, Weidlich S, Biasi M, Ursu S, Warth S, Buske C, Lukas M, Spinner CD, Scheidt MV, Condorelli G, Baumbach J, Laugwitz KL, List M, Bernlochner I.
SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype. Cell Death Dis.;12(1):50. doi: 10.1038/s41419-020-03333-9. PMID: 33414384
In this paper, the authors detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients.
2021 Jan 15. Philippe A, Chocron R, Gendron N, Bory O, Beauvais A, Peron N, Khider L, Guerin CL, Goudot G, Levasseur F, Peronino C, Duchemin J, Brichet J, Sourdeau E, Desvard F, Bertil S, Pene F, Cheurfa C, Szwebel TA, Planquette B, Rivet N, Jourdi G, Hauw-Berlemont C, Hermann B, Gaussem P, Mirault T, Terrier B, Sanchez O, Diehl JL, Fontenay M, Smadja DM. Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality. Angiogenesis; 1-13. doi: 10.1007/s10456-020-09762-6.
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SpringerLinkThis study looked at the endothelial dysfunction in COVID-19 patients. VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. The authors hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.
2020 Dec 24. Delrue M, Siguret V, Neuwirth M, Joly B, Beranger N, Sène D, Chousterman BG, Voicu S, Bonnin P, Mégarbane B, Stépanian A. von Willebrand factor/ADAMTS13 axis and venous thromboembolism in moderate-to-severe COVID-19 patients.Br J Haematol. Doi:10.1111/bjh.17216
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von Willebrand factor/ADAMTS13 axis and venous thromboembolism in moderate‐to‐severe COVID‐19 patients - Delrue - - British Journal of Haematology - Wiley Online LibraryThe authors conducted an exploratory study in moderate‐to‐severe COVID‐19 patients managed in hospital to analyse the implication of the VWF/ADAMTS13 axis in VTE (i.e., deep venous thrombosis or pulmonary embolisms. Their data highlights the role of the VWF/ADAMTS13 axis at the crossroads between lung system microthrombosis and venous macrothrombosis in COVID‐19.
Dec, 2020. Stefely JA, Christensen BB, Gogakos T, Cone Sullivan JK et al. Marked factor V activity elevation in severe COVID-19 is associated with venous thromboembolism. Am J Hematol. doi: 10.1002/ajh.25979.
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onlinelibrary.wiley.comIn this series of 102 with COVID-19 infection, patients with factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49,33%) compared to those with factor V activity <150 IU/dL (7/53,13%) (P = .03). Within this severe COVID-19 cohort, factor V activity associated with SARS-CoV-2 load in a sex-dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality.
Nov 12, 2020. Goudot G, Chocron R, Augy JL et al. Predictive Factor for COVID-19 Worsening: Insights for High-Sensitivity Troponin and D-Dimer and Correlation with Right Ventricular Afterload. Front Med (Lausanne). doi: 10.3389/fmed.2020.586307
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www.frontiersin.orgHs-cTnl appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with right ventricular dilatation probably reflects a myocardial injury due to an increased right ventricular wall tension.
Sep 22, 2020. Gerotziafas GT, Sergentanis TN, Voiriot G et al. Derivation and Validation of a predictive score for disease Worsening in patients with COVID-19. Thromb Haemost. doi: 10.1055/s-0040-1716544
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www.thieme-connect.deThe COMPASS-COVID-19 score derived from a prospective study is composed of easily assessable clinical and hematological predictors. The score has high sensitivity (81%) for the identification of hospitalized patients at high risk of disease worsening.
Aug 19, 2929. Chatterjee S, Sengupta T, Majumder S et al. COVID-19: a probable role of the anticoagulant Protein S in managing COVID-19-associated coagulopathy. Aging (Albany NY). 12(16):15954-15961. doi: 10.18632/aging.103869
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https://pubmed.ncbi.nlm.nih.gov/32826388/Most severely ill COVID-19 patients manifest a hyperactivated immune response, instigated by interleukin 6 (IL6) that triggers a so called "cytokine storm" and coagulopathy. Hypoxia is also associated with COVID-19. So far overlooked is the fact that both IL6 and hypoxia depress the abundance of a key anticoagulant, Protein S. The authors highlight a mechanism by which the IL6-hypoxia curse causes a deadly hypercoagulable state in COVID-19 patients, and suggest a path to therapy.
Oct. 12, 2020. Anti-Xa Monitoring improves low-molecular-weight heparin effectiveness in patients with SARS-CoV-2 infection.
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Trunfio M, Salvador E, Cabodj D, Marinaro L, Alcantarini C, Gaviraghi A, Trentalange A, Lipani F, Sciascia S, Roccatello D, Bonora S, Di Perri G, Calcagno A, for the e-COVID Study group - trhomb Res 2020.This research paper suggests that close anti-Xa monitoring of COVID-19 patients administered LMWH treatment along with dose-adjustment based on the result of the anti-Xa activity assay could be beneficial in terms of outcome.
Oct. 12, 2020. D-Dimer cut-off points and risk of venous thromboembolism in adult hospitalized patients with COVID-19.
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Choi JJ, Wehmeyer GT, Li HA, Alshak MN, Nahid M, Rajan M, Liu B, Schatoff EM, Elahjji Rn Abdelghany Y, D'Angelo D, Crossman D, Evans AT, Steel P, Pinheiro LC, Goyal P, Safford MM, Mints G, DeSancho MT - Thromb Res 2020.This paper confirms the importance of Dimer testing for prognosis evaluation in COVID-19 patients.
Oct. 12, 2020. Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.
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Voicu S, Delrue M, Chousterman BG, Stépanian A, Bonnin P, Malissin I, Deye N, Neuwirth M, Ketfi C, Mebazaa A, Siguret V, Mégarbane B - Eur Rev Med Pharmacol Sci 2020; 24:9161-8This paper shows that mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway and that D-dimer may be a useful biomarker at the bedside for suspicion of VTE.
Sep. 15, 2020. Pulmonary embolism, pulmonary microvascular thrombosis, or both in COVID-19?
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Paramo JA. Clin Appl Thromb Hemost. Jan-Dec; 26:1076029620933953. doi: 10.1177/1076029620933953Focusing on COVID-19 pathophysiology and the results of post-mortem examinations, the author differentiates pulmonary lesions between pulmonary embolism and intrapulmonary acute microvascular thrombosis and proposes to include the term "primary pulmonary thrombi" which develop directly in the lungs without traveling from DVT to refer to the most common thrombotic manifestations in patients with COVID-19 infection.
Sep. 15, 2020. Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory.
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Hardy M, Lecompte T, Douxfils J, Lessire S, Dogné JM, Chatelain B, Testa S, Gouin-Thibault I, Gruel Y, Medcalf RL, Ten Cate H, Lippi G, Mullier F. Thromb J. 2020 Sep 7; 18:17. doi: 10.1186/s12959-020-00230-1. eCollection 2020.This paper is a comprehensive review of the literature and provides a detailed focus on coagulation laboratory alteractions observed in COVID-19 patients, including routine, specialized and global assays, as well as on anticoagulation in COVID-19 patients and its monitoring.
Sep. 15, 2020. Evaluation of COVID-19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays.
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White D, MacDonald S, Edwards T, Bridgeman C, Hayman M, Sharp M, Cox-Morton S, Duff E, Mahajan S, Moore C, Kirk M, Williams R, Besser M, Thomas W. Int J Lab Hematol. 2020 Sep 5. doi: 10.1111/ijlh.13329.The authors looked at COVID-19-induced coagulation alteractions using thrombin generation and esoteric lab testing. This helps better understand COVID-19 infection physiopathology.
Sep. 15, 2020. Rotational thromboelastometry to assess hypercoagulability in COVID-19 patients.
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van Veenendaal N, Scheeren TWL, Meijer K, van der Voort PHJ. Thrombosis Research (2020).In this study, the authors looked at COVID-19-induced hypercoagulability using rotational thromboelastography. They confirmed the hypercoagulable state of COVID-19 patients admitted to the ICU. However, the study results do not support the use of ROTEM in identifying COVID-19 patients at risk for developing thromboembolic complications.
Sep. 15, 2020. In vitro hypercoagulability and ongoing in vitro activation of coagulation and fibrinolysis in COVID-19 patients on anticoagulation.
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Blasi A, von Meijenfeldt FA, Adlmeijer J, Calvo A, Ibañez C, Perdomo J, Reverter JC, Lisman T. J Thromb Haemost. 2020 Aug 6:10.1111/jth.15043. doi: 10.1111/jth.15043.In this paper, the authors confirm a hypercoagulable status of enhanced thrombin generating capacity, enhanced ex vivo clot formation likely related to hyperfibrinogenemia, and a decreased ex vivo fibrinolytic capacity in patients with COVID-19.
Sep. 15, 2020. COVID-19: a collision of complement, coagulation and inflammatory pathways.
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Chauhan AJ, Wiffen LJ, Brown TP. J Thromb Haemost. 2020 Jun 30:10.1111/jth.14981. doi: 10.1111/jth.14981.This paper focuses on interactions among the complement, coagulation and inflammatory pathways following COVID-19 infection. More specifically, this review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID-19 infection.
July 31, 2020. Are antiphospholipid antibodies associated with thrombotic complication in critically ill COVID-19 patients?
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Singuret V, Voicu S, Neuwirth M, Delrue M, Gayat E, Stépanian A, Mégarbane B. Thromb Res. 2020 Jul 8;195:74-76. doi: 10.1016/j.thromres.2020.07.016.The presence of antiphospholipid antibodies in COVID-19 patients has been widely reported in the literature as well as the high prevalence of thrombotic manifestations. This paper raises the question of the contribution of antiphospholipid antibodies to thrombosis and points out some limitations of lupus anticoagulant testing in these patients.
July 31, 2020. Hematological Manifestations of COVID-19: from Cytopenia to Coagulopathy.
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Agbuduwe C, Basu S. Eur J Haematol. 2020 Jul 14. doi: 10.1111/ejh.13491.In this paper, authors provide a comprehensive overview of all haemotological alterations observed in COVID-19 infection with a specific focus on the importance inflammation biomarkers. D-dimer and absolute lymphocyte count for patient's stratification and for monitoring response to therapy.
July 31, 2020. D-dimer level is associated with the severity of COVID-19.
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Yu HH, Qin C, Chen M, Wang W, Tian DS. Thromb Res 2020, High levels of D-dimer have been reported in COVID-19 patients.The study reported in this paper confirms the high level of D-dimer in patients with a poor outcome and a meta-analysis is on poor prognosis and elevated D-dimer is presented.
July 20, 2020. Thrombosis and coagulopathy in COVID-19: an illustrated review.
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Levi M, Hunt BJ. Res Pract Thromb Haemost. 2020 Jul 11;4(5):744-751. doi: 10.1002/rth2.12400. eCollection 2020 Jul. PMID: 32685883.This paper depicts as a cartoon the up-to-date knowledge on pathologysiology of COVID-19 infection coagulopathy and indicates the mos relevant parameters for severe patients' monitoring.
July 20, 2020. Antiphospholipid antibodies in patients with COVID-19: a relevant observation?
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Devreese KMJ, Linskens EA, Benoit D, Peperstraete H. J Thromb Haemost. 2020 Jul 3:10.1111/jth.14994. doi: 10.1111/jth.14994. Online ahead of print. PMID: 32619328.In this paper the potential contribution of frequently observed antiphospholipd antibodies in patients with severe COVID-19 infection presentation to the pathophysiology of thrombotic manifestations is discussed based on a literature review and personal authors' observation.
July 10, 2020. High prevalence of deep vein thrombosis in mechanically ventilated COVID-19 patients.
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Voicu S, Bonnin P, Stépanian A, Chousterman BG, Le Gall A, Malissin I, Deye N, Siguret V, Mebazaa A, Mégarbane B. J Am Coll Cardiol. 2020 May 29:S0737-1097(20)35462-0. doi: 10.1016/j.jaac.2020.05.053. Online ahead of print. PMID: 32479784.This study shows the high prevalence of DVT in mechanically ventilated COVID-19 patients. Furthermore, the potential of D-dimer for DVT diagnosis in these patients is underlined.
July 10, 2020. Incidence of Deep Vein Thrombosis among non-ICU Patients Hospitalized for COVID-19 despite pharmacological Thromboprophylaxis.
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Santoliquido A, Porfidia A, Nesci A, De Matteis G, Marrone G, Porceddu E, Cammà G, Giarretta I, Fantoni M, Landi F, Gasbarrini A, Pola R; GEMELLI AGAINST COVID-19 Group. J Thromb Haemost. 2020 Jul 6. doi: 10.1111/jth.14992.This paper shows the incidence of DVT in non-ICU COVID-19 patients despite prophylactic anticoagulation. Furthermore, the article highlights the potential role of D-dimer for DVT diagnosis.
June 22, 2020. Systemic Inflammatory response syndrome is a major contributor to COVID-19-Associated Coagulopathy: insights from a prospective SingleCenter Cohort study.
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Paul Masi, Guillaume Hékimian, Manon Lejeune et al. Circulation. 2020.This recent paper, published in Circulation, helps better understand the Covid-19 infection pathophysiology from a haemostasis perspective in patients with acute respiratory distress syndrome (ARDS), in comparison with non-Covid-19 ARDS patients. The test panel comprises core lab parameters along with data generated with the Quantra point of care viscoelastic analyser. This study confirms the ability of Quantra to show Covid-19-associated coagulopathy, as previously described by Ranucci et al. (please see article below), and to differentiate Covid-19 from non-Covid-19 ARDS coagulopathy.
May 29, 2020. Undestanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19.
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Joly BS, Siguret V, Veyradier A. Intensive Care Med. 2020 May 15;1-4. doi: 10.1007/s00134-020-06088-1.This short review uses easy-to-understand illustrations to summarize the complex mechanisms behind the haemostasis disorders observed in critically ill COVID-19 patients.
May 29, 2020. Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS-CoV-2.
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Huisman A et al. Int J Lab Hematol. 2020;00:1-2. doi: 10.1111/ijlh.13244As thrombotic microangiopathy (TMA) is one of the consequences of sepsis, authors measured ADAMTS13 and vWF levels in 12 patients with SARS-CoV-2 infection with a clinical suspicion of TMA. The combination of low ADAMTS13 activity and high vWF levels might contribute to the microangiopathic state observed in these patients.
Authors therefore suggest including ADAMTS13 and vWF in the diagnostic workup of patients infected with SARS-CoV-2 when a microangiopathic state is suspected.
May 29, 2020. COVID-19 and hypercoagulability in the outpatient setting.
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Emert R, Shah P, Zampella JG. Thromb Res. 2020 Aug; 192: 122-123. doi: 10.1016/j.thromres.2020.05.031This article raises the issue of hypercoagulability in outpatients with COVID-19 infection. Caution should be taken not to omit exploring the development of VTE in COVID-19 outpatients. Some of the issues raised in
T. Akel's article, which reported on outpatients who developed PE, are raised again here.The authors suggest that risk stratification and anticoagulation could also be requested for outpatients.
May 29, 2020. Fibrinolysis Shutdown correlates to thromboembolic events in severe COVID-19 infection.
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Wright FL, Vogler TO, Moore EE et al. J Am Coll Surgeons.In this paper, the authors highlight that the reduction of fibrinolysis, evidenced by an increased D-dimer level (proposed threshold 2600 ng/mL) and a complete failure in TEG clot lysis after 30minutes, is correlated with thromboembolic events and renal failure requiring hemodialysis. These results would therefore suggest the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.
May 20, 2020. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis.
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Klok FA, Kruip MJHA, van der Meer NJM, et al. Thromb Res. 2020 Apr 10. doi: 10.1016/j.thromres.2020.04.013.
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Middeldorp S, Coppens M, van Haaps TF, et al. J Thromb Haemost. 2020 May 5. doi: 10.1111/jth.14888.These two articles confirm the elevated incidence of thromboembolic events in ICU COVID-19 patients: 49% (95% CI: 41-57) at 14 days in Klok's study and 59% (95% CI: 42-72) at 21 days in Middeldorp's study. Chronic anticoagulation therapy at admission is recommended in both articles to improve survival.
May 20, 2020. Autopsy Findings and Venous Thromboembolism in patients with COVID-19.
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Wichmann D, Sperhake JP, Lügehetmann M et al. Ann Intern Med. 2020 May 6. doi: 10.7326/M20-2003.Complete autopsy was performed on 12 patients with confirmed COVID-19 infection. Atopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.
These findings underline the significant role of COVID-19-induced coagulopathy.
May 20, 2020. A proposal for staging COVID-19 coagulopathy.
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Thachil J, Cushman M, Srivastava A. Res Pract Thromb Haemost. 2020 May . Doi: 10.1002/rth2.12372COVID-19 is associated with thrombotic complications. This forum discusses the lungs as the epicenter for the haemostatic issues, puts forward a proposal for staging COVID-19 coagulopathy based on available diagnostic markers, and suggests current and future treatment options be considered based on these different stages.
High risk of thrombosis in patients with severe SARS CoV 2 infection: a multicenter prospective cohort study
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Helms J, Tacquard C, Severac F et al. Intensive Care Med. 2020 May 4. doi: 10.1007/s00134-020-06062-x.This study aims at evaluating the thrombotic risk in ARDS COVID-19 patients. Over 150 patients, 64 clinically relevant thrombotic complications were diagnosed (mainly pulmonary embolism, 17%). Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. 50/57 tested patients (87.7%) had positive lupus anticoagulant.
These results show that life-threatening thrombotic complications are frequent and that higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.
COVID-19 and its implications for thrombosis and anticoagulation
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Connors JM, Levy JH. Blood. 2020 Apr 27. doi: 10.1182/blood.2020006000.This paper reviews the coagulation abnormalities that occur in association with COVID-19, and clinical management questions likely to arise. Authors thus suggest to perform coagulation test screening, including the measurement of D-dimer and fibrinogen levels, and to manage coagulopathy as it would be for any critically ill patient. However, they do not suggest the use of full intensity anticoagulation doses unless otherwise clinically indicated.
Lupus Anticoaulant and Abnormal Coagulation Tests in Patients with Covid-19
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Bowles L, Platton S, Yartey N et al. N Engl J Med. 2020 May 5. doi: 10.1056/NEJMc2013656.In this study, aPTT prolongation has been investigated in 35 patients and 31 of them were positive lupus anticoagulant (91%) and often had an associated factor XII deficiency.
In general cases, a prolonged aPTT could be seen as a reason to avoid the use of anticoagulation at both therapeutic and prophylactic doses. However no factor deficiency, nor bleeding tendency were reported. Authors suggest that a prolonged aPTT should not be a barrier to the use of anticoagulation therapies in the prevention and treatment of venous thrombosis in patients with Covid-19.
Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia
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Rovina N, Akinosoglou K, Eugen-Olsen J et al. Crit Care. 2020 Apr 30;24(1):187. doi: 10.1186/s13054-020-02897-4.In this letter, authors suggest that the soluble urokinase plasminogen activator receptor (suPAR) may reflect the endothelial activation in patients with COVID-19 infection, and may thus be an early predictor of severe respiratory failure (SRF). Receiver operator characteristics curve analysis identified levels ≥ 6 ng/ml as the best predictor for SRF. At that cutoff point, the sensitivity, specificity, positive predictive value, and negative predictive value for the prediction of SRF was 85.7%, 91.7%, 85.7%, and 91.7%, respectively.
COVID-19 cytokine storm: the interplay between inflammation and coagulation.
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Jose RJ, Manuel A. Lancet Respir Med. 2020 Apr 27. doi: 10.1016/S2213-2600(20)30216-2.This letter reviews the interaction between coagulation and inflammatory systems in COVID-19 patients. The cytokine storm observed in patients enhances thrombin generation, and the thrombin generated may further augment inflammation via proteinase activated receptors (PARs). Authors thus suggest that targeting thrombin, coagulation factor Xa or PAR-1, might therefore be an attractive approach to reduce SARS-CoV-2 microthrombosis, lung injury, and associated poor outcomes.
Direct oral anticoagulant plasma levels striking increase in severe COVID-19 respiratory.
Syndrome patients treated with antiviral agents. The Cremona experience.
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Testa S, Prandoni P, Paoletti O et al. J Thromb Haemost. 2020 Apr 23. doi: 10.1111/jth.14871.The authors showed in this paper that DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels, with C‐trough levels 6.14 times higher during hospitalization than in pre‐hospitalization period. They recommend to replace DOAC with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.
COVID‐19 Coagulopathy in Caucasian patients.
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Fogarty H, Townsend L, Ni Cheallaigh C. Br J Haematol 2020 Apr 24. doi: 10.1111/bjh.16749.This paper shows haemostasis parameters depicting the coagulopathy in Caucasian patients (until now, most of reports reports were from Chinese patients).
Authors conclude that the marked increase in D-dimer levels is consistent with progressive coagulation activation, along with concurrent activation of fibrinolysis within the lungs. They also suggest that the pulmonary inflammation observed in COVID-19 is associated with a novel pulmonary-specific vasculopathy which they termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC.
Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19
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Whyte CS, Morrow GB, Mitchell JL et al. J Thromb Haemost. 2020 Apr 23. doi: 10.1111/jth.14872.It appears that in addition to high-dose anticoagulation, fibrinolytic therapy may be necessary to degrade microthrombi present in the pulmonary alveoli of COVID-19 patients with ARDS. This review presents the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated with ARDS. Nebulizer plasminogen activators, currently in Phase II clinical trial, may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.
Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2
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Beun R, Kusadasi N,Sikma M, et al. Int J Lab Hematol. 20 April 2020. Doi: 10.1111/ijlh.13230The high risk for arterial or venous thrombosis lead clinician to set up anticoagulant therapy in COVID-19 patients. As they observed heparin resistance in some patients, the authors suggest to monitor the heparin activity of UFH treatment based on anti-Xa levels with a target value of 0.3 - 0.7 U/L in all patients with SARS-CoV-2 instead of treatment based on aPTT levels.
Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID-19): a Meta-Analysis
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Xiong M, Liang X, Wei YD. Br J Haematol. 2020 Apr 18. doi: 10.1111/bjh.16725.In this article, authors pooled data from 9 studies performed in China evaluating coagulation abnormalities in COVID-19 patients, between severe and mild patients.
Pooled results revealed that prothrombin time and D-dimer levels were significantly higher in patients with severe COVID-19. However, no significant difference in PLT and APTT values between severe and mild patients were observed
The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome
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Ranucci M, Ballotta A, Di Dedda U, et al. J THromb Haemost, 17 April 2020. Doi: 10.1111/jth.14854Sixteen patients with COVID-19 ARDS were followed with haemostasis assays (aPTT, PT, platelet count, fibrinogen,D-dimer and antithrombin activity) and the Quantra® analyzer (Haemosonics, Charlottesville), a viscoelastic POC testing. The authors confirmed the pro‐coagulant pattern of these patients that may justify the thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.
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Tissue Plasminogen Activator (tPA) Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Case Series
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Wang J, Hajizadeh N, Moore EE et al. J Thromb Haemost. 2020 Apr 8. doi: 10.1111/jth.14828.As thrombosis and DIC are frequently observed in patients who die from COVID-19, an American team has reported the off-label use of tPA (Alteplase®) in 3 critically-ill patients. They report clinical improvement in these patients with a decrease in hypoxemia as long as the tPA infusion lasted. These preliminary data, subject to confirmation in independent study, provide insights for improving the anticoagulant and fibrinolytic strategy in critically ill COVID-19 patients. The risk of catastrophic bleeding from use of tPA must be considered in the context of patient treatment.
Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
Source:
Tang N, Li D, Wang X, Sun Z. J Thromb Haemost. 2020 Apr;18(4):844–7.Available from: In this paper, the coagulation features of patients with COVID-19 infection is described, by use of datacomparing survivors (n=162) and non-survivors (n=21). The non-survivors revealed significantly higher D-dimer and FDP levels, longer PT results (expressed in seconds) and significantly lower antithrombin levels compared with survivors on admission. A decrease in fibrinogen levels in non-survivors was found on days 10 and 14. DIC, mostly due to virus sepsis, appeared in most of the non-survivors.
Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
Source:
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. J Thromb Haemost [Internet]. 2020 Mar 27A paper retrospectively investigating the effect of anticoagulation on COVID-19 outcomes included 449 patients, 22% received treatment with UFH or LMWH. Use of anticoagulant treatment was associated with better prognosis in severe COVID‐19 patients meeting sepsis-induced coagulopathy criteria (SIC score) >4 or with markedly elevated D‐dimer (> 3 μg/L).
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