act of low molecular weight heparin administration on the clinical course of the COVID-19 disease

act of low molecular weight heparin administration on the clinical course of the COVID-19 disease

Background: Lymphopenia is the most important criterion of mortality and discharging feature for patients infected with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical impact of a low molecular weight heparin (LMWH) treatment on the clinical course of COVID-19. Materials and methods: Patients’ clinical symptoms, radiologic outcomes, hematologic, biochemical, D-dimer, and C-reactive protein (CRP) results were obtained from their medical records. Participants were separated into 2 groups: one was treated with LMWH and the other was not. Improvement in the patients was compared before and after treatment. Results: Ninety-six patients who were diagnosed with COVID-19 between April and May 2020 were retrospectively analyzed. The multivariable analysis showed that the count of lymphocytes, D-dimer, and CRP levels were significantly improved in the LMWH group, as compared to the control group (OR, (95% CI) 0.628 (0.248–0.965), P < 0.001); OR, (95% CI) 0.356 (0.089–0.674), P < 0.001, respectively). The area under the receiver operating characteristic (ROC) curve analysis was AUC: 0.679 ± 0.055, 0.615 ± 0.058, and 0.633 ± 0.057, respectively; the β-value was found to be –1.032, –0.026, and –0.465, respectively. Conclusion: The LMWH treatment group demonstrated better laboratory findings, including recovery in the lymphocyte count, CRP, and D-dimer results.Key words: Coronavirus disease-19, heparin, antiinflammatory, lymphocyte

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  • 1. Perlman S. Another decade, another coronavirus. The New England Journal of Medicine 2020; 382: 760-762.doi: 10.1056/ NEJMe2001126
  • 2. World Health Organization (WHO). Clinical Management of Severe Acute Respiratory Infection When Novel Coronavirus (2019-nCoV) Infection Is Suspected: Interim Guidance, WHO/2019-nCoV/clinical/2020.5; (2020).
  • 3. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. British Medical Journal Version 2. BMJ 2020; 368: 606- 613.doi: 10.1136/bmj.m606
  • 4. Liu Y, Yang Y, Zhang C, Huang F, Wang F et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life 2020; 63 (3): 364-374. doi: 10.1007/s11427-020-1643-8
  • 5. Chan MH, Wong VW, Wong CK, Chan PKS, Chu CM et al. Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome. Journal of Internal Medicine 2004; 255 (4): 512-518. doi: 10.1111/j.1365-2796.2004.01323.x
  • 6. Hou H, Zhang B, Huang H, Luo Y, Wu S et al. Using IL-2R/ lymphocytes for predicting the clinical progression of patients with COVID-19. Clinical Experimental Immunology 2020; 201(1): 76-84. doi: 10.1111/cei.13450
  • 7. Wang D, Hu B, Hu C, Zhu F, Li X et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus infected pneumonia in Wuhan, China. Journal of The American Medical Association 2020; 323 (11): 1061-1069. doi: 10.1001/ jama.2020.1585
  • 8. Terpos E, Ntanasis-Stathopoulos I, ElalamyI, Kastritis E, Sergentanis TN et al. Hematological findings and complications of COVID-19. American Journal of Hematology. 2020; 95 (7): 834-847. doi: 10.1002/ajh.25829
  • 9. Tang N, Bai H, Chen X, Gong J, Li D et al. Anticoagulant treatment is associated with decreased mortality in severe corona virus disease 2019 patients with coagulopathy. Journal of Thrombosis and Haemostasis 2020; 18 (5): 1094-1099. doi: 10.1111/jth.14817
  • 10. Tang N , Li D, Wang X , Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis 2020; 18 (4): 844-847. doi: 10.1111/jth.14768
  • 11. Chang YC, Yu CJ, Chang SC, Galvin JR, Liu HM et al. Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: evaluation withthin-section CT. Radiology 2005; 236 (3): 1067-1075. doi: 10.1148/radiol.2363040958
  • 12. Tichelaar YI, Kluin-Nelemans JCH, Meijeret K. Infections and inflammatory diseases as risk factors for venous thrombosis. A systematic review. Thrombosis and Haemostasis 2012; 107 (5): 827-837. doi: 10.1160/TH11-09-0611
  • 13. Downing LJ, Strieter RM, Kadell AM, Wilke CA, Greenfield LJ et al. Low-dose low-molecular-weight heparin is antiinflammatory during venous thrombosis. Journal of Vascular Surgery 1998; 28 (5): 848-854. doi: 10.1016/s0741- 5214(98)70060-6
  • 14. Ahmed T, Garrigo J, Danta I. Preventing broncho constriction in exercise-induced asthma within haled heparin. New England Journal of Medicine 1993; 329 (2): 90-95. doi: 10.1056/ NEJM199307083290204
  • 15. Li X, Wang L, Yan. S, Yang F, Xiang L et al. Clinical characteristics of 25 death cases infected with COVID-19 pneumonia: a retrospective review of medical records in a single medical center, Wuhan, China. International Journal of Infectious Disease 2020; 94: 128-132. doi: 10.1016 /j.ijid.2020.03.053
  • 16. Li L, Tian H, Yong W, Zheng W, Yuan L et al. COVID‐19 patients’ clinical characteristics, discharge rate, and fatality rate of meta‐analysis, Journal of Medical Virology 2020; 92 (6): 577-583. doi: 10.1002/jmv.25757
  • 17. Huang C, Wang Y, Li X, Ren L, Zhao J et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506. doi:10.1016/S0140- 6736(20)30183-5
  • 18. Ahmed T, Smith G, Vlahov I, Abraham WM. Inhibition of allergic airway responses by heparin derived oligosaccharides: identification of a tetrasaccharide sequence. Respiratory Research 2012; 13 (1): 6. doi: 10.1186/1465-9921-13-6
  • 19. Shastri MD, Stewart N, Eapen M, Peterson GM, Zaidi ST et al. Opposings of low molecular weight heparins on the release of inflammatory cytokines from peripheral blood mononuclear cells of asthmatics. PloS One 2015; 10 (3): e0118798. doi: 10.1371/journal.pone.0118798
  • 20. Shastri MD, Stewart N, Horne J, Peterson GM, Gueven N et al. In-vitro suppression of IL-6 and IL-8 release from human pulmonary epithelial cells by non-anticoagulant fraction of enoxaparin. PLoS One 2015; 10 (5): e0126763. doi: 10.1371/ journal. pone.0126763. eCollection 2015
  • 21. Shastri MD, Stewart N, Horne J, Zaidi ST, Sohal S et al. Nonanticoagulant fractions of enoxaparin suppress inflammatory cytokine release from peripheral blood mononuclear cells of allergic asthmatic individuals. PLoS One 2015; 10 (6): e0128803. doi: 10.1371/journal.pone.0128803
  • 22. Camprubi-Rimblas M, Guillamat-Prats R, Lebouvier T, BringueJ,Chimenti L et al. Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury. Respiratory Research 2017 May 10; 18 (1): 89-95. doi: 10.1186 /s12931-017-0572-3
  • 23. Paulsson M, Riesbeck K. How bacteria hack the matrix and dodge the bullets of immunity. European Respiratory Review 2018; 27 (148): 180018. doi: 10.1183/16000617.0018-2018
  • 24. Ek L, Gezelius E, Bergman B, Bendahl PO, Anderson H et al. Swedish lung cancer study group (SLUSG): randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial. Annals of Oncology 2018 ; 29 (2): 398-404. doi: 10.1093/annonc/mdx716
  • 25. He JL, Luo L, Luo ZD, Lyu JX, Ng MY et al. Diagnostic performance between CT and initial real-time RT-PCR forclinically suspected 2019 corona virus disease (COVID-19) patients outside Wuhan, China. Respiratory Medicine 2020; 168: 105980. doi: 10.1016/ j.rmed.2020.105980
  • 26. Liu P, Tan XZ. 2019 Novel Coronavirus (2019-nCoV) pneumonia. Radiology 2020 Feb 04: 200257. doi:10.1148/ radiol.2020200257
  • 27. Chung M, Bernheim A, Mei X, Zhang N, Huang M et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020 . doi: 10.1148/radiol.2020200230
  • 28. Zhang L, Yan Q, Fan H, Liu X, Liu Z et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. Journal of Thrombosis and Hemostasis: JTH. 2020; 18 (6): 1324-1329. doi: 10.1111/jth.14859
  • 29. Mousavi S, Moradi M, Khorshidahmad T, Motamedi.M. Antiinflammatory effects of heparin and its derivatives: a systematic review. Advances in Pharmacological Sciences 2015: 507151. doi: 10.1155/2015/507151
  • 30. Oldgren J, Fellenius C, Boman K, Jansson JH, Nilsson TK et al. Influence of prolonged dalteparin treatment on coagulation, fibrinolysis and inflammation in unstable coronary artery disease. Internal Medicine 2005; 258 (5): 420-427. doi: 10.1111/j.1365-2796.2005.01562.x
  • 31. Walters DL, Ray MJ, Wood P, Perrin EJ, Bett JHN et al. High-dose tirofiban with enoxaparin and inflammatory markers in high-risk percutaneous intervention. European Journal of Clinical Investigation 2010; 40 (2): 139-147. doi: 10.1111/j.1365-2362.2009.02237.x
  • 32. Montalescot G, Bal-dit-Sollier C, Chibedi D, Collet JP, Soulat T et al. Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients withunstable angina pectoris or non-ST-segment elevation acutemyocardial infarction (the ARMADA study), The American Journal of Cardiology 2003; 91 (8): 925-930. doi: 10.1016/s0002-9149(03)00105-x
  • 33. Tian S, Weidong H, Li N, Huan L, Haibo X et al. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. Journal of Thoracic Oncology 2020; 15 (5): 700-704. doi: 10.1016/j. jtho.2020.02.010
  • 34. Zhe X, Lei S, Yijin W, Jiyuan Z, Lei H et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respiratory Medicine 2020; 8 (4): 420-422. doi: 10.1016/S2213-2600(20)30076-X
  • 35. Fox SE, Aibek A, Jack LH, Guang L, Brown JQ et al. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respiratory Medicine 2020; 8 (7): 681-686. doi: 10.1016/ S2213-2600(20)30243-5
  • 36. Zuo Y, Srilakshmi Y, Hui S, Kelsey G, Melanie Zet al. Neutrophil extracellular traps in COVID-19. JCI Insight 2020; 5 (11): e138999. doi: 10.1172/ jci. insight.138999
  • 37. Barnes BJ, Jose MA, Baxter-Stoltzfus A, Borczuk A, CoolsLartigue J et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. Journal of Experimental Medicine 217, 2020 Jun 1; 217 (6): e20200652. doi: 10.1084/ jem.20200652
  • 38. Kapoor S, Opneja A, Nayak L. The role of neutrophils in thrombosis. Thrombosis Research 2018; 170: 87-96. doi:10.1016/j.thromres.2018.08.005
  • 39. Thalin C, Hisada Y, Lundstrom S, Mackman N, Wallen H. Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis. Arteriosclerosis Thrombosis and Vascular 2019; 39 (9): 1724-1738.doi: 10.1161/ ATVBAHA.119.312463
  • 40. Haznedaroğlu IC, Çelebier M. Anti-infective and woundhealing pleiotropicactions of Ankaferd hemostat. Turkish Journal of Medical Sciences 2020. doi: 10.3906/sag-2004-94
  • 41. Fan BE, Chong VCL, Stephrene Seok Wei C, GekHsiang L, Kian Guan Eric L et al. Hematologic parameters in patients with COVID-19 infection. American Journal of Hematology 2020; 95 (6): E131-E134. doi: 10.1002/ajh.25774
  • 42. Guan WJ, Zheng-YiNi, Hu Y, Liang WH, Chun-Quan O et al. Clinical characteristics of Coronavirus disease 2019 in China. The New England Journal of Medicine 2020; 382 (18): 1708- 1720. doi: 10.1056/NEJMoa2002032
  • 43. GongJ, Ou J, Qiu X, Jie Y, Yaqiong C et al. A tool to early predict severe corona virus disease 2019 (COVID-19) : a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clinical Infectious Diseases 2020; ciaa 443. doi: 10.1093/cid/ciaa443
  • 44. Chen R,Liang W, Jiang M, Guan W, Zhan C et al. Risk factors of fataloutcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest. 2020; 158 (1): 97-105. doi: 10.1016/j.chest.2020.04.010
  • 45. Dong Y, Zhou H, Li M, Zhang Z, Guo W et al. A novel simple scoring model for predicting severity of patients with SARSCoV2 infection. Transboundary and Emerging Diseases 2020 : doi: 10.1111/tbed.13651
  • 46. Qu PF, Li R, Xu C, Chai W, Li H et al. A clinical plot study to evaluate CD64 expression on blood monocytes as an indicator of periprosthetic joint infection. Journal of Bone and Joint Surgery American 2020; 102(17):e99. doi: 10.2106/ JBJS.20.00057
  • 47. Wu J, Wu X, ZengW, Guo D, Fang Z et al. Chest CT findings in patients with corona virus disease 2019 and its relationship with clinical features. Investigative Radiology 2020; 55 (5): 257-261. doi: 10.1097/RLI.0000000000000670
  • 48. Ooi GC, Khong PL, Müller NL, Yiu WC, Zhou LJ et al. Severe acute respiratory syndrome: temporal lungc hanges at thinsection CT in 30 patients. Radiology. 2004; 230: 836-844,doi: 10.1148/radiol.2303030853
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