Dynamic decrease of platelet count predicts poor outcome of acute respiratory distress syndrome_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHANG Donghui ^# , WANG Ying ^# , CHEN Cuicui , HOU Dongni , TANG Xinjun , JIANG Jinjun , YANG Dong , JU Mohan ,  SONG Yuanlin

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China;

Corresponding author：

SONG Yuanlin, Email: ylsong70@163.com

Keywords：

Acute respiratory distress syndrome; Platelets; Prognosis

DOI：

10.7507/1671-6205.201804026

Video：

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ObjectiveTo investigate the relationship between platelets changes and outcomes of acute respiratory distress syndrome (ARDS) patients.MethodsA total of 275 ARDS patients treated in Zhongshan Hospital of Fudan University were retrospectively enrolled from 2008 to 2015. Their clinical characteristics, experimental test results and disease outcomes were obtained from the archived medical records. The correlation between the decreasing of platelet within three days and the prognosis of ARDS and in each subgroup were analyzed by statistical methods, including COX analysis and Kaplan-Meier curve.ResultsThere were 233 patients validly selected through eliminating those with exclusion criteria. They were divided into a decreasing group and a non-decreasing group according to their platelet counts in three days. There was significant difference in the ontcome between the two groups with the univariate analysis, the COX analysis and Kaplan-Meier curve (all P<0.05). According to the initial platelet count and change of platelet in 3 days all the patients were categorized into 9 subgroups. The mortality among them was compared and two risk groups were defined, including a persistently low platelet group (the initial platelet count <139×10⁹/L with an increase less than 16×10⁹/L during the first three days after the diagnosis), and a decreased platelet group (the initial platelet count ≥139×10⁹/L and platelet count decreased more than 30×10⁹/L during the first three days after the diagnosis). The other subgroups made up a non-risk group. Merging two risk groups as one risk group and comparing with the non-risk group, there were significant differences in the outcome between two groups with the univariate analysis, the multiplicity COX analysis and Kaplan-Meier curve (all P<0.05), the differences of coagulation function indexes were not significant (allP>0.05). The platelet count of the risk group was also an independent risk factor for ARDS mortality in the surgery subgroup (P=0.003), the non-hypertension subgroup (P=0.018) and the pneumonia subgroup (P<0.001).ConclusionLow platelets and declining platelets are closely associated with poor prognosis in most ARDS patients, which might be applied in clinical prognosis evaluation.

Citation： ZHANG Donghui, WANG Ying, CHEN Cuicui, HOU Dongni, TANG Xinjun, JIANG Jinjun, YANG Dong, JU Mohan, SONG Yuanlin. Dynamic decrease of platelet count predicts poor outcome of acute respiratory distress syndrome. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(5): 492-498. doi: 10.7507/1671-6205.201804026 Copy

1.	Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med, 2000, 342(18): 1334-1349.
2.	Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med, 2013, 188(2): 220-230.
3.	Li G, Malinchoc M, Cartin-Ceba R, et al. Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota. Am J Respir Crit Care Med, 2011, 183(1): 59-66.
4.	邓宁,常为民, 王春全, 等. 急性呼吸窘迫综合征患者血管外肺水的动态变化与预后的关系. 中国呼吸与危重监护杂志, 2012, 11(6): 528-531.
5.	袁超,金娜. APACHEⅡ评分和血管性血友病因子对急性呼吸窘迫综合征肺损伤程度及预后的评估价值. 中国呼吸与危重监护杂志, 2016, 15(2): 142-146.
6.	Geboers DG, de Beer FM, Tuip-de Boer AM, et al. Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients. Intensive Care Med, 2015, 41(7): 1281-1290.
7.	Adamzik M, Broll J, Steinmann J, et al. An increased alveolar CD4+ CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality. Intensive Care Med, 2013, 39(10): 1743-1751.
8.	Lefrançais E, Ortiz-Muñoz G, Caudrillier A, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature, 2017, 544(7648): 105.
9.	Maniatis NA, Letsiou E, Orfanos SE, et al. Inhaled activated protein C protects mice from ventilator-induced lung injury. Crit Care, 2010, 14(2): R70.
10.	Caudrillier A, Kessenbrock K, Gilliss BM, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest, 2012, 122(7): 2661-2671.
11.	Looney MR, Nguyen JX, Hu Y, et al. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Invest, 2009, 119(11): 3450-3461.
12.	Scheiermann C, Kunisaki Y, Jang JE, et al. Neutrophil microdomains: linking heterocellular interactions with vascular injury. Curr Opin Hematol, 2010, 17(1): 25-30.
13.	Bozza FA, Shah AM, Weyrich AS, et al. Amicus or adversary: platelets in lung biology, acute injury, and inflammation. Am J Respir Cell Mol Biol, 2009, 40(2): 123-134.
14.	Wang TH, Liu Z, Wang ZX, et al. Thrombocytopenia is associated with acute respiratory distress syndrome mortality: an international study. PLoS One, 2014, 9(4): e94124.
15.	Wei, Y, Tejera P, Wang Z, et al. A missense genetic variant in LRRC16A/CARMIL1 improves acute respiratory distress syndrome survival by attenuating platelet count decline. Am J Respir Crit Care Med, 2017, 195(10): 1353-1361.
16.	Wu J, Sheng L, Wang S, et al. Analysis of clinical risk factors associated with the prognosis of severe multiple-trauma patients with acute lung injury. J Emerg Med, 2012, 43(3): 407-412.
17.	Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med, 1994, 149(3): 818.
18.	Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest, 2006, 116(12): 3211-3219.
19.	Kiefmann R, Heckel K, Schenkat S, et al. Role of p-selectin in platelet sequestration in pulmonary capillaries during endotoxemia. J Vasc Res, 2006, 43(5): 473-481.
20.	Rice TW, Wheeler AP. Coagulopathy in critically ill patients: part 1: platelet disorders. Chest, 2009, 136(6): 1622-1630.
21.	Greinacher A, Selleng K. Thrombocytopenia in the intensive care unit patient. Hematol Am Soc Hematol Educ Program, 2010, 2010(1): 135-143.
22.	Housinger TA, Brinkerhoff C, Warden GD. The relationship between platelet count, sepsis, and survival in pediatric burn patients. Arch Surg, 1993, 128(1): 65-67.
23.	Lopez-Delgado JC, Rovira A, Esteve F, et al. Thrombocytopenia as a mortality risk factor in acute respiratory failure in H1N1 influenza. Swiss Med Wkly, 2013, 143(16): w13788.
24.	Vanderschueren S, De Weerdt A, Malbrain M, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med, 2000, 28(6): 1871-1876.
25.	Gong MN, Thompson BT, Williams P, et al. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med, 2005, 33(6): 1191-1198.
26.	Moreau D, Timsit JF, Vesin A, et al. Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays. Chest, 2007, 131(6): 1735-1741.
27.	Brower RG, Matthay MA, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med, 2000, 342(18): 1301-1318.
28.	Silliman CC, Bjornsen AJ, Wyman TH, et al. Plasma and lipids from stored platelets cause acute lung injury in an animal model. Transfusion, 2003, 43(5): 633-640.
29.	Weyrich AS, Zimmerman GA. Platelets in lung biology. Annu Rev Physiol, 2013, 75: 569-591.
30.	Ortiz-Munoz G, Mallavia B, Bins A, et al. Aspirin-triggered 15-epi-lipoxin A4 regulates neutrophil-platelet aggregation and attenuates acute lung injury in mice. Blood, 2014, 124(17): 2625-2634.
31.	Erlich JM, Talmor DS, Cartin-Ceba R, et al. Prehospitalization antiplatelet therapy is associated with a reduced incidence of acute lung injury: a population-based cohort study. Chest, 2011, 139(2): 289-295.
32.	Kor DJ, Erlich J, Gong MN, et al. Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients. Crit Care Med, 2011, 39(11): 2393.
33.	O'Neal HR, Jr Koyama T, Koehler EA, et al. Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome. Crit Care Med, 2011, 39(6): 1343.
34.	Chen W, Janz DR, Bastarache JA, et al. Prehospital aspirin use is associated with reduced risk of acute respiratory distress syndrome in critically ill patients: a propensity-adjusted analysis. Crit Care Med, 2015, 43(4): 801.
35.	Boyle AJ, Di Gangi S, Hamid UI, et al. Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis. Crit Care, 2015, 19: 109.
36.	Kor DJ, Carter RE, Park PK, et al. Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department: The LIPS-A Randomized Clinical Trial. JAMA, 2016, 315(22): 2406-2414.
37.	Reilly JP, Christie JD. Is it possible to prevent ARDS?. JAMA, 2016, 315(22): 2403-2405.
38.	Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012, 307(23): 2526-2533.

1. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med, 2000, 342(18): 1334-1349.
2. Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med, 2013, 188(2): 220-230.
3. Li G, Malinchoc M, Cartin-Ceba R, et al. Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota. Am J Respir Crit Care Med, 2011, 183(1): 59-66.
4. 邓宁,常为民, 王春全, 等. 急性呼吸窘迫综合征患者血管外肺水的动态变化与预后的关系. 中国呼吸与危重监护杂志, 2012, 11(6): 528-531.
5. 袁超,金娜. APACHEⅡ评分和血管性血友病因子对急性呼吸窘迫综合征肺损伤程度及预后的评估价值. 中国呼吸与危重监护杂志, 2016, 15(2): 142-146.
6. Geboers DG, de Beer FM, Tuip-de Boer AM, et al. Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients. Intensive Care Med, 2015, 41(7): 1281-1290.
7. Adamzik M, Broll J, Steinmann J, et al. An increased alveolar CD4+ CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality. Intensive Care Med, 2013, 39(10): 1743-1751.
8. Lefrançais E, Ortiz-Muñoz G, Caudrillier A, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature, 2017, 544(7648): 105.
9. Maniatis NA, Letsiou E, Orfanos SE, et al. Inhaled activated protein C protects mice from ventilator-induced lung injury. Crit Care, 2010, 14(2): R70.
10. Caudrillier A, Kessenbrock K, Gilliss BM, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest, 2012, 122(7): 2661-2671.
11. Looney MR, Nguyen JX, Hu Y, et al. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Invest, 2009, 119(11): 3450-3461.
12. Scheiermann C, Kunisaki Y, Jang JE, et al. Neutrophil microdomains: linking heterocellular interactions with vascular injury. Curr Opin Hematol, 2010, 17(1): 25-30.
13. Bozza FA, Shah AM, Weyrich AS, et al. Amicus or adversary: platelets in lung biology, acute injury, and inflammation. Am J Respir Cell Mol Biol, 2009, 40(2): 123-134.
14. Wang TH, Liu Z, Wang ZX, et al. Thrombocytopenia is associated with acute respiratory distress syndrome mortality: an international study. PLoS One, 2014, 9(4): e94124.
15. Wei, Y, Tejera P, Wang Z, et al. A missense genetic variant in LRRC16A/CARMIL1 improves acute respiratory distress syndrome survival by attenuating platelet count decline. Am J Respir Crit Care Med, 2017, 195(10): 1353-1361.
16. Wu J, Sheng L, Wang S, et al. Analysis of clinical risk factors associated with the prognosis of severe multiple-trauma patients with acute lung injury. J Emerg Med, 2012, 43(3): 407-412.
17. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med, 1994, 149(3): 818.
18. Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest, 2006, 116(12): 3211-3219.
19. Kiefmann R, Heckel K, Schenkat S, et al. Role of p-selectin in platelet sequestration in pulmonary capillaries during endotoxemia. J Vasc Res, 2006, 43(5): 473-481.
20. Rice TW, Wheeler AP. Coagulopathy in critically ill patients: part 1: platelet disorders. Chest, 2009, 136(6): 1622-1630.
21. Greinacher A, Selleng K. Thrombocytopenia in the intensive care unit patient. Hematol Am Soc Hematol Educ Program, 2010, 2010(1): 135-143.
22. Housinger TA, Brinkerhoff C, Warden GD. The relationship between platelet count, sepsis, and survival in pediatric burn patients. Arch Surg, 1993, 128(1): 65-67.
23. Lopez-Delgado JC, Rovira A, Esteve F, et al. Thrombocytopenia as a mortality risk factor in acute respiratory failure in H1N1 influenza. Swiss Med Wkly, 2013, 143(16): w13788.
24. Vanderschueren S, De Weerdt A, Malbrain M, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med, 2000, 28(6): 1871-1876.
25. Gong MN, Thompson BT, Williams P, et al. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med, 2005, 33(6): 1191-1198.
26. Moreau D, Timsit JF, Vesin A, et al. Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays. Chest, 2007, 131(6): 1735-1741.
27. Brower RG, Matthay MA, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med, 2000, 342(18): 1301-1318.
28. Silliman CC, Bjornsen AJ, Wyman TH, et al. Plasma and lipids from stored platelets cause acute lung injury in an animal model. Transfusion, 2003, 43(5): 633-640.
29. Weyrich AS, Zimmerman GA. Platelets in lung biology. Annu Rev Physiol, 2013, 75: 569-591.
30. Ortiz-Munoz G, Mallavia B, Bins A, et al. Aspirin-triggered 15-epi-lipoxin A4 regulates neutrophil-platelet aggregation and attenuates acute lung injury in mice. Blood, 2014, 124(17): 2625-2634.
31. Erlich JM, Talmor DS, Cartin-Ceba R, et al. Prehospitalization antiplatelet therapy is associated with a reduced incidence of acute lung injury: a population-based cohort study. Chest, 2011, 139(2): 289-295.
32. Kor DJ, Erlich J, Gong MN, et al. Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients. Crit Care Med, 2011, 39(11): 2393.
33. O'Neal HR, Jr Koyama T, Koehler EA, et al. Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome. Crit Care Med, 2011, 39(6): 1343.
34. Chen W, Janz DR, Bastarache JA, et al. Prehospital aspirin use is associated with reduced risk of acute respiratory distress syndrome in critically ill patients: a propensity-adjusted analysis. Crit Care Med, 2015, 43(4): 801.
35. Boyle AJ, Di Gangi S, Hamid UI, et al. Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis. Crit Care, 2015, 19: 109.
36. Kor DJ, Carter RE, Park PK, et al. Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department: The LIPS-A Randomized Clinical Trial. JAMA, 2016, 315(22): 2406-2414.
37. Reilly JP, Christie JD. Is it possible to prevent ARDS?. JAMA, 2016, 315(22): 2403-2405.
38. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012, 307(23): 2526-2533.

Chinese Journal of Respiratory and Critical Care Medicine

Dynamic decrease of platelet count predicts poor outcome of acute respiratory distress syndrome

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