Author:
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
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-
1.
Mitra AK, Mawson AR, 2017. Neglected tropical diseases: Epidemiology and global burden. Trop Med Infect Dis 2: 36.
-
2.
Dhunputh P, Acharya R, Umakanth S, Shetty SM, Mohammed AP, Saraswat PP, 2021. Clinical profile of thrombocytopenia in acute febrile illnesses; A hospital-based study. Kathmandu Univ Med J 19: 248–252.
-
3.
Chrispal A, Boorugu H, Gopinath KG, Chandy S, Prakash JAJ, Thomas EM, Abraham AM, Abraham OC, Thomas K, 2010. Acute undifferentiated febrile illness in adult hospitalized patients: The disease spectrum and diagnostic predictors – An experience from a tertiary care hospital in South India. Trop Doct 40: 230–234.
-
4.
Adane T, Getawa S, 2021. Coagulation abnormalities in dengue fever infection: A systematic review and meta-analysis. PLoS Negl Trop Dis 15: e0009666.
-
5.
National Center for Vector Borne Disease Control Management of Dengue Case. Available at: https://ncvbdc.mohfw.gov.in/index4.php?lang=1&level=0&linkid=446&lid=3723. Accessed July 27, 2024.
-
6.
Logia P, Selvam V, Parasuraman V, Renuka MK, Rajagopalan RE, 2023. Predictors of clinically significant bleeding in thrombocytopenic dengue patients admitted to intensive care unit: A retrospective study. Indian J Crit Care Med 27: 888–894.
-
7.
Mammen JJ et al., 2022. The clinical demand and supply of blood in India: A national level estimation study. PLoS One 17: e0265951.
-
8.
Lee T-H, Wong JGX, Leo Y-S, Thein T-L, Ng E-L, Lee LK, Lye DC, 2016. Potential harm of prophylactic platelet transfusion in adult dengue patients. PLoS Negl Trop Dis 10: e0004576.
-
9.
Shaydakov ME, Sigmon DF, Blebea J, 2024. Thromboelastography. Treasure Island, FL: StatPearls Publishing.
-
10.
Marsden NJ, Van M, Dean S, Azzopardi EA, Hemington-Gorse S, Evans PA, Whitaker IS, 2017. Measuring coagulation in burns: An evidence-based systematic review. Scars Burn Heal 3: 2059513117728201.
-
11.
Gonzalez E, Moore EE, Moore HB, 2017. Management of trauma induced coagulopathy with thrombelastography. Crit Care Clin 33: 119–134.
-
12.
Amgalan A, Allen T, Othman M, Ahmadzia HK, 2020. Systematic review of viscoelastic testing (TEG/ROTEM) in obstetrics and recommendations from the women’s SSC of the ISTH.J Thromb Haemost 18: 1813–1838.
-
13.
Ak K, Isbir CS, Tetik S, Atalan N, Tekeli A, Aljodi M, Civelek A, Arsan S, 2009. Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: A prospective randomized study. J Card Surg 24: 404–410.
-
14.
Romlin BS, Wåhlander H, Berggren H, Synnergren M, Baghaei F, Nilsson K, Jeppsson A, 2011. Intraoperative thromboelastometry is associated with reduced transfusion prevalence in pediatric cardiac surgery. Anesth Analg 112: 30–36.
-
15.
Riley RD, Ensor J, Snell KIE, Harrell FE, Martin GP, Reitsma JB, Moons KGM, Collins G, van Smeden M, 2020. Calculating the sample size required for developing a clinical prediction model. BMJ 368: m441.
-
16.
Riaz M, Harun SNB, Mallhi TH, Khan YH, Butt MH, Husain A, Khan MM, Khan AH, 2024. Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: A multi-center retrospective analysis. BMC Infect Dis 24: 500.
-
17.
Gupta N, Joylin S, Ravindra P, Wilson W, Bhat R, Guddattu V, Neumayr A, Mukhopadhyay C, Saravu K, 2021. A diagnostic randomised controlled trial to study the impact of rapid diagnostic tests in patients with acute febrile illness when compared to conventional diagnostics (DRACO study). J Infect 82: e6–e8.
-
18.
Gupta N, Wilson W, Neumayr A, Saravu K, 2022. Kyasanur forest disease: A state-of-the-art review. QJM 115: 351–358.
-
19.
Patel GR, Thanvi I, Nadeem M, Kanwaria R, 2023. Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue – A single center observational study. Asian Pac J Trop Med 16: 65–71.
-
20.
Chua MN, Molanida R, de Guzman M, Laberiza F, 1993. Prothrombin time and partial thromboplastin time as a predictor of bleeding in patients with dengue hemorrhagic fever. Southeast Asian J Trop Med Public Health 24 Suppl 1: 141–143.
-
21.
Michels M et al., 2014. Platelet function alterations in dengue are associated with plasma leakage. Thromb Haemost 112: 352–362.
-
22.
Huang YH, Liu CC, Wang ST, Lei HY, Liu HL, Lin YS, Wu HL, Yeh TM, 2001. Activation of coagulation and fibrinolysis during dengue virus infection. J Med Virol 63: 247–251.
-
23.
Marchi R, Nagaswami C, Weisel JW, 2009. Fibrin formation and lysis studies in dengue virus infection. Blood Coagul Fibrinolysis 20: 575–582.
-
24.
Malavige GN, Ogg GS, 2017. Pathogenesis of vascular leak in dengue virus infection. Immunology 151: 261–269.
-
25.
Basu A, Chaturvedi UC, 2008. Vascular endothelium: The battlefield of dengue viruses. FEMS Immunol Med Microbol 53: 287–299.
-
26.
Cardier JE, Rivas B, Romano E, Rothman AL, Perez-Perez C, Ochoa M, Caceres AM, Cardier M, Guevara N, Giovannetti R, 2006. Evidence of vascular damage in dengue disease: Demonstration of high levels of soluble cell adhesion molecules and circulating endothelial cells. Endothelium 13: 335–340.
-
27.
Mariappan V, Adikari S, Shanmugam L, Easow JM, Balakrishna Pillai A, 2021. Expression dynamics of vascular endothelial markers: Endoglin and syndecan-1 in predicting dengue disease outcome.Transl Res 232: 121–141.
-
28.
Butthep P, Chunhakan S, Tangnararatchakit K, Yoksan S, Pattanapanyasat K, Chuansumrit A, 2006. Elevated soluble thrombomodulin in the febrile stage related to patients at risk for dengue shock syndrome. Pediatr Infect Dis J 25: 894–897.
-
29.
Sosothikul D, Seksarn P, Pongsewalak S, Thisyakorn U, Lusher J, 2007. Activation of endothelial cells, coagulation and fibrinolysis in children with dengue virus infection. Thromb Haemost 97: 627–634.
-
30.
Wills BA et al., 2002. Coagulation abnormalities in dengue hemorrhagic fever: Serial investigations in 167 Vietnamese children with dengue shock syndrome. Clin Infect Dis 35: 277–285.
-
31.
Libby P, Simon DI, 2001. Inflammation and thrombosis. Circulation 103: 1718–1720.
-
32.
Lye DC, Lee VJ, Sun Y, Leo YS, 2009. Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection. Clin Infect Dis 48: 1262–1265.
-
33.
Assir MZK, 2017. Time to stop prophylactic platelet transfusion for adult dengue. Lancet 389: 1583–1584.
-
34.
Sundar V, Bhaskar E, 2019. Effect of platelet transfusion on clot strength in dengue fever with thrombocytopenia related bleeding: A thromboelastography-based study. Transfus Med Hemother 46: 457–460.
-
35.
Savage SA, Zarzaur BL, Pohlman TH, Brewer BL, Magnotti LJ, Croce MA, Lim GH, Martin AC, 2017. Clot dynamics and mortality: The MA-R ratio. J Trauma Acute Care Surg 83: 628–634.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1404 | 1404 | 378 |
| Full Text Views | 38 | 38 | 13 |
| PDF Downloads | 37 | 37 | 15 |
Assessment of Bleeding in Acute Febrile Illness with Thrombocytopenia Using Thromboelastography and Conventional Coagulation Parameters in the Emergency Department (ABATE): A Prospective Cohort Study
Rachana Bhat
Rachana Bhat
Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Nitin Gupta
Nitin Gupta
Department of Infectious Diseases, Center for Tropical Febrile Illness (TroFI), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Prithvishree Ravindra
Prithvishree Ravindra
Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Praveen Kumar Tirlangi
praveen.tirlangi@manipal.edu
Praveen Kumar Tirlangi
Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Ganesh V. Mohan
Ganesh V. Mohan
Department of Immunohematology & Blood Transfusion, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Khalid Mohammad
Khalid Mohammad
Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Ankit Kumar Sahu
Ankit Kumar Sahu
Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India
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Ashwitha Bhat
Ashwitha Bhat
Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Jayaraj Mymbilly Balakrishnan
Jayaraj Mymbilly Balakrishnan
Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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Kavitha Saravu
Kavitha Saravu
Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India;
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ABSTRACT.
Acute febrile illnesses (AFIs) with thrombocytopenia, such as dengue, leptospirosis, and scrub typhus, are often associated with bleeding and present challenges in transfusion therapy during outbreaks. Conventional bleeding predictors, which involve platelet counts, do not assess clot strength or fibrinolysis defects and may lead to inappropriate or delayed transfusions. To predict bleeding, we aimed to create a scoring system using point-of-care thromboelastography (TEG) and other conventional coagulation parameters. In this prospective cohort study, patients with AFI and platelet counts <100,000/cu mm who presented to the emergency department were recruited, and samples were collected for conventional coagulation tests and TEG analysis at admission. Patients were monitored for 48 hours for bleeding events, blood product transfusions, and mortality within 7 days. Receiver operating characteristic curves were plotted for significant predictors identified in univariate analysis, and a scoring system was generated using stepwise logistic regression. Sixty-six patients were recruited, including 38 with dengue and 11 with leptospirosis. Nineteen patients experienced a bleeding event within 48 hours. Dyspnea and elevated aspartate transaminase levels were more prevalent among those who bled. Thromboelastography parameters (reaction time/maximum amplitude [R/MA]), prothrombin time, international normalized ratio (INR), and baseline platelet count were significant predictors of bleeding. A scoring system using R/MA, INR, and platelet count achieved an overall predictive accuracy of 83.3% for 48-hour bleeding, with a score ≥3 demonstrating a sensitivity of 68% and specificity of 77%. Thromboelastography in patients with dengue showed more significant coagulation abnormalities than in those with leptospirosis. Validation in larger, more homogeneous populations is necessary.
- Supplemental Materials (PDF 218.03 KB)
Author Notes
Financial support: This work was supported by the
Disclosure: The study was initiated after obtaining clearance from the institutional ethical committee (ref no: IEC 182/2023).
Current contact information: Rachana Bhat, Prithvishree Ravindra, Khalid Mohammad, Ashwitha Bhat, and Jayaraj Mymbilly Balakrishnan, Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, E-mails: rachana.bhat@manipal.edu or rachana2806@gmail.com, prithvishree.r@manipal.edu, khalid.mohammad@manipal.edu, ashwithabhat97@gmail.com, and jayaraj.mb@manipal.edu. Nitin Gupta, Center for Tropical Febrile Illness, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, E-mail: nitin.gupta@manipal.edu. Praveen Kumar Tirlangi and Kavitha Saravu, Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, E-mails: praveen.tirlangi@manipal.edu and kavitha.saravu@manipal.edu. Ganesh V. Mohan, Department of Immunohematology & Blood Transfusion, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, E-mail: ganesh.mohan@manipal.edu. Ankit Kumar Sahu, Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India, E-mail: ankitkumarsahu13@gmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Mitra AK, Mawson AR, 2017. Neglected tropical diseases: Epidemiology and global burden. Trop Med Infect Dis 2: 36.
-
2.
Dhunputh P, Acharya R, Umakanth S, Shetty SM, Mohammed AP, Saraswat PP, 2021. Clinical profile of thrombocytopenia in acute febrile illnesses; A hospital-based study. Kathmandu Univ Med J 19: 248–252.
-
3.
Chrispal A, Boorugu H, Gopinath KG, Chandy S, Prakash JAJ, Thomas EM, Abraham AM, Abraham OC, Thomas K, 2010. Acute undifferentiated febrile illness in adult hospitalized patients: The disease spectrum and diagnostic predictors – An experience from a tertiary care hospital in South India. Trop Doct 40: 230–234.
-
4.
Adane T, Getawa S, 2021. Coagulation abnormalities in dengue fever infection: A systematic review and meta-analysis. PLoS Negl Trop Dis 15: e0009666.
-
5.
National Center for Vector Borne Disease Control Management of Dengue Case. Available at: https://ncvbdc.mohfw.gov.in/index4.php?lang=1&level=0&linkid=446&lid=3723. Accessed July 27, 2024.
-
6.
Logia P, Selvam V, Parasuraman V, Renuka MK, Rajagopalan RE, 2023. Predictors of clinically significant bleeding in thrombocytopenic dengue patients admitted to intensive care unit: A retrospective study. Indian J Crit Care Med 27: 888–894.
-
7.
Mammen JJ et al., 2022. The clinical demand and supply of blood in India: A national level estimation study. PLoS One 17: e0265951.
-
8.
Lee T-H, Wong JGX, Leo Y-S, Thein T-L, Ng E-L, Lee LK, Lye DC, 2016. Potential harm of prophylactic platelet transfusion in adult dengue patients. PLoS Negl Trop Dis 10: e0004576.
-
9.
Shaydakov ME, Sigmon DF, Blebea J, 2024. Thromboelastography. Treasure Island, FL: StatPearls Publishing.
-
10.
Marsden NJ, Van M, Dean S, Azzopardi EA, Hemington-Gorse S, Evans PA, Whitaker IS, 2017. Measuring coagulation in burns: An evidence-based systematic review. Scars Burn Heal 3: 2059513117728201.
-
11.
Gonzalez E, Moore EE, Moore HB, 2017. Management of trauma induced coagulopathy with thrombelastography. Crit Care Clin 33: 119–134.
-
12.
Amgalan A, Allen T, Othman M, Ahmadzia HK, 2020. Systematic review of viscoelastic testing (TEG/ROTEM) in obstetrics and recommendations from the women’s SSC of the ISTH.J Thromb Haemost 18: 1813–1838.
-
13.
Ak K, Isbir CS, Tetik S, Atalan N, Tekeli A, Aljodi M, Civelek A, Arsan S, 2009. Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: A prospective randomized study. J Card Surg 24: 404–410.
-
14.
Romlin BS, Wåhlander H, Berggren H, Synnergren M, Baghaei F, Nilsson K, Jeppsson A, 2011. Intraoperative thromboelastometry is associated with reduced transfusion prevalence in pediatric cardiac surgery. Anesth Analg 112: 30–36.
-
15.
Riley RD, Ensor J, Snell KIE, Harrell FE, Martin GP, Reitsma JB, Moons KGM, Collins G, van Smeden M, 2020. Calculating the sample size required for developing a clinical prediction model. BMJ 368: m441.
-
16.
Riaz M, Harun SNB, Mallhi TH, Khan YH, Butt MH, Husain A, Khan MM, Khan AH, 2024. Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: A multi-center retrospective analysis. BMC Infect Dis 24: 500.
-
17.
Gupta N, Joylin S, Ravindra P, Wilson W, Bhat R, Guddattu V, Neumayr A, Mukhopadhyay C, Saravu K, 2021. A diagnostic randomised controlled trial to study the impact of rapid diagnostic tests in patients with acute febrile illness when compared to conventional diagnostics (DRACO study). J Infect 82: e6–e8.
-
18.
Gupta N, Wilson W, Neumayr A, Saravu K, 2022. Kyasanur forest disease: A state-of-the-art review. QJM 115: 351–358.
-
19.
Patel GR, Thanvi I, Nadeem M, Kanwaria R, 2023. Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue – A single center observational study. Asian Pac J Trop Med 16: 65–71.
-
20.
Chua MN, Molanida R, de Guzman M, Laberiza F, 1993. Prothrombin time and partial thromboplastin time as a predictor of bleeding in patients with dengue hemorrhagic fever. Southeast Asian J Trop Med Public Health 24 Suppl 1: 141–143.
-
21.
Michels M et al., 2014. Platelet function alterations in dengue are associated with plasma leakage. Thromb Haemost 112: 352–362.
-
22.
Huang YH, Liu CC, Wang ST, Lei HY, Liu HL, Lin YS, Wu HL, Yeh TM, 2001. Activation of coagulation and fibrinolysis during dengue virus infection. J Med Virol 63: 247–251.
-
23.
Marchi R, Nagaswami C, Weisel JW, 2009. Fibrin formation and lysis studies in dengue virus infection. Blood Coagul Fibrinolysis 20: 575–582.
-
24.
Malavige GN, Ogg GS, 2017. Pathogenesis of vascular leak in dengue virus infection. Immunology 151: 261–269.
-
25.
Basu A, Chaturvedi UC, 2008. Vascular endothelium: The battlefield of dengue viruses. FEMS Immunol Med Microbol 53: 287–299.
-
26.
Cardier JE, Rivas B, Romano E, Rothman AL, Perez-Perez C, Ochoa M, Caceres AM, Cardier M, Guevara N, Giovannetti R, 2006. Evidence of vascular damage in dengue disease: Demonstration of high levels of soluble cell adhesion molecules and circulating endothelial cells. Endothelium 13: 335–340.
-
27.
Mariappan V, Adikari S, Shanmugam L, Easow JM, Balakrishna Pillai A, 2021. Expression dynamics of vascular endothelial markers: Endoglin and syndecan-1 in predicting dengue disease outcome.Transl Res 232: 121–141.
-
28.
Butthep P, Chunhakan S, Tangnararatchakit K, Yoksan S, Pattanapanyasat K, Chuansumrit A, 2006. Elevated soluble thrombomodulin in the febrile stage related to patients at risk for dengue shock syndrome. Pediatr Infect Dis J 25: 894–897.
-
29.
Sosothikul D, Seksarn P, Pongsewalak S, Thisyakorn U, Lusher J, 2007. Activation of endothelial cells, coagulation and fibrinolysis in children with dengue virus infection. Thromb Haemost 97: 627–634.
-
30.
Wills BA et al., 2002. Coagulation abnormalities in dengue hemorrhagic fever: Serial investigations in 167 Vietnamese children with dengue shock syndrome. Clin Infect Dis 35: 277–285.
-
31.
Libby P, Simon DI, 2001. Inflammation and thrombosis. Circulation 103: 1718–1720.
-
32.
Lye DC, Lee VJ, Sun Y, Leo YS, 2009. Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection. Clin Infect Dis 48: 1262–1265.
-
33.
Assir MZK, 2017. Time to stop prophylactic platelet transfusion for adult dengue. Lancet 389: 1583–1584.
-
34.
Sundar V, Bhaskar E, 2019. Effect of platelet transfusion on clot strength in dengue fever with thrombocytopenia related bleeding: A thromboelastography-based study. Transfus Med Hemother 46: 457–460.
-
35.
Savage SA, Zarzaur BL, Pohlman TH, Brewer BL, Magnotti LJ, Croce MA, Lim GH, Martin AC, 2017. Clot dynamics and mortality: The MA-R ratio. J Trauma Acute Care Surg 83: 628–634.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1404 | 1404 | 378 |
| Full Text Views | 38 | 38 | 13 |
| PDF Downloads | 37 | 37 | 15 |