Prevention and treatment of thrombocytopenia in dengue patients: A narrative review

Year 2021, , 411 - 418, 29.12.2021

Nabeel Siddique

https://doi.org/10.26650/IstanbulJPharm.2021.854023

Abstract

Background and Aims: Dengue fever is a major health concern, especially in developed countries, because it often leads to undifferentiated febrile illness such as dengue haemorrhagic fever and dengue shock syndrome or expanded dengue syndrome, which are often reported with thrombocytopenia (TCP) and turn out to be hazardous to life. The WHO reported 23 million dengue cases and 82,000 deaths between 1955-2012. 2019 was a hallmark for the dengue epidemic from Latin America to South Asia. Due to unavailability of a dengue vaccine and antiviral therapies, additional medical attention and effort are required to treat thrombocytopenia (TCP). These approaches include thrombopoietin receptor agonists such as Oprelvekin, Eltrombopag, Romiplostim and corticosteroids, and platelet transfusion and intravenous immunoglobulin transfusions. The outcomes might not be achievable unless the proper assessment is carried out to evaluate these approaches to treat TCP in dengue patients. This narrative review aims to summarize the findings regarding the treatment of TCP in patients affected by the dengue virus. Methods: A total of 55 published articles, including clinical trials, descriptive studies and case studies were reviewed regarding treatment of TCP in the context of dengue infection. The electronic databases PubMed, Cochrane Library, Google Scholar and Science Direct were searched for articles published from January 1990 to June 2020. Conclusions: We concluded that dengue fever is becoming a global health concern. Premedical attention like the use of corticosteroids, Thrombopoietin receptor agonist (TPO-R) agonists and transfusions like (PT & IVIG) are not fully assessed by double-blind randomized clinical trials and cost-effectiveness analysis. However, as compared to other treatment approaches, the use of TPO-R agonists seems to be more suitable in TCP management due to its easy access and compliance.

Keywords

Thrombocytopenia in dengue, Dengue fever, TPO-R agonist

References

• 1. Monath TP. Dengue and yellow fever—challenges for the development and use of vaccines. New England Journal of Medicine. 2007;357(22):2222-5.
• 2. Ruberto I, Marques E, Burke DS, Van Panhuis WG. The availability and consistency of dengue surveillance data provided online by the World Health Organization. PLoS neglected tropical diseases. 2015;9(4).
• 3. Hosangadi D. THE GLOBAL RISE OF DENGUE INFECTIONS: www.outbreakobservatory.org; 2019 [updated March 21, 2019; cited 2020. Available from: https://www.outbreakobservatory.org/outbreakthursday-1/3/21/2019/the-global-rise-of-dengue-infections?rq=dengue.
• 4. WHO. Outbreak update – Dengue in Pakistan, 1 December 2019: Estern Mediterranean; 2019 [updated 1 December 2019. Available from: http://www.emro.who.int/pandemic-epidemic-diseases/dengue/outbreak-update-dengue-in-pakistan-1-december-2019.html.
• 5. Kalayanarooj S. Clinical manifestations and management of dengue/DHF/DSS. Tropical medicine and health. 2011:1112080193-.
• 6. Roy S. Thrombopoietin Receptor Agonists: Can These Be the Future Answer to the Deadly Thrombocytopenia in Dengue Fever? Cureus. 2019;11(4).
• 7. NHLBI. Thrombocytopenia 2020 [cited 2020. Available from: https://www.nhlbi.nih.gov/health-topics/thrombocytopenia.
• 8. Izak M, Bussel JB. Management of thrombocytopenia. F1000prime reports. 2014;6.
• 9. Organization WH, Research SPf, Diseases TiT, Diseases WHODoCoNT, Epidemic WHO, Alert P. Dengue: guidelines for diagnosis, treatment, prevention and control: World Health Organization; 2009.
• 10. Pesaro A, D'Amico E, Aranha LJAbdc. Dengue: cardiac manifestations and implications in antithrombotic treatment. 2007;89(2):e12-5.
• 11. Sridharan A, Chen Q, Tang KF, Ooi EE, Hibberd ML, Chen JJJov. Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice. 2013;87(21):11648-58.
• 12. Verma SP, Hamide A, Wadhwa J, Sivamani K. Corticosteroid responsive prolonged thrombocytopenia in a case of dengue fever. Case Reports. 2013;2013:bcr2013200249.
• 13. Recht M. Thrombocytopenia and anemia in infants and children. Emergency medicine clinics of North America. 2009;27(3):505-23.
• 14. Leong K, Srinivas P. Corticosteroid-responsive prolonged thrombocytopenia following dengue haemorrhagic fever. MEDICAL JOURNAL OF MALAYSIA. 1993;48:369-.
• 15. Health NIo. Livertox: clinical and research information on drug-induced liver injury. Nih gov https://livertox nih gov. 2017. 16. Dorner AJ, Goldman SJ, Keith JC. Interleukin-11. BioDrugs. 1997;8(6):418-29.
• 17. Medscape. oprelvekin (Rx): Medscape; 2020 [06 April 2020]. Available from: https://reference.medscape.com/drug/neumega-interleukin-11-oprelvekin-342165#10.
• 18. Nisar S, Shaban M, Shah S. Role of Recombinant Human Interleukin-11 in Thrombocytopenia Associated with Dengue Fever. INTERNATIONAL JOURNAL OF ADVANCED BIOTECHNOLOGY AND RESEARCH. 2018;9(1):1985-8.
• 19. Suliman MI, Qayum I, Saeed F. Randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia. J Coll Physician Surg Pak. 2014;24(3):164-8.
• 20. Rodriguez-Mejorada MS, Rosel-Gomez GC, Rosado-Castro RA, Ruiz-Argüelles GJ. Refractory Thrombocytopenia Associated with Dengue Hemorrhagic Fever Responds to Romiplostim. American Society of Hematology; 2010.
• 21. Vishnu P, Aboulafia DMJJoBM. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia. 2016;7:99.
• 22. FDA. PROMACTA® (eltrombopag) Aug 26, 2014 [cited 2020 06-23-2020]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207027s003lbl.pdf.
• 23. Sajib Chakraborty AK. Efficacy and Safety of Eltrombopag to correct thrombocytopenia in moderate to severe dengue patients- a Phase II Randomized Controlled Clinical Trial: Cochrane Central Register of Controlled Trials; 2019 [updated 15 June 2020; cited 2020 29-06-2020]. Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02071746/full?highlightAbstract=dengu%7Celtrombopag%7Cdengue.
• 24. Soff GA, Miao Y, Bendheim G, Batista J, Mones JV, Parameswaran R, et al. Romiplostim treatment of chemotherapy-induced thrombocytopenia. 2019;37(31):2892-8.
• 25. FDA U. Highlight of prescribing information 2008 [cited 2020 29-06-2020]. Nplate™ (romiplostim)]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/125268lbl.pdf.
• 26. Perez‐Ruixo J, Green B, Doshi S, Wang YM, Mould DJTJoCP. Romiplostim dose response in patients with immune thrombocytopenia. 2012;52(10):1540-51.
• 27. Jolles S, Sewell W, Misbah SJC, immunology e. Clinical uses of intravenous immunoglobulin. 2005;142(1):1.
• 28. Kumar V, Gupta K, Soneja M, Biswas AJCR. Intravenous immunoglobulin for severe thrombocytopenia in secondary dengue. 2018;2018:bcr-2018-224542.
• 29. Subbiah A, Mahajan S, Yadav RK, Agarwal SKJCR. Intravenous immunoglobulin therapy for dengue capillary leak syndrome in a renal allograft recipient. 2018;2018:bcr-2018-225225.
• 30. Kumar P, Charaniya R, Ghosh A, Sahoo RJJoC, JCDR DR. Intravenous immunoglobulin responsive persistent thrombocytopenia after dengue haemorrhagic fever. 2016;10(4):OD10.
• 31. Dimaano EM, Saito M, Honda S, Miranda EA, Alonzo MT, Valerio MD, et al. Lack of efficacy of high-dose intravenous immunoglobulin treatment of severe thrombocytopenia in patients with secondary dengue virus infection. The American journal of tropical medicine and hygiene. 2007;77(6):1135-8.
• 32. Lazarus AH, Freedman J, Semple JWJTs. Intravenous immunoglobulin and anti-D in idiopathic thrombocytopenic purpura (ITP): mechanisms of action. 1998;19(3):289-94.
• 33. Brinc D, Lazarus AHJH. Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn. 2009;2009(1):185-91.
• 34. Pannu AK, Bhalla A, Singhal M, Suri V, Shafiq N, Varma SJIjoccmp-r, official publication of Indian Society of Critical Care Medicine. Safety and efficacy of a single dose of Anti-D (WinRho®) in severe thrombocytopenia secondary to dengue virus infection. 2017;21(2):80.
• 35. Kharya G, Yadav SP, Katewa S, Sachdeva AJPH, Oncology. Management of severe refractory thrombocytopenia in dengue hemorrhagic fever with intravenous anti-D immune globulin. 2011;28(8):727-32.
• 36. Rajapakse S, de Silva NL, Weeratunga P, Rodrigo C, Fernando SD. Prophylactic and therapeutic interventions for bleeding in dengue: a systematic review. Trans R Soc Trop Med Hyg. 2017;111(10):433-9.
• 37. Kularatne S. Survey on the management of dengue infection in Sri Lanka: opinions of physicians and pediatricians. Southeast Asian journal of tropical medicine and public health. 2005;36(5):1198.
• 38. Medin CL, Rothman AL. Cell type–specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment. The Journal of infectious diseases. 2006;193(8):1070-7.
• 39. Min M, Aye M, Shwe T, Swe T. Hydrocortisone in the management of dengue shock syndrome. The Southeast Asian journal of tropical medicine and public health. 1975;6(4):573-9.
• 40. Pongpanich B, Bhanchet P, Phanichyakarn P, Valyasevi A. Studies on dengue hemorrhagic fever. Clinical study: an evaluation of steroids as a treatment. Journal of the Medical Association of Thailand. 1973;56(1):6-14.
• 41. Widya M, Martoatmodjo K. Clinical observations on dengue shock syndrome.(An evaluation of steroid treatment.). Paediatrica Indonesiana. 1975;15(5/6):151-60.
• 42. Sumarmo D, Talogo W, Asrin A, Isnuhandojo B, Sahudi A. Failure of hydrocortisone to affect outcome in dengue shock syndrome. Pediatrics. 1982;69(1):45-9.
• 43. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Pediatrics. 1993;92(1):111-5.
• 44. Kohli U, Saharan S, Lodha R, Kabra S. Persistent thrombocytopenia following dengue shock syndrome. The Indian Journal of Pediatrics. 2008;75(1):82-3.
• 45. Kularatne S, Walathara C, Mahindawansa S, Wijesinghe S, Pathirage M, Kumarasiri P, et al. Efficacy of low dose dexamethasone in severe thrombocytopenia caused by dengue fever: a placebo controlled study. Postgraduate medical journal. 2009;85(1008):525-9.
• 46. Boo Y, Lim S, P'ng H, Liam C, Huan N. Persistent thrombocytopenia following dengue fever: What should we do? Malaysian Family Physician: the Official Journal of the Academy of Family Physicians of Malaysia. 2019;14(3):71.
• 47. Tam DT, Ngoc TV, Tien NT, Kieu NT, Thuy TT, Thanh LT, et al. Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2012;55(9):1216-24.
• 48. Humbrecht C, Kientz D, Gachet C. Platelet transfusion: Current challenges. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2018;25(3):151-64.
• 49. Roy SJC. Thrombopoietin Receptor Agonists: Can These Be the Future Answer to the Deadly Thrombocytopenia in Dengue Fever? 2019;11(4).
• 50. Lye DC, Lee VJ, Sun Y, Leo YSJCid. Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection. 2009;48(9):1262-5.
• 51. Pothapregada S, Kamalakannan B, Thulasingam MJJovbd. Role of platelet transfusion in children with bleeding in dengue fever. 2015;52(4):304.
• 52. Lee T-H, Wong JG, Leo Y-S, Thein T-L, Ng E-L, Lee LK, et al. Potential harm of prophylactic platelet transfusion in adult dengue patients. 2016;10(3):e0004576.
• 53. Assir MZK, Ahmad FJBE-BM. Prophylactic platelet transfusion does not reduce risk of clinical bleeding in adults with dengue and thrombocytopaenia. 2017;22(6):225-.
• 54. Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, et al. Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study. 2019.
• 55. Soumya M, Das S, Kalyani RJo. Platelet Transfusion Practice in Dengue Epidemic; Current Trends and Challenges–an Institutional Study. J Blood Lymph 9: 255. 2019;3:11-20.