Abstract
Dengue infection has emerged as a global public health problem in recent decades. The clinical spectrum ranges from a simple fever to severe shock syndrome. The disease is characterized by capillary leak syndrome, bone marrow and hematopoiesis suppression with late recovery, liver dysfunction and rarely encephalopathy. Thrombocytopenia with bleeding manifestations warrants platelet transfusion. The use of prophylactic platelet transfusion is increasing in countries where dengue is endemic. This has led to risks of transfusion reactions and increased costs. Due to a lack of evidence-based guidelines, there is an inappropriate use of platelet transfusion widely. The current review aims to give an overview of the role of platelet transfusion in dengue patients with thrombocytopenia.
Introduction
Dengue fever is caused by the dengue virus, a member of the family Flaviviridae. There are antigenically four different viruses in the dengue virus complex, named as DENV-1, DENV-2, DENV-3 and DENV-4. The infection is transmitted from human to human by the bite of the mosquito vector Aedes aegypti. The World Health Organization, in 2009, revised the three types of infection: dengue without a warning sign, dengue with warning signs and severe dengue. The diagnosis of dengue is made either by detection of Non-structural protein 1 (NS1), using the enzyme-linked immunosorbent assay (ELISA).
Pathophysiology
Capillary leak syndrome is the cardinal feature in patients with dengue hemorrhagic fever due to an increase in capillary permeability. Leukopenia, thrombocytopenia and bleeding diathesis are typical findings in dengue infections. Some degree of thrombocytopenia is seen in both dengue and dengue hemorrhagic fever. The cause of thrombocytopenia is multifactorial which happens late in the course of the illness. Some of them include bone marrow hypocellularity and immune-mediated destruction. Elevation of liver transaminases is usually mild and common and is an indirect marker of disease severity.
Platelet Transfusion
Thrombocytopenia is very common in dengue and is a major concern for the patient as well as the physician. Many studies have reported that thrombocytopenia is not the only predictor of severe bleeding. Thrombocytopenia did not have any statistical association with major bleeding or predicting mortality. The important factors that did predict a high risk of bleeding include SGOT, SGPT, severe dengue and secondary dengue.
There is a controversy regarding the efficacy of prophylactic platelet transfusion and the exact trigger when to transfuse. Most guidelines recommend a trigger of 10,000/ul for stable thrombocytopenic patients without bleeding manifestations.
The lack of efficacy of prophylactic platelet transfusion has been reported in many studies by various authors. Preventive transfusions did not produce clinical improvement in coagulation status. Prophylactic platelet transfusion was the cause of fluid overload and prolonged hospital stay in a comparative study between patients with dengue shock syndrome who received platelets and those who didn’t. The trial of the Platelet Prophylaxis study of the UK revealed the safety of a therapeutic-only platelet transfusion strategy with no prophylactic transfusions.
In patients with severe dengue, shock is the main risk factor for severe bleeding. Hence, early detection and prevention of shock is the key to the management of severe dengue. It was also observed that in prophylactic platelet transfusion in such patients, the rise in platelet count was transient and returned to previous values in 5 hrs.
The major risks associated with the transfusion of platelets are febrile non-hemolytic transfusion reactions, allergic reactions, sepsis, transfusion-related acute lung injury, platelet refractoriness and other transfusion-transmitted infections.
Conclusion
Looking at thrombocytopenia as the only marker of disease severity and mortality leads to unwanted hospital admissions, unnecessary platelet transfusion and undue financial burden to the patient. More than thrombocytopenia, the major predictor of severe bleeding in dengue patients include elevated white cells, shock, deranged LFT and high SOFA score. The major emphasis is to look at the warning signs of severe dengue and prevent multiorgan failure, as most of the patients who required intensive care succumbed to the illness.
References
1. Paramjit Kaur and Gagandeep Kaur Transfusion support in patients with dengue fever. Int J Appl Basic Med Res. 2014 Sep; 4(Suppl 1): S8–S12.
2. R. N. Makroo, V. Raina, P. Kumar, and R. K. Kanth. Role of platelet transfusion in the management of dengue patients in a tertiary care hospital. Asian J Transfus Sci. 2007 Jan-Jun; 1(1): 4–7.
3. Kevin John John, Karthik Gunasekaran, John Davis Prasad,1Divya Mathew, Sohini Das, N. Sultan, Asha Mary Abraham, and Ramya Iyyadurai. Interdisciplinary Perspectives on Infectious Diseases. Volume 2019 | Article ID 4823791
Dr. S. Vijaya Kumar
Critical Care Specialist
Kauvery Hospital Chennai