Review Article

539

Dengue Prophylactic Platelet Transfusion—Changa Kurukularatne et al

When Less is More: Can We Abandon Prophylactic Platelet Transfusion in Dengue Fever?
Changa Kurukularatne,1,2MD, Frederico Dimatatac,1,2MD, Diana LT Teo,3MBBS, MSc, FRCPath, David C Lye,1,2,4 MBBS, FRACP, FAMS, Yee Sin Leo,1,2,5 M.Med (Int Med), FRCP, FAMS

Abstract
Dengue fever (DF) has several hematological manifestations including thrombocytopenia and increased bleeding risk. Prophylactic platelet transfusion—in the absence of major bleeding—is utilized in DF with thrombocytopenia with the intention of preventing hemorrhagic complications. However, prophylactic platelet transfusion in DF is neither standardized nor supported by clinical evidence. We conclude that risks, costs and poor resource utilization associated with prophylactic platelet transfusion in DF far outweigh any potential hematological benefit, and as such, should not constitute routine clinical practice. Ann Acad Med Singapore 2011;40:539-45 Key words: Thrombocytopenia, Preventitive, Arbovirus, Bleeding, Hemorrhage

Introduction Dengue fever (DF) is the most common mosquito-borne human viral illness worldwide, and has rapidly spread to reach hyper-endemic proportions in the urban tropics over the last quarter of a century.1 With an estimated 2.5 billion people at risk and a global annual incidence of 50 million cases, DF has been identified as an example of a potential international public health emergency.2 In understanding the unique pathophysiology of DF, revisiting the terminology is a useful first step. DF refers to the acute self-limited form, which by itself does not account for the mortality seen in this illness.3 Dengue Hemorrhagic Fever (DHF) is a complication which in contrast to other viral hemorrhagic fevers is not characterised by overt or dramatic hemorrhagic manifestations; rather, the hallmark increased capillary permeability leads to fluid shifts from intravascular to interstitial and serosal compartments.3 The most severe form of DHF—with significant intravascular volume depletion, hemodynamic compromise and poor organ and tissue perfusion—is termed Dengue Shock
1 2

Syndrome (DSS).3 Although the more recent World Health Organization (WHO) classification system has grouped the various forms of this illness into Probable Dengue, Dengue with Warning Signs and Severe Dengue,2 the classical terminology of DHF and DSS is still widely used today. The new WHO classification is more clinically relevant in its approach in assessing disease severity, triaging hospital admission and dengue case management, and covers disease manifestations beyond the DF/DHF/DSS classification.2 Methods We reviewed the published clinical data on prophylactic platelet transfusion and the basis for transfusion thresholds in dengue and non-dengue settings. We critically analysed the risks and benefits of prophylactic platelet transfusion as it applies specifically to DF. We examined existing clinical practice guidelines on prophylactic platelet transfusion. We then provide an evidence-based assessment of the utility of prophylactic platelet transfusion in DF.

Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore Communicable Disease Centre, Singapore 3 Blood Services Group, Health Sciences Authority, Singapore 4 Yong Loo Lin School of Medicine, National University of Singapore 5 Saw Swee Hock School of Public Health, National University of Singapore Address for Correspondence: Dr Changa Kurukularatne, 80 Mount Sinai Drive, #06-03, Singapore 277125. Email: changa_k@yahoo.com

Annals Academy of Medicine

Dengue Prophylactic Platelet Transfusion—Changa Kurukularatne et al

540

Results Prophylactic Platelet Transfusion Platelets are a crucial component of hemostasis. Conditions that compromise the number and function of platelets confer increased risks of hemorrhage. Since Duke’s initial 1910 description of patients with bleeding attributed to thrombocytopenia, and good response to whole blood transfusion,4 it was not until the last 50 years or so that platelet transfusions emerged as an intervention against hemorrhage.5 Platelet transfusion based solely on thrombocytopenia with the intent of preventing major bleeding (prophylactic platelet transfusion) is widely practised in various healthcare settings around the world. A 1992 study by the American Association of Blood Banks’ Transfusion Practice Committee reported that over 70% of hospitals transfused platelets primarily for prophylaxis, with an arbitrary transfusion threshold of 20 x 109/L or higher in 80% of these hospitals.6 This prophylactic platelet transfusion threshold can be traced to published data half a century ago, and was widely adopted for many years despite lack of clinical evidence that 20 x 109/L is the appropriate transfusion threshold.7 Data from randomized clinical trials suggest that a decrease in platelets counts of up to 10 x 109/L may be tolerated without the need for prophylactic platelet transfusion in the absence of major bleeding.8-10 In acute leukemic patients with chemotherapy-induced thrombocytopenia, major bleeding rates (any bleeding more than petechial, mucosal or retinal bleeding) were no different with prophylactic platelet transfusion thresholds of 10 x 109/L (21.5%) and 20 x 109/L (20%).10 In another study involving patients with acute myeloid leukemia, the rates of mild to severe blood loss was the same in groups with 10 x 109/L and 20 x 109/L platelet transfusion thresholds.8 Data also suggest that platelet counts even less than 10 x 109/L may be well tolerated without the need for prophylactic platelet transfusion, provided additional bleeding risks (significant coagulopathy, sepsis, anatomic aberrations, platelet function impairments) are absent: a single centre prospective analysis of 98 patients (2147 patient study days) demonstrated major bleeding in 1.39% (30/2147) of study days when platelet counts were 20 x 109/L.11 In the absence of additional bleeding risk factors, major hemorrhage was noted in 0.51% (11/2147) of study days when platelet counts were greater than or equal to 10 x 109/L. Following the introduction of a stringent prophylactic platelet transfusion policy with a trigger of 150 x 109/L, 12% among patients with platelet count of 100-149 x 109/L, 11% among patients with platelet count of 80-99 x 109/L, 10% among patients with platelet count of 50-79 x 109/L, 11% among patients with platelet count of 20-49 x 109/L, 13% among patients with platelet count of 10-19 x 109/L, and 0% among patients with platelet count