Platelet transfusion in Dengue Fever

Following the monsoon rains, we see several cases of Dengue in our ICUs. Many of these patients develop severe thrombocytopenia, with the counts often dropping below 20,000. I feel most clinicians would strongly consider prophylactic platelet transfusion (without any evidence of clinical bleeding) when the count drops to between 10–20,000. However, there is a reasonably sound body of knowledge which suggests that prophylactic platelet transfusions using arbitrary thresholds may not have any favorable effect. There are several retrospective studies and two randomized controlled studies that have clearly shown that there is no reduction in the incidence of bleeding with platelet transfusion using such arbitrary thresholds. Indeed, even the platelet counts do not seem to rise significantly following transfusion. In fact, there is a possibility of potential harm with transfusion of platelets in this manner.

In two pediatric studies, it has been shown that ADAMTS-13 levels may be relatively low in Dengue,  compared to Von Willebrand factor (VWF) levels. This may result in increased platelet adhesion to VWF multimers, and endothelial sequestration. Sequestrated platelets may lead to impaired microcirculatory flow and organ dysfunction (through a pathophysiological mechanism similar to TTP). Hence, it is possible that prophylactic platelet transfusion may cause harm by increased endothelial sequestration and worsening organ function. Furthermore, the harmful effects of transfusion, including transfusion-associated lung injury (TRALI) and fluid overload may have an adverse impact on clinical outcomes.

How do we offset the possible harm from platelet transfusion in Dengue? Clearly, if the ADAMTS-13 levels are low, there may be a compelling reason to replenish it using fresh frozen plasma, prior to transfusion of platelets. Cryo-reduced plasma, which is FFP from which cryoprecipitate has been removed is another rich source of ADAMTS-13. Recombinant ADAMTS-13 is also currently available.

Although based on a well-founded hypothesis, no clinical studies have been done to test the benefit of replenishing ADAMTS-13 levels in Dengue prior to platelet transfusions. I strongly feel we could undertake a multicentric study to assess clinical outcomes with such an intervention. The clinical outcomes to consider may include a rise in platelet counts to a sustained level and clinical bleeding with and without ADAMTS-13 supplementation with any of the aforementioned products.