Clinical guidelines recommend that patients who undergo invasive procedures have a platelet count level above 50×10^9/L; these guidelines historically have applied to all patients and do not specifically differentiate platelet count thresholds for those with chronic liver disease (CLD). Patients with CLD, especially patients with decompensated liver, can have platelet counts below 50×10^9/L. Although there is evidence in the literature that patients with CLD have a re-balanced hemostasis at lower platelet count levels, studies have shown an increased risk of bleeding among those with low platelet counts. Despite clinical guidelines being based on very-low-quality evidence, use of platelet transfusions (PTs) prior to procedures is a common medical practice.
To control bleeding, the standard-of-care for treatment in patients with CLD has been the use of PTs either prophylactically or peri-procedurally. The FDA in the last 18 months has approved two second-generation thrombopoietin-receptor agonists as safe and efficacious therapies for the treatment of thrombocytopenia in patients with CLD scheduled to undergo an invasive procedure. The approval of new pharmacotherapies for this patient population to raise platelet counts is an important development, as there is always risk of infection when patients, who are already medically vulnerable, receive a PT. Although quite rare and statistically improbable, these infections can have severe consequences, as in the case of a CDC-reported death in a CLD thrombocytopenia patient who received a PT prior to a procedure May, 2018.
To Transfuse Platelets or Not to Transfuse
For a study published in GastroHep, my colleagues and I compared clinical and economic outcomes between patients with CLD and thrombocytopenia who received PTs prior to an invasive procedure and those who did not. Patients receiving platelet transfusions experienced a 14% increase in the number of bleeding events, a 5% increase in the number of complications from transfusion-associated circulatory overload, and a 5% increase in transfusion-related acute lung injury (Figure).
Differences in clinical outcomes translated into higher expenses (mean delta of approximately $11,000). On average, patients who received PTs were hospitalized 1.4 days longer than those who did not. This analysis was supportive of similar findings from previous research based on a conceptual framework that included costs of generating the supply of platelets, the PT itself, adverse events associated with PT, and refractoriness to PT. In this prior study, the average total direct cost of a PT in patients with CLD and thrombocytopenia was estimated to be in the range of $5,258 to $13,117. The greatest percentages of cost were attributable to the actual transfusion ($3,723 to $4,436) and the cost of refractoriness ($874 to $7,578).
Studies have shown that PTs can be either ineffective in patients with CLD and thrombocytopenia or that if there is a response, the platelet count values return to baseline within hours. This short-term effectiveness is important, as there is often an increased risk of bleeding post-procedure, and maintaining elevated platelet counts for an extended period is needed to prevent delayed bleeding. The two recently approved second-generation thrombopoietin-receptor agonists have shown efficacy in maintaining platelet counts above 50×10^9/L for a longer period; one in particular has shown platelet counts above 50×10^9/L for up to 3 weeks on average. This affords physicians the confidence that platelet counts will remain at safe levels when there may still be an elevated bleeding risk for the patient. It also allows physicians to potentially complete multiple procedures with a single course of treatment.
Hepatologists, interventional radiologists, and surgeons all have a need for continued education on the risks associated with planned invasive procedures in patients with CLD, including the risk of procedure-related bleeding and when platelet counts should be elevated to medically acceptable thresholds through the use of the newly approved agents for use in this specific patient population. Physicians should also discuss with patients these likely safer and more efficacious pharmacotherapy alternatives to platelet transfusions, to ensure patients are able to understand the risks and benefits of the different treatment modalities.