A 55-year-old woman, with a history of pregnancies 30 and 25 years ago, is undergoing her second cycle of consolidation chemotherapy for acute myeloid leukaemia. By the seventh day after completing the cycle, her morning platelet count has been below 10 × 109/l for ten days. Despite daily prophylactic platelet transfusions she has developed a widespread purpuric rash on her legs and trunk, blood blisters on the oral mucosa and recurrent episodes of epistaxis severe enough to need nasal packing. She has been febrile for seven days despite intravenous broad-spectrum antibiotic therapy. Repeated blood cultures are negative and she was started on intravenous amphotericin B two days ago. Her platelet count before the latest transfusion is 3 × 109/l. The platelet count is 5 × 109/l one hour after transfusion of one adult therapeutic dose (4 units) of platelets and 3 × 109/l 18 hours after the transfusion.
What are the most likely causes of her failure to respond to platelet transfusions?
What investigations would you perform?
How would you manage her bleeding problem?
It is standard practice in haematology units to give prophylactic platelet transfusions to patients with temporary bone marrow suppression after chemotherapy when their count falls below a predetermined trigger level, commonly 10 × 109/l.1 It is important to note that the effectiveness of prophylactic, as opposed to therapeutic (i.e. to treat bleeding episodes), platelet transfusions in this setting has not been established by randomized controlled trials.2
Refractoriness to platelet transfusions is defined as the repeated failure to obtain a satisfactory response to platelet transfusions.1 Although the response of a bleeding episode to transfusion of platelets is the most clinically relevant marker, it is usual to assess the response to prophylactic platelet transfusions by measuring the increase in platelet count in response to the transfusion. To standardize the response in terms of the patient’s size and the dose of platelets transfused, formulae such as platelet recovery and corrected count increment have been derived. However, these are of limited value in routine clinical practice as they require knowledge of the precise platelet content in each unit transfused. Simpler indicators, such as failure of the 1-hour platelet increment to exceed the ‘transfusion trigger’ or a rise of less than 10 × 109/l after 20 to 24 hours, can be used as measures of unsatisfactory response. Because the response to individual platelet transfusions is variable, the diagnosis of refractoriness should only be made after an unsatisfactory response to two or more transfusions.
Historically, platelet refractoriness has been reported in more than 50% of patients receiving repeated transfusions and the causes can be categorized as immune or non-immune. The non-immune causes are associated with increased platelet consumption, often related to infection and its treatment, and constitute the large majority of cases in ...