Optimal use of blood and platelet support transfusion in patients with Hematological Cancers in Uganda

Abstract

Globally, cancer incidence and mortality are growing rapidly especially in emerging economies. Cancer is a major cause of morbidity and mortality in sub-Saharan Africa (SSA). Transfusion of blood and blood components plays an essential supportive and life-saving role particularly in patients with hematologic malignancies who are predisposed to anemia, thrombocytopenia, and bleeding because of their disease conditions and treatment. Unfortunately, in Africa blood products are scarce, expensive, and may be associated with serious adverse effects. The shortages of products may be exacerbated partly by lack of empirical guidance for the practice of transfusion and partly by the lack of appreciation for potential adverse effects related to transfusions. Optimal decision-making regarding blood transfusion requires appropriate knowledge of transfusion medicine among doctors as well as guidelines-based transfusion practice based on available evidence. Objectives: The objectives of this PhD research study were to assess blood transfusion knowledge, attitudes and practices among physicians working at the Uganda Cancer Institute (UCI); to evaluate the need and availability of blood products for patients with hematological malignancies at UCI; and to implement “local guidelines” for optimal platelet transfusions in cancer patients with thrombocytopenia. Methods: Different study designs were needed to achieve the above objectives. We conducted a cross-sectional self-administered survey of UCI physicians’ knowledge, attitudes, and practices regarding blood transfusion. In consultation with transfusion medicine experts, 30 questions were developed, 10 questions for each of 3 domains: knowledge, attitudes, and practices. We created a knowledge score for the knowledge domain equal to the number of questions correctly answered out of 10. Next, we prospectively studied the demand and supply of blood for patients with thrombocytopenia (platelet count ≤50x109/L), anemia (hemoglobin ≤10g/dL), and bleeding (WHO grade ≥ 2). We used Poisson generalized estimating equation (GEE) regression models to account for correlation among longitudinal binary outcomes measured in the same participant. Finally, we followed cohorts of patients admitted to the UCI with a hematological malignancy in three sequential 4-month time-periods using incrementally lower thresholds for prophylactic platelet transfusion: platelet counts ≤ 30 x 109/L in period 1, ≤ 20 x 109/L in period 2, and ≤ 10 x 109/L in period 3. Clinically significant bleeding was defined as WHO grade ≥ 2 bleeding. We used GEE to compare the frequency of clinically significant bleeding and platelet transfusions by study period, adjusting for age, sex, cancer type, chemotherapy, baseline platelet count, and baseline hemoglobin. Results: In the study to assess the knowledge, attitudes and reported practices among 28 doctors at UCI regarding blood and platelet transfusion, the mean knowledge score was 5.3 (SD=1.7), [median = 5.5 (IQR = 4-7)], and 9 (32%) correctly answered at least 7 of 10 questions. Almost all doctors understood the importance of proper patient identification prior to transfusion and identification error as the most common cause of fatal transfusion reactions. Over 60% of the doctors acknowledged they lacked knowledge and needed additional training in transfusion medicine. In the study to assess the need and availability of blood products for patients with hematological malignancies at UCI among 91 patients, with a median age of 26 years (IQR, 11-47), thrombocytopenia occurred overall on 49% of hospital days and on at least one day in 58%. Platelets transfusions were provided to 39% of patients. The mean number of platelet units requested per day by physicians on the cancer ward was 16.2 (range 0-30); however, a mean of 5.1 units (range 0-15) were received. Anemia occurred on at least one day in 90% of patients; on 78% of days; and 68% received at least one blood transfusion. The mean number of blood units requested by physicians was 36 (range 8-57) units per day but only a mean of 14 (range 0-30) were received. Bleeding occurred on at least one day in 19% of patients on 8% of hospital days. In the study to implement “local guidelines” for platelet transfusions in Ugandan cancer patients with thrombocytopenia, 188 patients were enrolled with a median age of 22 years (range 1-80). Platelet transfusions were given to 42% of patients in period 1, 55% in period 2, and 45% in period 3. These transfusions occurred on 8% of days in period 1, 12% in period 2, and 8% in period 3. In adjusted models, relative to period 1 period 3 had significantly fewer transfusions than period 1 (RR = 0.6, 95% CI 0.4-0.9; p = 0.01) and period 2 (RR=0.5, 95% CI 0.4-0.7; p<0.001). Eighteen patients (30%) had clinically significant bleeding on at least one day in period 1, 23 (30%) in period 2, and 15 (23%) in period 3. Clinically significant bleeding occurred on 8% of patient-days in period one, 9% in period two, and 5% in period three (adjusted p = 0.41). Thirteen (21%) patients died in period one, 15 (22%) in period two, and 11 (19%) in period three (adjusted p = 0.96). Conclusion: Thrombocytopenia and anemia were common, but blood product availability was substantially below that requested. Strategies for increased blood collection and adherence to strict transfusion triggers would be great strategies to improve blood availability. While doctors at UCI have basic knowledge in transfusion, most reported gaps in their knowledge and all expressed a need for additional education in the basics of blood transfusion. Transfusion training and evidence-based guidelines are needed to reduce inappropriate transfusions and improve patient care. Peer influence in transfusion decision making requires more understanding. Finally, lowering the threshold for platelet transfusion led to fewer transfusions and did not change the incidence of clinically significant bleeding or mortality, suggesting that a threshold of 10 x 109/L platelets, as used in resource-rich countries, may be implemented as a safe level for transfusions in SSA. However, there is need for a clinical trial with bigger sample size, as a future study for a more definitive conclusion.