Platelet dose for prophylactic platelet transfusions

Although guidelines exist to deal with some aspects of platelet transfusion practice, many important clinical issues have not been addressed in large randomized controlled trials (RCTs). Slichter et al. conducted a RCT of prophylactic platelet transfusions to determine the effects of the dose of platelets on clinical signs of bleeding, the use of platelet and red cell transfusions, changes in the recipient's post-transfusion platelet count, days to next transfusion and adverse events (Effects of Prophylactic Platelet Dose on Transfusion Outcomes [PLADO] trial). The primary end point of the study (i.e., the percentage of patients in each group with at least one episode of bleeding of grade 2 or higher according to the WHO criteria) was not significantly different (71, 69 and 70% of patients in the low-, medium- and high-dose group, respectively). According to these data, one can conclude that the dose of platelets transfused has no significant effect on the incidence of bleeding in patients with hypoproliferative thrombocytopenia and platelet counts no greater than 10 × 10?/l.     

Optimal dosing and triggers for prophylactic use of platelet transfusions.

Despite the reliance on platelet transfusion support in patients receiving myeloablative therapy, controversies surround platelet transfusion practices. These include the appropriate platelet dose and the threshold at which prophylactic platelet transfusions will be most effective. These issues bear directly on patient outcome (donor exposure and bleeding complications), cost effectiveness of transfusion, and maintenance of adequate platelet inventories. This review examines the recent studies that have taken on the task of resolving these questions in order to provide optimal platelet transfusion guidelines. Studies now have convincingly demonstrated that a 10,000/microL threshold for prophylactic platelet transfusion is safe and effective in uncomplicated thrombocytopenic patients. Although platelet dosages vary, in general, smaller doses are both effective and inventory-sparing in the more complicated inpatient setting, while larger platelet doses allow for an increased transfusion interval for chronic outpatient support.     

Prediction of bleeding and prophylactic platelet transfusions in cancer patients with thrombocytopenia

Studies on markers for bleeding risk among thrombocytopenic cancer patients are lacking. This prospective observational cohort study investigated whether platelet parameters and a standardised bleeding questionnaire predicted bleeding or prophylactic platelet transfusions in patients with cancer and thrombocytopenia. Admitted adult patients with cancer and platelet count <80 × 10⁹/L were enrolled, but excluded if they experienced surgery or trauma within 7 days or platelet transfusion within 14 days. Patients were interviewed, blood samples collected and, subsequently, spontaneous bleeding and prophylactic platelet transfusion within 30 days were registered.

Of 197 patients enrolled, 56 (28%) experienced bleeding. In multivariate analyses, predictors of bleeding were infection (adjusted odds ratio (OR) = 2.65 and 95% confidence interval (95% CI) 1.04–6.74); treatment with platelet inhibitors, heparin or warfarin OR = 2.34, 95% CI 1.23–4.48; urea nitrogen OR = 1.15, 95% CI 1.07–1.25; creatinine OR = 1.01, 95% CI 1.01–1.01; and haemoglobin OR = 0.62, 95% CI 0.41–0.93. Specific information regarding previous gastrointestinal bleeding OR = 3.33, 95% CI 1.19–9.34 and haematuria OR = 3.00, 95% CI 1.20–7.52 predicted bleeding whereas the standardised bleeding questionnaire did not.

Prophylactic platelet transfusions were administered to 97 patients. Predictors of prophylactic platelet transfusions were: platelet count OR = 0.96, 95% CI 0.94–0.97; fibrinogen OR = 0.88, 95% CI 0.83–0.95; mean platelet volume OR = 0.69, 95% CI 0.49–0.97; platelet aggregometry with OR = 2.48, 95% CI 1.09–5.64 for collagen-induced platelet aggregation within the lowest quartile; and albumin OR = 1.07, 95% CI 1.01–1.15.

In conclusion, except for immature platelet fraction (IPF), platelet parameters predicted prophylactic platelet transfusion but not bleeding. Bleeding risk factors were previous haematuria or gastrointestinal bleeding, infection, antiplatelet or anticoagulant treatment, high urea nitrogen, low haemoglobin or high creatinine.     

High dose intravenous gammaglobulin and platelet transfusions in leukaemic HLA-immunized patients

3 aplastic patients with acute leukaemia, strongly HLA-immunized and refractory to platelet transfusions, received polyvalent gammaglobulin i.v. infusions (0.4 g/kg/d for 5 or 6 d) in association with daily random platelet transfusions. Platelet recovery was obtained in 2 patients. The 3rd patient did not show any significant rise in platelet count. The ability of gammaglobulin to prolong the life-span of incompatible transfused platelets could facilitate the management of HLA-immunized patients.     

Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia

Age-group analyses were conducted of patients in the prophylactic platelet dose trial (PLADO), which evaluated the relation between platelet dose per transfusion and bleeding. Hospitalized patients with treatment-induced hypoproliferative thrombocytopenia were randomly assigned to 1 of 3 platelet doses: 1.1 × 10(11), 2.2 × 10(11), or 4.4 × 10(11) platelets/m(2) per transfusion, given for morning counts of ≤ 10 000 platelets/μL. Daily hemostatic assessments were performed. The primary end point (percentage of patients who developed grade 2 or higher World Health Organization bleeding) was evaluated in 198 children (0-18 years) and 1044 adults. Although platelet dose did not predict bleeding for any age group, children overall had a significantly higher risk of grade 2 or higher bleeding than adults (86%, 88%, 77% vs 67% of patients aged 0-5 years, 6-12 years, 13-18 years, vs adults, respectively) and more days with grade 2 or higher bleeding (median, 3 days in each pediatric group vs 1 day in adults; P < .001). The effect of age on bleeding differed by disease treatment category and was most pronounced among autologous transplant recipients. Pediatric subjects were at higher risk of bleeding over a wide range of platelet counts, indicating that their excess bleeding risk may be because of factors other than platelet counts.     

Survey on the threshold for platelet transfusions

We carried out a survey on platelet transfusions performed in nine general hospitals. We evaluated 303 adults who received a total of 24455 units over 1864 platelet transfusions. The underlying diseases were hematologic disorders with chemotherapy (59.7%), hematologic disorders without chemotherapy (15.5%), hematopoietic stem cell transplantation (18.5%), and others (2.0%). The patient platelet count before transfusion (platelet trigger value) was measured in only 77.1%. The platelet trigger value differed greatly between the hospitals, with an average of 2.2 x 10(4)/microl, a minimum of 1.3 x 10(4)/microl, and maximum of 3.2 x 10(4)/microl. Only 55.3% of the platelet transfusions carried out complied with the Platelet Transfusion Guideline published by the Ministry of Health, Labour and Welfare. The hospitals surveyed could be divided into those who gave mainly around 10 units and those who gave over 10 units. The total dose of platelets transfused was more in the hospitals that used mainly 15 or more unit-PCs than in the hospitals that used mainly 10 unit-PCs. These results indicate that platelet transfusion may be greatly reduced by complying with the 2 x 10(4)/microl of platelet transfusion threshold and by selecting less than 10 units of PC per transfusion.     

Strategies for managing refractoriness to platelet transfusions

The availability of platelet transfusions made possible intensive, myelosuppressive therapy. Chronic transfusion support is often complicated by refractoriness to platelet transfusions characterized by inadequate post-transfusion platelet count increments. Refractoriness is most commonly associated with a variety of clinical factors. Aggressive treatment of these clinical conditions often corrects the response to platelet transfusions. Fewer patients develop immune-mediated platelet destruction associated with alloantibodies to class I human leukocyte antigens (HLAs) and occasionally to platelet-specific antigens. The majority of these patients are successfully supported with HLA-matched or cross-match compatible single-donor platelet concentrates.     

Clinical aspects of platelet transfusions

Refractoriness is the most important complication of platelet transfusion therapy, occurring in about 50% of patients receiving repeated transfusions. The major causes are HLA alloimmunization and non-immune platelet consumption associated with clinical factors such as septicaemia. DIC and splenomegaly. Initial management of alloimmunized patients who are refractory to platelet transfusions from random donors is the use of HLA-matched platelet transfusions, which improve responses to transfusions in about 65% of patients. It may be difficult to provide effective platelet transfusion support for alloimmunized patients not responding to HLA-matched transfusions. There has been much interest in methods for the prevention of HLA alloimmunization. Primary HLA alloimmunization is dependent on the presence of HLA class II antigen-bearing cells in transfusions; pure platelet transfusions are non-immunogenic as platelets only express HLA class I antigens. The use of leucocyte-depleted blood components in multitransfused patients has resulted in a reduction in HLA alloimmunization and platelet refractioness. Improvements in the techniques for leucocyte-depletion of red cell and platelet concentrates and the possibility of inactivation of HLA class II antigen-bearing cells by UV irradiation makes prevention of alloimmunization an attainable goal.     

A radiolabeled antiglobulin test for crossmatching platelet transfusions

Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, we investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The principle of the test is that of an indirect Coombs test using 125I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test (RAGT) index. Using this technique, we performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to random donor platelets and receiving varying degrees of HLA-matched platelets. Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment (CCI) determined at 1 and 20 hr. When the RAGT index was 1.9 or less, the mean CCI at 1 lhr was 17,570 +/- 7003/cu mm, n = 55. When the RAGT index was 2.0 or greater, the mean CCI was 4237 +/- 4100/cu mm, n = 34. At 20 hr when the RAGT index was 1.9 or less, the mean CCI was 8722 +/- 3143/cu mm, n = 33, and when the index was 2.0 or greater, the mean CCI was 571 +/- 1286/cu mm, n = 23. Using this technique, one false negative resulted. Nine positive crossmatches with good increments at 1 hr were found; at 20 hr, however, the survival of these units was zero. These data suggest that this method is a useful adjunct in the selection of platelets in the refractory patient.