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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00128713.

Figures

Figure 1

Relation between age group and percentage of patients experiencing bleeding of various grades, in all patients and stratified by disease treatment category. Age group comparisons with pairwise P values < .05 are noted (A: 0-5 years vs 6-12 years; B: 0-5 years vs 13-18 years; C: 0-5 years vs ≥ 19 years; D: 6-12 years vs 13-18 years; E: 6-12 years vs ≥ 19 years; F: 13-18 years vs ≥ 19 years). (A) At least 1 day with grade 2 or higher bleeding (overall test for age group, P < .001; interaction of age group with disease treatment category, P = .04), (B) ≥ 1 day with grade 3 or higher bleeding (overall test for age group, P = .02; P for interaction = .13), (C) ≥ 1 day with grade 4 bleeding (P = .12, P for interaction not estimable).

Figure 2

Relation between age group and time from HSCT to grade 2 or higher bleeding in all patients who received HSCT and by type of HSCT. (A) All patients who received HSCT (overall test for age group, P < .001, each pediatric age group significantly different from adults; interaction of age group with type of transplantation, P < .001). (B) Patients who receive autologous/syngeneic HSCT (overall test for age group, P < .001, each pediatric age group significantly different from adults). (C) Patients who received allogeneic HSCT (overall test for age group, P < .001, 6-12 and 13-18 years significantly different from adults).

Figure 3

Relation between morning platelet count category and the occurrence of grade 2 or higher bleeding on that day, in pediatric and adult age groups. (A) All patients (P ≤ .001 for age group and P < .001 for platelet count category), (B) autologous/syngeneic HSCT (P ≤ .001 for age group and P < 0.001 for platelet count category), (C) allogeneic HSCT (P = .053 for age group, and P = .004 for platelet count category), (D) chemotherapy without HSCT for hematologic malignancy (logistic model did not converge because of some categories having no days with bleeding).

Figure 4

Percentage of patients in each age group that experienced grade 2 or higher bleeding in each organ system. Age group comparisons with pairwise P values < .05 are noted (A: 0-5 years vs 6-12 years; B: 0-5 years vs 13-18 years; C: 0-5 years vs ≥ 19 years; D: 6-12 years vs 13-18 years; E: 6-12 years vs ≥ 19 years; F: 13-18 years vs ≥ 19 years).

Figure 5

Relation between age group and transfusion resource requirements, in all patients and within disease treatment category. Age group comparisons with pairwise P values < .05 are noted (A: 0-5 years vs 6-12 years; B: 0-5 years vs 13-18 years; C: 0-5 years vs ≥ 19 years; D: 6-12 years vs 13-18 years; E: 6-12 years vs ≥ 19 years; F: 13-18 years vs ≥ 19 years). (A) Number of platelet transfusions per patient (overall test for age group, P < .001; interaction between age group and disease treatment category, P < .001), (B) total number of platelets transfused per BSA, based on at-issue count (overall test for age group, P < .001; interaction between age group and disease treatment category, P < .001). (C) Percentage of patients who received ≥ 1 red cell transfusion (overall test for age group, P = .11; P for interaction not estimable), (D) total number of RBC transfusion events (overall test for age group, P = .045; interaction between age group and disease treatment category, P < .001).

Figure 5

Relation between age group and transfusion resource requirements, in all patients and within disease treatment category. Age group comparisons with pairwise P values < .05 are noted (A: 0-5 years vs 6-12 years; B: 0-5 years vs 13-18 years; C: 0-5 years vs ≥ 19 years; D: 6-12 years vs 13-18 years; E: 6-12 years vs ≥ 19 years; F: 13-18 years vs ≥ 19 years). (A) Number of platelet transfusions per patient (overall test for age group, P < .001; interaction between age group and disease treatment category, P < .001), (B) total number of platelets transfused per BSA, based on at-issue count (overall test for age group, P < .001; interaction between age group and disease treatment category, P < .001). (C) Percentage of patients who received ≥ 1 red cell transfusion (overall test for age group, P = .11; P for interaction not estimable), (D) total number of RBC transfusion events (overall test for age group, P = .045; interaction between age group and disease treatment category, P < .001).