Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial

Abstract

Bleeding remains a significant problem for many thrombocytopenic hematology/oncology patients in spite of platelet transfusions. Factors that might contribute to bleeding were analyzed for 16 320 patient-days on or after their first platelet transfusion in 1077 adult patients enrolled in the Platelet Dose (PLADO) trial. All patients had a greatly increased risk of bleeding at platelet counts of ≤5 × 10⁹/L (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.0-4.8) compared with platelet counts ≥81 × 10⁹/L. Platelet counts between 6 × 10⁹/L and 80 × 10⁹/L were also associated with a somewhat elevated bleeding risk in patients receiving allogeneic stem cell transplants (SCTs) or chemotherapy but not in those undergoing autologous SCTs. Other significant laboratory predictors of bleeding were hematocrit ≤25% (OR, 1.29; 95% CI, 1.11-1.49), activated partial thromboplastin time (aPTT) 30 to ≤50 seconds (OR, 1.40; 95% CI, 1.08-1.81; P = .01), aPTT >50 seconds (OR, 2.34; 95% CI, 1.54-3.56), international normalized ratio (INR) 1.2 to 1.5 (OR, 1.46; 95% CI, 1.17-1.83), and INR >1.5 (OR, 2.05; 95% CI, 1.43-2.95). Transfusion of either platelets or red blood cells (RBCs) on days with bleeding was often not sufficient to change bleeding outcomes on the following day. Because bleeding occurred over a wide range of platelet counts among patients undergoing allogeneic SCT or chemotherapy and because platelet transfusions may not prevent bleeding, other risk factors may be involved. These may include low hematocrit and coagulation abnormalities. This trial was registered at www.clinicaltrials.gov as #NCT00128713.

Figure 1.

Relationship between morning platelet count and patient-days with bleeding outcomes. (A) Unadjusted percentages of patient-days (95% CIs) with grade ≥2A (grade 2A+) bleeding. (B) ORs (95% CIs) for grade ≥2A bleeding compared with the reference category of ≥81 × 10⁹/L, taking into account within-person correlation. The 16 df test for any association between morning platelet count category and grade ≥2A bleeding had P < .001. (C) Unadjusted percentages of patient-days (95% CIs) with grade ≥3 (grade 3+) bleeding. (D) ORs (95% CIs) for grade ≥3 bleeding compared with the reference category of ≥81 × 10⁹/L, taking into account within-person correlation. The 16 df test for any association between morning platelet count category and grade ≥3 bleeding had P = .85.

Figure 2.

Association between morning platelet count and grade ≥2A bleeding by stratum. (A) Unadjusted percentages of patient-days with grade ≥2A bleeding by stratum. (B-D) ORs (95% CIs), taking into account the within-patient correlation, comparing morning platelet count categories to the reference category of ≥81 × 10⁹/L for (B) ALLO, (C) AUTO, and (D) CHEMO strata.

Figure 3.

Relationship between morning hematocrit and percentage of patient-days with bleeding outcomes. (A) Unadjusted percentages of patient-days (95% CIs) with grade ≥2A bleeding. (B) ORs (95% CIs) for grade ≥2A bleeding compared with the reference category of hematocrit >29%, taking into account within-person correlation. The 2 df test for any association between morning hematocrit category and grade ≥2A bleeding had P = .002. (C) Unadjusted percentages of patient-days (95% CIs) with grade ≥3 bleeding. (D) ORs (95% CIs) for grade ≥3 bleeding compared with the reference category of hematocrit >29%, taking into account within-person correlation. The 2 df test for any association between morning hematocrit category and grade ≥3 bleeding had P < .001.

Figure 4.

Relationship between bleeding grade and availability of fibrinogen, aPTT, and INR data. The y-axis indicates percentage of patient days with laboratory test performed among all patient days within specified bleeding grade.

Figure 5.

Relationship between aPTT category and percentage of days with bleeding outcomes. (A) Unadjusted percentages of patient-days (95% CIs) with grade ≥2A bleeding. (B) ORs (95% CIs) for grade ≥2A bleeding compared with the reference category of aPTT ≤30, taking into account within-person correlation. The 2 df test for any association between aPTT category and grade ≥2A bleeding had P = .002. (C) Unadjusted percentages of patient-days (95% CIs) with grade ≥3 bleeding. (D) ORs (95% CIs) for grade ≥3 bleeding compared with the reference category of aPTT ≤30, taking into account within-person correlation. The 2 df test for any association between aPTT category and grade ≥3 bleeding had P = .40.

Figure 6.

Relationship between INR category and percentage of days with bleeding outcomes. (A) Unadjusted percentages of patient-days (95% CIs) with grade ≥2A bleeding. (B) ORs (95% CIs) for grade ≥2A bleeding compared with the reference category of INR ≤1.2, taking into account within-person correlation. The 2 df test for any association between INR category and grade ≥2A bleeding had P < .001. (C) Unadjusted percentages of patient-days (95% CIs) with grade ≥3 bleeding. (D) ORs (95% CIs) for grade ≥3 bleeding compared with the reference category of INR ≤1.2, taking into account within-person correlation. The 2 df test for any association between INR category and grade ≥3 bleeding had P = .04.