Methods	Parallel RCT (enrolled April 1991 to November 1995). Single centre. United States
Participants	Inclusion criteria: Unequivocal diagnosis of acute leukaemia (AML, ALL in relapse, acute undifferentiated leukaemia or MDS transformed to AML). Age > 17 years. Person undergoing initial induction chemotherapy or re-induction following relapse Exclusion criteria: APL. Inherited clotting disorder. Uncontrolled infection at randomisation. History of a bleeding diathesis. DIC at randomisation into the study. Prior entry into the study. Concomitant malignancy or AIDS diagnosis. History of platelet refractory status N = 82 entered into study; 4 ineligible (2 delayed cytogenetic diagnosis of APL. 2 not assessable, transferred to ITU within 24 hrs of registration with severe infections) Arm 1: N = 37 Arm 2: N = 41
Interventions	Comparison between prophylactic platelets with different transfusion triggers Arm 1 (Low transfusion trigger). If platelet count ≤ 10 × 109/L Arm 2 (High transfusion trigger). If platelet count ≤ 20 × 109/L Platelets given in both arms if serious or life-threatening bleeding and for procedures at discretion of physician Platelet dose: 1 apheresis unit (approximately 4 to 4.9 × 1011 of platelets) Platelet type: apheresis. Leucodepleted
Outcomes	Main or primary outcome not stated Outcomes mentioned: Survival (at time of analysis) Remission rates (time period not stated) Bleeding episodes per participant Transfusion requirements (platelets, red cells) Hospital stay Adverse events Number of days participants on study (median): Arm 1: 24 days Arm 2: 24 days
Bleeding scale	Severity was graded using a standardised toxicity scale (Ajani 1990) Grade 1: petechiae, minimum blood loss, blood transfusion not required Grade 2: blood loss requiring transfusion of 1 to 2 units of blood Grade 3: blood loss requiring transfusion of 3 to 4 units of blood Grade 4: blood loss requiring transfusion of > 4 units of blood Definition of significant bleeding: requirement for therapeutic platelet transfusion (unpublished) Definition of life-threatening bleeding: not stated
Bleeding assessment	Bleeding episodes defined as blood loss documented in physician or nursing notes or observed by an investigator
Red cell transfusion policy	Not stated
Notes	Participants randomised: no definition Follow-up of participants: until unsupported platelet count > 30 × 109/L for 2 days OR transfer to intensive care for > 2 days OR discharge from hospital OR death Stopping guideline: not reported Source(s) of funding: Iowa Leukemia and Cancer Research Fund; The Dr. Richard O. Emmons Memorial Fund; L. McGilliard-T. Johannes Memorial Fund; The Mamie C. Hopkins Fund Conflicts-of-interest statement: not stated
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Random allocation “by selecting randomised cards from envelopes”. No comment on how cards were randomised Randomisation stratified by 4 groups (new diagnosis < 60 years; new diagnosis = 60 years; relapse < 60 years; relapse = 60 years)
Allocation concealment (selection bias)	Unclear risk	Attempt to conceal allocation not described. It was not mentioned whether envelopes were opaque or sealed
Blinding of participants and personnel (performance bias) Participant	Unclear risk	It was unclear whether participants were blinded to the intervention, this was not reported in the published study
Blinding of participants and personnel (performance bias) Physician/Medical Staff	High risk	Bleeding assessors were not blinded to the intervention (additional data supplied by the author and reported in Estcourt 2013). Bleeding assessors included medical staff (nurses and physicians routinely involved with patient care)
Blinding of outcome assessment (detection bias) All outcomes	High risk	Bleeding assessors were not blinded to the intervention (additional data supplied by the author and reported in Estcourt 2013). Bleeding assessors were a mixture of medical staff (nurses and physicians routinely involved with patient care) and trained research nurses/research investigators
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient reporting to allow assessment
Selective reporting (reporting bias)	Unclear risk	No study protocol available, and outcomes not clearly stated
Other bias	Unclear risk	Insufficient information to assess
Protocol Deviation balanced?	High risk	In Arm 1 30/311 transfusions deviated from the protocol, whereas in Arm 2 only 7/457 transfusions deviated from the protocol. This affected 14/37 participants in Arm 1 and 6/41 participants in Arm 2 (P = 0.02)