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Stanworth S, et al. "A no-prophylaxis platelet-transfusion strategy for hematologic cancers". The New England Journal of Medicine. 2013. 368(19):1771-80.
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Clinical Question

In adult patients with hematologic malignancies, does a prophylactic platelet transfusion strategy as compared to no prophylaxis reduce bleeding episodes?

Bottom Line

Patients who underwent prophylactic platelet transfusion with a threshold of 10x10^9/mL had fewer bleeding episodes and a longer time to first bleeding episode when compared to a population not receiving prophylaxis.

Major Points

Patients with hematologic malignancies receiving chemotherapy or stem cell transplantation develop severe prolonged thrombocytopenia and often clinically significant bleeding. Prophylactic platelet transfusions are common practice, but the necessity of this and at what threshold has been contended. This trial aimed to address whether a no-prophylaxis approach was non-inferior to providing platelet transfusion prophylaxis at a restrictive threshold of 10 x10^9/L in reducing clinically significant bleeding episodes. Platelet transfusion prophylaxis reduced the number of overall bleeding events by 7%, however the vast majority being WHO grade 2 bleeding events. Overall there were few grade 3-4 bleeding episodes in this study and no significant difference was observed . Other important observations were that the time to the first bleeding episode was prolonged and the days with significant bleeding were reduced in the prophylaxis group, with the tradeoff of an increase in platelet dose transfusion requirements. Other prospective trials with similar study designs have come to similar conclusions that a prophylactic strategy does reduce bleeding events in this patient population [1][2], however the baseline level of bleeding in either strategy remains as high as 50% in this patient population.


  • There are no current guidelines that reflect the results of this trial.
  • ASCO guidelines published in 2001 suggest a prophylactic platelet transfusion threshold of 10 x 109/L for acute leukemia (grade IA) and hematopoietic stem cell transplantation (grade IIIB) [3].


  • Multicenter randomized open-label non-inferiority trial
  • N=600
    • N=301 no platelet transfusion prophylaxis
    • N=299 platelet transfusion prophylaxis if morning platelet count below 10 x10^9/L
  • Setting: 14 centres in the UK and Australia
  • Enrollment: August 2006 - August 2011
  • Mean follow-up: 30 days after randomization
  • Analysis: Intention to treat
  • Primary outcome: Bleeding events (WHO class 2-4) within 30 days of randomization


Inclusion Criteria

  • Undergoing chemotherapy or stem cell transplantation for a hematologic malignancy
  • Expected to have a platelet count under 50 x10^9/L for at least 5 days
  • Age 16 or older

Exclusion Criteria

  • Prior serious bleeding episode (WHO grade 3-4)
  • Bleeding episode (WHO grade 2) on current admission
  • Inherited hemostatic or thrombotic disorder
  • Requirement for therapeutic anticoagulation
  • Hematologic diagnosis of acute promyelocytic leukemia (APL)
  • Known platelet HLA antibodies

Baseline Characteristics

  • Mean age: 55 years
  • Male sex: 65%
  • Diagnosis
    • AML: 18%
    • ALL: 1%
    • CML: 1%
    • Lymphoma: 35%
    • Myeloma: 41%
    • Other: 4%
  • Treatment plan
    • Chemotherapy: 17%
      • Induction: 12%
      • Consolidation: 5%
    • Stem cell transplant: 83%
      • Autologous: 70%
      • Allogeneic: 13%
  • Mean platelet count: 44 x10^9/L


  • Central computer unblinded randomization
    • Experimental arm: no prophylactic platelet transfusion
    • Control arm: prophylactic platelet transfusion (1 adult dose) if daily platelet count was under 10 x10^9/L
  • Both arms received therapeutic platelet tranfusions for bleeding, invasive procedures or other reasons at clinician's discretion
  • Data collection
    • Inpatients: daily bleeding assessment forms administered by study staff
    • Outpatients: bleeding diaries followed by bleeding forms by study staff if bleeding events
  • Follow up for 30 days after randomization
    • Patients were followed and treated per protocol as inpatients or outpatients during this period
    • Taken off protocol if serious bleeding episode (WHO grade 3-4), with further transfusions at clinician's discretion


Comparisons are no prophylaxis vs. platelet transfusion prophylaxis groups

Primary Outcome

WHO grade 2-4 bleeding events (% of patients)
50% vs. 43%; absolute difference 8.4%, 90% CI 1.7-15.2; P=0.06

Secondary Outcomes

Number of days with bleeding episodes
1.7 vs. 1.2; ratio 1.52, 90% CI 1.14-2.03; P=0.004
Time to first bleeding episode (days)
17.2 vs. 19.5; ratio 1.3, 90% CI 1.04-1.64; P=0.02
Serious bleeding (WHO grade 3-4) (% of patients)
2 vs. <1%; ratio 6.05, 90% CI 0.73-279.72; P=0.13
Number of platelet units transfused per patient
1.9 vs. 3.2; ratio 0.67, 90% CI 0.55-0.82; P<0.001
Number of red cell units transfused per patient
3.0 vs. 2.8; ratio 1.24, 90% CI 1.04-1.47; P=0.02
Number of days with platelet count under 20 x10^9/L
6.9 vs. 6.1 days; ratio 1.18, 90% CI 1.08-1.30; P<0.001
Time to platelet recovery
14 days (both groups); range 10-18
Time in hospital
12 days (both groups); range 9-18

Subgroup Analysis

Significant bleeding in patients receiving chemotherapy
Receiving chemotherapy: 58 vs 38%; absolute difference 20%, 90% CI 7.9-32.2; P=0.04
Receiving autologous stem cell transplant: 47 vs. 45%, P=ns

Adverse Events

  • 6% in both groups (sepsis, respiratory depression)
  • 1 patient in prophylaxis group had transfusion adverse event (angioedema)


  • Large proportion of included patients (70%) were undergoing autologous stem cell transplant and had shorter periods of severe thrombocytopenia and less significant bleeding
  • Most of documented bleeding episodes were WHO grade 2 and included skin bleeding, which can be of heterogeneous significance
  • High number of patients in control group (43%) despite prophylaxis


Supported by grants from the National Health Service Blood and Transplant Research and Development Committee and the Australian Red Cross Blood Service. Funding agencies had no role in analysis or revision of manuscript. No commercial funding.

Further Reading

  1. Slichter SJ et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N. Engl. J. Med. 2010. 362:600-13.
  2. Wandt H et al. Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study. Lancet 2012. 380:1309-16.
  3. Schiffer CA et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J. Clin. Oncol. 2001. 19:1519-38.