Richard M. Kaufman, MD; Benjamin Djulbegovic, MD, PhD; Terry Gernsheimer, MD; Steven Kleinman, MD; Alan T. Tinmouth, MD; Kelley E. Capocelli, MD; Mark D. Cipolle, MD, PhD; Claudia S. Cohn, MD, PhD; Mark K. Fung, MD, PhD; Brenda J. Grossman, MD, MPH; Paul D. Mintz, MD; Barbara A. O'Malley, MD; Deborah A. Sesok-Pizzini, MD; Aryeh Shander, MD; Gary E. Stack, MD, PhD; Kathryn E. Webert, MD, MSc; Robert Weinstein, MD; Babu G. Welch, MD; Glenn J. Whitman, MD; Edward C. Wong, MD; Aaron A.R. Tobian, MD, PhD
Acknowledgment: The authors thank Theresa Wiegmann for her outstanding skill and dedication in guiding this project and Jacqlyn Riposo for her superb logistic support.
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589.
Requests for Single Reprints: Richard M. Kaufman, MD, Department of Pathology, Brigham and Women's Hospital, Blood Bank, Amory 260, 75 Francis Street, Boston, MA 02115; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Kaufman: Department of Pathology, Brigham and Women's Hospital, Blood Bank, Amory 260, 75 Francis Street, Boston, MA 02115.
Dr. Djulbegovic: University of South Florida, 3515 East Fletcher Avenue, Health/Therapy 1201, Health/College of Medicine 27, Tampa, FL 33612.
Dr. Gernsheimer: University of Washington, 1959 NE Pacific Street, Box 356330, Seattle, WA 98195.
Dr. Kleinman: University of British Columbia, 1281 Rockcrest Avenue, Victoria, British Columbia V9A 4W4, Canada.
Dr. Tinmouth: Clinical Epidemiology Research Unit, Ottawa Hospital Research Institute, General Campus, Box 201, Room 1812-C, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
Dr. Capocelli: Department of Pathology, Children's Hospital Colorado, B120, Aurora, CO 80045.
Dr. Cipolle: Christiana Care Health System, Surgical and Critical Care Associates, 4755 Ogletown-Stanton Road, Suite 1320, Newark, DE 19713.
Dr. Cohn: Department of Laboratory Medicine and Pathology, University of Minnesota, Mayo D242, Mayo Mail Code 609, 420 Delaware Street Southeast, Minneapolis, MN 55455.
Dr. Fung: Department of Pathology, University of Vermont and Fletcher Allen Health Care, 111 Colchester Avenue, Burlington, VT 05401.
Dr. Grossman: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, St. Louis, MO 63110.
Dr. Mintz: Division of Hematology Clinical Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993.
Dr. O'Malley: Department of Pathology, Wayne State University School of Medicine, 3990 John R. Road, Harper University Hospital, Detroit Medical Center, Detroit, MI 48202.
Dr. Sesok-Pizzini: Children's Hospital of Philadelphia, 5136 Main Hospital, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104-4399.
Dr. Shander: Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, 350 Engle Street, Englewood, NJ 07631.
Dr. Stack: Yale School of Medicine, Pathology and Laboratory Medicine Service/113, 950 Campbell Avenue, West Haven, CT 06516-2770.
Dr. Webert: Canadian Blood Services, 35 Stone Church Road, Suite 200, Ancaster, Ontario L9K 1S5, Canada.
Dr. Weinstein: University of Massachusetts Medical School, 55 Lake Avenue North, LA-113, Worcester, MA 01655.
Dr. Welch: University of Texas Southwestern Medical Center, 5161 Harry Hines Boulevard, CS5.112, Dallas, TX 75390-8855.
Dr. Whitman: Division of Cardiac Surgery, Johns Hopkins University, Suite 7107/Zayed Tower, 1800 Orleans Street, Baltimore, MD 21287.
Dr. Wong: Division of Laboratory Medicine, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010.
Dr. Tobian: Department of Pathology, Division of Transfusion Medicine, Johns Hopkins University, Carnegie 437, 600 North Wolfe Street, Baltimore, MD 21287.
Author Contributions: Conception and design: R.M. Kaufman, B. Djulbegovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth, B.J. Grossman, P.D. Mintz, D.A. Sesok-Pizzini, G.E. Stack, K.E. Webert, R. Weinstein, A.A.R. Tobian.
Analysis and interpretation of the data: R.M. Kaufman, B. Djulbegovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth, K.E. Capocelli, C.S. Cohn, M.K. Fung, B.J. Grossman, P.D. Mintz, B.A. O'Malley, D.A. Sesok-Pizzini, A. Shander, G.E. Stack, K.E. Webert, R. Weinstein, B.G. Welch, G.J. Whitman, E.C. Wong, A.A.R. Tobian.
Drafting of the article: R.M. Kaufman, B. Djulbegovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth, K.E. Capocelli, M.D. Cipolle, D.A. Sesok-Pizzini, A. Shander, B.G. Welch, A.A.R. Tobian.
Critical revision of the article for important intellectual content: R.M. Kaufman, B. Djulbegovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth, K.E. Capocelli, M.D. Cipolle, M.K. Fung, B.J. Grossman, P.D. Mintz, B.A. O'Malley, D.A. Sesok-Pizzini, A. Shander, K.E. Webert, R. Weinstein, G.J. Whitman, E.C. Wong, A.A.R. Tobian.
Final approval of the article: R.M. Kaufman, B. Djulbegovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth, K.E. Capocelli, C.S. Cohn, M.K. Fung, B.J. Grossman, P.D. Mintz, B.A. O'Malley, D.A. Sesok-Pizzini, A. Shander, K.E. Webert, R. Weinstein, B.G. Welch, E.C. Wong, A.A.R. Tobian.
Provision of study materials or patients: B. Djulbegovic.
Statistical expertise: B. Djulbegovic.
Administrative, technical, or logistic support: M.K. Fung, A.A.R. Tobian.
Collection and assembly of data: B. Djulbegovic, G.E. Stack, A.A.R. Tobian.
The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients.
These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence)
The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence)
The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence)
The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence)
The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence)
The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence)
Table 1. Approximate Per-Unit Risks for Platelet Transfusion in the United States
Appendix Table 1. Panel Members' Conflicts of Interest
Appendix Table 2. Search Strategy Used for Systematic Review of the Literature
Table 2. Summary of the Modified WHO Bleeding Scale
Appendix Table 3. Prophylactic Platelet Transfusion Versus No Prophylactic Platelet Transfusion in Therapy-Induced Hypoproliferative Thrombocytopenia
Appendix Table 4. Higher Versus Lower Platelet Count Thresholds for Prophylactic Platelet Transfusions in Therapy-Induced Hypoproliferative Thrombocytopenia
Appendix Table 5. Standard-Dose Versus Low-Dose Prophylactic Platelet Transfusions in Therapy-Induced Hypoproliferative Thrombocytopenia
Appendix Table 6. High-Dose Versus Standard-Dose Prophylactic Platelet Transfusions in Therapy-Induced Hypoproliferative Thrombocytopenia
Appendix Table 7. Prophylactic Platelet Transfusion for Central Venous Catheter Placement
Appendix Table 8. Prophylactic Platelet Transfusion Versus No Prophylactic Platelet Transfusion for Lumbar Puncture
Appendix Table 9. Prophylactic Platelet Transfusion Versus No Prophylactic Platelet Transfusion for Surgery
Appendix Table 10. Platelet Transfusion Versus No Platelet Transfusion for Coronary Artery Bypass Graft Surgery
Appendix Table 11. Platelet Transfusion Versus No Platelet Transfusion in Patients Who Were Thrombocytopenic and Had a Traumatic Brain Injury
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James P. AuBuchon, Yanyun Wu
Puget Sound Blood Center
December 4, 2014
What is a "Low-Dose" Platelet Unit?
We commend the authors of these platelet guidelines for their careful evaluation of the literature and development of rational indications for platelet transfusion.We note that the guideline references the results of the Platelet-Dose (PLADO) Study showing that “low dose” platelets yield equivalent prophylactic protection against Grade 2 or greater hemorrhage in hospitalized patients with therapy-induced hypoproliferative thrombocytopenia. The guideline refers to this transfusion dose as a “half unit” of apheresis platelets, but simply dividing a unit into two halves may provide suboptimal dosing for many patients.The content of “low-dose” platelet units in the PLADO Study was defined as 1.1 x 1011/m^2. In the US, the average male body surface area (BSA) is 1.7 m2, and for females it is 1.4 m2.1 The FDA-required minimum is 3.0 x 10^11 platelets in an apheresis platelet unit; in the current era, when the majority of such units are collected as “multiple” units from a single donor, the content is usually found to be 3.5 – 4.0 x 10^11 platelets; in our center, the median is 3.7 x 10^11, and the average is 3.8 x 10^11 platelets.Half of an “average” unit would therefore provide the intended “low-dose” prophylactic platelet transfusion only if the patient’s BSA were less than 1.7m^2. This would correspond to a 5 foot 8 inch 135 pound male recipient (BMI: 22 kg/m^2), or a 5 foot 5 inch 145 pound female (BMI: 24.1 kg/m^2). For larger patients, and for the half of units below the median of 3.7 x 10^11 platelets in the full unit, the dose of platelets would be less than expected.Therefore, although the size of an adult platelet recipient is usually not taken into account when selecting units for transfusion, the size of the recipient and the actual content of the unit may be more important if lower doses are utilized. If a standard “low-dose” platelet were to be created, it might more safely be sized closer to two-thirds the average apheresis unit so as to avoid difficulties in unit selection and inadvertent (and unsuspected) under-dosing in larger patients. The effects of prophylactic platelet transfusion with doses below the “low-dose” definition used in the PLADO study have not been examined in clinical trials.James P. AuBuchon, MD, FCAP, FRCP(Edin)Yanyun Wu, MD, PhDPuget Sound Blood CenterSeattle, WashingtonReference1. McDowell MA, Fryar CD, Ogden CL, Flegal KM. Anthropomorphic reference data for children and adults: United States, 2003-2006. National Health Statistics Report. 10:1-45, October 22, 2008. DHHS Publication No. (PHS) 2009-1250. Centers for Disease Control and Prevention, Hyattsville, MD, 2008.
Richard Kaufman, MD
Brigham and Women's Hospital
March 18, 2015
In Reply: What is a "Low-Dose" Platelet Unit?
We wish to thank Drs. AuBuchon and Wu for raising the issue of the definition of a “low dose” platelet unit. We agree that for larger recipients, transfusing “half” apheresis platelet units may not provide a platelet dose equal to what was used in the low dose arm of the PLADO trial in every case. We think that this is an important point for blood banks to consider. The specific language chosen for the AABB clinical practice guideline on platelet transfusion was a simplification, and this was intentional. The primary target audience of our guideline was front-line clinicians who order platelets, rather than blood banks that prepare platelets.
The PLADO manuscript states:
“For a typical adult, the medium dose was equivalent to the standard dose currently used in clinical practice. The low dose was half the medium dose, and the high dose was twice the medium dose”(1).
This was also a simplification. But it concisely conveyed what “low dose” meant in the context of the PLADO trial: for a typical adult, “about half” of an apheresis unit, as opposed to e.g. “about 2%” of an apheresis unit. Similarly, we sought to express the concept of low dose platelets in terms that would be meaningful to prescribing clinicians. The alternative would have been to recommend doses of, for instance, 1.1 X 10^11 platelets/m^2 to providers who typically order platelets by the unit without considering recipient body surface area, and who may not be aware that the minimum required platelet content for an apheresis unit is 3 X 10^11 platelets (2).
Additionally, the acceptable range for a low dose platelet transfusion in the PLADO study was 1.1 X 10^11 platelets/m^2 ± 25% (1), a wider range than that cited by AuBuchon and Wu. A dose of 1.1 X 10^11 platelets per m^2 body surface area may not constitute an absolute lower limit of safety based on PLADO. Among 1223 acceptable “low dose” platelet transfusions given to adults in the PLADO study, 572 (46.8%) were in the range of 0.825 X 10^11 to 1.1 X 10^11 platelets/m^2 (Assmann SF, personal communication.) To date, hospitals have demonstrated relatively little interest in adopting low dose platelets. While a “3 doses from 2 apheresis units” strategy as suggested by AuBuchon and Wu might be a reasonable manufacturing approach, splitting apheresis units in half would be a simpler approach.
Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet Transfusion: A Clinical Practice Guideline From the AABB. Ann Intern Med. 2015;162:205–213. doi: https://doi.org/10.7326/M14-1589
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Published: Ann Intern Med. 2015;162(3):205-213.
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