Transfusion Medicine Bulletin
 Vol. 2, No. 2 - July 1999
Provided in conjunction with America's Blood Centers�.

Indications for Platelet Transfusion Therapy

The increasing demand for platelet transfusions coupled with the recognition of associated risks of infectious disease trans-mission and alloimmunization have focused attention on the need to assure that platelet transfusions are used appropriately. Ideally, practice guidelines for platelet transfusions should be based on well-designed, randomized, controlled trials (level I evidence). However, despite universal agreement that platelet transfusions provide hemostasis in thrombocytopenic patients, controversy persists as to the optimal dose of platelets to use, and the appropriate platelet count level at which to transfuse the non-bleeding patient.1


Platelet Transfusions in the Bleeding Patient

The beneficial effect of platelets in the control and prevention of thrombocytopenic hemorrhage was noted early in this century. In 1910, Duke showed that the platelets contained in transfused whole blood decreased the bleeding time and controlled bleeding.2 In 1962 Gaydos et al first documented the relationship between platelet count and the occurrence of hemorrhage in patients with leukemia.3 Hemorrhage was not observed until the platelet count fell to less than 50,000/uL. At counts under 5,000/uL, 90% of patients had some form of bleeding. Slichter later showed that blood loss in stable aplastic patients accelerated only when the count fell to less than 10,000/uL, and markedly increased at counts under 5,000/uL.4

From these data and others, an NIH-sponsored consensus development conference held in 1986 determined that at platelet counts of 50,000/uL or greater, bleeding is unlikely to be caused by thrombocytopenia.5 Severe, life-threatening hemorrhage is a risk when the count is under 5,000/uL. Between 5,000/uL and 10,000/uL, there is an increased risk of spontaneous hemorrhage. Between 10,000/uL and 50,000/uL there is an increased risk of hemorrhage during hemostatic challenge. Similar conclusions were reached by a conference held in the United Kingdom a decade later.6,7


Prophylactic Platelet Transfusions

Although 20,000/uL is often used as a "transfusion trigger" for platelet transfusions, the study most often cited in support of this never made this assertion and was widely misinterpreted.3,8 Moreover, the patient population on which the study was performed (acute leukemia) was almost certainly given aspirin-as the platelet function defect caused by this drug was only recognized a decade later. Gmur demonstrated that a more stringent platelet transfusion protocol, in which stable thrombocytopenic patients were transfused at 5,000/uL was a safe alternative.9 According to the protocol, the presence of fever or minor bleeding moved the platelet transfusion trigger up to 10,000/uL, and 20,000/uL was used for patients with coagulation disorders or heparin therapy.9 Each of three additional studies in which patients were randomized to receive prophylactic platelet transfusions at 10,000/uL or 20,000/uL found that the 10,000/uL platelet transfusion trigger resulted in fewer platelet transfusions being given with no excess bleeding.10-12


Platelet Dosing

"Standard" platelet doses vary widely. In many European centers a "standard" platelet dose may consist of a pool of 3 or 4 random donor platelet concentrates, whereas in many US centers, a pool of 6 to 10 units is common.13 In 1998 Norol et al performed a dose response study with platelet transfusions, using medium (4 - 6 X 1011), high (6 - 8 X 1011) and very high (>8 X 1011) doses of platelets in a group of 82 adults and children. They found that high and very high platelet doses resulted in greater post-transfusion increments and significant lengthening of the inter-transfusion interval (2.6 to 4.1 days).14 Although there was a decrease in transfusion events with the larger doses of platelets, there were apparently no differences in hemorrhagic events. An "optimal" dose of 0.07 X 1011 per kg was suggested for stable thrombocytopenic patients and 0.15 X 1011/kg for patients with clinical factors known to result in platelet consumption.11 This compares with an optimal dose of 6 X 1011 for an average size adult suggested by Strauss.15 These doses are in the same range as those proposed in the Platelet Transfusion Therapy Consensus Conference guidelines (1 platelet concentrate per 10 kg body weight),5 assuming that an average platelet concentrate contains 7.5 X 1010 platelets. Although these dose recommendations may produce optimal increments and inter-transfusion intervals, they have not been shown to be superior to smaller, more frequent doses in preventing bleeding.


Single Donor Platelets vs Pooled Platelet Concentrates

So-called "single donor" platelets or Platelets, Pheresis (i.e. a dose of platelets collected from a single donor using apheresis techniques) represent a reduction in donor exposures and risk of alloimmunization over pools of platelet concentrates made from whole blood collections. Other potential advantages of single donor platelets over pooled donor platelets are decreased risk of bacterial contamination and ease of handling, because the need to pool multiple platelet concentrates is eliminated.

Recently, modifications in collection protocols and equipment allow Platelets, Pheresis to be collected in a leukocyte-reduced state, obviating the need for post-collection filtration to remove contaminating white blood cells.

However, in the non HLA-alloimmunized patient, there are no data supporting single donor platelets over pooled platelet concentrates for prevention and control of hemorrhage. Moreover, in the recent TRAP study,16 pooled platelet concentrates were comparable to single donor apheresis platelets in reducing the rate of HLA alloimmunization if both were rendered leukocyte reduced by filtration. When patients are alloimmunized to HLA, single donor platelets are preferred since a hemostatic dose of platelets can be collected from a single HLA-matched, or platelet crossmatch-compatible donor.


An Example of a Guideline for Platelet Transfusion

Transfusions of platelets are appropriate to prevent or control bleeding associated with deficiencies in platelet number or function.5 A platelet concentrate produced from a unit of whole blood contains, on average, 7.5 X 1010 platelets and should increase the platelet count by 5 to 10 X 109/L (5,000 - 10,000/uL) in a 70 kg recipient. Apheresis platelet concentrates generally contain 3 - 6 X 1011 platelets, depending on local collection practice, and physicians should be cognizant of the doses provided in their community. A pool of 4 - 8 platelet concentrates or a single donor platelet usually is sufficient to provide hemostasis in a thrombocytopenic, bleeding patient. The efficacy of platelet transfusions can be influenced by other conditions in the recipient such as uremia, medications, concomitant coagulation disorders, alloimmunization to HLA, or platelet antigens, infections or splenomegaly.


  1. Platelet concentrate infusions can be administered to patients without further justification in the following circumstances:
  1. Active bleeding and platelet count less than 50,000/uL or platelet function defect *
  2. Non bleeding patients with:
  1. Temporary myelosuppression due to chemo-radiotherapy or underlying disease in a stable patient with platelet count less than 10,000/uL.9-12 Patients with temporary myelosuppression due to chemotherapy or underlying disease (e.g. leukemia) may require prophylactic transfusions at levels between 10,000 and 20,000/uL in the presence of fever or minor hemorrhagic signs.9
  2. Impending surgery or invasive procedures involving the CNS (including eye), or other critical areas in which microvascular bleeding is harmful and a platelet count of less than 100,000/uL.**
  3. Other surgery or invasive procedures where the operative field can be visualized or external pressure can be utilized to maintain hemostasis and a platelet count of less than 50,000/uL.**5
  4. Surgery or invasive procedure and documented qualitative platelet function defect.* (DDAVP (0.3ug/kg) should be considered for patients with von Willebrand disease or qualitative platelet function defects, e.g. cirrhosis or uremia).
  1. Open heart surgery patients with:
  1. Microvascular bleeding and platelet count less than 150K**
  2. Microvascular bleeding and non-diagnostic coagulation panel abnormality (e.g. post-operative chest tube drainage greater than 500 ml within 6 hours)
  3. Microvascular bleeding and platelet function defect*
  1. Active microvascular bleeding with a platelet count of less than 75K**


  1. Contraindications for Platelet Transfusions
  1. Platelet transfusions generally are contraindicated in thrombotic thrombocytopenic purpura (TTP) and immune thrombocytopenias including heparin-induced thrombocytopenia (HIT) unless life-threatening hemorrhage exists.
  2. Prophylactic platelet transfusions generally are not indicated for patients with chronic aplastic anemia or myelodysplastic diseases. Platelet transfusion for symptomatic thrombocytopenia (minor or moderate bleeding) is a more rational approach in such patients.5
  3. There is no role for prophylactic platelet transfusion in routine primary open heart surgery.17

*Platelet function defect should be documented by template bleeding time greater than two times the upper limit of normal, or greater than 12 minutes, or presumed defect based on medication ingestion, hypothermia, or instrumentation affecting platelet function.

**Platelet counts listed represent maximal levels; procedures have been performed at lower levels without hemorrhage.


Outcome Indicators

A platelet count should be obtained within 24 hours of transfusion. If refractoriness to platelet transfusion is suspected, it is recommended that a platelet count be performed within one hour after transfusion. Patients receiving HLA-matched or crossmatch-compatible platelets should have platelet counts performed ten minutes to six hours after the transfusion.18

A single unit of random platelets (i.e. derived from one unit of whole blood) should increase the platelet count 5,000 to 10,000/uL in a 70 kg recipient.


References

  1. Slichter SJ. Optimizing platelet transfusions in chronically thrombocytopenic patients. Semi hematol 1998;35:269-78.
  2. Duke WW. The relation of blood platelets to hemorrhagic disease. Description of a method for determining the bleeding time and the coagulation time. JAMA 1910;55:1185-92; reprinted in JAMA 1983;250:1201-9
  3. Gaydos LA et al. The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J M 1962;266:905-9
  4. Slichter SJ, Harker LA. Thrombocytopenia: Mechanism and man-agement of defects in platelet production. Clin Hematol 1978;7:523-39
  5. Consensus Conference, Platelet Transfusion Therapy. JAMA 1987;257:1777-80
  6. Norfolk DR, et al Consensus conference on platelet transfusion, Royal College of Physicians of Edinburgh, 27-28 November 1997. Br J Haematol 1998;101:609-17
  7. Contreras M, The appropriate use of platelets: an update from the Edinburgh Consensus Conference. Br J Haematol 1998;101(Suppl 1):10-12
  8. Beutler E. Platelet transfusions: the 20,000/uL trigger. Blood 1993;81: 1411-13
  9. Gmur J et al. Safety of stringent prophylactic platelet transfusion policy for patients with acute leukemia. Lancet 1991;338;1223-6
  10. Heckman KD et al. Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000 /uL Vs 20,000/uL. J Clin Onco 1997;15:1143-9
  11. Rebulla P et al: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. N Engl J Med 1997;337: 1870-5
  12. Wandt H et al. Safety and cost effectiveness of a 10 X 109/L trigger for prophylactic platelet transfusions compared to the tra-ditional 20 X 109/L: A prospective comparative trial in 105 pa-tients with acute myeloid leukemia. Blood 1998;91:3601-06
  13. Pisciotto PT et al. Prophylactic vs therapeutic platelet transfusion practices in hematology and/or oncology patients. Transfusion 1995;35:498-502
  14. Norol R. et al. Platelet Transfusion: a dose-response study. Blood 1998;92:1448-53
  15. Strauss, RG. Clinical perspectives of platelet transfusions: Defining the optimal dose. Clin Apheresis 1995;10:124-27
  16. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfu-sions. The trial to reduce alloimmunization to platelets study group. N Engl J Med 1997;337:1861-9
  17. Goodnough LT, et al. The variability of transfusion practice in coronary artery bypass surgery. JAMA 1991;265:86-90
  18. O'Connell B. et al. The value of 10-minute post-transfusion platelet counts. Transfusion. 1988;28:66-7
Blood Bulletin is issued periodically by America's Blood Centers�. Editor: D. Michael Strong, Ph.D. The opinions expressed herein are opinions only and should not be construed as recommendations or standards of ABC or its board of trustees. Publication Office: Suite 700, 725 15th St., NW, Washington, DC 20005. Tel: (202) 393-5725; Fax: (202) 393-1282; E-mail: [email protected]. Copyright America's Blood Centers, 1998-2000. Reproduction is forbidden unless permission is granted by the publisher. (ABC members need not obtain prior permission if proper credit is given.)

Revised: 02/16/05

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