Valerie Lyons, M.D., Fellow
Darrell J. Triulzi, M.D., Medical Director, Patient Transfusion Services
Platelet transfusion plays an important role in the support of
surgical, hematological, oncological, and transplant patients. Platelet refractoriness
continues to challenge clinicians. The threshold for transfusing these platelets to
patients continues to stimulate debate.
DESCRIPTION OF COMPONENTS
Platelets are prepared by donor whole blood centrifugation. A single
unit of random donor platelets (RDP) contains a minimum of 5.5 x 1010 platelets
suspended in 50 mL of plasma. Single donor platelets (SDP) are collected by apheresis and
contain a minimum of 3.0 x 1011 platelets suspended in 200-600 mL of plasma.
Leukoreduction (filtration) of platelets is frequently performed to remove the white blood
cells responsible for alloimmunization and CMV transmission.
Platelet products may be stored for 5 days with continuous agitation.
Once pooled, platelets outdate in 4 hours. Unused platelets must be returned to the blood
bank within 30 minutes of issue.
Platelets are ABO and Rh typed. ABO identical or compatible units are
preferred, but not required. In adults, ABO incompatible platelets may be used because the
volume of plasma in the product is usually not clinically significant. Apheresis units may
contain 350 mL of plasma, but passive transfer of antibodies rarely results in hemolysis.
Cross-matching is not necessary because the volume of RBCs is <2 mL in each platelet
component. However, 1 mL of RBCs is capable of causing alloimmunization to the D antigen.
Rh compatibility is therefore recommended in women of childbearing age and children to
prevent D antibody formation and potential hemolytic disease of the newborn. When Rh
incompatible transfusions are necessary, prophylaxis with Rh Immune Globulin (300m ) should be considered.
RDP is dosed at 1 unit per 10 kg of body weight. Stable patients who
are not refractory to platelet transfusions can be expected to have a platelet count
increase between 5,000-7,000 per unit. SDP is dosed at 1 apheresis unit per transfusion
episode, which is generally equivalent to 6-8 units of pooled RDP.
Platelet transfusions are indicated to control or prevent bleeding
associated with thrombocytopenia or platelet dysfunction. Guidelines for transfusing
patients with thrombocytopenia include:
- stable patients with platelet counts <10,000/m L
- patients with platelet counts <20,000/m L associated with
minor bleeding, fever or splenomegaly
- patients with platelet counts < 50,000/m L with
significant bleeding or undergoing an invasive procedure
- patients with documented platelet function abnormalities
Patients who have ingested aspirin products 48 hours or longer prior to
surgery are not at increased risk for bleeding due to platelet dysfunction.
CONTRAINDICATIONS AND PRECAUTIONS FOR PLATELET TRANSFUSIONS
- thrombotic thrombocytopenic purpura
- hemolytic uremic syndrome
- heparin induced thrombocytopenia
- platelet count >100,000/m L without evidence of platelet
- idiopathic thrombocytopenic purpura, unless bleeding is life threatening
- prophylactically following routine cardiac surgery
COMPLICATIONS OF TRANSFUSION
A febrile non-hemolytic transfusion reaction (FNHTR) is the most common
complication of platelet transfusion. FNHT reactions occur in approximately 1% of all
transfusion reactions. This increases to as much as 30% in patients who have multiple
transfusions. This is due to either recipient antibodies to donor WBCs or cytokines, i.e.,
IL-1, IL-6 and TNF in the platelet components that are released from the WBCs during
storage. Symptoms include an increase in temperature, chills/rigors, tachycardia, and
dyspnea. The reaction generally subsides within 30 minutes of stopping the transfusion.
Most FNHTR do not recur. Patients with recurrent FNHTR may benefit from leukoreduced
platelet components, particularly those leukoreduced prior to storage. A preexisting fever
is not a contraindication for platelet transfusion.
Allergic reactions occur in approximately 1% of platelet transfusions.
These reactions are generally mild and respond to antihistamines. Rare reactions to
platelets include bacterial sepsis, transfusion related acute lung injury, and transfusion
associated graft vs host disease. Fever and chills may be the presenting symptoms of acute
hemolysis, bacterial sepsis, or FNHTR. Therefore, it is important to stop the transfusion
and follow hospital policy for reporting transfusion reactions to the blood bank so that
an investigation can determine the cause of the reaction.
MANAGEMENT OF PLATELET REFRACTORINESS
Patients exposed to foreign platelet antigens may develop
alloantibodies that cause platelet immune refractoriness or alloimmunization. Previous
exposure occurs through pregnancy or transfusion. Alloimmunization is most often due to
patient antibodies against donor HLA class I antigens on the platelet surface. The risk of
alloimmunization is greatly reduced by leukoreduction, with no difference in risk between
leukoreduced RDP and SDP. To assess platelet response, a one hour post-platelet count is
necessary. Patients with an adequate platelet increment of >10,000-15,000/m L at one hour are unlikely to be alloimmunized and are more likely
to have poor platelet survival. This is due to clinical factors such as fever, sepsis,
bleeding, or splenomegaly. Such patients may benefit from larger doses or more frequent
platelet transfusions. A one hour post-platelet count increment of <10,000-15,000/m L, on two separate occasions, reflects a poor platelet response.
This may be due to immune-mediated platelet destruction. Patients suspected of
alloimmunization should have an HLA antibody screen. If positive, HLA antigen typing
should be performed. In patients who do not respond to HLA matched SDP, a trial of IVIG or
AMICAR may be beneficial. These patients may also benefit from ABO identical platelets.
The trend in transfusion medicine is toward pre-storage leukoreduction
of all blood components, including platelets. This advancement should significantly reduce
the number of FNHT reactions, as well as alloimmunization.
Although transmission of infectious disease through blood transfusion
has been markedly reduced, a small risk remains despite rigorous donor screening and
improved viral screening assays. The residual risk is the impetus for the development of
virally inactivated blood components and blood substitutes.
A method of viral inactivation used for platelets involves the use of
psoralens, a photochemical compound designed to inactivate lipid enveloped viruses.
(Photochemical inactivation is ineffective for non-enveloped viruses.) Psoralens react
with nucleic acid when exposed to ultraviolet light (UVA), producing an oxygen radical
which attacks the viral envelope. After decontamination, psoralen is removed from the
component. Preliminary studies have shown platelet yield and function to be adequate.
Potential problems include the safety risk associated with residual psoralen in platelet
components after treatment because psoralens are known mutagens1. A novel
psoralen, S-59, is currently under phase II clinical trials.
Platelet substitutes include thrombospheres and infusible platelet
membranes (IPM). These products improve bleeding times, albeit transiently (48 hours).
Their clinical utility seems to be in patients with thrombocytopenia and active bleeding.
These products augment the function of normal circulating platelets. They are not
thrombogenic. Heat inactivated human plasma is used in the manufacturing process of these
products. Therefore, they could theoretically transmit pathogens. However, the potential
advantages to these products include minimal viral and bacterial contamination as a result
of heat treatment, reduced alloimmunization, prolonged shelf life (36 months), and reduced
1. Pehtra JC. Laboratory Medicine 1994; 25:2.
2. Alung BM, et al. Transfusion 1997; 34: 866-76