Platelet Transfusion

As early as 1910, platelet transfusions were shown to have a beneficial effect in bleeding patients.18 In the 1960s, the development of plastic blood collection and storage bags allowed the ready concentration and storage of platelets. In 1964, investigators at the National Cancer Institute reported the efficacy of platelet transfusions in patients undergoing therapy for leukemia.18

Thrombocytopenia or decreased platelet function are common complications in patients with hemato-logic malignancies. Patients with decreased platelet number or function are at increased risk for hemorrhage. The normal lifespan of a platelet is approximately 9.5-10.5 days and approximately 4-5 days for the transfused platelet.101920 The splenic pool accounts

Table 104.1 Transfusion support for patients undergoing ABO-mismatched allogeneic HPC transplanation10

Phase I Phase II Phase III

First Next

Mismatch All choice choice All

Recipient Donor type components RBCs platelets platelets0 FFP components

AB O Minor Recipient O AB A; B; O AB Donor

AB A Minor Recipient A AB A; B; O AB Donor

AB B Minor Recipient B AB B; A; O AB Donor

O AB Major Recipient O AB A; B; O AB Donor

A AB Major Recipient A AB A; B; O AB Donor

B AB Major Recipient B AB B; A; O AB Donor

A B Minor & major Recipient O AB A; B; O AB Donor

B A Minor & major Recipient O AB B; A; O AB Donor

"Platelet concentrates should be selected in the order presented.10

HPC = hematopoietic progenitor (stem) cell; Phase I = from the time when the patient/recipient is prepared for HPC transplantation; Phase II = from the initiation of myeloablativle therapy until (1) for RBC - DAT is negative and antidonor isohemagglutinins are no longer detectable (i.e., the reverse typing is donor type) and (2) for FFPs - recipients erythrocytes are no longer detectable (i.e., the forward typing is consistent with donor's ABO group); Phase III = after the forward and reverse type of the patient are consistent with donor's ABO group. Beginning from Phase I all cellular components should be irradiated and leukocyte reduced. (From Ref 10, used with permission.)

for approximately 30-35% of the total body platelet mass.19 20 However, platelet lifespan decreases with increasing thrombocytopenia.21 A number of conditions in the patient with hematologic malignancy can potentially alter platelet numbers or function and can be associated with hemorrhage (Table 104.2). Platelets are generally indicated in bleeding patients with thrombocytopenia and/or platelet dysfunction. Platelet transfusion is generally not indicated in platelet-consumptive states (e.g., ITP or TTP) unless life-threatening bleeding is present.1921-23

Assuming a steady-state condition, there is a fairly direct linear relationship between the platelet count and the bleeding time as the platelet count decreases below 100,000/^L.21 Serious spontaneous hemorrhage usually does not occur until the platelet count falls below 10,000/^L, and this threshold is used by many physicians for the prophylactic administration of platelets.2425 Indeed, otherwise stable thrombocy-topenic patients can probably tolerate platelets counts in the 5000-10,000/^L range.22'23 A higher platelet transfusion "trigger" may be considered in those patients with underlying complications of fever or infection, other coagulation defects (e.g., hypofibrino-genemia), intracranial pathology, or other conditions that affect platelet function or number.19 22 23 Higher platelet counts are also warranted in those thrombocy-topenic patients undergoing invasive procedures or surgery. A platelet count of 50,000/^L is generally felt to be adequate for many surgeries, and a count in the 30,000-40,000/^L range is probably adequate for needle biopsies.19-23 26 However, only minimal evidence-based data is available as to what constitutes an optimal platelet count for various invasive procedures.

Platelet components for transfusion are prepared by two primary methods: platelet concentrates (random platelets) or platelets pheresis (apheresis platelets).1027 A single platelet concentrate is the unit of platelets obtained from an individual unit of randomly donated whole blood. A platelet concentrate contains at least 5.5 X 1010 platelets suspended in 40-70 mL of plasma. The approximate dose for platelet concentrates is 1 unit/ 10 kg of patient body weight. Thus, in the adult patient, the usual transfusable dose would be 4-6 units pooled as a single unit. As each platelet concentrate in a pooled product comes from an individual donor, each pooled transfusion exposes the recipient to that number of donors. Although the risk of transfusion-transmitted infection bears some relationship to the number of donor exposures, the increasing efficacy of donor screening and testing has decreased concerns in this area. Apheresis platelets are collected using cell separator technology, and 1 unit of apheresis platelets contains >3.0 X 1011 platelets suspended in 100-500 mL of plasma. Thus, in the adult patient, a unit of apheresis platelets contains one transfusable dose of platelets.

Table 104.2 Causes of thrombocytopenia and hemorrhage in patients with hematologic malignancies

Decreased platelet production Bone marrow injury or failure Chemotherapy/drugs Radiation Infection

Infiltration by carcinoma, leukemia, or lymphoma Marrow fibrosis Aplastic anemia

Hereditary quantitative disorders (e.g., May-Hegglin anomaly, Wiskott-Aldrich syndrome)

Nutritional deficiencies Vitamin B12 deficiency Folic acid deficiency Iron deficiency

Accelerated platelet destruction Immune causes Autoantibody

Immune/idiopathic thrombocytopenic purpura (ITP) Drug-related (e.g., quinidine, heparin) Alloantibody Anti-HLA antibodies Anti-platelet antibodies Post-ransfusion purpura (PTP)

Nonimmune causes Disseminated intravascular coagulopathy (DIC) Thrombotic thrombocytopenic purpura (TTP) Hemolytic-uremic Syndrome (HUS) Hemorrhage Infection

Impaired platelet function

Hereditary qualitative disorders (e.g., von Willebrand disease, Bernard—Soulier syndrome, Gray platelet syndrome)

Paraproteinemia (e.g., marcroglobulinemia, multiple myeloma)

Hepatic and/or renal failure Drugs

Disordered platelet distribution


Massive transfusion

Both preparations of platelets are stored at room temperature (20-24°C) for up to 5 days after collection. Room temperature storage has been shown to be conducive to the potential growth of contaminating bacteria and this complication has prompted blood banks to recently institute bacterial surveillance systems for platelets.28 Transfusion-transmitted bacterial infection should be considered in any patient who develops fever during a platelet transfusion, and appropriate cultures from the platelet product and the patient should be obtained.29 Novel platelet products, such as frozen platelets, cold-stored liquid platelets, and lyophilized platelets are in various stages of research and development.30

The response to platelet transfusion will depend on the patient's clinical status and can be assessed by (1) whether or not bleeding stops following transfusion and/or (2) measuring the posttransfusion platelet increment 10-60 min after transfusion. The corrected count increment (CCI) is one accurate measure of patient response to platelet transfusion.102026 The CCI is calculated as follows:

CCI = (posttransfusion count |>L] -pretransfusion count [^L]) X BSA(m2)/ (platelets transfused (X1011)), where BSA is the patient's body surface area (m2). The CCI is generally >7500 at 10-60 min after transfusion and >4500 at 24 h. The predicted platelet count increment (PPCI) and the percent platelet recovery (PPR) are also measures that have been used to evaluate the expected response to platelet transfusion.10,20,21,26 Others have more simply defined a poor response to prophylactic platelet transfusion as a failure to increase the platelet count above the "trigger" count prior to the transfusion.22,23

Platelet refractoriness is defined as the repeated failure (two or more times) to achieve a satisfactory response to platelet transfusions.22 23 Some authors have used two consecutive failures to achieve a satisfactory response as indicative of refractoriness, while others have used two to three failures (not necessarily consecutive) over a 2-week period. A number of immune and nonimmune factors can contribute to decreased platelet increments following transfusions (Table 104.2).19,22,23,31 The primary immune cause of platelet refractoriness is HLA alloimmunization, but its incidence has declined in recent years primarily due to the recognition that leukocyte reduction of blood components helps to prevent HLA alloimmunization. Nonimmune causes of platelet refractoriness, such as infection and splenomegaly, are important reasons associated with decreased platelet survival following transfusion. The Trial to Reduce Alloimmunization to Platelets (TRAP) Study Group found that for patients with AML, the incidence of HLA alloimmunization was 33% in those who had never been pregnant and 62% in those who had been pregnant.32 In patients who received leukocyte-reduced blood components, the incidence of HLA alloimmunization was 9% and 32%, respectively.32

The management of patients refractory to platelet transfusion can present many challenges.26 Platelets expressing HLA class I antigens and antibodies to these antigens is one of the primary causes of immunemediated platelet refractoriness. While HLA matching between the donor and the recipient has been the traditional approach to selecting platelets for alloimmunized patients, other methods, such as platelet crossmatching, have shown efficacy.26 Blood centers or blood banks that have established standardized platelet crossmatch techniques and procedures can often supply compatible apheresis platelets from their inventory in relatively short periods of time. As blood group A and B antigens are also expressed on platelets, ABO matching of platelets should also be considered in the patient who is refractory.26 33-35 In addition, anecdotal experience supports a trial of random, pooled platelet concentrates for the patient who has been receiving only apheresis platelets. A random mix of HLA types in a pooled platelet concentrate might "bypass" the patient's HLA antibodies. Other approaches to platelet refractoriness, such as the use of intravenous immunoglobulin (IVIG), intravenous Rh-immune globulin, or continuous platelet drips have not been supported by controlled studies.26 While there is no definitive or standardized approach to managing platelet refractoriness, our approach is presented in Figure 104.1.

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