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2382 Part XIII: Transfusion Medicine Chapter 139: Preservation and Clinical Use of Platelets 2383

TABLE 139–1. General Criteria for World Health transfusion threshold compared to the higher transfusion thresholds. A
platelet transfusion threshold of less than 10 × 10 /L in stable patients
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Organization Bleeding Grade Categories Including Grade 2a has been recommended by both the American Association of Blood
Modification Banks (AABB) and Sanquin Blood Supply in 2014. Patients with
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Grade 1 Grade 2 Grade 3 Grade 4 active infection, fever, or who are bleeding may require higher transfu-
Minor Bleeding requires Bleeding Bleeding sion thresholds. 23
bleeding intervention or requires red that is fatal
treatment, e.g., nasal cell transfu- or life- Prophylactic Versus Therapeutic Platelet Transfusions
packing, bladder sion related to threatening WHO Grade 4 bleeding that causes life threatening hemorrhage or
irrigation, platelet treatment of death is a rare occurence. Several prospective trials have evaluated
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transfusion or bleeding the potential bleeding risk of withholding platelet transfusions until
medications, to treat or WHO Grade 2 bleeding occurs with the assumption that Grade 4
bleeding Significant bleeding would very rarely take place before Grade 2 bleeding was
Grade 2a: Grade 2 intervention to observed. A trial comparing a therapeutic-only transfusion strategy
bleeding excluding treat bleeding, versus prophylactic platelet transfusion given routinely for a morn-
skin manifestations e.g., endoscopy ing platelet count of less than 10 × 10 /L in 396 patients who were
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or surgery undergoing intensive chemotherapy for acute myeloid leukemia
(AML) (n = 190) or autologous HSCT patients (n = 201) monitored
patients for bleeding according to the WHO bleeding scale. Despite
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randomization to the therapeutic-only transfusion arm, 30 percent of
bleeding over a wide range of platelet counts, indicating that their excess patients were transfused with platelets prophylactically and 22 percent
bleeding risk may be a result of factors other than just platelets. for extended petechiae or bruising. The primary end point (number
of platelet transfusions) was 33.5 percent higher in the prophylactic
Platelet Transfusion Therapy in the Patient with Hematologic transfusion group. However, Grade 4 bleeding occurred in 14 patients
Malignancy with AML in the therapeutic-only transfusion arm, two of which were
Hematologic malignancies accounted for approximately 9 percent of all fatal cerebral hemorrhages. No Grade 4 bleeding occurred in patients
new cancers reported in the United States in 2012. More aggressive undergoing autologous HSCT. In the Therapeutic or Prophylactic
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therapies have led to increased 5-year survival rates, but also resulted Platelet Study (TOPPS), 600 patients with acute leukemia, lymphoma,
in substantial increases in the demand for platelet transfusions to sup- or myeloma undergoing chemotherapy alone (n = 98), autologous
port extended periods of marrow failure. The disturbance of endothelial HSCT (n = 411) or reduced-intensity allogeneic HSCT (n = 74) were
integrity that frequently occurs with these therapies and the associated randomized to a therapeutic-only or prophylactic transfusion strat-
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inflammation can induce hemorrhage in periods of thrombocytopenia. egy. Patients in the therapeutic-only transfusion arm had a signifi-
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Mucositis, GVHD, infection, and organ dysfunction can all increase cantly shorter time to their first Grade 2 or greater bleeding event,
daily platelet consumption and negatively affect posttransfusion platelet and they also experienced more bleeding overall. Although both of
increments and life span. Multiple strategies have been evaluated for these studies showed a decrease in the number of platelet transfusions
maximizing the hemostatic effect of platelets while minimizing platelet administered in the therapeutic-only arms compared to the prophy-
use. Prospective randomized controlled trials have evaluated the rela- lactic transfusion arms, and there were no differences in the number
tive safety of different platelet count thresholds for transfusion, whether of red cell transfusions, this strategy cannot be considered safe in the
platelets should be transfused prophylactically or can be administered majority of patients undergoing HSCT or induction chemotherapy for
therapeutically at the first sign of bleeding, and optimal platelet dose for acute leukemia.
platelet transfusion.
Platelet Dose
Platelet Transfusion Threshold It has been estimated that 4.8 × 10 platelets are used daily to maintain
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Prophylactic platelet transfusions were shown to decrease the incidence endothelial integrity in an individual weighing 70 kg with an estimated
of bleeding into vital organs noted at autopsy of leukemia patients as blood volume of 5 L. As long as this minimal number of platelets is
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early as 1966, and have become an integral part of treatment regimens provided, higher platelet doses do not appear to decrease the incidence
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for hematologic malignancy. However, maintaining platelet counts may of bleeding in patients with hematologic malignancy. The PLADO trial
be difficult owing to very short platelet survivals in severely throm- studied more than 1200 patients with hematologic malignancies who
bocytopenic patients. 2,6,15 Several prospective randomized platelet were receiving prophylactic platelet transfusions at a threshold of less
transfusion trials have shown no differences in spontaneous bleeding than 10 × 10 /L during chemotherapy or HSCT. Patients were ran-
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events when patients are transfused at platelet counts below 10 × 10 /L domized to one of three platelet doses; the accepted current standard
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versus 20 × 10 /L 16–18 or even versus 30 × 10 /L, and a threshold for dose of 2.2 × 10 platelets/m (expected to be equivalent to four to six
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transfusion as low as 5 × 10 /L may be safe. In one study, 85 patients pooled platelet concentrates or one apheresis platelet [AP] collection
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with acute leukemia were randomized to receive prophylactic platelet in most adults), a low dose of 1.1 × 10 /m (half of standard), or a
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transfusions when their platelet count fell to 20 × 10 /L, 10 × 10 /L, high dose of 4.4 × 10 /m (twice standard). WHO Grade 2 bleeding
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or 5 × 10 /L. An aliquot of each patient’s red cells were labeled with was common in all patients and similar at all doses. Seventy percent
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radioactive chromium and daily stool collections were performed to of patients had at least one episode of Grade 2 or greater bleeding
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quantify the amount of gastrointestinal mucosal bleeding. There were with no significant differences among the dose groups (71 percent, 69
no differences in stool blood loss, red blood cell transfusion rates, or percent, and 70 percent, respectively). Grade 3 bleeding occurred in 8
incidence of bleeding events among the three study arms. However, percent of patients and Grade 4 in only 2 percent with no differences
there was a significant decrease in both the frequency and number of among the groups. Only one hemorrhagic death occurred, in a patient
platelet transfusions required among patients randomized to the lower in the high-dose group. By treatment category, 79 percent of patients
Kaushansky_chapter 139_p2381-2392.indd 2383 9/18/15 2:22 PM