Threshold for Transfusion

Several studies have evaluated prophylactic platelet transfusion thresholds for patients with thrombocytopenia because of myelosuppressive therapy. Most patients undergoing progenitor cell transplantation received prophylactic platelet transfusions when their platelet counts were 10-20 x 109/L, indicating that a threshold of 20 x 109/L was most common (33) (Fig. 1). Only 9% of hemorrhagic events reported in this study occurred when platelet counts were <10 x 109/L.

Two prospective, randomized studies evaluated the relative merits of platelet transfusion thresholds of 10-20 x 109/L for patients with leukemia receiving chemotherapy

30-39

40-49

50-99

30-39

40-49

50-99

Morning Platelet Count x 109/L

Fig. 1. Percentage of patient days in which platelet transfusions were administered to patients with a range of morning platelet counts. In a multicenter study of patients undergoing autologous (n = 456) or allogeneic (n = 335) hematopoietic stem cell transplantation, nearly two-thirds of patients received prophylactic platelet transfusion when platelet counts were between 10 and 20 X 109/L.

(34,35). Lower transfusion threshold is associated with 22% fewer platelet transfusions (34). In an analysis of hemorrhagic complications, number of red blood cell transfusions, duration of hospital stay, and mortality, no differences were seen between the two thresholds. In a second study, a platelet threshold of 10 x 109/L was safe and effective compared with the 20 x 109/L threshold (35). Of 105 patients in this study, 2 (1.9%) died of hemorrhagic complications, each with a platelet count >30 x 109/L at the time of death.

Standards of the American Association of Blood Banks require that 75% of aphere-sis products contain >3 x 1011 platelets and that 75% of platelet concentrates contain >5.5 x 1010 platelets (36); however, no consensus exists for a standardized platelet dose. Table 4 presents the platelet doses used in several recent studies and shows the broad range of platelet doses used. In an evaluation of our own hospital-based aphere-sis program, 32% of products contained 3-4 x 1011 platelets and 32% of products contained 4-5 x 1011 platelets (37). Leukoreduction of apheresis platelets or platelet concentrates results in approx 20% loss of platelets (25).

Mathematical modeling has suggested that low-dose platelet therapy would be more beneficial in patients with thrombocytopenia who are receiving prophylactic platelet transfusions (38). The relationship between patient platelet count and in vivo platelet survival is illustrated in Fig. 2 (39). A fixed platelet requirement for hemostasis is estimated to be 7.1 x 109/L/d, and platelet consumption above this threshold is mainly a result of

Table 4

Platelet Doses Used in

Studies

Study

Platelet dose (x 1011/mm3)

TRAP study (25) Six unmodified pooled platelet concentrates Six F-PC filtered units6 One F-AP filtered unitc Goodnough et al. (37) One apheresis unit Rubella et al. (34) Apheresis

Pooled concentrates

b F-PC filtered, pooled platelet concentrates from random donors. c F-AP filtered platelets obtained by apheresis from single random donors. d Median (range).

a Median-SD.

b F-PC filtered, pooled platelet concentrates from random donors. c F-AP filtered platelets obtained by apheresis from single random donors. d Median (range).

Fig. 2. The relationship between patient platelet count and in vivo platelet survival. Survival data are points obtained from normal individuals and patients with hypoplastic or aplastic marrows (18) and patients with myeloproliferative disease.

platelet senescence. For patients who become thrombocytopenic owing to myeloablative therapy, platelet survival decreases with increasing severity of thrombocytopenia. Thus, platelet survival is 5-7 d in patients with platelet counts in the normal range, but only 1-2 d in patients with platelet counts of 10-20 x 109/L—levels at which most patients with thrombocytopenia are maintained to prevent hemorrhage.

A mathematical model predicts that low-dose platelet therapy provides a 22% decrease in donor exposures (and total number of platelets) while maintaining patients at a platelet threshold >10 x 109/L (38), even with a shorter transfusion-free interval and a greater daily relative risk of receiving additional transfusions (40).

A randomized clinical trial addressed the issue of high-dose platelet therapy (41). Standard, high, and very high platelet doses (4.6 x 1011, 6.5 x 1011, and 8.9 x 1011 platelets, respectively) were administered to patients receiving prophylactic platelet transfusions. The high-dose and very high-dose cohorts had greater incremental increases in platelet count and prolonged time to next transfusion than the standarddose cohort. Interestingly, the platelet half-life estimate (i.e., slopes) for the patient cohorts was not different for post-transfusion platelet counts ranging from approx 50-110 x 109/L (Fig. 3). These data suggest that the in vivo platelet life span of transfused platelets cannot be normalized in this setting, even at higher platelet counts. Further studies of platelet transfusion dosage strategies are needed.

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