Review question
We evaluated the evidence about whether low-dose platelet transfusions (platelet transfusions containing a lower number of platelets (1.1 x 1011/m2 ± 25%)) given to prevent bleeding in people with low platelet counts were as effective and safe as standard-dose (2.2 x 1011/m2 ± 25%) or high-dose platelet transfusions (platelet transfusions containing a larger number of platelets (4.4 x 1011/m2 ± 25%)) given regularly to prevent bleeding (prophylactically). Our target population was children and adults with blood cancers who were receiving intensive chemotherapy treatments or stem cell transplantation.
Background
Children and adults with blood cancers may have low platelet counts because of their underlying cancer. Blood cancers may be treated with chemotherapy and stem cell transplantation, and these treatments can also cause low platelet counts.
Platelet transfusions are used to prevent or treat bleeding in people with low platelet counts. Platelet transfusions are given to prevent bleeding when the platelet count falls below a prespecified threshold platelet count (for example 10 x 109/L). Platelet transfusions are given to treat bleeding when the patient has bleeding (such as a prolonged nosebleed or multiple bruises).
Study characteristics
The evidence is current to July 2015. In this update, we identified seven randomised controlled trials that compared different doses of prophylactic platelet transfusions given to prevent bleeding in people with blood cancers. We reviewed seven randomised controlled trials with a total of 1814 participants. These trials were conducted between 1973 and 2015. Six of these trials were conducted during one course of treatment (chemotherapy or a stem cell transplant); the seventh trial was conducted over a longer time period involving several courses of chemotherapy and could not be included in any of the analyses. One trial contained only children, two trials contained adults and children, and four trials contained only adults.
Five of the seven studies reported funding sources. None of the studies that reported funding sources were industry sponsored.
Key results
Overall, platelet transfusions containing smaller number of platelets appeared to have similar effects to platelet transfusions containing larger numbers of platelets. There was no difference in the number of participants who bled, the frequency of bleeding, or the severity of bleeding between participants receiving a low, standard, or high number of platelets within each platelet transfusion. This was unaffected by the participant's age (children or adults), underlying treatment, or diagnosis.
There was a clear increase in the number of platelet transfusion episodes in the low-dose group, compared to the standard-dose and high-dose groups. A high-dose transfusion strategy did not lead to a decrease in the number of transfusion episodes in the largest study.
A high-dose transfusion strategy may lead to an increase in transfusion-related adverse events compared to a standard-dose or low-dose strategy.
None of the seven studies reported any quality-of-life outcomes.
Quality of the evidence
The evidence for most of the findings was of low or moderate quality because the studies were at risk of bias or the estimates were imprecise.
In haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found no evidence to suggest that a low-dose platelet transfusion policy is associated with an increased bleeding risk compared to a standard-dose or high-dose policy, or that a high-dose platelet transfusion policy is associated with a decreased risk of bleeding when compared to a standard-dose policy.
A low-dose platelet transfusion strategy leads to an increased number of transfusion episodes compared to a standard-dose strategy. A high-dose platelet transfusion strategy does not decrease the number of transfusion episodes per participant compared to a standard-dose regimen, and it may increase the number of transfusion-related adverse events.
Findings from this review would suggest a change from current practice, with low-dose platelet transfusions used for people receiving in-patient treatment for their haematological disorder and high-dose platelet transfusion strategies not being used routinely.
Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.
This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses.
To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT).
We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015.
Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 x 1011/m2 ± 25%, standard dose 2.2 x 1011/m2 ± 25%, high dose 4.4 x 1011/m2 ± 25%).
We used the standard methodological procedures expected by The Cochrane Collaboration.
We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT).
Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.
Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence).
Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference -0.17, 95% CI -0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants).
Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% CI 0.82 to 1.77; low-quality evidence); or high-dose and standard-dose groups (one study; 855 participants; RR 1.11, 95% CI 0.73 to 1.68; low-quality evidence).
Two studies reported the time to first bleeding episodes; we were unable to perform a meta-analysis. Both studies (959 participants) individually found that the time to first bleeding episode was either the same, or longer, in the low-dose group compared to the standard-dose group. One study (855 participants) found that the time to the first bleeding episode was the same in the high-dose group compared to the standard-dose group.
Three studies reported all-cause mortality within 30 days from the start of the study. There was no difference in all-cause mortality between treatment arms (low-dose versus standard-dose: three studies; 1070 participants; RR 2.04, 95% CI 0.70 to 5.93; low-quality evidence; low-dose versus high-dose: one study; 849 participants; RR 1.33, 95% CI 0.50 to 3.54; low-quality evidence; and high-dose versus standard-dose: one study; 855 participants; RR 1.71, 95% CI 0.51 to 5.81; low-quality evidence).
Six studies reported the number of platelet transfusions; we were unable to perform a meta-analysis. Two studies (959 participants) out of three (1070 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a standard-dose. One study (849 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a high-dose strategy. One study (855 participants) out of three (1007 participants) found no difference in the number of platelet transfusions between the high-dose and standard-dose groups.
One study reported on transfusion reactions. This study's authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events.
None of the studies reported quality-of-life.