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Transfusion of blood and blood components has been a routine practice for more than half a century. The rationale
supporting this practice is that replacement of blood loss should be beneficial for the patient. This assumption has
constituted the underpinning of transfusion medicine for many decades. Only over the past 20 years, we have seen a
more concerted effort to answer very basic questions regarding the value of transfusion therapy. An assessment of the
value of transfusion based on well-designed and appropriately powered randomized, controlled trials is the first step in
optimizing transfusion practices. Systematic reviews provide the second step by building the knowledge base
necessary to assess the impact of transfusion practice on patient outcomes. The third step is the development of
clinical practice guidelines, and this occurs when systematic reviews are interpreted by individuals with expertise in
transfusion medicine. Such guidelines are typically supported by professional organizations and/or health authorities.
Implementation of clinical practice guidelines can be challenging, especially in an area as heterogeneous as
transfusion medicine. However, clinical practice guidelines are necessary for the practice of evidence-based medicine,
which optimizes patient care and improves patient outcomes. This review focuses on clinical practice guidelines for
transfusion of three blood components: RBCs, platelets and plasma. In addition, we provide the approach used to
implement clinical practice guidelines at our own institution.
MODS indicates multiple-organ dysfunction syndrome; FOCUS, Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical hip Fracture Repair; RCT, randomized, controlled trial; TRICC,
Restrictive transfusion strategy is
inability to walk at 60 d
decreases transfusion
with acute myocardial
Guidelines for RBC transfusion
requirements without
The development of clinical practice guidelines for RBC transfusion
has been challenged by a limited availability of high-quality evidence
to support practice recommendations. There is general agreement that
outcomes
follow-up
RBC transfusion is typically not indicated for hemoglobin (Hb) levels
of 10 g/dL and that transfusion of RBCs should be considered when
Hb is 7 to 8 g/dL depending on patient characteristics.6,7 The
decision to transfuse RBCs should be based on a clinical assessment of
the patient that weighs the risks associated with transfusion against the
complications
dysfunction
atic review of randomized, controlled trials evaluating transfusion
thresholds.8 (selected trials are presented in Table 1) These guide-
lines recommend adhering to a restrictive transfusion strategy and
consider transfusion when Hb is 7 to 8 g/dL in hospitalized, stable
patients. This strong recommendation is based on high-quality
Stable, critically ill children Restrictive (Hb 7 g/dL) vs Death within 28 d of randomization,
evidence from clinical trials comparing outcomes in liberal versus
Stable, critically ill patients Restrictive (Hb 7 g/dL) vs Death within 30 d of randomization
Adult patients with severe Restrictive (Hb 7 g/dL) vs Death within 45 d of randomization
Adults 50 y of age with Restrictive (Hb 8 g/dL) vs Death or inability to walk across a
development or progression of
restrictive transfusion strategies in this patient population.9-11 A
restrictive transfusion strategy is also recommended for patients Primary outcome(s)
with preexisting cardiovascular disease. In this population, transfu-
room at 60 d follow-up
sion should be considered when Hb levels are 8 g/dL or for
symptoms such as chest pain, orthostatic hypotension, tachycardia
unresponsive to fluid resuscitation, or congestive heart failure.8 This
weak recommendation is based on moderate-quality evidence due to
Transfusion Requirements in Critical Care; and TRIPICU, Transfusion Requirements in Pediatric Intensive Care Unit.
Table 1. Selected recent multicenter randomized, controlled trials informing RBC guidelines
MODS
limited clinical trial data directly addressing this population of
patients. Additional clinical practice guidelines exist that specify Hb
targets for critical care patients with conditions including sepsis,
ischemic stroke, and acute coronary syndrome.12,13
Transfusion threshold
upper gastrointestinal
bleeding
(2016)
(838)
(637)
(921)
RCT
RCT
RCT
RCT
(N)
(FOCUS)
Hematology 2013
thrombocytopenia; plt and Primary outcome was
RBC transfusion met by 49.2% in the
requirements; interval low-dose group vs
between transfusions; 51.7% in the high-dose
modeling of bleeding risk group (RR 1.052;
over the next 24 h 95% CI, 0.74-1.5). It is
unclear if the higher rate
of grade 4 bleeding in the
low-dose arm (5.2% vs
0%) was due to chance
or represented a real
difference
Slichter et al21 (PLADO) RCT (1272) Inpatients with HT due to Low-dose arm (1.1 1011 Occurrence of grade 2 or The highest grade of bleeding; There was no difference in
HSCT or chemotherapy and plt/m2) vs medium-dose higher bleeding total number of plt grade 2 or higher
weight 10-135 kg; no age arm (2.2 1011 plt/m2) transfused; number of plt bleeding at doses
limitations; plt transfusion if vs high-dose arm transfusions between 1.1 1011 and
plt 10 000/L (4.4 1011 plt/m2) 4.4 1011 plt/m2.
Low-dose arm resulted in
decreased number of plt
transfused but increased
number of transfusions
Josephson et al20 RCT: pediatric Inpatients with HT due to As above; 4 age groups (0-5 Occurrence of grade 2 or The highest grade of bleeding; Plt dose did not predict
(PLADO pediatric) (198), adult HSCT or chemotherapy and y; 6-12 y, 13-18 y and higher bleeding total number of plt bleeding for any age
(1044) weight 10-135 kg; no age adults) transfused; number of plt group. Children had a
limitations; plt transfusion if transfusions significantly higher risk of
plt 10 000/L; age group grade 2 or higher
analysis of PLADO data bleeding than adults and
(children 18 y) more days with grade 2
or higher bleeding.
Pediatric subjects were
at higher risk of bleeding
over a wide range of plt
counts
641
Table 3. Continued
642
Study Design (N) Population Study groups Primary outcome(s) Secondary outcome(s) General conclusions
Prophylactic vs therapeutic
plt transfusion
Wandt et al24 RCT (391) AML or auto HSCT patients; Therapeutic strategy (either The number of plt Clinically relevant bleeding Therapeutic strategy
age 16- 80 y bleeding or plt count transfusions over 14 d reduced number of
10 000/L) vs observation period transfusions by 33.5% in
prophylactic strategy (plt all patients. No increased
count 10 000/L) risk of bleeding in auto
HSCT recipients but
increase nonfatal grade 4
in AML recipients
Stanworth et al23 (TOPPS) RCT/NI (600) HSCT or chemotherapy No-prophylaxis group (not Bleeding grade 2, 3, or 4 Number of days with bleeding The results support the
receiving patients 16 y receiving plt for plt count up to 30 d after grade 2 or higher; time from need for prophylactic
10 000/L) vs randomization randomization to bleeding transfusions with the
prophylaxis group grade 2 or higher; bleeding shown benefit in
(receiving plt for plt count event of grade 3 or 4; reducing bleeding.
10 000/L) numbers of plt and RBC Overall bleeding risk in
transfusions; days with plt these groups is high.
count 20 000/L; time to Primary outcome was
recovery from met by 50% in the
thrombocytopenia; time in no-prophylaxis group vs
the hospital 43% in the prophylaxis
group (P .06). More
days with bleeding and a
shorter time to first
bleeding in the no-
prophylaxis group.
Reduced use of plt in
no-prophylaxis group.