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Clinical and laboratory aspects of platelet transfusion

therapy
Authors: Shan Yuan, MD, Dennis Goldfinger, MD
Section Editor: Arthur J Silvergleid, MD
Deputy Editor: Jennifer S Tirnauer, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2021. | This topic last updated: Jan 19, 2021.

INTRODUCTION

Hemostasis depends on an adequate number of functional platelets, together with an intact

coagulation (clotting factor) system. This topic covers the logistics of platelet use and the
indications for platelet transfusion in adults. The approach to the bleeding patient,
refractoriness to platelet transfusion, and platelet transfusion in neonates are discussed
separately.

● Evaluation of bleeding – (See "Approach to the adult with a suspected bleeding disorder".)
● Refractoriness to platelet transfusion – (See "Refractoriness to platelet transfusion
therapy".)
● Neonates – (See "Neonatal thrombocytopenia: Clinical manifestations, evaluation, and
management", section on 'Platelet transfusion'.)

COLLECTION

There are two ways that platelets can be collected: by isolating and pooling platelets from units
of donated whole blood or by collecting platelets via apheresis directly from a donor.

● Pooled platelets – A single unit of platelets can be isolated from every unit of donated
blood by centrifuging the blood within the closed collection system to separate the
platelets from the red blood cells (RBCs). The number of platelets per unit varies according
to the platelet count of the donor; a yield of 7 x 1010 platelets is typical [1]. Since this
 number is inadequate to raise the platelet count in an adult recipient, four to six units are
pooled to allow transfusion of 3 to 4 x 1011 platelets per transfusion [2]. These units are
called whole blood-derived platelets, platelet concentrates, or random donor pooled
platelets.

Advantages of pooled platelets include lower cost and ease of collection and processing (a
separate donation procedure and pheresis equipment are not required). The major
disadvantage is recipient exposure to multiple donors in a single transfusion and logistic
issues related to bacterial testing.

● Apheresis (single donor) platelets – Platelets can also be collected from volunteer donors
in a one- to two-hour apheresis procedure. Platelets are selectively removed along with
some white blood cells and plasma, and most RBCs and plasma are returned to the donor.
A typical apheresis platelet unit provides the equivalent of six or more units of platelets
from whole blood (ie, 3 to 6 x 1011 platelets) [2]. In larger donors with high platelet counts,
up to three units can be collected in one session. These are called apheresis or single donor
platelets.

Advantages of single donor platelets are exposure of the recipient to a single donor rather
than multiple donors, and the ability to match donor and recipient characteristics such as
HLA type, cytomegalovirus (CMV) status, and blood type for certain recipients. (See
'Ordering platelets' below.)

Issues related to the effects of platelet pheresis on the donor are covered elsewhere. (See
"Blood donor screening: Procedures and processes to enhance safety for the blood
recipient and the blood donor", section on 'Apheresis platelet donors'.)

Both pooled and apheresis platelets contain some white blood cells (WBC) that were collected
along with the platelets. These WBC can cause febrile non-hemolytic transfusion reactions
(FNHTR), alloimmunization, and transfusion-associated graft-versus-host disease (ta-GVHD) in
some patients.

Platelet products also contain plasma, which can be implicated in adverse reactions including
transfusion-related acute lung injury (TRALI) and anaphylaxis. (See 'Complications' below.)

Several strategies are used to prevent the complications associated with WBC and plasma
contamination of platelets. (See 'Ordering platelets' below.)

Platelets concentrates also contain a small number of RBCs that express Rh antigens on their
surface (platelets do not express Rh antigens). The small numbers of RBCs in apheresis platelets
negates the issue of Rh alloimmunization in most patients. However, blood banks avoid giving
platelets from Rh+ donors to Rh- females of childbearing potential because of the potential risk
of Rh alloimmunization and subsequent hemolytic disease of the newborn. (See "RhD
alloimmunization in pregnancy: Overview".)

STORAGE

Room temperature storage — Platelets are routinely stored at room temperature, because
cold induces clustering of von Willebrand factor receptors on the platelet surface and
morphological changes of the platelets, leading to enhanced clearance by hepatic macrophages
and reduced platelet survival in the recipient [3-6].

All cells are more metabolically active at room temperature, so platelets are stored in bags that
allow oxygen and carbon dioxide gas exchange. Citrate is included to prevent clotting and
maintain proper pH, and dextrose is added as an energy source [2].

The shelf life of platelets stored at room temperature is generally only five days because of the
bacterial infection risk that increases in relationship to the storage duration. This short shelf life
contributes to the greater sensitivity of platelet inventory to shortages. However, facilities can
store platelets for up to seven days if they use a container cleared or approved by the US Food
and Drug Administration (FDA) for seven-day storage and if the individual platelet units are
subsequently tested for bacteria using a bacterial detection device cleared by the FDA and
labeled for use as a "safety measure." The use of platelet storage containers must be
performed consistent with the instructions for use of the device.

Cold storage (investigational) — Storage of platelets in the cold (refrigerator temperature; 2°

to 6°C) is investigational.

Cold-stored platelets could potentially reduce the risk of bacterial growth. However, there are
concerns about poorer recovery and survival of cold-stored platelets [3,7,8].

Small preliminary studies suggest that platelets stored in the cold have similar efficacy and
safety as platelets stored at room temperature [9,10].

Strategies for reducing pathogens — A disadvantage of room temperature storage is the

increased growth of bacteria compared with blood products stored in the refrigerator or
freezer. (See 'Complications' below.)

Strategies for reducing exposure to pathogens in the platelet product include:

 ● Donor screening for bloodborne pathogens (see "Blood donor screening: Laboratory
testing", section on 'Infectious disease screening' and "Blood donor screening: Procedures
and processes to enhance safety for the blood recipient and the blood donor", section on
'Protection of the recipient')

● Proper skin sterilization techniques during collection, and discarding the first 15 to 30 mL of
blood collected, which is most likely to be contaminated by skin bacteria

● Performing tests to screen for bacterial contamination, such as automated culture-based

assays, and rapid point-of-issue tests (see "Transfusion-transmitted bacterial infection",
section on 'Detection of contamination')

● Using blood products that have been subjected to pathogen inactivation or reduction
treatment (see "Pathogen inactivation of blood products", section on 'Platelets')

The US Food and Drug Administration (FDA) issued a guidance document on September 30,
2019, to further reduce the risk of bacterial contamination of platelet products [11]. By October
1, 2021, facilities must select and implement additional safety measures beyond a primary
bacterial culture:

● Platelets collected by apheresis may be pathogen reduced, or they must undergo either
secondary culture or secondary rapid testing after the primary culture. Alternatively, large
volume delayed sampling of platelets collected by apheresis can be cultured no sooner
than 36 hours after collection.

● Pre-storage pools of whole blood-derived platelets have similar testing requirements for
secondary cultures, rapid testing after the primary culture, or large volume delayed
sampling cultured no sooner than 36 hours.

● Single units of whole blood-derived platelets, which are constrained by volume, require
either rapid testing or primary cultures.

The guidance also outlines conditions for extending platelet storage up to seven days [11].

Cryopreservation — Cryopreserved platelets have the potential to dramatically increase shelf-

life (to years rather than days) and in turn to greatly improve inventory and availability as well
as to reduce the risk of transfusion-transmitted bacterial infection. Cryopreserved platelets are
not clinically available in the United States, but they have been used in military settings and are
in use or development in some countries in Europe, Asia, and Australia [12].
The largest trial of cryopreserved platelets (the cryopreserved versus liquid platelet [CLIP-I]
trial) randomly assigned 121 adults undergoing cardiac surgery to receive up to three units of
cryopreserved or room temperature-stored (liquid) platelets if they needed a platelet
transfusion [13]. The cryopreserved platelets were prepared from apheresis units from group O
donors and frozen in DMSO as a preservative; after thawing they were reconstituted with AB or
group-specific plasma. The control platelets (referred to as liquid storage) could be prepared
from red blood cell units or by apheresis (see 'Collection' above). All measures of blood loss,
need for red blood cell transfusion, and frequency of adverse events were similar between
groups, and there were no thrombotic events associated with cryopreserved platelets.
Compared with the control group, the group that assigned to cryopreserved platelets had a
lower platelet count increment (median platelet count on the first postoperative day, 150,000 in
controls versus 112,000/microL for cryopreserved platelets); the cryopreserved platelet group
also received more platelet transfusions. A reduced platelet count increment with
cryopreserved platelets versus controls was also seen in a trial in a small number of
hematology-oncology patients who were transfused with platelets in the setting of bleeding
and thrombocytopenia [14].

This trial suggests that cryopreserved platelets are likely to be safe and effective in a surgical
setting. Cryopreserved platelets could potentially be a useful way to augment blood inventories
and improve product availability in settings such as combat, in remote locations, or to alleviate
shortages in urban areas with high usage. However, additional trials are needed in other
patient populations with other clinical indications. Considerable regulatory hurdles must also
be addressed [15].

Another potential concern with cryopreserved platelets is the delay in obtaining the unit due to
thawing and reconstitution with plasma [15]. This delay is approximately 10 minutes if thawed
plasma is available for reconstitution and 30 to 40 minutes if plasma also has to be thawed [13].

INDICATIONS FOR PLATELET TRANSFUSION

Platelets can be transfused therapeutically (ie, to treat active bleeding or in preparation for an
invasive procedure that would cause bleeding), or prophylactically (ie, to prevent spontaneous
bleeding).

Actively bleeding patient — Actively bleeding patients with thrombocytopenia should be

transfused with platelets immediately to keep platelet counts above 50,000/microL in most
bleeding situations including disseminated intravascular coagulation (DIC), and above
100,000/microL if there is central nervous system bleeding [16]. (See "Disseminated
intravascular coagulation (DIC) in adults: Evaluation and management", section on 'Treatment'
and "Spontaneous intracerebral hemorrhage: Treatment and prognosis", section on 'Urgent
treatment'.)

Other factors contributing to bleeding should also be addressed. These include:

● Surgical or anatomic defect

● Fever
● Infection or inflammation
● Coagulopathy
● Acquired or inherited platelet function defect

The dose and frequency of platelet transfusions will depend on the platelet count and the
severity of bleeding. (See 'Dose' below.)

Preparation for an invasive procedure — Platelets are transfused in preparation for an

invasive procedure if the thrombocytopenia is severe, if there is insufficient time to use other
therapies to raise the platelet count when indicated (eg, if there is insufficient time to
administer intravenous immune globulin or glucocorticoids in an individual with immune
thrombocytopenia [ITP]), and if the risks of bleeding are deemed high.

Most of the data used to determine bleeding risk come from retrospective studies of patients
who are afebrile and have thrombocytopenia but not coagulopathy [17,18]. Typical platelet
count thresholds that are used for some common procedures are as follows:

● Neurosurgery or ocular surgery – 100,000/microL

● Most other major surgery – 50,000/microL
● Endoscopic procedures – 50,000/microL for therapeutic procedures; 20,000/microL for low
risk diagnostic procedures (see "Gastrointestinal endoscopy in patients with disorders of
hemostasis")
● Bronchoscopy with bronchoalveolar lavage (BAL) – 20,000 to 30,000/microL [19]
● Central line placement – 20,000/microL [20]
● Lumbar puncture – 10,000 to 20,000/microL in patients with hematologic malignancies and
40,000 to 50,000 in patients without hematologic malignancies; lower thresholds may be
used in patients with immune thrombocytopenia (ITP) [21-23]
● Epidural anesthesia – 80,000/microL [23]
● Bone marrow aspiration/biopsy – 20,000/microL

Prevention of spontaneous bleeding — We use prophylactic platelet transfusion to prevent

spontaneous bleeding in most afebrile patients with platelet counts below 10,000/microL due to
bone marrow suppression.

We use higher thresholds (ie, 20,000 to 30,000/microL) in patients who are febrile or septic.
Patients with acute promyelocytic leukemia (APL) have a coexisting coagulopathy, and for them
we use a platelet transfusion threshold of 30,000 to 50,000/microL. (See 'Leukemia,
chemotherapy, and HCT' below.)

The threshold for prophylactic transfusion can also vary depending on the patient and on the
clinical scenario. (See 'Specific clinical scenarios' below.)

There are no ideal tests for predicting who will bleed spontaneously [24]. Studies of patients
with thrombocytopenia suggest that patients can bleed even with platelet counts greater than
50,000/microL [25]. However, bleeding is much more likely at platelet counts less than
5000/microL. Among individuals with platelet counts between 5000/microL and 50,000/microL,
clinical findings can be helpful in decision-making regarding platelet transfusion.

● The platelet count at which a patient bled previously can be a good predictor of future
bleeding.

● Petechial bleeding and ecchymoses are generally not thought to be predictive of serious
bleeding, whereas mucosal bleeding and epistaxis (so-called "wet" bleeding) are thought to
be predictive.

● Coexisting inflammation, infection, and fever also increase bleeding risk.

● The underlying condition responsible for a patient's thrombocytopenia also may help in
estimating the bleeding risk. As an example, some patients with ITP often tolerate very low
platelet counts without bleeding, while patients with some acute leukemias that are
associated with coagulopathy (eg, acute promyelocytic leukemia) can have bleeding at
higher platelet counts (eg, 30,000 to 50,000/microL). (See 'Specific clinical scenarios' below.)

● Compared with adults, children with bone marrow suppression may be more likely to
experience bleeding at the same degree of thrombocytopenia. In a secondary subgroup
analysis of the PLADO trial, in which patients were randomly assigned to different platelet
doses, children had more days of bleeding, more severe bleeding, and required more
platelet transfusions than adults with similar platelet counts [26]. However, these findings
do not suggest a different threshold for platelet transfusion in children, as the increased
risk of bleeding was distributed across a wide range of platelet counts.

● Tests for platelet-dependent hemostasis (ie, bleeding time, thromboelastography, and

other point of care tests) are generally not used to predict bleeding in thrombocytopenic
 patients. (See "Platelet function testing", section on 'The in vivo bleeding time' and "Platelet
function testing", section on 'Instruments that simulate platelet function in vitro'.)

Therapeutic versus prophylactic transfusion — By convention, most authors use the term
"therapeutic transfusion" to refer both to transfusion of platelets to treat active bleeding and
transfusion of platelets in preparation for an invasive procedure that could cause bleeding. The
term "prophylactic transfusion" is used to refer to platelet transfusion given to prevent
spontaneous bleeding.

The findings from clinical trials support the use of prophylactic transfusion for patients with
hematologic malignancies and hematopoietic cell transplant (HCT), as discussed below.
Although reserving platelet transfusion for active bleeding may be safe for some adults
undergoing autologous HCT, such a strategy requires intensive monitoring and the ability to
perform immediate imaging for suspected central nervous system (CNS) or ocular bleeding. We
do not recommend reserving platelet transfusion for active bleeding in patients with HCT
outside of a clinical trial or a specific protocol in a highly specialized center with the ability to
support this level of vigilance. (See 'Leukemia, chemotherapy, and HCT' below.)

Patients with platelet consumption disorders (eg, immune thrombocytopenia [ITP],

disseminated intravascular coagulation) and platelet function disorders are typically transfused
only for bleeding or, in some cases, invasive procedures. Platelets should not be withheld in
bleeding patients with these conditions due to fear of "fueling the fire" of thrombus formation.
(See 'Immune thrombocytopenia (ITP)' below and 'TTP or HIT' below and 'Platelet function
defects' below.)

Given the need to balance the risk of spontaneous bleeding with the potential complications of
unnecessary platelet transfusion, the decision of whether to transfuse platelets based upon a
clinical event (ie, for active bleeding or invasive procedures) or at a particular threshold (ie, to
prevent spontaneous bleeding) is challenging. Standard practice has evolved to transfusion of
platelets at a threshold platelet count of 10,000 to 20,000/microL for most patients with severe
hypoproliferative thrombocytopenia due to hematologic malignancies, cytotoxic chemotherapy,
and HCT [27]. However, the risks and benefits of reserving platelet transfusion for active
bleeding episodes in these patients continue to be evaluated [17,28-31].

Two randomized trials have evaluated outcomes with platelet transfusion for bleeding versus
routine prophylactic transfusions:

● In a 2012 trial from Germany, 400 patients with acute myeloid leukemia (AML; patients with
APL were excluded) and patients undergoing autologous HCT for hematologic malignancies
were randomly assigned to receive platelet transfusions when morning platelet counts
 were ≤10,000/microL or only for active bleeding [32]. Patients transfused only for active
bleeding received fewer platelet transfusions during the 14-day period after induction or
consolidation chemotherapy (1.63 versus 2.44 per patient, a 33.5 percent reduction).
However, among patients with AML who were transfused only for active bleeding, there
were more episodes of major bleeding (six cerebral, four retinal, and one vaginal) and there
were two fatal intracranial hemorrhages compared with four retinal hemorrhages among
patients transfused for a platelet count ≤10,000/microL. Patients undergoing HCT also
experienced more bleeding episodes when transfused only for active bleeding, but most of
these were minor.

● In the 2013 TOPPS trial (Trial of Prophylactic Platelets), 600 patients with hematologic
malignancies receiving chemotherapy, autologous, or allogeneic HCT were randomly
assigned to receive platelet transfusion for a platelet count ≤10,000/microL or only for
active bleeding [33,34]. Compared with those who received prophylactic transfusions,
patients transfused only for active bleeding received fewer platelet transfusions during the
30-day period after randomization, but had a higher incidence of major bleeding (50 versus
43 percent) and a shorter time to first bleed (1.2 versus 1.7 days) [35]. There were no
differences in the duration of hospitalization, and no deaths due to bleeding. In a
predefined subgroup analysis, patients undergoing autologous (but not allogeneic) HCT
had similar rates of major bleeding whether they were transfused for a platelet count
≤10,000/microL or only for active bleeding (45 and 47 percent). However, this may reflect a
shorter duration of severe thrombocytopenia in this population and more aggressive, early
treatment of suspected bleeding in the context of a clinical trial, rather than an inherently
different rate of bleeding.

SPECIFIC CLINICAL SCENARIOS

There are several common clinical scenarios that raise the questions of whether to transfuse
patients prophylactically to prevent bleeding, and, if prophylactic transfusion is used, of what
platelet count is the best threshold for transfusion.

Leukemia, chemotherapy, and HCT — Patients with leukemia, or those being treated with
cytotoxic chemotherapy or undergoing hematopoietic cell transplant (HCT) have a suppressed
bone marrow that often cannot produce adequate platelets. We use prophylactic transfusion in
these settings, assuming the patient is hospitalized, afebrile, and without active infection. We
generally use a threshold platelet count of 10,000/microL (ie, transfuse for a platelet count
<10,000/microL). An exception is acute promyelocytic leukemia (APL), for which the threshold is
higher (ie, transfuse for a platelet count of <30,000 to 50,000/microL) due to a higher bleeding
risk. If fever, sepsis, or coagulopathy is present, or if the patient is not hospitalized and/or
cannot be closely monitored, higher thresholds may be needed.

This approach is in line with the 2017 American Society for Clinical Oncology (ASCO) guidelines (
table 1) and a 2015 practice guideline from the AABB [36,37]. It is supported by randomized
trials comparing prophylactic (ie, threshold-based) and therapeutic platelet transfusion, in
which patients who did not receive prophylactic transfusion had more severe bleeding
[32,35,38]. While the 2017 ASCO guideline suggests that some individuals undergoing
autologous HCT may omit prophylactic platelet transfusions if they are being treated in a highly
specialized center, we do not believe there is sufficient evidence to support this approach in
most practice settings and clinical scenarios, and we continue to use prophylactic transfusions
in our practice unless the patient is enrolled in a clinical trial or is following a specific
institutional protocol, as discussed above. (See 'Therapeutic versus prophylactic transfusion'
above.)

● Acute myeloid leukemia (AML) – Patients with AML can have suppressed bone marrow
from AML, chemotherapy, or HCT. We use standard dose prophylactic transfusion of these
patients at a threshold platelet count of 10,000/microL, and transfusion for any bleeding
greater than petechial bleeding. (See 'Dose' below.)

● Acute promyelocytic leukemia (APL) – Patients with APL differ from other patients with
AML because they often have an associated coagulopathy that puts them at high risk for
disseminated intravascular coagulation and bleeding. We prophylactically transfuse these
patients at a platelet count of 30,000 to 50,000/microL, and treat any sign of bleeding,
especially central nervous system bleeding, with immediate platelet transfusion. (See
"Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic
leukemia in adults", section on 'Coagulopathy and APL' and "Initial treatment of acute
promyelocytic leukemia in adults", section on 'Control of coagulopathy'.)

● Acute lymphoblastic leukemia (ALL) – Patients with ALL have thrombocytopenia from
bone marrow suppression. In addition, these patients are often treated with L-
asparaginase, which causes severe hypofibrinogenemia. However, the risk of life-
threatening bleeding is low. As an example, in over 2500 children with ALL, only two
intracranial hemorrhages occurred, and they were associated with hyperleukocytosis in one
case and intracerebral fungal infection in the other [21]. We transfuse adults with ALL at a
threshold platelet count of 10,000/microL. The use of platelet transfusion in children with
ALL is discussed separately. (See "Overview of the treatment of acute lymphoblastic
leukemia/lymphoma in children and adolescents", section on 'Bleeding'.)
 ● Chemotherapy for solid tumors – Cancer chemotherapy often makes patients
thrombocytopenic from bone marrow suppression. Randomized trials of platelet
transfusion threshold in this population have not been performed. Observational studies
support a prophylactic platelet transfusion threshold of 10,000/microL [38]. A threshold of
20,000/microL may be appropriate for patients with necrotic tumors.

● Hematopoietic cell transplant (HCT) – Chemotherapy and radiation therapy administered

as part of the conditioning regimen for HCT can be highly bone marrow suppressive,
depending on the doses used. We use standard dose prophylactic transfusion of these
patients at a threshold platelet count of 10,000/microL, and therapeutic transfusion for any
bleeding greater than petechial bleeding. As noted above, patients in the TOPPS trial who
were undergoing autologous HCT had similar rates of major bleeding whether they were
transfused for a platelet count ≤10,000/microL or only for active bleeding; however, there
are several caveats that limit the use of this approach in the vast majority of patients
undergoing HCT. (See 'Therapeutic versus prophylactic transfusion' above and
"Hematopoietic support after hematopoietic cell transplantation", section on 'Platelet
transfusion'.)

● Aplastic anemia – Patients with aplastic anemia do not have a malignancy, but they may
have severe thrombocytopenia, and they may be candidates for HCT. Issues related to
platelet transfusion in these patients are discussed separately. (See "Treatment of aplastic
anemia in adults" and "Acquired aplastic anemia in children and adolescents" and
"Inherited aplastic anemia in children and adolescents" and "Dyskeratosis congenita and
other short telomere syndromes" and "Management and prognosis of Fanconi anemia".)

Immune thrombocytopenia (ITP) — Individuals with immune thrombocytopenia produce

antiplatelet antibodies that destroy circulating platelets and megakaryocytes in the bone
marrow. Circulating platelets in patients with ITP tend to be highly functional, and platelet
counts tend to be well above 30,000/microL. Bleeding is rare even in patients with severe
thrombocytopenia (ie, platelet count <30,000/microL). (See "Immune thrombocytopenia (ITP) in
adults: Clinical manifestations and diagnosis", section on 'Pathogenesis'.)

Our general approach to platelet transfusion in patients with ITP is to transfuse for bleeding
rather than at a specific platelet count. (See "Immune thrombocytopenia (ITP) in adults: Initial
treatment and prognosis", section on 'Overview of decision-making'.)

TTP or HIT — Thrombotic thrombocytopenic purpura (TTP) and heparin-induced

thrombocytopenia (HIT) are disorders in which platelet consumption causes thrombocytopenia
and an increased risk of bleeding; but the underlying platelet activation in these conditions also
increases the risk of thrombosis.

Platelet transfusions can be helpful or even life-saving in patients with these conditions who are
bleeding and/or have anticipated bleeding due to a required invasive procedure (eg, placement
of a central venous catheter), and platelet transfusion should not be withheld from a bleeding
patient due to concerns that platelet transfusion will exacerbate thrombotic risk. However,
platelet transfusions may cause a slightly increased risk of thrombosis in patients with these
conditions; thus, we do not use prophylactic platelet transfusions routinely in patients with TTP
or HIT in the absence of bleeding or a required invasive procedure.

Support for this approach comes from a large retrospective review of hospitalized patients with
TTP and HIT, in which platelet transfusion was associated with a very slight increased risk of
arterial thrombosis but not venous thromboembolism [39]. In contrast, the review found that
patients with immune thrombocytopenia (ITP) had no increased risk of arterial or venous
thrombosis with platelet transfusion. Of note, this was a retrospective study in which sicker
patients were more likely to have received platelets, and the temporal relationships between
platelet transfusions and thromboses were not assessed.

● TTP – Of 10,624 patients with TTP in the large review mentioned above, approximately 10
percent received a platelet transfusion [39]. Arterial thrombosis occurred in 1.8 percent of
patients who received platelets, versus 0.4 percent of patients who did not (absolute
increase, 1.4 percent; adjusted odds ratio [OR], 5.8; 95% CI, 1.3-26.6). The rate of venous
thrombosis was not different in those who received platelets and those who did not
(adjusted OR 1.1; 95% CI 0.5-2.2).

In contrast, a systematic review of patients with TTP who received platelet transfusions,
which included retrospective data for 358 patients and prospective data for 54 patients, did
not find clear evidence that platelet transfusions were associated with adverse outcomes
[40].

● HIT – Of 6332 patients with HIT in the large review mentioned above, approximately 7
percent received a platelet transfusion [39]. Arterial thrombosis occurred in 6.9 percent of
patients who received platelets, versus 3.1 percent of patients who did not (absolute
increase, 3.8 percent; adjusted OR, 3.4; 95% CI, 1.2-9.5). The rate of venous thrombosis was
not different in those who received platelets and those who did not (adjusted OR 0.8; 95%
CI 0.4-1.7).

In a series of four patients with HIT who received platelet transfusions, two of three with
active bleeding had cessation of bleeding following platelet transfusion, and no
 thromboses occurred; a literature review was not able to identify any complications clearly
attributable to platelet transfusion [41].

Management of TTP and HIT is discussed in detail separately. (See "Acquired TTP: Initial
treatment" and "Management of heparin-induced thrombocytopenia".)

Liver disease and DIC — Patients with liver disease and disseminated intravascular
coagulation (DIC) have a complex mixture of procoagulant and anticoagulant defects along with
thrombocytopenia, and therefore they are at risk for thrombosis and bleeding. There is no
evidence to support the administration of platelets in these patients if they are not bleeding.
However, platelet transfusion is justified in patients who have serious bleeding, are at high risk
for bleeding (eg, after surgery), or require invasive procedures. (See "Disseminated
intravascular coagulation (DIC) in adults: Evaluation and management", section on
'Prevention/treatment of bleeding' and "Hemostatic abnormalities in patients with liver
disease", section on 'Bleeding'.)

Platelet function defects — Platelet function defects can be inherited or acquired, and may be
associated with thrombocytopenia or a normal platelet count. Platelet transfusion in these
settings is typically reserved for bleeding.

● Inherited diseases – Platelet function is impaired in Wiskott-Aldrich syndrome, Glanzmann

thrombasthenia, and Bernard-Soulier syndrome. Bleeding in patients with these conditions
is treated with platelet transfusion, along with other hemostatic agents discussed below.
(See "Congenital and acquired disorders of platelet function", section on 'Inherited
disorders of platelet function' and 'Alternatives to platelet transfusion' below.)

● Acquired conditions – Uremia, diabetes mellitus, myeloproliferative disorders, and other

medical conditions can impair platelet function. Bleeding risk can be reduced by treating
the underlying condition. Platelet transfusion is typically reserved for major bleeding in
these conditions. (See "Congenital and acquired disorders of platelet function", section on
'Acquired platelet functional disorders'.)

Patients who are febrile or septic can have impaired platelet function. We transfuse these
patients for bleeding. We also use a higher threshold for when fever or sepsis coexist with
thrombocytopenia (eg, in patients with leukemia). (See 'Leukemia, chemotherapy, and HCT'
above.)

Antiplatelet agents — Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), dipyridamole,

ADP receptor (P2Y12) inhibitors (eg, clopidogrel, ticlopidine), and GPIIb/IIIa antagonists (eg,
abciximab, eptifibatide) are used to prevent thrombosis by interfering with normal platelet
function. The antiplatelet effects of NSAIDs and aspirin are relatively weak compared with the
other antiplatelet agents, but the inhibitory effects of aspirin are irreversible during the lifespan
of the platelets. (See "Platelet biology", section on 'Drugs with antiplatelet actions'.)

Typically, the approach to treating mild bleeding in a patient taking an antiplatelet agent is to
discontinue the drug, assuming a favorable risk-benefit ratio. For more severe bleeding or
urgent surgical procedures, high quality evidence regarding the benefit of platelet transfusion
is lacking, and some evidence suggests that platelet transfusion may be deleterious. These
cases can be complex, however, and we favor an individualized approach based on the
complete clinical picture.

Evidence suggesting platelet transfusion is not effective in some sites of severe bleeding comes
from the following:

● The 2016 PATCH trial (Platelet Transfusion in Cerebral Hemorrhage) randomly assigned 190
patients with intracerebral hemorrhage (ICH) in the setting of aspirin or another
antiplatelet agent to receive platelet transfusion or standard care without platelet
transfusions [42]. Compared with controls, patients who received platelet transfusions had
a higher incidence of a composite outcome of death or shift toward a worse score on the
modified Rankin Scale for functional independence. When analyzed separately, the increase
in mortality did not reach statistical significance. Serious adverse events were greater with
platelet transfusion (42 versus 29 percent); enlargement of the ICH was similar in both
groups at approximately 15 percent. The authors did not identify a clear mechanism for the
inferior outcomes with platelet transfusion but offered several hypotheses, including the
possibility of concomitant ischemia, possible proinflammatory effects of platelets, or
characteristics of the hemorrhage such as location or etiology. A subsequent reanalysis of
the trial by the original authors suggested that the arms of the trial were not balanced at
baseline (patients in the platelet transfusion arm had a larger ICH volume and more peri-
hemorrhage edema), which might account for some portion of the difference in outcomes
[43].

The management of ICH is discussed in detail separately. (See "Spontaneous intracerebral

hemorrhage: Treatment and prognosis".)

● A 2017 study retrospectively reviewed outcomes in 204 individuals with gastrointestinal

bleeding associated with an antiplatelet agent who received platelet transfusion as part of
their management with 204 matched controls who did not receive platelet transfusions
[44]. None of the people in the study had thrombocytopenia. In a multivariate analysis,
platelet transfusion was associated with a higher risk of death (adjusted odds ratio [OR] 5.6;
 95% CI 1.5-27). It is very possible that the individuals who received a platelet transfusion
had increased baseline risk factors for mortality compared with controls.

The role of platelet transfusion in the setting of urgent surgical procedures (eg, coronary artery
bypass grafting, neurosurgical interventions, and others) is also not well defined. Some
clinicians give prophylactic platelet transfusions to patients taking antiplatelet drugs who
require major surgery, while other clinicians use platelet transfusion only to treat excessive
surgical bleeding [45,46]. There is no compelling evidence to support platelet transfusions in
such scenarios, especially when platelet counts are within normal range; at the same time,
there are limitations of the studies cited above (associating platelet transfusions with no clear
benefits and possibly harm), making it challenging to interpret and extrapolate the data. The
AABB has noted the low quality of the evidence and does not recommend for or against platelet
transfusion for patients receiving antiplatelet therapy who have traumatic or spontaneous
intracranial hemorrhage [36]. This decision continues to be individualized according the specific
patient factors and the judgment of the treating clinician.

Other medications may impair platelet function. As an example, the Bruton tyrosine kinase
(BTK) inhibitor ibrutinib inhibits platelet aggregation by interfering with activation signals. The
role of platelet transfusion in patients with ibrutinib-associated bleeding despite a sufficient
platelet count is unknown, and decisions are individualized according to the platelet count and
the severity and site of bleeding. This association is discussed in more detail separately. (See
"Treatment of relapsed or refractory chronic lymphocytic leukemia", section on 'Ibrutinib'.)

Massive blood loss — Patients with massive blood loss from surgery or trauma are transfused
with red blood cells (RBC), resulting in partial replacement of the blood volume with a product
lacking platelets and clotting factors. In this setting, we transfuse RBC, fresh frozen plasma
(FFP), and random donor platelet units in a 1:1:1 ratio. As an example, a patient transfused with
six units of RBC would also receive six units of pooled platelets or one apheresis unit (both of
which provide approximately 5 x 1011 platelets) and six units of FFP. (See "Initial management of
moderate to severe hemorrhage in the adult trauma patient".)

Cardiopulmonary bypass — Patients who undergo prolonged cardiopulmonary bypass can

have thrombocytopenia and impaired platelet function. The use of platelet transfusion in the
cardiopulmonary bypass setting is discussed separately. (See "Congenital and acquired
disorders of platelet function", section on 'Cardiopulmonary bypass' and "Early noncardiac
complications of coronary artery bypass graft surgery", section on 'Bleeding'.)

Neonates — This subject is discussed separately. (See "Neonatal thrombocytopenia: Clinical

manifestations, evaluation, and management", section on 'Platelet transfusion'.)
ORDERING PLATELETS

When ordering platelets, one should consider platelet dose; whether to use single donor versus
random donor platelets; whether to include leukoreduction, irradiation, or platelets in platelet
additive solution (PAS); whether cytomegalovirus (CMV)-negative platelets are required; and
whether to match HLA, ABO, and Rh type.

Dose — A standard dose of platelets for prophylactic therapy in adults is approximately one
random donor unit per 10 kg of body weight, which translates to four to six units of pooled
platelets or one apheresis unit, both providing approximately 3 to 4 x 1011 platelets [2,36]. A
standard pediatric dose is 5 to 10 mL/kg. For prophylactic transfusion there is generally no
reason to transfuse platelets more often than once a day. This platelet dosing is expected to
raise the platelet count by approximately 30,000/microL within 10 minutes of the infusion. (See
'Platelet count increment' below.)

Clinical trials comparing standard platelet dosing with other doses have been limited to
patients with hypoproliferative thrombocytopenia due to bone marrow suppression (eg,
leukemia, hematopoietic cell transplant, or chemotherapy). Two large studies that evaluated the
use of higher or lower platelet doses in these groups have conflicting results, as illustrated
below.

● In the PLAtelet DOse (PLADO) trial, 1272 patients with thrombocytopenia due to
chemotherapy or hematopoietic cell transplant (HCT) were randomly assigned to receive
standard-dose (2.2 x 1011 platelets per m2), half-dose (1.1 x 1011 per m2), or double-dose
(4.4 x 1011 per m2) platelet transfusions [25]. The primary endpoint of prolonged mucosal
or deep bleeding was similar among all groups (67 to 69 percent). The half-dose group
received a higher median number of platelet transfusions during the 30-day study period
(five in the half-dose group versus three in the other groups) but received fewer platelets
overall (9.25 × 1011 versus 11.25 × 1011 and 19.63 × 1011 in the standard- and double-dose
groups, respectively).

● In the Strategies for Transfusion of Platelets (SToP) trial, patients with hypoproliferative
thrombocytopenia were randomly assigned to receive platelet transfusion at standard dose
(3 to 6 x 1011 platelets, equivalent to approximately 5 to 10 units) or half dose (1.5 to 3 x
1011 platelets, equivalent to approximately 3 to 5 units) when platelet counts fell below a
trigger value (most participating institutions used 10,000/microL) [47]. The trial was halted
prematurely (at 119 patients) because of life-threatening bleeding or bleeding requiring
 transfusion in the low dose arm (3 of 58 patients versus none of 61 in the standard dose
arm).

Based on review of these and other trials as well as a study examining prophylactic transfusion
of low-dose (half of the standard dose), standard dose, or high-dose (approximately two times
the standard dose) platelet transfusions in hospitalized patients with therapy-induced
hypoproliferative thrombocytopenia, the AABB recommends transfusions of up to a single
standard-dose apheresis unit of platelets (or the equivalent) and states that "greater doses are
not more effective, and lower doses are equally effective" [25,36,47-49]. However, given the
logistical issues associated with more frequent platelet transfusions when low-dose units are
used, and at times conflicting results from available studies, most centers continue to use
standard-dose transfusion until further data become available.

In contrast to prophylactic transfusion, patients who are being transfused therapeutically (ie,
for active bleeding or in preparation for an invasive procedure), or who have a rapidly dropping
platelet count, may require higher dose or more frequent platelet transfusions.

Infusion rate — For an average-sized adult, six units of pooled platelets or one apheresis unit
of platelets are transfused over approximately 20 to 30 minutes. Patients at risk for transfusion-
associated circulatory overload (TACO) can be transfused at a slower rate as long as the
transfusion is completed within four hours of issuance from the blood bank. (See "Transfusion-
associated circulatory overload (TACO)", section on 'Prevention'.)

Pooled versus apheresis platelets — The platelet count increment and hemostatic effects of
pooled and apheresis platelets are comparable [38].

Apheresis platelets have the advantages of limiting the recipient exposure to a single donor,
which potentially reduces the possibility of infection and alloimmunization; some centers use
apheresis platelets exclusively. Many believe it is logistically easier to perform bacterial testing
on apheresis platelets compared with pooled platelets. (See 'Complications' below.)

Use of apheresis platelets also permits transfusion of platelets from specific donors selected
based on HLA matching or platelet cross-matching, cytomegalovirus (CMV) status, and ABO
group. Patients with confirmed immune mediated platelet refractoriness due to anti-HLA
antibodies should receive HLA-matched platelets or platelets negative for the corresponding
antigen(s) or cross-match compatible platelets; in other cases, either pooled and apheresis
platelets can be used [50].

Leukoreduction — Leukoreduction removes most of the contaminating white blood cells (WBC)
from the platelet transfusion [51]. In some centers leukoreduction is standard practice. In other
centers, leukoreduction is used for the following indications:

● Reduction of HLA alloimmunization

● Reduction of CMV transmission
● Reduction of transfusion-associated immunomodulation
● Reduction of lung injury during and after cardiopulmonary bypass
● Reduction of febrile nonhemolytic transfusion reactions (FNHTR)

Leukoreduction is done by passing platelets through a filter that blocks passage of most white
blood cells. Apheresis platelets can be leukoreduced during collection, and pooled platelets can
be leukoreduced shortly after collection or at bedside before transfusion.

Leukoreduction can reduce the risks of several potential complications of contaminating WBC,
but it is not adequate to prevent transfusion-associated graft-versus-host disease (ta-GVHD),
because some WBC can pass through the leukoreduction filter. Therefore, irradiation must be
used to prevent ta-GVHD. (See "Transfusion-associated graft-versus-host disease", section on
'Prevention' and "Leukoreduction to prevent complications of blood transfusion", section on
'Transfusion-associated graft-versus-host disease'.)

Leukoreduction at the bedside (ie, post storage) is not optimal for reducing FNHTR because
bedside leukoreduction does not remove cytokines released from WBC during storage. (See
"Leukoreduction to prevent complications of blood transfusion", section on 'Febrile
nonhemolytic transfusion reactions'.)

The only drawback of leukoreduction is the cost.

Irradiation — Platelet irradiation is used to prevent ta-GVHD, in which contaminating WBCs

attack host tissues and cause serious, even fatal, outcomes in both immunosuppressed and
some immunocompetent individuals. Irradiation damages the nuclei of donor lymphocytes in
the transfusion, so that they cannot proliferate and mount an immune response against the
recipient. Platelets are anucleate, so their functions are unaffected by irradiation, although
there may be a slight effect on platelet survival due to membrane damage [52]. Platelets are
irradiated by exposing the bag to 25 Gy from a Cesium source.

Irradiation is not a substitute for leukoreduction, because lymphocytes inactivated by

irradiation still express human leukocyte antigens (HLA) on their surfaces and can elicit an anti-
HLA antibody response from the host. Irradiation is also inadequate to kill pathogens such as
bacteria and viruses. Irradiation is used for the following indications [53-55]:
 ● Immunosuppression or imminent immunosuppression from hematopoietic cell transplant,
solid organ transplant, and cytotoxic chemotherapy.
● Congenital immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome, Leiner's
disease, 5' nucleotidase deficiency).
● Fludarabine therapy.
● Hodgkin lymphoma and other hematologic malignancies.
● Neonatal exchange transfusion.
● Premature, low birth weight neonates. (See "Neonatal thrombocytopenia: Clinical
manifestations, evaluation, and management", section on 'Platelet transfusion'.)
● Intrauterine transfusion.
● A subset of donor-recipient pairs who may be closely, but not completely, HLA matched (ie,
relatives and genetically homogeneous populations) [56]. The rationale for this is discussed
separately. (See "Transfusion-associated graft-versus-host disease", section on 'Partial HLA
matching'.)

Irradiation may not be necessary if platelets have been subjected to pathogen reduction
protocols that also prevent lymphocyte proliferation (eg, photochemical treatments) [56]. These
protocols, which have the added advantage of not requiring a radioactive source, are discussed
separately. (See "Pathogen inactivation of blood products", section on 'Methods that damage
nucleic acids'.)

CMV — Some cytomegalovirus (CMV) seronegative transfusion recipients (eg,

immunosuppressed patients) are at greater risk of adverse outcomes from receiving CMV-
contaminated blood products than the general population. The AABB (formerly the American
Association of Blood Banks) considers transfusion of platelets from CMV-negative donors to be
equivalent to leukoreduction in reducing this risk. (See "Leukoreduction to prevent
complications of blood transfusion", section on 'Viral diseases'.)

ABO, Rh, and HLA matching — Platelets express ABO antigens on their surface, as well as HLA
class I antigens. They do not express Rh or HLA class II antigens.

ABO and HLA compatible platelets appear to cause a greater platelet count increment in the
recipient, and they can be used to improve responses in patients who have become refractory
to platelet transfusion due to alloimmunization [25]. (See "Refractoriness to platelet transfusion
therapy", section on 'Management of the alloimmunized patient'.)

Due to inventory constraints, most transfusion services issue ABO mismatched platelets when
type-specific platelet products are not available. Clinically significant hemolytic transfusion
reactions secondary to transfusion of ABO-incompatible platelet products (eg, group O platelets
given to group A patient) are uncommon, but they do occur [57].

To limit such hemolytic reactions, some transfusion services monitor and limit the volume of
ABO incompatible plasma given to a patient via platelet transfusions, or volume-reduce or wash
the ABO incompatible platelet products to reduce the plasma content. Some also screen for
platelet products with high anti-A or anti-B titers and give products with high titers only to
group O patients. However, the critical threshold has not been determined for either the
volume of incompatible plasma or the anti-A/B titers. (See "Red blood cell antigens and
antibodies", section on 'Blood component transfusion' and "Hemolytic transfusion reactions".)

The possibility of alloimmunization to red blood cell (RBC) antigens causing hemolytic disease of
the fetus and newborn (HDFN) in a pregnant woman raises another important issue related to
Rh matching of platelets [58]. Although platelets do not express Rh antigens, platelet products
contain small numbers of RBCs, which could be Rh incompatible with the recipient. Thus, when
an RhD-negative woman of childbearing age receives a platelet transfusion, platelets from an
RhD-negative donor are used, in order to prevent alloimmunization and HDFN. The Royal
College of Obstetricians and Gynaecologists (RCOG) advises administration of anti-D immune
globulin (also called Rho[D] immune globulin) in this setting [59]. Even if this is not done and
platelets from an RhD-positive donor are used, the risk of alloimmunization remains low. This
was illustrated in a retrospective analysis of 1014 RhD-negative patients who received 6043
platelet transfusions from Rh+ donors (89 percent from pooled platelets); in this series no
patients who received only apheresis platelets developed anti-RhD antibodies, and 12 of 315
(3.8 percent) who received pooled platelets developed anti-RhD antibodies [60]. However, in a
series of 59 RhD-negative patients transfused with platelets from an RhD-positive donor for a
non-hematologic condition such as pneumonia or surgery (typical dose, one to three units,
given without anti-D immune globulin), alloantibodies to RhD were detected in eight (13.5
percent) [61].

To further reduce the risk of alloimmunization if only Rh+ platelets are available, anti-D immune
globulin can be coadministered with platelet transfusions. Each dose of anti-D immune globulin
is considered sufficient to prevent alloimmunization for up to 15 mL of RhD-positive RBCs, and
most units of platelets do not contain more than 0.5 mL of RBCs. Thus, a single dose of anti-D
immune globulin is likely to be sufficient even if several units of platelets are transfused. If
necessary, this can be repeated once every eight weeks (ie, a similar interval to that used to
prevent HDFN). (See "RhD alloimmunization in pregnancy: Overview" and "RhD
alloimmunization: Prevention in pregnant and postpartum patients".)
White blood cells present in HLA matched platelet products can cause transfusion-associated
graft-versus-host disease (ta-GVHD), so all HLA-matched platelets must be irradiated. (See
"Transfusion-associated graft-versus-host disease", section on 'Partial HLA matching'.)

Platelet additive solutions — After collection, platelets can be resuspended in one of several
platelet additive solutions (PAS), as a substitute for a portion of the associated plasma. PAS
consist of salts, buffers, and sometimes glucose [62]. Use of PAS platelets decreases but does
not eliminate donor plasma exposure, and PAS may provide a less labor-intensive option for
reducing allergic transfusion reactions than platelet washing or volume-reduction.

Clinical experience with PAS platelets is limited, and decisions regarding when to use them may
depend on the incremental costs and expected benefits. Local availability of PAS platelets may
vary, and institution-specific guidelines regarding their use should be followed. One strategy is
to use PAS apheresis platelets, which contain less plasma, for patients without a coagulopathy
and/or patients who have had minor allergic transfusion reactions [63].

A reduction in allergic transfusion reactions with PAS platelets has been demonstrated in two
randomized trials using PAS available in Europe [64,65].

● In one trial of patients receiving multiple platelet transfusions (324 transfusions in 21

patients), platelets resuspended in 65 percent PAS with 35 percent plasma were associated
with fewer allergic reactions than platelets in 100 percent plasma (5 versus 12 percent) [65].
The platelet count increases following transfusion were slightly lower with PAS platelets
than non-PAS platelets (corrected count interval [CCI] at 20 hours 10,000 versus
12,000/microL). (See "Refractoriness to platelet transfusion therapy", section on 'Measuring
response to platelet transfusion'.)

● In a trial that randomly assigned 168 patients to PAS versus non-PAS platelets, mild
transfusion reactions were seen less commonly with PAS compared with non-PAS platelets
(2 versus 6 percent) [64]. CCI was slightly lower with PAS compared with non-PAS platelets
in this trial as well (CCI at 24 hours 7000 versus 8000/microL).

Neither trial showed a difference in bleeding complications with PAS versus non-PAS platelets.

A large retrospective study (5078 patients) compared outcomes with apheresis platelets
resuspended a PAS solution approved by the US Food and Drug Administration (InterSol, 65
percent, with 35 percent plasma) versus 100 percent plasma [63]. The incidence of allergic
transfusion reactions was reduced with PAS apheresis platelets (PAS AP) compared with non-
PAS AP (1.01 versus 1.85 percent; relative risk [RR] 0.54; 95% CI 0.30-0.99). The incidence of
febrile non-hemolytic transfusion reactions did not differ. Among individuals for whom paired
PAS AP and non-PAS AP transfusions could be compared, there was no difference in the CCI at
12 to 24 hours, although PAS AP were associated with a slight reduction in CCI at four hours
compared with non-PAS AP.

The use of PAS platelets may not be possible when HLA matched or CMV-negative products are
needed. PAS platelets can be irradiated.

Other special modifications — Patients with known IgA deficiency who have a history of
anaphylactic transfusion reactions or demonstrate anti-IgA antibodies can be transfused with
platelets that have been washed to remove IgA-containing plasma or obtained from IgA
deficient donors. (See "Selective IgA deficiency: Management and prognosis", section on 'Safe
administration of blood products'.)

In addition, volume-reduced platelets can be used when exposure to ABO incompatible plasma
needs to be limited, or for transfusion of volume-sensitive patients.

As noted above and separately, platelets can also be treated with a pathogen-inactivation
method. (See 'Storage' above and "Pathogen inactivation of blood products", section on
'Platelets'.)

COMPLICATIONS

Platelet transfusion carries several risks including infection, transfusion reactions,

alloimmunization, and post-transfusion purpura.

Complication rate with apheresis versus whole blood-derived platelets — The relative
frequency of complications with apheresis versus whole blood-derived, pooled platelets has not
been studied in large randomized trials.

● A 2008 systematic review and meta-analysis that evaluated several small randomized trials
(mostly with fewer than 100 patients) found a greater incidence of reactions with whole
blood-derived platelets; however, this was no longer significant after controlling for the use
of leukoreduction [66].

● A 2016 study involving almost 800,000 platelet transfusions in France found that apheresis
platelets were associated with a greater frequency of adverse reactions (approximately 6
per 1000 for apheresis platelets versus 2 per 1000 for whole blood-derived platelets) [67].
In this study, all platelets were leukoreduced (during collection for apheresis, and before
storage for whole blood-derived). However, comparison may be difficult due to the
 different size of apheresis versus pooled platelet units and the challenges of calculating the
incidence per unit when multiple units are administered.

Additional data are needed before a clear conclusion on relative risk of complications can be
made.

Infection — Donor screening procedures and pathogen inactivation do not completely

eliminate the risk of bacterial and other bloodborne infections, and infection by bacterially
contaminated platelets represents a serious hazard of platelet transfusion that may be fatal [68-
71]. This is because platelets are stored at room temperature, where bacteria can proliferate
rapidly. The incidence of bacterial contamination is higher for platelets (approximately 1 in
2000) than it is for red blood cells (approximately 1 in 30,000) [72,73]. A 2020 meta-analysis that
included 22 studies (over 5 million platelet units) found a bacterial contamination rate of 1:1961,
with lower rates for apheresis units and platelet rich plasma collection versus buffy coat
collection and a gradual decline in contamination rate year over year [74].

Evaluation and management of septic transfusion reactions are discussed separately. (See
"Transfusion-transmitted bacterial infection".)

Measures that appear to reduce the rate of bacterial contamination include enhancements to
the skin preparation technique, Gram staining or culturing the product, and using pathogen-
inactivation technologies.

● A change to the skin preparation technique in 2012 in the United States was associated
with a decrease from 4.2 instances of bacterial contaminants per year to 0.8 per year
[75,76].

● Culture of the product 24 to 36 hours after collection to identify and remove contaminated
units was associated with a decrease from 492 to 82 septic transfusion reactions per million
units [75]. Enhanced primary culture methods are under development.

As noted above, guidance from the US Food and Drug Administration (FDA) issued in late 2019
will require additional procedures to reduce infectious risks. (See 'Strategies for reducing
pathogens' above.)

Alloimmunization — Platelets express Class I human leukocyte antigen (HLA) antigens, which
can be recognized by the recipient's immune system as foreign. Production of anti-HLA
antibodies can adversely affect the response to future platelet transfusions. The incidence of
alloimmunization depends on the number of transfusions a patient has received. (See
"Refractoriness to platelet transfusion therapy", section on 'Alloimmunization' and 'Platelet
count increment' below.)

Platelet products also contain small volumes of red blood cells (RBCs), and alloimmunization to
RBC antigens can occur as a result. This is especially of concern in RhD-negative women of
childbearing potential, who are at risk for hemolytic disease of the fetus and newborn (HDFN) if
they have an RhD-positive pregnancy. As noted above, this is one of the settings in which it may
be appropriate to use matched platelets and/or to administer anti-D immune globulin (also
called Rho[D] immune globulin). (See 'ABO, Rh, and HLA matching' above.)

Transfusion reactions — Transfusion of any blood product, including platelets, can lead to the
following transfusion reactions:

● Transfusion-related acute lung injury (TRALI) – Transfusion-related acute lung injury

(TRALI) is a form of acute lung injury that causes respiratory distress following transfusion.
The true incidence of TRALI from platelet transfusion is unknown; it has decreased since
institution of TRALI mitigation strategies in the late 2000s [77]. (See "Transfusion-related
acute lung injury (TRALI)", section on 'Epidemiology'.)

● Transfusion-associated circulatory overload (TACO) – Platelet transfusion introduces

approximately 200 mL of intravascular volume per transfusion. The incidence of TACO is in
the range of one to three per 100,000 transfusions and is higher in patients predisposed to
volume overload (eg, with comorbidities such as congestive heart failure, renal failure,
respiratory failure, and positive fluid balance). (See "Transfusion-associated circulatory
overload (TACO)".)

● Allergic and anaphylactic reactions – Allergic reactions to platelet transfusion are

relatively common. They are usually due to IgE directed against proteins in the donor
plasma. Common symptoms include urticaria and pruritus in mild cases, and wheezing,
shortness of breath and hypotension in more severe cases. (See "Immunologic transfusion
reactions", section on 'Urticarial (allergic) reactions'.)

Patients with a history of allergic transfusion reactions who require additional platelet
transfusions may benefit from platelets in additive solution (PAS), which contain less
plasma than non-PAS platelets. Those who continue to have allergic reactions with PAS
platelets may receive concentrated or washed platelets. (See 'Platelet additive solutions'
above and 'Other special modifications' above.)

Anaphylactic reactions (ie, severe allergic reactions) are a very rare complication of platelet
transfusion. These are associated with rapid onset of shock, angioedema, and respiratory
 distress. Many cases occur due to the production of anti IgA antibodies in recipients who
are IgA deficient. (See "Immunologic transfusion reactions", section on 'Anaphylactic
transfusion reactions'.)

● Febrile non-hemolytic transfusion reactions (FNHTR) – These reactions are mediated by

various inflammatory mediators and leukocytes and may manifest as fevers, chills, and
rigors. (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic
reactions' and "Leukoreduction to prevent complications of blood transfusion", section on
'Febrile nonhemolytic transfusion reactions'.)

● Ta-GVHD – Transfusion-associated graft-versus-host disease (ta-GVHD) can occur with any

type of transfusion that contains lymphocytes, given the correct immunologic setting. Its
incidence continues to drop due to irradiation of blood products for at-risk patients, such as
patients with hematopoietic cell transplantation, immunodeficiency, or other types of
immunosuppression.

A second and potentially less obvious situation that can lead to ta-GVHD in individuals who
are completely immunocompetent is partial HLA matching (ie, a donor-recipient pair who
are closely, but not completely, HLA matched, as can occur in relatives and genetically
homogeneous populations) [56]. In this case, the HLA antigens on the donor lymphocytes
are seen by the recipient lymphocytes as self, so recipient lymphocytes do not attack the
donor lymphocytes; however, recipient cells also express unique HLA antigens that the
donor lymphocytes recognize as foreign. This can result in donor lymphocytes destroying
the recipient's tissues (eg, bone marrow, skin and liver), which can be fatal. (See 'Irradiation'
above and "Transfusion-associated graft-versus-host disease".)

Post-transfusion purpura — Post-transfusion purpura (PTP) is a rare transfusion reaction to

any platelet-containing product, in which thrombocytopenia develops 5 to 10 days following
transfusion. This can occur in the <2 percent of individuals who lack the platelet antigen PIA1,
now known as human platelet antigen 1a (HPA-1a), and have become previously sensitized to
the antigen (eg, during pregnancy or prior transfusion). Transfused platelets are removed by an
antibody-mediated mechanism; the patient's own HPA-1a-negative platelets are also destroyed
by an incompletely understood process. Treatment is with intravenous immune globulin (IVIG),
with or without a glucocorticoid, and HPA-1a-negative products should be used whenever
possible if platelet transfusion is indicated. (See "Immunologic transfusion reactions", section
on 'Post-transfusion purpura'.)

PLATELET COUNT INCREMENT

Following a platelet transfusion, the platelet count should rise, with a peak at 10 minutes to one
hour and a gradual decline over 72 hours. A general rule of thumb is that transfusion of six
units of pooled platelets or one apheresis unit should increase the platelet count by
approximately 30,000/microL in an adult of average size.

Platelet count increment is typically measured within 24 hours in patients given prophylactic
platelet transfusions. For patients undergoing invasive procedures, it is prudent to check that
the desired platelet count was achieved before performing the procedure, which can be done
within 10 minutes of the transfusion. For actively bleeding patients, cessation of bleeding is a
more important clinical endpoint than the post-transfusion platelet count.

The length of time platelets have been stored has a modest effect on their survival in the
recipient. As an example, compared with platelets stored for two or three days, platelets stored
for five days produce a smaller increment in platelet count. This information is not usually
factored into assessment of a patient's response to platelet transfusion.

Many patients who receive platelet transfusions reproducibly show a less-than-expected

increase in platelet count. The definition of platelet refractoriness and its management are
discussed separately. (See "Refractoriness to platelet transfusion therapy", section on
'Diagnostic approach' and "Refractoriness to platelet transfusion therapy", section on
'Management of the alloimmunized patient'.)

ALTERNATIVES TO PLATELET TRANSFUSION

There are no substitutes for platelet transfusion to rapidly increase the platelet count in a
bleeding patient. Reversal of thrombocytopenia due to autoimmune platelet destruction,
platelet consumption, or bone marrow suppression can take days to weeks, depending on the
underlying cause.

Patients with ongoing bleeding not responsive to platelet transfusion and other interventions
can also be given procoagulant bypass agents, such as prothrombin complex concentrates or
recombinant factor VIIa [50]. (See "Platelet dysfunction in uremia", section on 'Desmopressin
(DDAVP)' and "Medical management of the dialysis patient undergoing surgery", section on
'Bleeding diathesis'.)

In some settings, fibrinolytic inhibitors such as tranexamic acid have been effective. (See
"Coagulopathy in trauma patients", section on 'Pharmaceutical hemostatic agents' and
"Managing an episode of severe or prolonged uterine bleeding", section on 'Tranexamic acid'.)
Stimulation of bone marrow megakaryocytes with thrombopoietin receptor agonists can take
up to seven days (ie, the time it takes for new platelets to form). This might be appropriate for
selected indications for preventing bleeding. (See "Clinical applications of thrombopoietic
growth factors", section on 'Use of TPO receptor agonists'.)

Investigational approaches such as the use of human leukocyte antigen (HLA)-deleted platelets
generated from induced pluripotent stem cells (iPSCs) (see "Genetics: Glossary of terms",
section on 'Induced pluripotent stem cell (iPSC)') or the use of platelet substitutes (eg, synthetic
or acellular biological materials that could replace the primary hemostatic function of platelets)
have not reached clinical trials [78-81].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Immune
thrombocytopenia (ITP) and other platelet disorders" and "Society guideline links: Transfusion
and patient blood management".)

SUMMARY AND RECOMMENDATIONS

● Means of collection and content of a unit – A unit of platelets isolated from a unit of
donated blood contains approximately 7 x 1010 platelets, and four to six of these units are
typically pooled for transfusion. Single donor (apheresis) platelets contain approximately 3
to 6 x 1011 platelets (ie, the equivalent of six or more units) per unit. (See 'Collection' above.)

● Storage – Platelets are stored at room temperature; consequently their shelf life is only
approximately five days under most circumstances. Pathogen-reduced platelets are
clinically available, and cryopreservation is an area of active study. (See 'Storage' above.)

● Indications

• Bleeding – Platelet transfusion can be lifesaving in bleeding patients with

thrombocytopenia or reduced platelet function. Platelets should be transfused in any
patient who is bleeding with a platelet count <50,000/microL (100,000/microL for
central nervous system or ocular bleeding), or in any patient with an acquired or
inherited platelet function defect regardless of platelet count. Platelet transfusion may
also be indicated in thrombocytopenic patients undergoing invasive procedures,
 depending on the procedure and the platelet count. (See 'Actively bleeding patient'
above and 'Preparation for an invasive procedure' above.)

Other conditions that impair hemostasis (eg, coagulopathy, fever infection, anatomic
defects) should be corrected in thrombocytopenic patients when possible to reduce
active bleeding and to lessen the risk of spontaneous bleeding. (See 'Actively bleeding
patient' above.)

• Prophylaxis – We use prophylactic platelet transfusion to prevent spontaneous

bleeding in most hospitalized afebrile patients with platelet counts below
10,000/microL due to bone marrow suppression. Patients with acute promyelocytic
leukemia (APL) have a coexisting coagulopathy, and we use a platelet transfusion
threshold of 30,000 to 50,000/microL in these patients. We use higher thresholds in
patients who are febrile or septic. (See 'Prevention of spontaneous bleeding' above and
'Therapeutic versus prophylactic transfusion' above and 'Specific clinical scenarios'
above.)

● Platelet consumption disorders – Patients with platelet consumption disorders, including

immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), heparin-
induced thrombocytopenia (HIT), disseminated intravascular coagulation (DIC), liver
disease, as well as those with platelet function disorders, are typically transfused only for
bleeding or, in some cases, invasive procedures. Platelets should not be withheld in
bleeding patients with these conditions due to fear of "fueling the fire" of thrombosis. (See
'Specific clinical scenarios' above.)

● Potential complications – Platelet transfusion has risks, including sepsis/infection,

transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload
(TACO), alloimmunization, allergic and anaphylactic transfusion reactions, febrile non-
hemolytic transfusion reactions (FNHTR), transfusion-associated graft-versus-host disease
(ta-GVHD), and post-transfusion purpura (PTP). The US Food and Drug Administration (FDA)
issued guidance in late 2019 to reduce the risk of transfusion-transmitted infections from
platelet products. (See 'Complications' above and 'Strategies for reducing pathogens'
above.)

● Approach to refractoriness – Refractoriness to platelet transfusion is discussed separately.

(See "Refractoriness to platelet transfusion therapy".)

● Dosing and special modifications – When ordering platelets, one should consider platelet
dose; whether to use single donor versus random donor platelets; whether to include
leukoreduction, irradiation, or platelets in platelet additive solution (PAS); whether
 cytomegalovirus (CMV)-negative platelets are required; and whether to match HLA, ABO,
and Rh type. (See 'Ordering platelets' above.)

● Alternatives to platelet transfusion – There are limited alternatives to platelet transfusion

for the acute treatment of thrombocytopenia-associated bleeding. Longer term alternatives
include discontinuation of drugs that affect platelet function, treatment of underlying
conditions, and other strategies to increase platelet production. (See 'Actively bleeding
patient' above and 'Alternatives to platelet transfusion' above and 'Platelet function defects'
above.)

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Topic 7918 Version 78.0
GRAPHICS

Information from the ASCO 2017 platelet transfusion guidelines

Platelet products
Source of platelets

Platelets can be prepared from units of whole blood and pooled ("pooled platelets") or obtained by apheresis ("single-donor
platelets"). The efficacy and risks of these products are similar, and they can be used interchangeably in most
circumstances. In most centers, pooled platelets are less expensive. Single-donor platelets are necessary when
histocompatible platelet transfusions (eg, HLA-A- and HLA-B-antigen-matched) are needed.

Rh(D) alloimmunization

Rh(D) alloimmunization in Rh(D)-negative recipients can be prevented/reduced by using products from Rh(D)-negative
donors or by using anti-D immunoprophylaxis. The major risks of Rh(D) alloimmunization are related to hemolytic disease
of the fetus and newborn (HDFN). Thus, these approaches may be used for females with the potential for future
childbearing. However, rates of Rh(D) alloimmunization are low in patients with cancer, and these approaches need not be
applied universally.

Leukoreduction

White blood cells (WBCs) present in the platelet product may cause alloantibody-mediated refractoriness to platelet
transfusion in some individuals; leukoreduction can reduce this risk. It is appropriate to provide leukoreduced blood
products (including platelets) to individuals with AML from the time of diagnosis. Leukoreduced products may also be
useful for individuals with other types of leukemia, those with other types of cancer who are receiving chemotherapy, or
those with other bone marrow disorders who require frequent transfusions. Other advantages of prestorage
leukoreduction include reduction in the rates of transfusion reactions and CMV transmission. The majority of blood
products are prestorage leukoreduced in many countries.

Prophylactic platelet transfusion thresholds*

Hematologic malignancies and allogeneic HCT

Transfuse for a platelet count <10,000/microL. Higher thresholds may apply in certain circumstances (eg, active bleeding,
need for invasive procedure, fever, hyperleukocytosis, rapidly declining platelet count, anticipated delay in seeking care for
bleeding [eg, outpatient who lives far from the treatment center], coagulation abnormalities such as in acute promyelocytic
leukemia, or other indications based on the judgment of the treating clinician).

Autologous hematopoietic stem cell transplantation

Children: Same as described above for hematologic malignancies and allogeneic HCT.

Adults: For the majority of patients, same as described above for hematologic malignancies and allogeneic HCT. In some
experienced centers, it may be appropriate to transfuse at the first sign of bleeding rather than prophylactically ¶, based on
evidence that the risk of severe bleeding is similar with this approach and platelet usage may be decreased. This approach
requires ability to monitor the patient closely and to intervene rapidly at the first sign of bleeding. Clinical judgment applies.

Chronic stable severe thrombocytopenia in the absence of active treatment (eg, MDS, AA)

It may be appropriate to transfuse for bleeding or an invasive procedure or during active treatment. Clinical judgment
applies.

Solid tumors

The risk of bleeding is related to the depth and duration of thrombocytopenia. Transfusion for a platelet count
<10,000/microL is appropriate for most patients. Higher thresholds may apply in certain circumstances (eg, active bleeding,
need for invasive procedure, fever, necrotic tumor).

Surgical or invasive procedures

Major procedures: Transfusion for a platelet count <40,000 to 50,000/microL is appropriate for most procedures in most
patients.

Minor procedures: Transfusion for a platelet count <20,000/microL is appropriate for selected procedures such as bone
marrow aspirate/biopsy or insertion/removal of a central venous catheter.

Lumbar puncture: High-quality data are lacking. Other guidelines have suggested transfusion for a platelet count
<50,000/microL.
 Refractoriness to platelet transfusion
Diagnosis

Refractoriness to platelet transfusion may be suspected when the platelet count does not increase as expected following
transfusion. In such cases, a post-transfusion platelet count should be obtained 10 to 60 minutes after all platelet
transfusions if possible. Refractoriness to platelet transfusion may be diagnosed when transfusion of ABO-compatible
platelets stored for <72 hours fails to result in a reasonable increase in platelet count 10 to 60 minutes after transfusion on
at least two occasions. The expected increase may be determined by calculating the CCI; a CCI of ≥5000/microL is
reasonable. Alternatively, an increment of ≥2000/microL for each unit in a pooled concentrate or ≥10,000/microL for each
unit of single donor (apheresis) platelets is reasonable. For children, an increment of ≥3500/square meter for each
apheresis unit is reasonable.

Management

Refractoriness may be due to immune or non-immune causes. Non-immune causes include fever, sepsis splenomegaly, and
medications. Individuals with alloimmune refractoriness to platelet transfusions are best managed with transfusions from
histocompatible donors matched for HLA-A and HLA-B antigens. Refer to the UpToDate topic on platelet refractoriness for
further details.

The table refers to children and adults unless otherwise specified. Platelet transfusions in newborns are discussed separately in
UpToDate. Refer to UpToDate and the ASCO guideline for additional details and supporting evidence.

ASCO: American Society of Clinical Oncology; HLA: human leukocyte antigen; AML: acute myeloid leukemia; CMV: cytomegalovirus; HCT:
hematopoietic cell transplantation; MDS: myelodysplastic syndrome; AA: aplastic anemia; CCI: corrected count increment.
* Prophylactic platelet transfusions are administered to prevent bleeding in patients with thrombocytopenia when the platelet count
drops below a certain threshold. The threshold depends on the patient's diagnosis, clinical status, and other treatments being
administered.
¶ Refer to UpToDate for a discussion of UpToDate authors' approaches.

Modified from: Schiffer CA, Bohlke K, Delaney M, et al. Platelet transfusion for patients with cancer: American Society of Clinical Oncology clinical
practice guideline update. J Clin Oncol 2017; 35.

Graphic 115892 Version 1.0

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