DEVELOPMENT OF THE PLATELET ANNEX FOR THE
NATIONAL BLOOD SUPPLY CONTINGENCY PLAN (NBSCP)
Executive Summary
The following document details the purpose, methodology and clinical consensus statements that have been
developed by the Blood Service on behalf of the NBA regarding the clinical indications for platelets and their
respective priority in a time of supply shortage.
Table of Contents
Introduction
Page 2
Background
Page 2
Part A: Clinical indications for platelet transfusion
Page 3
Consensus Statement 1 – Clinical indications for platelet transfusion for patients with
Page 3
clinically significant bleeding
Consensus Statement 2 – Clinical indications for prophylactic platelet transfusion for
Page 3
prevention of bleeding
Consensus Statement 3 – Clinical contraindications for platelet transfusion
Part B: Clinical guidance to assist in prioritisation of platelet supply during periods of
Page 4
Page 5
supply constraints
Consensus Statement 4 - Platelet Priority 1
Page 5
Consensus Statement 5 - Platelet Priority 2
Page 6
Consensus Statement 6 - Platelet Priority 3
Page 6
Part C: Consensus Methodology
Page 7
Part D: Supporting evidence
Page 8
Disclaimer:
This document has been prepared by the Australian Red Cross Blood Service on behalf of the National Blood
Authority and is being released for consultation for the purpose of gaining consensus for the clinical indications of
platelets. Appropriate processes were followed to ensure the accuracy of the information included in the
document as at the date of publication. The Blood Service and the National Blood Authority take no responsibility
for reliance on the information contained in the document by any third party.
Introduction
Whilst it is acknowledged that Patient Blood Management (PBM) is influencing transfusion practice by moving the
focus from appropriate use of blood components to appropriate patient management, by necessity, this
document focuses on platelet components and provides guidance to the clinical approach that may be required
during periods of reduced availability of platelets. As context, the document also contains guidance as to the
appropriate indications for platelet therapy during periods where supply is not constrained. The indications for
platelet transfusion included in this document are based, where possible on the recommendations and practice
points included in the National Blood Authority (NBA) PBM Guidelines, their supporting literature review and
expert consensus.
Background
The National Blood Supply Contingency Plan (NBSCP) was developed by the NBA to facilitate and coordinate a
rapid national response in the event of a domestic threat or disaster that affects the provision of a safe and
adequate blood supply in Australia. It outlines the crisis planning, preparation and mitigation of a crisis, response
framework and recovery arrangements for a crisis affecting the supply of blood and blood products. It also
provides guidance on the escalation of contingency management from NBSCP arrangements to the Australian
Health Protection Principal Committee (AHPPC). As part of this framework the NBA has prepared NBSCP Annex C
– Platelets to support the response to a range of risks identified for platelet supply including the prioritisation of
requests for platelets during periods when platelet supply is constrained.
Platelets have a short shelf-life and for this reason an interruption to production or a sudden, large unexpected
increase in demand will have a rapid impact on supply. Similarly, the short shelf-life of platelets makes
redistribution between centres and between jurisdictions within a useful time-frame more challenging compared
with other blood components.
As agreed by consensus, the NBSCP Annex C – Platelets does not require further categorisation into specific
platelet types because during periods of supply constraints the available mix of apheresis derived and whole
blood derived platelets is likely to be significantly different to the planned supply mix because strategies to
increase demand will be influenced by the immediately available surge capacity of both panels.
The platelet count is the primary criteria used for prioritising patients who require platelet therapy, with clinical
risk factors for bleeding and the extent of bleeding also influencing the decision to transfuse.
The document is presented in three sections as follows:

Part A: Clinical indications for platelet transfusion

Part B: Clinical guidance to assist in prioritisation of platelet supply during periods of supply constraints

Part C: Consensus methodology

Part D: Supporting evidence
2
Part A: Clinical indications for platelet transfusion
Platelet transfusion can be given for prevention or treatment of bleeding due to thrombocytopenia or defects of
platelet function. As with all transfusion decisions, the benefit achieved with the prescription and transfusion of
platelets should be balanced against the associated risk.
Consensus Statement 1 – Clinical indications for platelet transfusion for patients with clinically
significant bleeding
The clinical indications for platelet transfusion for patients with clinically significant bleedinga are as follows:
1. Platelet transfusion is indicated for all patients with clinically significant bleeding in whom thrombocytopenia
is thought to be a major contributory factor, even if the platelet count is >10x109/L.
2. In patients with critical bleeding requiring massive blood transfusion. In these patients, the use of a Massive
Transfusion Protocol (MTP) which includes platelet transfusions may reduce the risk of mortality.
3. Platelet transfusion is indicated for patients with congenital or acquired functional platelet defects (including
complex cardiac surgery and/or patients on dual antiplatelet therapy requiring surgical intervention) who are
actively bleeding, although platelet counts are not a reliable indicator in this case.
4. Whilst there is no consensus on a target platelet threshold for the management of bleeding patients with
thrombocytopenia secondary to Disseminated Intravascular Coagulopathy (DIC), aiming to maintain platelet
counts >50x109/L would seem to be reasonable, as well as correction of the underlying aetiology and
replacement of coagulation factors. Platelet transfusion is not indicated for patients with chronic DIC or for
whom there is no bleeding.
5. In general, platelet transfusion is not indicated in immune thrombocytopenia unless there is clinically
significant bleeding
Consensus Statement 2 – Clinical indications for prophylactic platelet transfusion for prevention
of bleeding
The clinical indications for prophylactic platelet transfusion for prevention of bleeding are as follows:
1. Patients with severe thrombocytopenia undergoing chemotherapy and haematopoietic stem cell
transplantation should receive prophylactic platelet transfusion at a platelet count of <10x109/L in the
absence of risk factors and at <20x109/L in the presence of risk factors (e.g. fever).
2. In critically ill patients, in the absence of acute bleeding, the administration of platelet transfusion may be
considered appropriate at a platelet count of <20x109/L. The administration of platelet transfusion may be
considered appropriate at a higher platelet count for neonates, such as <25x109/L for term neonates and
<30-50x109/L for preterm neonates or any neonate with Neonatal Alloimmune Thrombocytopenia (NAIT).
Although in NAIT it is preferable to give platelets without the relevant HPA antigen, random donor platelets
may be effective
3. For patients with other causes of bone marrow failure with chronic failure of platelet production (e.g.
myelodysplasia and aplastic anaemia), a specific threshold for transfusion may not be appropriate and such
patients should be managed on an individual basis. Long term prophylactic platelet transfusion may be best
avoided because of the risk of complications.
a
Webert Bleeding Severity Measurement Scale defines clinically significant bleeding (Grade 2). Webert KE, Arnold DM, Lui Y, Carruthers J,
Arnold E, Heddle NM. A new tool to assess bleeding severity in patients with chemotherapy-induced thrombocytopenia (CME). Transfusion.
2012 Nov; 52 (11): 2466-2474
3
4. In patients undergoing invasive procedures, there is insufficient evidence to define a threshold platelet count
that is associated with increasing risk of bleeding, however:

In general, for patients undergoing procedures such as insertion of central venous catheters, endoscopy
and biopsy, lumbar puncture and laparotomy, a platelet count ≥50 x109/L is considered safe.

A lower threshold may be tolerated for minor procedures such as dental extractions, skin biopsy and
insertion of peripherally inserted central catheters (PICC) where adequate surface pressure can be
applied.

For patients undergoing intracranial, intraocular and neuraxial surgery, it is generally suggested that the
platelet threshold be raised to ≥100x109/L.
5. In patients with head injury, it is suggested to keep the platelet count >100x109/L.
6. Functional platelet disorders include inherited or acquired platelet function disorders. In these groups of
patients, prophylactic platelets may be considered before invasive procedures.
Consensus Statement 3 – Clinical contraindications for platelet transfusion
The clinical contraindications for platelet transfusions are as follows:
1. Platelet transfusion is contraindicated in patients where bleeding is unrelated to a decreased platelet count or
to functional platelet defects.
2. For patients with Heparin Induced Thrombocytopenia (HIT) and Thrombotic Thrombocytopenic Purpura (TTP),
platelet transfusion is contraindicated unless there is life-threatening haemorrhage as it can exacerbate the
underlying conditions. There are limited case reports regarding the successful use of platelets in patients
with Haemolytic Uraemic Syndrome (HUS) and TTP to cover invasive procedures that cannot be postponed
until the underlying disease has been resolved (e.g. central line placement for plasma exchange therapy).
3. The routine prophylactic use of platelets after cardiac surgery is not supported.
4
Part B: Clinical guidance to assist in prioritisation of platelet supply during
periods of supply constraints
During periods of platelet supply constraints, it may be necessary to prioritise the supply of platelet transfusions
to patients with the greatest clinical need and to delay the supply of platelets to other patients pending stock
availability (such as when infectious disease screening is completed). In this scenario, all clinically appropriate
requests for platelet supply are able to be met, albeit the supply for some patients may be briefly delayed.
Prioritisation of platelet supply in this scenario is undertaken by medical staff at the Australian Red Cross Blood
Service.
However, where the supply constraint is more severe, it may be necessary to restrict the supply of platelets to
particular patient categories. In these situations, the NBSCP will be activated and there will be communication
between stakeholders, including the NBA, Jurisdictional Blood Committee (JBC), AHPPC and the Blood Service.
Prescribing clinicians will be informed about the necessity to reduce the demands for platelets.
This document provides guidance for the prioritisation of requests for platelets during periods when platelet
supply is constrained. In descending order of urgency, patients can be classified in Platelet Priority 1-3, with
patients in Platelet Priority 1 having the highest priority for transfusion.
Consensus Statement 4 - Platelet Priority 1
During periods when platelet supply is constrained, the following patients have the highest priority for platelet
transfusion and are classified as “Platelet Priority 1”.
Patients with clinically significant bleedingb

Patients with clinically significant bleeding in whom thrombocytopenia or platelet dysfunction is thought
to be a major contributory factor.

Patients with critical bleeding requiring massive blood transfusion.

Patients with clinically significant bleeding in the presence of acute Disseminated Intravascular
Coagulopathy (DIC) and a platelet count <50x109/L.
Patients requiring platelet support for immediate or urgent surgeryc

Patients who require immediate or urgent surgery with a platelet count <50 x109/L or with functional
platelet defects.

Patients who require immediate or urgent neurosurgery, intraocular or neuroaxial surgery with a platelet
count <100x109/L or with functional platelet defects.
b
Webert Bleeding Severity Measurement Scale defines clinically significant bleeding (Grade 2). Webert KE, Arnold DM, Lui Y, Carruthers J,
Arnold E, Heddle NM. A new tool to assess bleeding severity in patients with chemotherapy-induced thrombocytopenia (CME). Transfusion.
2012 Nov; 52 (11): 2466-2474
c
Immediate: Immediate life, limb or organ-saving operation. Resuscitation simultaneous with surgical treatment. Operation within
minutes of decision to operate (e.g. laparotomy / thoracotomy for control of haemorrhage).
Urgent: Acute onset or deterioration of conditions that threaten life, limb or organ survival or for relief of distressing symptoms.
Operation within hours of decision to operate and normally once resuscitation completed (e.g. laparotomy for perforation). Australia &
New Zealand Gastric & Oesophageal Surgery Association Audit Data Dictionary. Version 3. Morbidity Audits Department Research,
Audit and Academic Surgery Division; Jan 2013. Urgency of Surgery; p. 43.
5
Consensus Statement 5 - Platelet Priority 2
During periods when platelet supply is constrained, the following patients have moderate priority for platelet
transfusion and are classified as “Platelet Priority 2”.
Patients at high risk of critical bleeding

Patients with head injury and a platelet count <100x109/L.

Neonates with Neonatal Alloimmune Thrombocytopenia (NAIT) (platelet count <30x109/L).

Neonates with severe thrombocytopenia (<25x109/L for term neonates and <30-50x109/L for preterm
neonates).
Patients requiring prophylactic platelet transfusion for prevention of bleeding

Patients with severe thrombocytopenia undergoing chemotherapy and haematopoietic stem cell
transplantation with a platelet count of <10x109/L in the absence of risk factors and at <20x109/L in the
presence of risk factors (e.g. fever).

Critically ill patients with a platelet count of <20x109/L.
Consensus Statement 6 - Platelet Priority 3
During periods when platelet supply is constrained, the following patients have the lowest priority for platelet
transfusion and are classified as “Platelet Priority 3”.
Patients requiring platelet support for expedited surgeryd or invasive procedures

Patients who require expedited surgery with a platelet count <50x109/L or with functional platelet
defects.

Patients who require expedited neurosurgery, intraocular or neuroaxial surgery with a platelet count
<100x109/L or with functional platelet defects.

Patients requiring expedited invasive procedure or biopsy with a platelet count <50x109/L or with
functional platelet defects.
Patients requiring platelet support for elective surgerye

Elective surgery in patients who may require platelet support for thrombocytopenia or functional platelet
defects.
d
Expedited: Stable patient requiring early intervention for a condition that is not an immediate threat to life, limb or organ survival.
Operation within days of decision to operate). Australia & New Zealand Gastric & Oesophageal Surgery Association Audit Data Dictionary.
Version 3. Morbidity Audits Department Research, Audit and Academic Surgery Division; Jan 2013. Urgency of Surgery; p. 43.
e
Elective: Surgical procedure planned or booked in advance of routine admission to hospital. Operation at a time to suit both patient and
surgeon. ). Australia & New Zealand Gastric & Oesophageal Surgery Association Audit Data Dictionary. Version 3. Morbidity Audits
Department Research, Audit and Academic Surgery Division; Jan 2013. Urgency of Surgery; p.43.
6
Part C: Consensus Methodology
Criteria for establishing the consensus group:
As part of the NBA Platelets Project deliverables, the Blood Service was required to assemble a group of external
expert clinicians to assist with the review of the NBSCP Annex C - Platelets and develop consensus statements
incorporating:


Clinical indications and contraindications for platelet transfusion
Clinical guidance to assist in prioritisation of platelet supply during periods of supply constraints
The Blood Service external Advisory Committee members were engaged as the consensus group members for this
process. In addition, a Consultant Haematologist with paediatric and obstetric expertise was targeted to ensure
broad clinical representation within the group. Final membership included representation from clinical and
laboratory haematology, transfusion medicine, intensive care, microbiology, infectious diseases, molecular
genetics, transplantation, research, anaesthetics, orthopaedics and oncology. A representative from the NBA was
also included in the consensus group as an observer of the process. As part of the selection process, consensus
group members had to be able to commit themselves to the consensus process and timelines for the project.
Drafting of the consensus statements:
The PBM guidelines were used as the basis for the development of the clinical indications and contraindications
for platelet transfusions. A targeted literature search was also conducted in order to develop the background
paper and 6 associated consensus statements.
The consensus statements and supporting information were initially reviewed by the Blood Service National Blood
Transfusion Committee. Membership of this committee includes internal and external haematology and
transfusion medicine experts. A subsequent review and final approval was conducted by Blood Service personnel
with laboratory and clinical haematology expertise prior to being disseminated to the consensus group members
for consideration.
7
Part D: Supporting evidence
D1: Sourced from the NBA PBM Modules
A multilevel management framework was established by the National Blood Authority (NBA) to coordinate
the development of the new patient blood management guidelines. The management framework consisted
of:

A Steering Committee, responsible for the overall development and governance of the entire project.

An Expert Working Group (EWG), responsible for clinical oversight and integration of the six modules.

Clinical/Consumer Reference Groups (CRGs – one for each of the six modules), with membership
including representation from relevant colleges, societies and consumer groups, to provide expert
knowledge and input.

Systematic reviewers and a technical writer, contracted by the NBA to review the literature and develop a
draft of each module.

An independent systematic review expert, to provide advice and mentoring to the systematic reviewers,
technical writer and CRGs; and to ensure that the development process and the guidelines produced
comply with National Health and Medical Research Council (NHMRC) requirements.
Each patient blood management module has been endorsed by the NHMRC and this endorsement is valid for a
period of 5 years. The date of endorsement for each of the modules is as follows:

Module 1: Critical Bleeding/ Massive Transfusion was approved by the NHMRC on 12 November 2010 and
released on 1 March 2011.

Module 2: Perioperative was approved by the NHMRC on 15 November 2011 and released on 9 March
2012.

Module 3: Medical was approved by the NHMRC on 18 July 2012 and released on 19 September 2012.

Module 4: Critical Care was approved by the NHMRC on 14 December 2012 and released on 5 April 2013.
Each module includes:

Recommendations – based on evidence from the systematic review.

Practice points – based on consensus decision making, where the systematic review found insufficient
high-quality data to produce evidence-based recommendations, but where it was considered that
clinicians require guidance to ensure good clinical practice.
The indications for platelet transfusion included in this document are based, where possible, on the
recommendations and practice points included in the NBA Patient Blood Management modules, their supporting
literature review and expert consensus.
The following information, relevant to platelet transfusion, has been extracted from the NBA Patient Blood
Management Guidelines.
8
Patient Blood Management Guidelines: Module 1 Critical Bleeding / Massive Transfusion
Recommendations:

It is recommended that institutions develop a Massive Transfusion Protocol (MTP) that includes the dose,
timing and ratio of blood component therapy for use in trauma patients with, or at risk of, critical
bleeding requiring massive transfusion (Ref 4, 5).
Practice Points:

Practice Point 1: In patients with critical bleeding requiring massive transfusion, the following parameters
should be measured early and frequently: temperature, acid–base status, ionised calcium, haemoglobin,
platelet count, PT/INR, APTT and fibrinogen level. With successful treatment, values should trend towards
normal.

Practice Point 2: Values indicative of critical physiologic derangement include temperature < 35°C, pH <
7.2, base excess > –6, lactate > 4 mmol/L, ionised calcium < 1.1 mmol/L, platelet count < 50×109/L, PT >
1.5 × normal, INR > 1.5, APTT > 1.5 × normal and fibrinogen level < 1.0 g/L.

Practice Point 3: In critically bleeding patients requiring, or anticipated to require, massive transfusion, a
MTP should be used.

Practice Point 4: In patients with critical bleeding requiring massive transfusion, insufficient evidence was
identified to support or refute the use of specific ratios of RBCs to blood components.

Practice Point 7: In patients with critical bleeding requiring massive transfusion, the use of an MTP to
facilitate timely and appropriate use of RBC and other blood components may reduce the risk of mortality
and ARDS.

Practice Point 10: In patients with critical bleeding requiring massive transfusion, suggested doses of
blood components are FFP: 15 mL/kg, platelets: 1 adult therapeutic dose and cryoprecipitate: 3–4 g. Or as
directed by the haematologist/transfusion specialist in specific clinical situations, such as obstetrics.
Literature Review:
Five studies calculated the odds of predicting mortality (or survival) among patients with critical bleeding
requiring massive transfusion (Ref 15, 61, 64, 65, 68). Although not strictly a study of massive transfusion
(because patients included received ≥ 5 units RBCs within 24 hours of admission), Mitra (Ref 15) found that a
number of factors were independent predictors of mortality:
•
hypothermia (odds ratio [OR] = 0.72; 95%CI: 0.56, 0.92; p = 0.01)
•
thrombocytopenia (OR = 0.99; 95%CI: 0.98, 1; p< 0.01)

increased international normalised ratio (INR) (OR = 1.62; 95%CI: 1.18, 2.24; p< 0.01)

prolonged partial thromboplastin time (OR = 1.01; 95%CI: 1.01, 1.02; p< 0.01)
•
low fibrinogen level (OR = 0.52; 95%CI: 0.28, 0.99; p = 0.05)
•
low pH (OR = 0.01; 95%CI: 0, 0.29; p = 0.01)
•
low bicarbonate levels (OR = 0.86; 95%CI: 0.77, 0.96; p = 0.01).
9
Insufficient studies were found to provide an evidence statement on the effects of hypothermia,
metabolic acidosis, thrombocytopenia and coagulopathy on morbidity or transfusion rate.
A survival advantage is associated with decreasing the ratio of RBCs to fresh frozen plasma (FFP), platelets or
cryoprecipitate/fibrinogen administered to patients undergoing massive transfusion (Ref 65, 76, 78, 89). The
decrease in mortality associated with administering low versus high ratios of RBCs to blood components was
associated with a significant decrease in deaths from exsanguination. This decrease was attributed to
administration of lower ratios of RBCs to FFP, platelets, apheresis platelets and fibrinogen (Ref 61, 65, 76, 79).
More deaths were reported in patients receiving high ratios of RBCs to blood components compared with lowratio recipients. However, these results should be interpreted carefully, because of the potential for survival bias
(that is, patients who die early are more likely to have received a higher RBC: component ratio) (Ref 84).
The types and content of the studies varied in terms of blood components and the ratios given; therefore, the
optimum target ratio is difficult to determine. In trauma patients, a ratio of RBC: FFP: platelets of ≤ 2:1:1 was
associated with improved survival (Ref 5, 70, 71). A number of these studies used a ratio of, or near to, 1:1 (ref 4,
5, 70, 71, 76, 78, 79, 85, 89). Other studies used a ratio of < 2:1:1 (Ref 5, 70, 71). However, based on analysis of
the available studies and the possibility of survival bias, it is not possible to recommend a target ratio of RBC: FFP:
platelets.
In non-trauma patients, there were insufficient data to support or refute the use of a defined ratio of blood
component replacement. Although these patients do not have the initial coagulopathy commonly seen in trauma,
critical bleeding may still result in development of hypothermia, acidosis and coagulopathy. Coordination of the
management of these patients through use of an MTP is recommended. Blood component replacement should be
guided by clinical assessment and results of coagulation tests.
Four Level III studies examined the effect of FFP or platelet transfusion on mortality or morbidity (Ref 5, 61, 75,
95). An RBC: FFP ratio of ≤ 2:1 was reported to be associated with reduced mortality (Ref 61, 75). However, this
outcome is potentially confounded by survivor bias. No studies investigated the use of fibrinogen or
cryoprecipitate as an intervention.
References (from PBM Guidelines: Module 1 Critical Bleeding / Massive Transfusion):
Ref 4: Cotton BA, Au BK, Nunez TC, Gunter OL, Robertson AM and Young PP (2009). Predefined massive
transfusion protocols are associated with a reduction in organ failure and postinjury complications. Journal of
Trauma 66(1):41–48.
http://www.ncbi.nlm.nih.gov/pubmed/19131804
Ref 5: Dente CJ, Shaz BH, Nicholas JM, Harris RS, Wyrzykowski AD, Patel S, Shah A, Vercruysse GA, Feliciano DV,
Rozycki GS, Salomone JP and Ingram WL (2009). Improvements in early mortality and coagulopathy are
sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian
level I trauma center. Journal of Trauma 66(6):1616–1624.
http://www.ncbi.nlm.nih.gov/pubmed/19509623
Ref 15: Mitra B, Mori A, Cameron PA, Fitzgerald M, Street A and Bailey M (2007). Massive blood transfusion
and trauma resuscitation. Injury 38(9):1023-1029.
http://www.ncbi.nlm.nih.gov/pubmed/17572415
Ref 61: Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D,
Wade CE and Holcomb JB (2007). The ratio of blood products transfused affects mortality in patients
receiving massive transfusions at a combat support hospital. Journal of Trauma 63(4):805-813.
http://www.ncbi.nlm.nih.gov/pubmed/18090009
Ref 64: Gonzalez EA, Moore FA, Holcomb JB, Miller CC, Kozar RA, Todd SR, Cocanour CS, Balldin BC and
10
McKinley BA (2007). Fresh frozen plasma should be given earlier to patients requiring massive
transfusion. Journal of Trauma 62(1):112-119.
http://www.ncbi.nlm.nih.gov/pubmed/17215741
Ref 65: Stinger HK, Spinella PC, Perkins JG, Grathwohl KW, Salinas J, Martini WZ, Hess JR, Dubick MA,
Simon CD, Beekley AC, Wolf SE, Wade CE and Holcomb JB (2008). The ratio of fibrinogen to red cells
transfused affects survival in casualties receiving massive transfusions at an army combat support
hospital. Journal of Trauma 64(2 Suppl):S79-85.
http://www.ncbi.nlm.nih.gov/pubmed/18376176
Ref 68: Moore FA, Nelson T, McKinley BA, Moore EE, Nathens AB, Rhee P, Puyana JC, Beilman GJ and Cohn
SM (2008). Massive transfusion in trauma patients: tissue hemoglobin oxygen saturation predicts
poor outcome. Journal of Trauma 64(4):1010-1023.
http://www.ncbi.nlm.nih.gov/pubmed/18404069
Ref 70: Cinat ME, Wallace WC, Nastanski F, West J, Sloan S, Ocariz J and Wilson SE (1999). Improved survival
following massive transfusion in patients who have undergone trauma. Archives of Surgery 134(9):964–968.
http://www.ncbi.nlm.nih.gov/pubmed/10487591
Ref 71: Gunter OL, Jr., Au BK, Isbell JM, Mowery NT, Young PP and Cotton BA (2008). Optimizing outcomes in
damage control resuscitation: identifying blood product ratios associated with improved survival. Journal of
Trauma 65(3):527–534.
http://www.ncbi.nlm.nih.gov/pubmed/18784564
Ref 75: Duchesne JC, Hunt JP, Wahl G, Marr AB, Wang YZ, Weintraub SE, Wright MJ and McSwain NE, Jr.
(2008). Review of current blood transfusions strategies in a mature level I trauma center: were we
wrong for the last 60 years? Journal of Trauma 65(2):272-276.
http://www.ncbi.nlm.nih.gov/pubmed/18695461
Ref 76: Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, Gonzalez EA, Pomper
GJ, Perkins JG, Spinella PC, Williams KL and Park MS (2008). Increased plasma and platelet to red
blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Annals of
Surgery 248(3):447-458.
http://www.ncbi.nlm.nih.gov/pubmed/18791365
Ref 78: Maegele M, Lefering R, Paffrath T, Tjardes T, Simanski C and Bouillon B (2008). Red-blood-cell to
plasma ratios transfused during massive transfusion are associated with mortality in severe
multiple injury: a retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft fur
Unfallchirurgie. Vox Sanguinis 95(2):112-119.
http://www.ncbi.nlm.nih.gov/pubmed/18557827
Ref 79: Perkins JG, Andrew CP, Spinella PC, Blackbourne LH, Grathwohl KW, Repine TB, Ketchum L,
Waterman P, Lee RE, Beekley AC, Sebesta JA, Shorr AF, Wade CE and Holcomb JB (2009). An
evaluation of the impact of apheresis platelets used in the setting of massively transfused trauma
patients. Journal of Trauma 66(4 Suppl):S77-84.
http://www.ncbi.nlm.nih.gov/pubmed/19359974
Ref 84: Snyder CW, Weinberg JA, McGwin G, Jr., Melton SM, George RL, Reiff DA, Cross JM, Hubbard-Brown J,
Rue LW, 3rd and Kerby JD (2009). The relationship of blood product ratio to mortality: survival benefit
or survival bias? Journal of Trauma 66(2):358-362.
http://www.ncbi.nlm.nih.gov/pubmed/19204508
Ref 85: Sperry JL, Ochoa JB, Gunn SR, Alarcon LH, Minei JP, Cuschieri J, Rosengart MR, Maier RV, Billiar TR,
Peitzman AB and Moore EE (2008). An FFP:PRBC transfusion ratio >/=1:1.5 is associated with a lower risk of
mortality after massive transfusion. Journal of Trauma 65(5):986–993.
http://www.ncbi.nlm.nih.gov/pubmed/19001962
Ref 89: Zink KA, Sambasivan CN, Holcomb JB, Chisholm G and Schreiber MA (2009). A high ratio of plasma and
platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large
11ulticentre study. American Journal of Surgery 197(5):565–570.
http://www.ncbi.nlm.nih.gov/pubmed/19393349
11
Ref 95: Bochicchio GV, Napolitano L, Joshi M, Bochicchio K, Meyer W and Scalea TM (2008). Outcome analysis of
blood product transfusion in trauma patients: a prospective, risk-adjusted study. World Journal of Surgery
32(10):2185-2189.
http://www.ncbi.nlm.nih.gov/pubmed/18575931
12
Patient Blood Management Guidelines: Module 2 Perioperative
Practice points:

Practice Point 17 - In general, patients with a platelet count ≥50 × 109/L or an INR ≤2 can undergo invasive
procedures without any serious bleeding; however, lower platelet counts and higher INRs may be
tolerated.

Practice Point 18 - Specialist guidelines or haematology advice should be sought for at-risk patients
undergoing intracranial, intraocular and neuraxial procedures, and for patients with severe
thrombocytopenia or coagulopathy.

Practice Point 19 - The prophylactic use of platelets after cardiac surgery is not supported.
Literature Review
The systematic review identified 16 relevant studies (6 Level II and 10 Level III, of fair to good quality)
examining the effect of abnormal coagulation parameters on outcomes in patients undergoing surgery or
invasive procedures (Ref 241- 255). These studies included a diverse range of invasive procedures, including
biopsies (visceral, endoscopic and laparoscopic), central venous cannulation, lumbar puncture, nephrostomy
and femoral arteriography. There was insufficient evidence to define a threshold platelet count, fibrinogen
level or INR that is associated with significant adverse events (Ref 241-255). Worsening thrombocytopenia may
be associated with an increase in minor bleeding complications (Ref 242, 243, 248, 252, 256). Appendix E
Three fair-quality Level III studies that investigated the effect of platelet transfusion on patient outcomes in a
perioperative population were identified (Ref 259 -261). All studies were in cardiac surgery patients. The largest
and smallest of these studies demonstrated an association between the administration of platelets, and hospital
mortality and morbidity (Ref 260, 261). The remaining study did not demonstrate this association (Ref 259).
References
References (from PBM Guidelines: Module 2 Perioperative):
Ref 241: Dillon JF, Simpson KJ and Hayes PC (1994). Liver biopsy bleeding time: an unpredictable event. Journal of
gastroenterology and hepatology 9(3):269-271.
http://www.ncbi.nlm.nih.gov/pubmed/8054526
Ref 242: Doerfler ME, Kaufman B and Goldenberg aS (1996). Central venous catheter placement in patients
with disorders of hemostasis. Chest 110(1):185-188.
http://www.chestjournal.org/cgi/doi/10.1378/chest.110.1.185
Ref 243: Fisher NC and Mutimer DJ (1999). Central venous cannulation in patients with liver disease and
coagulopathy--a prospective audit. Intensive care medicine 25(5):481-485.
http://www.ncbi.nlm.nih.gov/pubmed/10401942
Ref 244: Foster PF, Moore LR, Sankary HN, Hart ME, Ashmann MK and Williams JW (1992). Central venous
catheterization in patients with coagulopathy. Archives of Surgery 127(3):273-275.
http://www.ncbi.nlm.nih.gov/pubmed/1550472
Ref 245: Howard SC (2000). Safety of lumbar puncture for children with acute lymphoblastic leukemia and
thrombocytopenia. Journal of the American Medical Association 284(17):2222-2224.
http://jama.ama-assn.org/cgi/doi/10.1001/jama.284.17.2222
Ref 246: Mainwaring CJ, Natarajan A, Peckham C, Readett D, Singhal R, Vazzalwar R, et al. (Untreated
thrombocytopenia and lumbar puncture-related bleeding risk at diagnosis of childhood acute lymphoblastic
leukemia (ALL) [abstract]. In: Poster Presentations, Conference of the British Society for Haematology; April
27–30 1998; Glasgow, Scotland.
13
Ref 247: Martin JH, Rosser CJ, Linebach RF, McCullough DL and Assimos DG (2000). Are coagulation studies
necessary before percutaneous nephrostomy? Techniques in urology 6(3):205-207.
http://www.ncbi.nlm.nih.gov/pubmed/10963488
Ref 248: McVay PA and Toy PT (1990). Lack of increased bleeding after liver biopsy in patients with mild
hemostatic abnormalities. American journal of clinical pathology 94(6):747-753.
http://www.ncbi.nlm.nih.gov/pubmed/2123077
Ref 249: Misra S, Gyamlani G, Swaminathan S, Buehrig CK, Bjarnason H, McKusick MA, et al. (2008). Safety and
diagnostic yield of transjugular renal biopsy. Journal of Vascular and Interventional Radiology 19(4):546-551.
http://www.ncbi.nlm.nih.gov/pubmed/18375299
Ref 250: Ray CE and Shenoy SS (1997). Patients with thrombocytopenia: outcome of radiologic placement of
central venous access devices. Radiology 204(1):97-99.
http://www.ncbi.nlm.nih.gov/pubmed/9205228
Ref 251: Ruell J, Karuvattil R, Wynn R and Will A (2007). Platelet count has no influence on traumatic and
bloody lumbar puncture in children undergoing intrathecal chemotherapy. British journal of haematology
136(2):347-348.
http://www.ncbi.nlm.nih.gov/pubmed/17156399
Ref 252: Vavricka SR, Walter RB, Irani S, Halter J and Schanz U (2003). Safety of lumbar puncture for adults
with acute leukemia and restrictive prophylactic platelet transfusion. Annals of hematology 82(9):570573.
http://www.ncbi.nlm.nih.gov/pubmed/12904898
Ref 253: Weigand K, Encke J, Meyer FJ, Hinkel UP, Munder M, Stremmel W, et al. (2009). Low levels of
prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central
venous catheters. Medizinische Klinik 104(5):331-335.
http://www.ncbi.nlm.nih.gov/pubmed/19444412
Ref 254: Weiss SM, Hert RC, Gianola FJ, Clark JG and Crawford SW (1993). Complications of fiberoptic
bronchoscopy in thrombocytopenic patients. Chest 104(4):1025-1028.
http://www.ncbi.nlm.nih.gov/pubmed/8404159
Ref 255: Wolf AT, Wasan SK and Saltzman JR (2007). Impact of anticoagulation on rebleeding following
endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage. American Journal of
Gastroenterology 102(2):290-296.
http://www.ncbi.nlm.nih.gov/pubmed/17100959
Ref 256: Darcy MD, Kanterman RY, Kleinhoffer MA, Vesely TM, Picus D, Hicks ME, et al. (1996). Evaluation of
coagulation tests as predictors of angiographic bleeding complications. Radiology 198(3):741-744.
http://www.ncbi.nlm.nih.gov/pubmed/8628863
Ref 257: Casbard AC, Williamson LM, Murphy MF, Rege K and Johnson T (2004). The role of prophylactic
fresh frozen plasma in decreasing blood loss and correcting coagulopathy in cardiac surgery. A systematic
review. Anaesthesia 59(6):550-558.
http://www.ncbi.nlm.nih.gov/pubmed/15144294
Ref 258: Sarani B, Dunkman WJ, Dean L, Sonnad S, Rohrbach JI and Gracias VH (2008). Transfusion of fresh
frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Critical care
medicine 36(4):1114-1118.
http://www.ncbi.nlm.nih.gov/pubmed/18379235
Ref 259: Karkouti K, Wijeysundera DN, Yau TM, Callum JL, Meineri M, Wasowicz M, et al. (2006). Platelet
transfusions are not associated with increased morbidity or mortality in cardiac surgery. Canadian Journal of
14
Anesthesia 53(3):279-287.
http://www.ncbi.nlm.nih.gov/pubmed/16527794
Ref 260: McGrath T, Koch CG, Xu M, Li L, Mihaljevic T, Figueroa P, et al. (2008). Platelet transfusion in cardiac
surgery does not confer increased risk for adverse morbid outcomes. Annals of Thoracic Surgery 86(2):543-553.
http://www.ncbi.nlm.nih.gov/pubmed/18640332
Ref 261: Spiess BD, Royston D, Levy JH, Fitch J, Dietrich W, Body S, et al. (2004). Platelet transfusions during
coronary artery bypass graft surgery are associated with serious adverse outcomes. Transfusion 44(8):11431148.
http://www.ncbi.nlm.nih.gov/pubmed/15265117
15
Patient Blood Management Guidelines: Module 3 Medical
Recommendations:

Recommendation 8 - In patients undergoing chemotherapy and haematopoietic stem cell transplantation,
the recommended strategy for prophylactic use of platelets is transfusion at a platelet count of <10 ×
109/L in the absence of risk factors, and at <20 × 109/L in the presence of risk factors (e.g. fever, minor
bleeding).
Practice Points:



Practice Point 20 - Platelet transfusion may be indicated for the prevention and treatment of
haemorrhage in patients with thrombocytopenia or platelet function defects. Platelet transfusions are not
indicated in all causes of thrombocytopenia, and may be contraindicated in certain conditions (e.g. TTP
and HIT). Thus, the cause of the thrombocytopenia should be established and expert opinion sought.
Practice Point 21 - In patients with chronic failure of platelet production (e.g. myelodysplasia or aplastic
anaemia), a specific threshold for transfusion may not be appropriate. These patients are best managed
on an individual basis, in consultation with a relevant expert. Long-term prophylactic platelet transfusions
may be best avoided because of the risk of complications (e.g. alloimmunisation and platelet
refractoriness). Therapeutic platelet transfusions could be considered for treatment of bleeding.
Practice Point 22 - In patients undergoing chemotherapy and haematopoietic stem cell transplantation,
there is no evidence to support a lower trigger for prophylactic platelet transfusion for patients with risk
factors (e.g. fever, minor bleeding) or a strategy of therapeutic-only platelet transfusions (i.e. for
treatment of clinically significant bleeding). Further research to determine the safety and efficacy of a
lower platelet transfusion trigger is underway.
Literature Review:
Platelet transfusion is a therapeutic intervention used for the prevention and treatment of bleeding in patients
with thrombocytopenia or significant platelet dysfunction. The different methods for producing platelets result
in differences in the final products (e.g. in dose and risk profile); this should be taken into account when
comparing studies. The focus of this systematic review was to first compare prophylactic and therapeutic
transfusion strategies, and then compare different platelet transfusion doses.
Prophylactic and therapeutic transfusion strategies
A small number of eligible studies were identified; all involved patients with cancer, including haematological
malignancies. Thrombocytopenia was most commonly due to chemotherapy or stem cell transplantation. One
additional study was a multivariate analysis of association between transfusions and venous thromboembolism,
arterial thromboembolism and mortality in a broad population of hospitalised patients with cancer (Ref 90). No
studies were found that included populations of special interest, such as patients receiving treatment with
antifibrinolytic or antiplatelet therapy.
In patients with haematological malignancies receiving chemotherapy, mortality was reported in two
studies: an RCT (Level II) (Ref 131) that was inadequately powered to detect any clinically or statistically
significant differences, and a cohort study (Level IV) (Ref 132) that did not report any comparative data,
but reported a mortality rate of 4.3% in patients receiving platelet transfusions.
The cohort study (Level III-2) in a broad population of hospitalised cancer patients (Ref 90) found that
platelet transfusion was independently associated with in-hospital mortality, and venous and arterial
thromboembolism. This study controlled for a range of variables; however, as a cohort study, it could not
establish causality.
16
Two studies reported the incidence of bleeding events. One RCT (Level II) (Ref 133) reported no significant
difference between study arms, and one cohort study (Level IV) (Ref 132) found an incidence rate of 58.0% for
grade 2 bleeding and 5.1% for grade 3 – 4 bleeding.
Four cohort studies reported the incidence of transfusion-related adverse events in patients receiving platelet
transfusions (Ref 132,134-136). The incidences of adverse events ranged widely between studies. However,
these discrepancies can probably be accounted for by differences in the study populations and the type of
platelet product transfused.
Clinical guidance
Platelet transfusion doses
Five RCTs (Level II) assessed platelet dose in patients with haematological malignancies receiving
chemotherapy (Ref 137-141). The definitions of thrombocytopenia and the assessed dose ranges varied widely
between the studies. Mortality was reported in only one study (Ref 137); this study found no significant
difference between any of the assessed platelet doses, but was underpowered.
3
Four studies reported the incidence of bleeding events. Slichter et al (Ref 137) and Heddle et al (ref 138)
found no significant difference between study arms in any of the dose comparisons presented. Tinmouth et
al found a higher risk of experiencing a minor bleed in patients receiving three platelet units than five
platelet units, but no significant difference between different platelet doses for the incidence of major
bleeds (Ref 139). The study by Sensebé et al was underpowered to detect an effect of platelet dose on the
incidence of haemorrhage (ref 141).
There was no significant difference between study arms in the two studies that reported the incidence of
transfusion-related serious adverse events (ref 132, 137). However, the overall rate of serious adverse events
was relatively high in both studies.
There is controversy over the benefit of using FFP, cryoprecipitate and platelet concentrates to improve
haemostasis in both procedural and non-procedural settings. In the absence of high-quality evidence,
clinicians have traditionally relied on laboratory indexes for making decisions about transfusion of these
products. The systematic review considered purported ‘transfusion-trigger’ levels of these various indexes,
excluding studies of patients with massive bleeding or requiring warfarin reversal.
The use of prophylactic platelet transfusions in patients receiving myelosuppressive chemotherapy or
undergoing allogeneic haematopoietic stem cell transplantation (HSCT) is significant. It currently accounts for
most of the platelet concentrate usage in Australia. In this clinical setting – in the absence of acute bleeding or
the need for an invasive procedure – prophylactic platelet transfusion is usually guided by platelet counts. The
review examined studies concerning platelet count and bleeding risk, together with the intervention of platelet
transfusion, but excluded studies in perioperative or acute bleeding settings.
The review identified four RCTs (Level II) comparing different platelet transfusion triggers. Three studies (ref
147-149) compared a platelet transfusion trigger of 10 × 109/L with one of 20 × 109/L. Another study used 30
× 109/L as the higher trigger (Ref 150). Of these studies, three (ref 147, 14, 150) did not demonstrate a
significant difference in mortality between the two study arms. These three studies reported bleeding events,
but none observed a significant difference in bleeding rates between the two study arms, nor in bleeding rates
in relation to a more restrictive platelet transfusion trigger. RBC transfusion rates were reported in all four
studies. None of the studies demonstrated significant differences in number of RBC units transfused, or in the
number of transfusions, between study arms.
17
Based on these results, in patients undergoing myelosuppressive chemotherapy or HSCT, the
recommended strategy for prophylactic platelet transfusion is at a platelet count of <10 × 109/L in the
absence of risk factors, and at <20 × 109/L in the presence of risk factors (see recommendation R8 above).
There is no evidence at this time to support a lower threshold for prophylaxis, or for the absence of
prophylaxis. However, these questions are the current focus of two major international RCTs.
References (from PBM Guidelines: Module 3 Medical):
Ref 14: National Health and Medical Research Council (NHMRC) (2009). NHMRC levels of evidence and grades for
recommendations for developers of guidelines, NHMRC, Canberra, Australia.
http://www.nhmrc.gov.au/guidelines/consult/consultations/add_levels_grades_dev_ guidelines2.htm
Ref 90: Khorana AA, Francis CW, Blumberg N, Culakova E, Refaai MA and Lyman GH (2008). Blood transfusions,
thrombosis, and mortality in hospitalized patients with cancer. Archives of Internal Medicine 168(21):2377 –
2381.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L352743994,
http://archinte.ama-assn.org/cgi/reprint/168/21/2377
Ref 131: Solomon J, Bofenkamp T, Fahey JL, Chillar RK and Beutel E (1978). Platelet prophylaxis in acute nonlymphoblastic leukaemia. Lancet 1:267.
Ref 132: McCullough J, Vesole DH, Benjamin RJ, Slichter SJ, Pineda A, Snyder E, et al. (2004). Therapeutic
efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: The
SPRINT trial. Blood 104(5):1534 – 1541.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L39166535
References
Ref 133: Higby DJ, Cohen E, Holland JF and Sinks L (1974). The prophylactic treatment of thrombocytopenic
leukemic patients with platelets: A double blind study. Transfusion 14(5):440 – 446.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L5164451
F
Ref 134: Heim D, Passweg J, Gregor M, Buser A, Theocharides A, Arber C, et al. (2008). Patient and product
factors affecting platelet transfusion results. Transfusion 48(4):681 – 687.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L351430354
Ref 135: Osselaer JC, Messe N, Hervig T, Bueno J, Castro E, Espinosa A, et al. (2008). A prospective
observational cohort safety study of 5106 platelet transfusions with components prepared with
photochemical pathogen inactivation treatment. Transfusion 48(6):1061 – 1071.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L351793479
Ref 136: Slichter SJ (1997). Leukocyte reduction and ultraviolet B irradiation of platelets to prevent
alloimmunization and refractoriness to platelet transfusions. New England Journal of Medicine 337(26):1861 –
1869.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L28053025
Ref 137: Slichter SJ, Kaufman RM, Assmann SF, McCullough J, Triulzi DJ, Strauss RG, et al. (2010). Dose of
prophylactic platelet transfusions and prevention of hemorrhage. New England Journal of Medicine 362(7):
600 - 613. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L358334244
Ref 138: Heddle NM, Cook RJ, Tinmouth A, Kouroukis CT, Hervig T, Klapper E, et al. (2009). A randomized
controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with
thrombocytopenia. Blood 113(7):1564 – 1573.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L354286700
18
Ref 139: Tinmouth A, Tannock IF, Crump M, Tomlinson G, Brandwein J, Minden M, et al. (2004). Low-dose
prophylactic platelet transfusions in recipients of an autologous peripheral blood progenitor cell transplant
and patients with acute leukemia: A randomized controlled trial with a sequential Bayesian design.
Transfusion 44(12):1711 – 1719.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L39644055
Ref 140: Goodnough LT, Kuter DJ, McCullough J, Slichter SJ, DiPersio J, Romo J, et al. (2001). Prophylactic
platelet transfusions from healthy apheresis platelet donors undergoing treatment with
thrombopoietin. Blood 98(5):1346 – 1351.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L35119599
Ref 141: Sensebé L, Giraudeau B, Bardiaux L, Deconinck E, Schmidt A, Bidet ML, et al. (2005). The efficiency of
transfusing high doses of platelets in hematologic patients with thrombocytopenia: Results of a prospective,
randomized,
open,
blinded
end
point
(PROBE)
study.
Blood
105(2):862
–
864.
http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L40070776
Ref 147: Rebulla P, Finazzi G, Marangoni F, Avvisati G, Gugliotta L, Tognoni G, et al. (1997). The threshold for
prophylactic platelet transfusion in adults with acute myeloid leukemia. New England Journal of Medicine
337:1870 – 1875.
Ref 148: Heckman KD, Weiner GJ, Davis CS, Strauss RG, Jones MP and Burns CP (1997). Randomized study of
prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10 000/microL
versus 20 000/microL. Journal of Clinical Oncology 15:1143 – 1149.
Ref 149: Zumberg MS, Del Rosario MLU, Nejame CF, Pollock BH, Garzarella L, Kao KJ, et al. (2002).A prospective
randomized trial of prophylactic platelet transfusion and bleeding incidence in hematopoietic stem cell transplant
recipients: 10 000/(mu)L versus 20 000/(mu)L trigger. Biology of Blood and Marrow Transplantation 8(10):569 –
576.
Ref 150: Diedrich B, Remberger M, Shanwell A, Svahn BM and Ringden O (2005). A prospective randomized trial
of a prophylactic platelet transfusion trigger of 10 109 per L versus 30 109 per L in allogeneic hematopoietic
progenitor cell transplant recipients. Transfusion 45:1064 – 1072.
19
Patient Blood Management Guidelines: Module 4 Critical Care
Practice Points:

Practice Point 10 - The effect of platelet transfusion on transfusion-related serious adverse events is
uncertain. The decision to transfuse platelets to an individual patient should take into account the relative
risks and benefits.

Practice Point 11 - In critically ill patients, in the absence of acute bleeding, the administration of platelets
may be considered appropriate at a platelet count of <20 × 109/L.

Practice Point 12 - Assessment of bleeding risk is complex and requires careful consideration of patients’
clinical status and laboratory parameters. Specialist haematology advice may also be required. However,
patients with a platelet count ≥50 × 109/L can generally undergo invasive procedures within the ICU
without any serious bleeding; lower platelet counts may be tolerated in certain clinical situations.
Literature Review:
The systematic review identified little evidence regarding the use of FFP, cryoprecipitate, fibrinogen
concentrate and platelets in this population. The literature search identified evidence relating to the use
of platelets in two critically ill populations, being trauma patients and critically ill elderly patients.
Three poor-quality prospective cohort studies were identified that assessed the use of platelets in trauma
patients (Ref 12, 49, 50). Of the two studies that reported the association between platelet transfusion and
mortality, (Ref 12, 50) neither found a significant association, although one of these studies (Ref 12) was
probably underpowered. Transfusion-related serious adverse events were reported in all three included
studies; however, only one study (Ref 49) reported that platelet transfusion was independently associated
with a range of transfusion-related serious adverse events.
One retrospective cohort study (Level III) studied the effects of platelet transfusion in 122 medical ICU
patients (Ref 21). This study found that platelet transfusion was significantly and independently associated
with ARDS or ALI.
References (from PBM Guidelines: Module 4 Critical Care):
Ref 12: Bochicchio GV, Napolitano L, Joshi M, Bochicchio K, Meyer W and Scalea TM (2008). Outcome
analysis of blood product transfusion in trauma patients: A prospective, risk-adjusted study. World Journal
of Surgery 32(10):2185–2189.
http://www.ncbi.nlm.nih.gov/pubmed/18575931
Ref 21: Khan H, Belsher J, Yilmaz M, Afessa B, Winters JL, Moore SB, et al. (2007). Fresh-frozen plasma and
platelet transfusions are associated with development of acute lung injury in critically ill medical patients.
Chest 131(5):1308–1314.
http://www.ncbi.nlm.nih.gov/pubmed/17400669
Ref 49: Bochicchio GV, Napolitano L, Joshi M, Bochicchio K, Shih D, Meyer W, et al. (2008). Blood product
transfusion and ventilator-associated pneumonia in trauma patients. Surgical Infections 9(4):415–422.
http://www.ncbi.nlm.nih.gov/pubmed/18759678
Ref 50: Watson GA, Sperry JL, Rosengart MR, Minei JP, Harbrecht BG, Moore EE, et al. (2009). Fresh frozen
plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress
syndrome. Journal of Trauma - Injury, Infection and Critical Care 67(2):221–227.
http://www.ncbi.nlm.nih.gov/pubmed/19667872
20
Patient Blood Management Guidelines: Module 5 &6
Obstetrics and Paediatrics/ Neonates modules are yet to be developed.
D2: Other literature
1. Stanworth SJ et al. The Effect of a No-Prophylactic Versus Prophylactic Platelet Transfusion Strategy On
Bleeding in Patients with Hematological Malignancies and Severe Thrombocytopenia (TOPPS trial). A
Randomized Controlled, Non-Inferiority Trial. 54th ASH Annual Meeting Plenary Scientific Session 2012.
Available at https://ash.confex.com/ash/2012/webprogram/Session4376.html
The results of the TOPPS trial were presented at the American Society of Haematology (ASH) Annual Meeting in
December 2012. TOPPS aimed to test the hypotheseis that a policy of no prophylactic platelet transfusions is as
effective and safe as a policy of prophylactic platelet transfusions in patients with haematological malignancies
and severe thrombocytopenia. The trial was a randomised, parallel group, open-label, non-inferiority trial, with
600 patients recruited from 14 UK and Australian hospitals over a 5 year period between August 2006 and August
2011. The primary outcome was the proportion of patients with a clinically significant bleeding up to 30 days from
randomisation. The study results did not prove that a policy of no prophylaxis platelet transfusions is non-inferior
to a policy of prophylactic platelet transfusions. Clinically significant bleeding (WHO Grade 2-4) occurred in 50% of
patients in the no prophylaxis group versus 43% of the patients in the prophylaxis group (p value for noninferiority 0.06). Patients in the no prophylaxis group had a shorter time to their first bleed, and had more days
with WHO Grade 2-4 bleeding (1.7 versus 1.2 days). Whilst patients in the no prophylaxis group had more WHO
Grade 3-4 bleeds, this did not reach statistical significance.
2. Stanworth SJ. Thrombocytopenia, bleeding, and use of platelet transfusions in sick neonates. Hematology Am
Soc Hematol Educ Program 2012; 2012: 512-6.
This presentation by Simon Stanworth from ASH 2012 notes that in the United Kingdom, a telephone survey of all
tertiary level neonatal units has shown variations in platelet transfusion practice, and the most common
thresholds for transfusion in healthy or stable term and preterm infants were 25 x 109/L and 30 x109/L,
respectively.
3. BSCH Transfusion guidelines for neonates and older children. British Journal of Haematology 2004; 124: 433453.
Thrombocytopenia is common in sick preterm infants and is associated with an increased risk of severe
periventricular bleeding (PVH) (Andrew et al, 1987). However, the administration of platelets to manage
moderate thrombocytopenia (platelets 50–100 × 109/l) did not appear to reduce the severity of bleeding (Andrew
et al, 1993). In the absence of randomized, controlled trials in this patient group, recommendations for platelet
transfusion must be made on the basis of clinical experience. Term infants are unlikely to bleed if the platelet
count is maintained above 20 × 109/l but in small, preterm babies a higher threshold is generally recommended,
particularly during the first few days when the risk of PVH is highest or if there is a co-existent coagulopathy (level
IV evidence, grade C recommendation). In neonatal alloimmune thrombocytopenia, HPA-compatible platelets will
be required, in addition to high dose intravenous immunoglobulin. In these patients, a minimum platelet count of
30 × 109/l is recommended because the HPA antibody can impair platelet function (level IV evidence, grade C
recommendation) (see also British Committee for Standards in Haematology, 2003b; Table III). Recommendations
from Table III for transfusion thresholds for administration of platelets include: Preterm or term neonate with
bleeding (50 × 109/l); Sick preterm or term infant not bleeding (30 × 109/l); Stable preterm or term infant not
bleeding (20× 109/l).
21
4. Ruggenenti P, Noris M & Remuzzi G. Thrombotic microangiopathy, haemolytic uraemic syndrome, and
thrombotic thrombocytopaenic purpura. Kidney International 2001; 60(3): 831-846.
There are some case reports regarding the use of platelets in patients with HUS and TTP to cover invasive
procedures that cannot be postponed until the underlying disease has been resolved (e.g. central line placement
for plasma exchange therapy).
22