Guideline for the Use of Platelets in Transfusion

1. Introduction
   1.1 Rationale
   1.2 Evidence Base
2. Available Components
   2.1 Storage & Shelf Life
3. Indications for Use
   3.1 Bone Marrow Failure
   3.2 Massive Blood Transfusion
   3.3 Prophylaxis for Surgery
   3.4 Platelet Function Disorders (acquired & congenital)
   3.5 Disseminated Intravascular Coagulation (DIC)
   3.6 Cardiopulmonary Bypass
   3.7 Liver Transplant Surgery
   3.8 Auto-immune Thrombocytopenia
   3.9 Neonatal Allo-immune Thrombocytopenia (NAIT)
   3.10 Post Transfusion Purpura
4. Contra-indications to Platelet Transfusions
   4.1 Thrombotic Thrombocytopenia Purpura (TTP)
   4.2 Haemolytic Uraemic Syndrome (HUS)
   4.3 Heparin-induced Thrombocytopenia & Thrombosis (HITT)
5. Written Informed Consent for Transfusion of Platelets
6. Requesting & Documentation
7. Platelet Selection
   7.1 ABO Compatibility
   7.2 RhD Compatibility
   7.3 Irradiated Platelets
   7.4 CMV-seronegative Platelets
   7.5 HEV -negative Platelets
   7.6 Apheresis Platelet Concentrates
   7.7 Platelet Transfusion in times of Shortage
8. Dosage
9. Administration
10. Management of Adverse Effects
11. Platelet Refractoriness
    11.1 Causes of Platelet Refractoriness
    11.2 Investigation of Platelet Refractoriness
    11.3 Management of Platelet Refractoriness
    11.4 Alternatives
12. Glossary of Terms
    Appendix 1. Management of Platelet Refractoriness
    Appendix 2. Clinical indications for CMV Negative components
    Appendix 3. Clinical indications for HEV Negative components
    Appendix 4. NICE Transfusion Guideline Algorithm

1. Introduction

The transfusion of platelet concentrates to a patient with severe thrombocytopenia can be life-saving.  However, as with all donated blood components, there are associated risks.  Particular hazards associated with platelets are:-

• Anaphylactic/allergic reactions and Transfusion Related Acute Lung Injury (TRALI)- an especial risk with all plasma-rich components
• Platelet concentrates are stored at room temperature; therefore the risk of bacterial contamination is higher than with red cells.
• Repeated platelet transfusion may result in 'platelet refractoriness' because of the development of HLA (Human Leucocyte Antigen) and/or HPA (Human Platelet Antigen) antibodies.
• Most platelet transfusions are given prophylactically rather than to treat clinical bleeding episodes. The benefits of this approach are uncertain and have not been confirmed by clinical trials.
• There are certain contraindications to platelet transfusion (see section 4) and certain clinical situations, such as autoimmune thrombocytopenia, where the benefit of transfusion is limited.

For these reasons, the prescriber must be in no doubt that the potential benefits are greater than the risks of transfusion.  The cause of thrombocytopenia must first be established.  Where there is uncertainty, requests for platelet transfusion should be discussed with a Consultant Haematologist, Specialist Registrar or, in some circumstances, with a Senior Biomedical Scientist in Blood Bank.

1.1 Rationale

The purpose of this document is:

• To give general guidance to medical staff about when it may be appropriate to prescribe platelet concentrates and when platelet transfusions are contraindicated
• To give guidance on the correct procedures for prescribing, requesting, ordering and administering platelets.
• To give guidance on the management of platelet refractoriness.

1.2 Evidence Base

British Committee for Standards in Haematology (2003).  Guidelines for the use of Platelet Transfusions.  British Journal of Haematology, 122 (1): 10-23

Guidelines for the use of platelet transfusions (2016) British Journal of Haematology, 2017, 176, 365-394

British Committee for Standards in Haematology (2016).  Guidelines on transfusion for foetuses, neonates and older children.  (Addendum August 2020)
British Society for Haematology Guidelines on transfusion for fetuses, neonates and older children (Br J Haematol. 2016;175:784–828).
Addendum August 2020 - New - 2020 - British Journal of Haematology - Wiley Online Library

British Committee for Standards in Haematology (2015).  A Practical Guideline for the Haematological Management of Major Haemorrhage.  British Journal of Haematology, 170, 780-803

British Committee for Standards in Haematology (2012). Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic Microangiopathies.  British Journal of Haematolgy, 158, 323-335.

NICE (2016) Guideline-Blood transfusion https://www.nice.org.uk/guidance/ng24

National Blood Transfusion Committee, Indication Codes for Transfusion (2016).

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2. Available Components

• Pooled buffy coat platelet concentrate – ‘adult therapeutic dose’ (ATD) derived from four donations of whole blood.
• Single–donor apheresis platelet concentrate – equivalent to a pool of 4 donor units (a single donation procedure may yield one to three adult therapeutic doses).
  Both the above are provided as standard issue platelet concentrates by the National Blood  Service.
• HLA matched - selected platelets - Indicated for patients’ refractory to random platelet components because of development of HLA antibodies after previous transfusions.  Patients with congenital platelet function disorders may also receive HLA matched platelets.  HLA platelets are Irradiated to prevent Transfusion Associated Graft versus Host Disease (TA-GvHD)
• Platelets for Neonatal Transfusion – are free of clinically significant irregular blood group antibodies, including high titre anti-A and anti-B.  Components are negative for cytomegalovirus (CMV) antibodies.  Neonatal platelets are prepared by splitting an adult therapeutic dose apheresis platelet pack (often into four) and are labelled 'platelets for neonatal use'
• Platelets for Intrauterine Transfusion – are hyper-concentrated and prepared from apheresis platelets with the aim of limiting the volume of the transfusion to the fetus. Components are CMV negative and must be irradiated & labelled “platelets for IUT”. These platelets are only available by special arrangement with the National Health Blood and Transplant Service (NHSBT).

2.1 Storage and Shelf Life
Storage is at 22^oC ± 2^oC with continual agitation for up to five to seven days from donation. Platelets should be transfused as soon as possible once being received on to the ward.

To ensure correct platelet function, PLATELETS MUST NEVER BE REFRIGERATED.

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3. Indications for Use

Platelet transfusions are indicated for the prevention and treatment of haemorrhage in patients with thrombocytopenia or platelet function defects. World Health Organisation (WHO) categorise the different grades of bleed from Grade 0 to Grade 4 depending on type of bleeding.

Table 1.  Modified World Health Organisation bleeding score (Stanworth et al,2013a)

*Please refer to Massive Haemorrhage Guidelines

Therapeutic platelet transfusions

Platelet transfusions should be offered to thrombocytopenic patients who are clinically significantly bleeding (World Health Organisation [WHO] grade 2) and a platelet count below 30x10⁹/L

A higher platelet threshold, up to 100x10⁹/L, should be applied for patients with thrombocytopenia and either of the following-

• Severe bleeding (WHO grades 3 and 4)
• Bleeding in critical sites, such as the central nervous system and eyes.

Platelet transfusions are indicated for the prevention and treatment of haemorrhage in patients with thrombocytopenia or platelet function defects.

Prophylactic platelet transfusions

Dose for prophylaxis - one adult therapeutic dose.
Prior to invasive procedure to treat bleeding, consider patient size, previous increments and target count.  Refer to Table 2 for guidance.

3.1 Bone marrow failure syndromes
Reversible Bone Marrow Failure syndromes (due to disease, chemotherapy or irradiation)
Bone marrow failure caused by the primary disease and/or chemotherapy is a common problem in the management of haematological malignancy or cancer patients receiving cytotoxic chemotherapy.  Prophylactic platelets have become standard practice for patients with reversible bone marrow failure.  Clinical trial data comparing the use of prophylactic strategy is better than a non-prophylactic strategy for patients with haematological malignancies.

Irreversible Bone Marrow Failure syndromes (myelodysplastic syndromes, aplastic anaemia, paroxysmal nocturnal haemoglobinuria-PNH)

Prophylactic platelet transfusions are not indicated in chronic stable thrombocytopenia without a history of bleeding.

Recommendations for Prophylactic platelet based on NBTC, British Committee for Standards in Haematology (BSCH) and NICE guidelines are given in Table 2.

3.2 Massive Blood Transfusion
Thrombocytopenia is considered a late event in massive haemorrhage, typically seen after a loss of at least 1.5 blood volumes.

(Refer to LTHT Guidelines for the Management of Massive Haemorrhage), adult, paediatric and obstetric versions are available.

The need for platelet transfusion should be dictated by timely full blood count monitoring and discussion with a Clinical Haematologist / Senior Biomedical Scientist in Blood Transfusion Laboratory as necessary.

• Maintain the platelet count >50x 10⁹/L in patients with acute bleeding.
• Maintain the platelet count > 100 x 10⁹/L in patients with multiple trauma or central nervous system injury or when platelet function is known to be abnormal.

N.B Currently the LTHT holds 2 units of platelets that can be issued in a Massive Haemorrhage event.  Please liaise with the Blood Transfusion Laboratory staff regarding the provision of platelets and order for elective use as soon as possible to allow for timely replenish of stocks

3.3 Prophylaxis for Surgery

• Bone marrow aspiration and trephine biopsy may be performed in patients with severe thrombocytopenia without platelet transfusion.
• For lumbar puncture, epidural anaesthesia, gastroscopy and biopsy, insertion of indwelling lines, transbronchial biopsy, liver biopsy, laparotomy or similar procedures the platelet count should be raised to at least 40 x 10⁹/L. The recommended threshold for spinal or epidural anaesthesia in pregnancy is 80x10⁹/l.
• For surgery to critical sites, e.g. brain and eyes, the platelet count should be raised to 100 x 10⁹/L.
• As  long as this does not have a negative impact on patient care, platelets should be administered immediately before the invasive procedure and a post-transfusion platelet count must be checked (whenever possible) to ensure the above thresholds have been reached as there is significant inter-individual variation in platelet recovery and increment after transfusion.

3.4 Platelet Function Disorders Acquired and Congenital

Platelet functions disorders (acquired e.g. uraemia, secondary to Aspirin etc,)

Patients with platelet function disorders rarely require platelet transfusion.  The following recommendations are for the management of bleeding or for prophylaxis before invasive procedures for patients with known or suspected platelet function disorders:-

• Consider withdrawing drugs known to have anti-platelet activity, such as aspirin, clopidogrel, ticegralor, dabigatran or rivaroxaban seven days prior to elective surgery, taking cardiovascular and cerebrovascular risks into account (seek expert advice from Consultant Cardiologists or Neurologists if uncertain.

N.B. The above anti-coagulants cause irreversible platelet inhibition and the active metabolite circulates for approximately 18 hours after the last dose.  Platelet transfusion within this time will not reliably reverse the action of Clopidogrel.

• Correct the haematocrit to >0.30 l/l in patients with renal-failure either with recombinant erythropoietin (EPO) or with red cell transfusion.
• Consider the use of DDAVP (Desmopressin (Octim^®)) or cryoprecipitate in patients with uraemia (N.B. discuss with Haematologist).

Platelet function disorders (congenital)

• Glanzmann Thromasthenia (GT) is usually a severe bleeding disorder in which patients do not express αIIBβ3 integrin on the platelet surface.  This increases the risk of alloimunisation to platelet antigens and refractoriness to platelet transfusion, which may prevent the effective treatment of bleeding.
• Recombinant FVIIa is licensed as a pro-heamostatic treatment for GT patients.
• If pharmaceutical therapies are contraindicated, ineffective or if there is high risk of bleeding, consider transfusion of platelets. In GT cases HLA matched-platelets should be considered.
• For other congenital platelet function disorders, such as Bernard-Soulier syndrome, TXA and desmopressin may sufficient for haemostasis
• Patients with inherited platelet defects need management in conjunction with a Consultant Haematologist +/- their Haemophilia Centre.
• Use platelet transfusions only where the above methods are not appropriate or are ineffective

3.5 Disseminated Intravascular Coagulation (DIC)
DIC may spontaneously resolve when the underlying condition is managed correctly. Treatment of DIC should consider both clinical and laboratory information.   Blood component therapy should not be issued solely on laboratory results.  Blood component therapy, including platelets, is recommended for patients with active bleeding, patients who are require an invasive procedure and patients who are at risk of bleeding complications.

The threshold for transfusion platelets depends on the clinical state of the patient.

• Patients with thrombocytopenia  aim to maintain the platelet count >50 x 10⁹/L if there is active bleeding or if an invasive procedure is planned
• Prophylactic platelet transfusions are NOT recommended in non-bleeding patients unless it is perceived that there is a high risk of bleeding. In non-bleeding patients a much lower threshold of 10-20 x 10⁹/L is applied
• IC is an extremely dynamic condition therefore frequent laboratory tests, including platelet count, aPTT, PT and fibrinogen degradation products, should be performed.  The patients underlying clinical condition may influence laboratory results.  Refer to LTHT pathology services for further advice Test and Tubes (leedsth.nhs.uk)

In chronic DIC, or in the absence of bleeding, platelet transfusions should not be given merely to correct a low platelet count.

3.6 Cardiopulmonary Bypass
Withhold non-steroidal anti-inflammatory drugs and anti-platelet drugs (where clinically appropriate) in patients attending for elective surgical revascularisation. A review of medications should take place in surgical pre-assessment.  In acute situations, consider the use of anti-fibrinolytic agents to reduce bleeding risk. There is no place for routine prophylactic transfusion of platelets in patients undergoing cardiopulmonary bypass. The use of thromboelastography (TEG) may help in the decision making process about appropriate platelet transfusion.

• The use of platelet transfusion should be reserved for those patients experiencing excessive post-operative bleeding and in whom a surgical cause has been excluded

3.7 Liver Transplant Surgery
Reduced haemostasis due to a combination of reduced coagulation, enhanced fibrinolysis and thrombocytopenia is found in patients with liver failure. This is exacerbated during liver transplantation as a result of massive transfusion and hyperfibrinolysis, which occurs on reperfusion of the donor liver.

• Current practice is to use thromboelastography (TEG) to guide the need for platelet transfusion

3.8 Auto-Immune Thrombocytopenia (ITP)

• Platelet transfusions should be reserved for the immediate treatment of patients with life-threatening bleeding associated with severe thrombocytopenia before specific treatments become effective.
• A high dose of platelets, administered frequently, may be required to achieve haemostasis as a result of reduced survival of transfused platelets (judge by clinical response).
• Other therapies such as intravenous steroids and immunoglobulin should be given at the same time to maximise the chances of stopping the haemorrhage and raising the platelet count.

Table 2. Indications for use of Platelet Transfusion in Adults.  Guidelines for the use of platelet transfusions (British Journal of Haematology, 2017)

3.9 Neonatal Allo-immune Thrombocytopenia (NAIT)

NAIT is caused by feto-maternal incompatibility for platelet antigens and is a serious fetal disorder with no maternal consequences. The most frequently implicated antibodies are anti-HPA-1a (80-90% of cases) and anti-HPA-5b (5-15%). The first born is affected in 40-60% of cases and subsequent pregnancies are usually affected with similar or increasing severity. Thrombocytopenia may be an incidental finding or the neonate may have a petechial rash. In severe cases there is intracerebral bleeding or intra-uterine death.

• The most common presentation is haemorrhage in thrombocytopenia in an otherwise healthy neonate.
• The platelet count may continue to fall during the first 48 hours after birth.
• Significant thrombocytopenia warrants an ultrasound scan for possible intracranial haemorrhage.
• In suspected cases, pre-transfusion samples should be sent after discussion with Blood Transfusion Laboratory and the National Blood Service-
      Maternal-20ml EDTA and 10ml clotted (red top bottle with black ring)
      Paternal-20ml EDTA
      Neonate or cord blood if possible-1ml EDTA
  • The samples must be labelled as per the labelling policy with full name, date of birth and the unique ID number on the patient’s wristband.
• The transfusion of HPA-1a negative, HPA_-5b negative platelet concentrates (routinely available from the National Blood Service following discussion) will result in least delay in providing treatment and will be effective in around 95% of cases of NAIT. Any decision on what should be supplied will be by a Haematology Consultant at the National Blood Service
• In extreme emergencies: the use of random donor platelets should be considered.  Any decision as to what to use should be discussed with a Haematology Consultant at the National Blood Service
• Platelets are indicated to treat bleeding or as prophylaxis in some cases (see Table 2).  It is not necessary to wait for laboratory confirmation of the diagnosis as delay in treatment may result in an increased risk of severe haemorrhage.

Table 3. Thresholds to guide the decision to transfuse platelets in thrombocytopenic neonates: Randomized Trial of Platelet-Transfusion Thresholds in Neonates (A Curley et al 2019)

See also LTHT Guideline on Use of Blood Components on the Neonatal Unit

3.10 Post Transfusion Purpura (PTP)

• PTP is a rare but serious complication of blood transfusion, characterised by the sudden onset of severe thrombocytopenia 5-10 days following a transfusion.  Thrombocytopenia is caused by antibody mediated destruction of both patient and donor platelets. Most affected patients are parous females who are negative for the HPA-1a platelet antigen.
• Intravenous immunoglobulin (IVIg) 2g/kg given over 2-5 days is effective treatment in 85% of patients.
  • AS IVIg & ITS USE FOR TREATING PTP IS A NON-RED TREATMENT INDICATION CODE, ITS USE MUST FIRST BE APPROVED BY A MEMBER OF THE DECISION PANEL (contact during & outside of office hours via switchboard). Pharmacy will not issue IVIg until this process has been followed. For further advice see: Immunoglobulin Panel - Leeds Teaching Hospitals NHS Trust
  • Also an IVIg request form must be completed before administration. For guidance on use, ordering & prescription of IVIg see: LTHT policy on the use of immunoglobulin products: Immunoglobulin Panel - Leeds Teaching Hospitals NHS Trust
• Platelet transfusions are often ineffective but may have to be used (in large doses) in an attempt to control severe bleeding in the acute phase before there has been a response to IVIg.

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4. Contra-indications to Platelet Transfusions

4.1 Thrombotic Thrombocytopenic Purpura (TTP)
TTP is a clinical diagnosis characterised by the classic pentad of:

• thrombocytopenia
• microangiopathic haemolytic anaemia (MAHA)
• fluctuating neurological symptoms and signs
• renal impairment
• fever

Classical neurological problems (headache, bizarre behaviour, transient sensorimotor deficits, fits, coma) may be absent in up to 35% of patients.  Fever and renal impairment may be absent in atypical cases.  Haemolytic uraemic syndrome may be difficult to differentiate clinically from TTP.  Normal coagulation test results help to distinguish TTP from disseminated intravascular coagulation (DIC).  A raised LDH is a useful diagnostic marker in TTP. Most cases are caused by acquired deficiency of ADAMTS.

Platelet transfusions are contraindicated unless there is life threatening haemorrhage as they have been associated with exacerbation of TTP, rapid deterioration and even death.

Management of TTP should be guided by a Consultant Haematologist and may involve repeated plasma exchanges with solvent detergent-treated pooled fresh frozen plasma (FFP), e.g. Octaplas.

4.2 Haemolytic Uraemic Syndrome (HUS)
Characterised by a triad of:

• acute renal insufficiency
• microangiopathic haemolytic anaemia (MAHA)
• Thrombocytopenia.

Severe thrombocytopenia is uncommon.  As in Thrombotic Thrombocytopenic Purpura, platelet transfusions are relatively contraindicated and may exacerbate the condition.

4.3 Heparin-Induced Thrombocytopenia and Thrombosis (HITT) 
HITT is a drug-induced thrombocytopenia that may be associated with arterial and venous thrombosis.  Current Guidelines state that platelet transfusions should not be administered unless life-threatening bleeding occurs as they may cause acute arterial thrombosis. However, a recent review of the literature found minimal evidence to support this and suggests that platelet transfusion is indicated in patients with HITT and life-threatening bleeding (an uncommon situation).

Management should be guided by a Consultant Haematologist.

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5. Written Informed Consent for Transfusion of Platelets

ALL patients are required to give their written informed consent before transfusion of any blood or blood component (wherever clinically possible). This consent and the discussion of the risks explained to the patient must be recorded on consent form 1 (adults) and consent form 2 (paediatrics) either on the pre-printed ‘blood/blood components’ version or on the consent form being used for the patient’s surgery / invasive procedure.  This consent process should be backed-up with the offer of a Patient Information Leaflet on transfusion (available in all clinical areas or from the Hospital Transfusion Team). For further information see the LTHT policy on obtaining written informed consent for blood / blood components

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6. Requesting and Documentation

Because of their short shelf-life, platelets are not routinely stored in the hospital but ordered from the National Health Service Blood and Transplant (NHSBT) as required. Request for platelets should be made at the earliest possible opportunity by telephoning the hospital Blood Transfusion Laboratory (Ext: 23398 (LGI) & ext: 65559 (SJUH)), followed by the relevant blood sample if the patient’s blood group is unknown to the Lab. Once the request is received the Transfusion Laboratory will order platelets to be delivered from the National Blood Service Centre.

N.B. Requests may take up to 2 hours before delivery to the clinical area depending on availability, type of request (eg irradiated) and level of traffic between NHSBT and the hospital.

In emergency situations such as major haemorrhage, plan ahead and communicate early with the Blood Transfusion Laboratory. SJUH 65559, LGI 23398.

ALL transfusions must be documented in a clear and precise manner on the dedicated transfusion prescription chart (order code: WPG 602) and the clinical indication for, and outcome of, the transfusion clearly indicated in the patient’s case notes.  The donation number of each unit transfused must be recorded on the dedicated transfusion prescription chart. To ensure traceability (a legal requirement), the act of transfusing a unit to a particular patient must be recorded using the electronic Autofate system or by signing the attached manila tag and sending it to the Transfusion Laboratory within 24 hours.

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7. Platelet Selection

7.1 ABO Compatibility

• Platelet concentrates from donors of the same ABO group as the patient are the components of choice and will be provided wherever possible. Group O platelets should, where possible, only be given to group O patients as the plasma contains anti-A and anti-B antibodies. Transfusion of group O platelets concentrates to patients of other ABO groups may cause haemolysis, especially in small children. Group AB platelets are not collected from donors and patients of this group should be given group A or B.
• If ABO identical platelets are not available, then platelets will be issued according Table 3.  It is acceptable to use ABO incompatible platelets to reduce wastage.

Table 4 Platelet Compatibility

HT Negative platelets have been tested for high-titre IgG Anti-A and Anti-B antibodies and will be labelled as ‘Neg HT’ (this reduces but does not eliminate the risk of haemolysis).

7.2 RhD Compatibility

• RhD negative platelets should wherever possible be given to RhD negative women of child-bearing potential.
• If there is no option but to transfuse RhD positive platelets to a RhD negative woman of child-bearing potential then anti-D Immunoglobulin must be given.  A dose of 500 iu anti-D Ig should be sufficient to cover five adult therapeutic doses of Rh-D positive platelets within a six week period.  Anti-D must be given subcutaneously in thrombocytopenic patients.
• It is not necessary to administer anti-D to Rh-D negative men or women without childbearing potential who receive RhD-positive platelets.

7.3 Irradiated Platelets
Please refer to the LTHT Guideline for the Use of Irradiated and CMV negative Blood / Blood Components in Transfusion.

Fatal transfusion-associated graft versus host disease (TA-GVHD) may follow the transfusion of cellular blood components to certain immuno-incompetent patients. Patients at risk of TA-GVHD must be given irradiated platelets. 

Patients at special risk include:

• Bone marrow and stem cell transplant patients
• Hodgkin disease patients
• Following purine analogue drugs e.g. Fludarabine
• Following Anti Lymphocyte Globulin (ALG) & Anti Thymocyte Globulin (ATG)
• Following Campath (and other T-cell directed antibodies)
• Transfusion of HLA matched platelets
• Intrauterine Transfusions (IUT)
• Transfusions in neonates who have received  IUT
• Transfusion of  granulocyte concentrates
• Aplastic Anaemia

Please contact the Blood Bank for advice regarding the Irradiated blood component requirements.  Irradiated components are often condition and therapy dependent.  The blood bank MUST be informed if a decision has been made NOT to give Irradiated components to any patient with any of the listed conditions.
To ensure a patient receives irradiated blood components it is essential to fully and correctly complete the transfusion request card (detailing the patient’s diagnosis and reason for request).  The need for irradiated platelets must be indicated on the patient’s transfusion prescription chart and must have a “patient is at risk of TA-GVHD ‘Alert Sticker’ placed on the front of the patient’s case notes. The patient should be then offered a Patient Information Leaflet (PIL) on why they need irradiated blood components and be offered an ‘alert card’ to carry with them at all times. PIL’s are available from the Hospital Transfusion Team (HTT).

7.4 CMV-seronegative Platelets
Cytomegalovirus is a herpes virus that gives rise to chronic, persistent and, for the most part, asymptomatic infection in a majority of adults. The risk has been much diminished since routine leucodepletion of blood components was instituted. See appendix 3.

Patients requiring CMV negative platelets include:

• All intrauterine and neonatal transfusions
• All pregnant women except for transfusions at delivery or in an emergency situation where CMV seronegative components are not available
• All children less than 6 months old

7.5 HEV-negative Platelets

• All platelets are sero-negative for HEV.

7.6 Apheresis Platelet Concentrates

• Platelets for neonatal transfusion are prepared by splitting one adult apheresis pack to reduce donor exposure.
• Please liaise with the Blood Transfusion Laboratory if you require apheresis platelets .

7.7 Platelet Transfusion in times of Shortage

In the times of reduced availability those patients with a greater clinical need for platelet therapy will be given priority over other patients. Table 4 is a guide to what category of treatment may be treated as priority.  During time of platelet shortage the NHSBT will liaise with the LTHT Emergency preparedness team which should communicate the proposed action plan to all clinical teams involved.  Emergency Blood Management Arrangements for the Trust can be found Emergency Preparedness, Resilience and Response (EPRR)

Table 5 Platelet Transfusion in Times of Shortage (Guidelines for the use of platelet transfusions, British Journal of Haematology. 2017)

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8. Dosage

• One Adult Therapeutic Dose - one 4 unit pool or one apheresis platelet pack - is appropriate for most adult patients.
• One Adult Therapeutic Dose will increase the platelet count by at least 20 x 10⁹/L at 1-18 hours post transfusion, providing that the patient is not refractory.
• When platelets are given to treat active bleeding, a larger dose may be indicated and should be discussed with a Consultant Haematologist.
• In children <15kg, 10-20 ml/kg is usually administered and for children >15kg, a single adult dose can be used (approx. 300mls).

It is recommended that an adult dose of platelets is administered over around 30 minutes. In a paediatric setting, this approximates to a rate of 20-30 ml/kg/hr.

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9. Administration of Platelet Transfusions

See LTHT Policy for Safer Transfusion Procedures

In addition, the following points should be noted regarding platelet transfusion:

• Platelets must be collected from the laboratory immediately before administration.
• Platelets must never be refrigerated.
• Because platelets are stored at room temperature, they are prone to bacterial growth and should be inspected by both Blood Bank staff and by clinical staff at the bedside for evidence of unusual colour or turbidity. If in doubt, return to the Transfusion Laboratory
• Platelets must be transfused through a normal blood administration set with a 200 micron in-line screen filter
• Platelets must not be transfused through giving sets that have been previously used for red cells.
• A repeat full blood count can be taken 10 minutes following a platelet transfusion to determine the platelet count/increment - this is best practice as may prevent additional unnecessary platelet transfusions.
• For neonatal transfusion, the platelets must be drawn up through a blood giving set before transferring into a syringe driver.

ALL patients receiving platelet concentrates must be observed and monitored for adverse reactions. Baseline temperature, pulse, blood pressure and respiration rate must be recorded before the transfusion begins and pulse and temperature must be recorded 15 minutes after the start of each transfusion. Pulse, temperature and blood pressure must be repeated at the end of the transfusion. All transfusion observations must be recorded either on the transfusion authorisation chart, e-obs or in the patients notes.

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10. Management of Adverse Effects

See LTHT Policy for Safer Transfusion Procedures

• If a mild adverse reaction (rise in temperature <2ºC +/- urticaria) is suspected, turn off the infusion and seek medical attention. Administer anti-histamine for urticaria and / or paracetamol for pyrexia. Re-start the infusion 20 minutes later
• If a severe adverse reaction (rise in temperature >2ºC +/- severe or life threatening symptoms) occurs, discontinue the transfusion immediately and seek urgent medical attention. Contact the Blood Transfusion Laboratory and take blood samples as requested. Complete a Datix web form for the attention of the Hospital Transfusion Team. Always consider the possibility of bacterial transmission. Blood cultures should always be taken if the reaction is severe enough to stop the transfusion. In the event of a suspected bacterial transmission, it is imperative to alert the Blood Transfusion Laboratory as other components from the same donation (e.g. platelets, red cells and plasma) may be awaiting transfusion to another patient. Please ensure that the donor pack is returned to the Blood Bank as soon as possible to enable the Blood Bank to send the pack to NHSBT for investigation.

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11. Platelet Refractoriness

Platelet refractoriness is defined as the repeated failure to obtain satisfactory responses to platelet transfusions.  It can occur in patients requiring multiple platelet transfusions although it is less common since the introduction of universal leucodepletion of blood and platelets.  Some patients may have a poor response to one platelet transfusion and good responses to subsequent transfusions.  A diagnosis of refractoriness should only be made after a poor response to two or more platelet transfusions.

11.1 Causes of Platelet Refractoriness

• Non-immune causes are the most common:
  • infection
  • antibiotics and antifungal drugs
  • disseminated intravascular coagulation (DIC)
  • splenomegaly
• Immune causes:
  • HLA (Human Leucocyte Antigen) alloimmunization, predominantly in women sensitised by previous pregnancy
  • HPA (platelet specific antigens) alloimmunization
  • ABO incompatibility
  • Platelet auto antibodies
  • Drug-related platelet antibodies
• In patients’ refractory to platelets, the identification of those with transfusion failure due to HLA antibodies is important as HLA-matched platelets can improve responses.

11.2 Investigation of Platelet Refractoriness

• If platelet refractoriness occurs on at least two occasions, a clinical assessment should be made for factors likely to be associated with non-immune platelet consumption.  If these are excluded then tests for HLA (Human Leucocyte Antigen) antibodies should be carried out (see algorithm in Appendix 1).

Samples required (after discussion with Blood Transfusion Laboratory and National Blood Service): 10ml clotted + 10ml EDTA.

11.3 Management of Platelet Refractoriness: (See: Appendix 1)

If HLA (Human Leucocyte Antigen) antibodies are detected then HLA–matched platelets are transfused if required. These are ordered specially from the NHSBT and are subject to availability.

Responses to HLA-matched platelets must be carefully monitored with post-transfusion platelet counts at 1 hour and 24 hours (for out-patients a 15 minute post transfusion count will suffice).  If the platelet increment is less than 10 x 10⁹/L then other reasons for refractoriness should be considered (see above).  Further serological investigations may be indicated at this stage e.g. testing for anti – HPA antibodies / platelet cross-matching and advice will be needed from a specialist in Transfusion Medicine.

If refractoriness is not overcome by transfusing HLA-matched platelets then prophylactic platelet transfusions should be discontinued and random platelets given only to treat bleeding (large doses usually required). Again, discussion with a Transfusion Medicine Consultant is important.

11.4 Alternatives

Antifibrinolytic agents

Tranexamic acid, TXA, reduces mortality in trauma without increasing vascular events and reduces blood loss and transfusion requirements during surgery.  NICE guidance 24 recommends the use of TXA in adults undergoing surgery when blood loss is expected to be greater than 500ml.  TXA should be considered as a platelet alternative or in addition to therapeutic platelet transfusion in patients with chronic thrombocytopenia caused by bone marrow failure.

Desmopressin

Desmopressin promotes coagulation by stimulating factor VIII release from endothelial stores and increasing von Willebrand factor activity.  In trauma, this is recommended for patients receiving aspirin and, in the perioperative setting, in patients with uraemia or inherited platelet defects.

Fibrinogen

Fibrinogen concentrate is currently only licenced in the UK for congenital deficiency.  However studies have recommended the use of fibrinogen concentrate for haemorrhage where there is evidence of fibrinogen deficiency. 

Thrombopoietin receptor agonists and other therapies

Romiplostim and Eltrombopag are licenced and NICE-approved for treatment in ITP.

Erythropietin has been observed to reduce both red cell and platelet transfusion requirements in patients following HSCT and iron chelation has been reported to improve haematopoiesis in patients with iron overload.

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