Platelets (for transfusion)

DESCRIPTION

• Human platelet-rich product for transfusion

INDICATIONS

1. Treatment of bleeding due to severely decreased platelet production, abnormal platelets, or low platelet count (see transfusion thresholds below)
2. Because my ROTEM / TEG algorithm told me to give some (EXTEM A5 <35mm and FIBTEM A5 >10mm, and likely also when EXTEM A5 <25mm and FIBTEM A5<10mm)

ADMINISTRATION / DOSING

• Intravenous (IV)
• Adults:
  • One apheresis unit will increase platelet count of an adult by 20-40 x10⁹L
  • The usual dose in an adult is one unit, and doses may require repeating every 1-3 days due to the lifespan of a platelet
• Children (from RCH guidelines):
  • < 15kg patient, the dose is 10 mL/kg
  • > 15kg can have a single adult unit of platelets
  • One paediatric apheresis unit would be expected to increase the platelet count of an 18 kg child by about 20 x10⁹/L
• Administration:
  • Transfuse through blood administration set incorporating a standard 170-200 µm filter (most pump sets include a 200 µm filter)
  • Administer units as fast as you need to (except in paediatrics)
  • Units must be used within four hours after removal from storage

PREPARATION

• Apheresis collection:
  • 1-3 doses of platelets are prepared from a single apheresis platelet donation
  • Donor’s blood is separated into components with retention of the platelets and a portion of plasma
  • Red and white cells and most of the plasma is either returned to the patient or collected for preparation of the appropriate component types
  • Leucocyte depletion is performed during collection
  • Platelet additive solution is added to achieve the pre-determined final platelet concentration with about 30% donor plasma
• Pooled collection:
  • Adult dose of platelets is obtained from a pool of buffy coats from ~4 ABO identical donors and resuspended in Platelet Additive Solution (PAS)
  • The pool is then filtered to remove most leucocytes
• Paediatric apheresis platelets (pedipaks)
  • One unit of apheresis platelets may be divided into three equal packs
• Platelets are irradiated prior to issue
• Modifications available to platelets:
  • CMV Seronegative
  • Irradiated
  • Phenotyped
  • HLA-compatible
  • Phenotyped
  • Low anti-A/B

PHARMACEUTICS

• Presentation:
  • In a gas-permeable, fluid-impervious, semi-transparent polyolefin bag (non-PVC)Platelets apheresis in PAS, leucocyte depleted
    • Volume: 209 (+/- 21) mL
    Platelets paediatric apheresis in PAS, leucocyte depleted
    • Volume: 56 (+/- 2) mL
  • Platelets pooled in PAS, leucocyte depleted
    • Volume: 367 (+/- 16) mL
• Contents:
  • Platelets apheresis in PAS, leucocyte depleted
    • Platelet count: 277 (+/- 42) x10⁹/unit
    • pH: 7.2 (+/- 0.1) at expiry
    • Leucocyte count: 0.2 (+/- 0.2) x10⁶/unit
    • PAS:Plasma = 60:40
  • Platelets paediatric apheresis in PAS, leucocyte depleted
    • Platelet count: 75 (+/- 10) x10⁹/unit
    • pH: 7.0 (+/- 0.1) at expiry
    • Leucocyte count: Initial unit prior to splitting <1.0 x10⁶/unit
    • PAS:Plasma = 60:40
  • Platelets pooled in PAS, leucocyte depleted
    • Platelet count: 288 (+/- 49) x10⁹/unit
    • pH: 7.0 (+/- 0.1) at expiry
    • Leucocyte count: 0.2 (+/- 0.06) x10⁶/unit
• Excipients:
  • Platelet Additive Solution (PAS) is SSP+ (reduces load of plasma which is associated with transfusion reactions)
    • Ratio of PAS:Plasma
      • Apheresis: 60:40
      • Pooled: 70:30
    • Sodium chloride 405 mg/100mL
    • Sodium acetate trihydrate  442 mg/100mL
    • Sodium citrate dihydrate 318 mg/100mL
    • Sodium dihydrogenphosphate 105 mg/100mL
    • Di-sodium hydrogenphosphate 305 mg/100mL
    • Potassium chloride 37 mg/100mL
    • Magnesium chloride 30 mg/100mL
• Storage:
  • Stored at 20-24^oC
  • Shelf-life of 5 days following collection
  • Platelet components must be agitated gently and continuously in a single layer on a platelet agitator (the platelets need to “breathe!”)

GROUP / CROSSMATCH

• Available in groups O, A and B with RhD positive and negative
• AB needs to be requested in advance
• Platelets SHOULD be ABO and RhD compatible with the patient, however, compatibility testing is not necessary routinely
• ABO-incompatible platelets may be used if ABO match is not available. Residual plasma present in ABO-incompatible units may trigger a low-grade haemolytic reaction and result in a positive direct antiglobulin test (DAT)
• If RhD-positive platelets are transfused to a RhD-negative female of childbearing age, prevention of RhD with immunisation should be considered
• Following HLA or HPA alloimmunisation patients may become refractory to platelet transfusion or have significantly shortened survival of the same. HLA-compatible or HPA-matched may be indicated.

ADVERSE EFFECTS

• Please see transfusion risks / reactions
• Early
  • Fever
  • Allergy: Mild –> Anaphylaxis
  • Air embolism
  • Hypothermia
  • Acute haemolytic reaction
  • TRALI (Transfusion-related acute lung injury)
  • Volume Overload
  • Citrate Toxicity
• Late
  • Viral infection
  • Bacterial infection
  • Parasitic infection:
  • Prion infection:
  • GVHD (Graft versus Host Disease)
  • Immune sensitisation (Rh D antigen)
  • TRIM (Transfusion-related immunomodulation)

LOCATION OF ACTION

MECHANISM OF ACTION

• There are three general steps in platelet activation (depending on where you read / who taught you):
  • Platelet adhesion
  • Platelet activation
  • Platelet aggregation
• When there is damage to a blood vessel, tissue factor (TF), collagen, and von Willebrand Factor (vWF) are exposed
• Passing platelets adhere to and are activated by collagen and vWF. They are also activated by thrombin (Factor IIa) which itself is activated by TF and the clotting cascade
• As platelets are activated, they morph from disc to stellate-shaped and release several hormones and molecules which promote haemostasis and coagulation, including:
  • Serotonin and thromboxane A₂ are both potent vasoconstrictors (aspirin blocks thromboxane A₂)ADP helps to activate the next “wave” of platelets and binds to the platelet ADP receptor (which clopidogrel, ticagrelor and prasugrel block)
  • Platelet-activating factor (PAF), thrombin, fibrinogen (Factor I), calcium ions, vWF and platelet-derived growth factor (PDGEF) are also released which help to amplify the platelet aggregation and formation of a platelet “plug”
• When platelets are activated, glycoprotein IIb/IIIa receptors (inhibited by abciximab) are expressed at the platelet surface – this receptor allows for platelet aggregation and cross-linking with Fibrinogen and vWF to other platelets
• This cross-linking of platelets forms a soft platelet plug which is then reinforced by fibrin as the fibrinogen strands are converted thanks to thrombin and Factor XIIIa (the last step in the clotting cascade)
• An easy way to think about the whole process is just to look at the cell-based model of coagulation which also has 3 steps (again, depending on where you read) and involves initiation, amplification, and propagation. This is all outlined in the below YouTube video.

CONTRAINDICATIONS

• Use in syndromes associated with platelet destruction such as: ITP (Immune thrombocytopenic purpura), TTP (thrombotic thrombocytopenic purpura), HIT (heparin-induced thrombocytopenia), HUS (haemolytic uraemic syndrome), HELLP syndrome (Haemolysis, elevated liver enzymes and low platelets) unless life-threatening bleeding

TRANSFUSION THRESHOLDS

This list of transfusion thresholds is an amalgamation of National Blood Authority of Australia, RCH, SOAP, and UpToDate recommendations. Please check your local protocols / with your local haematologist.

<10 x10⁹/L

• Clinically stable patients undergoing chemotherapy for haematological malignancies or post-haematopoietic stem cell transplantation (HSCT) (without risk factors for bleeding)
• Clinically stable patients with solid tumours (except for bladder, brain or necrotic tumours, where higher targets may be clinician directed)

<20 x10⁹/L

• Undergoing chemotherapy, or HSCT and has risk factors (e.g. fever, sepsis, minor bleeding, mucositis, DIC without bleeding)
• Critically ill patients with no bleeding or risk factors (e.g. sepsis, renal failure, medications etc.)
• NGT insertion
• IM injections
• Insertion of a central line (compressible location, e.g. IJ or femoral)
• Bone marrow aspirate/biopsy
• Diagnostic endoscopic procedures

<30 x10⁹/L

• Bronchoscopy with alveolar lavage
• Lumbar Puncture (LP) with ongoing chemotherapy-induced thrombocytopenia

<50 x10⁹/L

• Most major surgery and endoscopic procedures
• For vaginal or caesarean birth
• LP in patients without haematological malignancies
• Critically ill patients requiring invasive procedures (including subclavian CVC)

<70 x10⁹/L

• Neuraxial anaesthesia/analgesia

<100 x10⁹/L

• Neurosurgery or ocular surgery

References and Links

FOAMEd

• Learn about the cell-based model of coagulation

References

• Australian Red Cross Lifeblood. (2020, June). Blood Component Information: An Extension of Blood Component Labels. Retrieved January 27, 2023, from https://www.lifeblood.com.au/sites/default/files/resource-library/2021-12/78.-Blood_Component_Information_1.pdf
• Bauer ME, Arendt K, Beilin Y, Gernsheimer T, Perez Botero J, James AH, Yaghmour E, Toledano RD, Turrentine M, Houle T, MacEachern M, Madden H, Rajasekhar A, Segal S, Wu C, Cooper JP, Landau R, Leffert L. The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia. Anesth Analg. 2021 Jun 1;132(6):1531-1544. doi: 10.1213/ANE.0000000000005355. PMID: 33861047. [Free Full Text]
• Chambers, D., Huang, C.L.-H. and Matthews, G. (2015) “7 – Oxygen Transport, 8 – Carbon Dioxide Transport, 68 – Transfusion,” in Basic physiology for Anaesthetists. Cambridge: Cambridge University Press.
• Crankshaft Publishing. (n.d.). Hemostasis and Its Regulation Part 1. Retrieved January 31, 2023, from http://what-when-how.com/acp-medicine/hemostasis-and-its-regulation-part-1/
• D, J. (2007, April 22). File:coagulation full.svg. Retrieved January 17, 2023, from https://commons.wikimedia.org/wiki/File:Coagulation_full.svg
• Holland, C. (2021, August 04). The cell-based model of coagulation – learnhaem: Haematology Made Simple. Retrieved January 27, 2023, from https://www.learnhaem.com/courses/coagulation/lessons/normal-haemostasis/topic/the-cell-based-model-of-coagulation/
• Macopharma. (2021, March 18). SSP+ platelet additive solution. Retrieved January 31, 2023, from https://www.macopharma.com/products/ssp-platelet-additive-solution/
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 1 Critical Bleeding/Massive Transfusion. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/documents/Module%201.pdf
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 2 Perioperative. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/documents/pbm-module-2.pdf
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 3 Medical. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/documents/20180424-PBM-Module3.pdf
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 4 Critical Care. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/documents/20180424-Module-4.pdf
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 5 Obstetrics and Maternity. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/documents/20180426-Module5-WEB.pdf
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 6 Neonatal and Paediatrics. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/14523_NBA-Module-6-Neonat_Paediatrics_internals_5_updated_14_May_2020.pdf  
• National Blood Authority Australia. (2023, January 01). What blood products are supplied – national product price list. Retrieved January 18, 2023, from https://www.blood.gov.au/national-product-price-list
• The Royal Children’s Hospital Melbourne. (n.d.). Ordering Blood Products. Retrieved January 27, 2023, from https://www.rch.org.au/bloodtrans/blood_provision/Ordering_Blood_Products/
• Yuan, S. (2022, November). Platelet transfusion: Indications, ordering, and associated risks. Retrieved January 18, 2023, from https://www.uptodate.com/contents/platelet-transfusion-indications-ordering-and-associated-risks?search=platelet%20transfusion&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

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