Transfusion medicine

Transfusion therapy

Platelet use



Topic Completed: 12 January 2021

Minor changes: 12 January 2021

Copyright: 2020-2021, PathologyOutlines.com, Inc.

PubMed Search: Platelet use[TIAB] transfusion

Rachel Jug, M.B.B.Ch., B.A.O.
Katerina Pavenski, M.D.
Page views in 2020: 68
Page views in 2021 to date: 226
Cite this page: Jug R, Pavenski K. Platelet use. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedplatelet.html. Accessed December 2nd, 2021.
Definition / general
  • Platelets are derived from single donor apheresis or pooled whole blood (from 4 - 6 donors) collections
  • Platelet transfusions may be indicated prophylactically in thrombocytopenic patients or therapeutically in bleeding patients
Essential features
  • Apheresis and whole blood derived platelets are collected from volunteer donors who meet the donor health questionnaire and other screening requirements
  • Platelet units are tested for infectious diseases (viral and bacterial)
  • Clinical practice recommendations for platelet use in adult inpatients include the following indications (with recommended platelet count threshold):
    • Nonimmune thrombocytopenia, including prophylactic transfusion of hypoproliferative thrombocytopenic patients (≤ 10 × 10⁹/L)
    • Prior to procedures not associated with significant blood loss (including some percutaneous procedures) (< 20 × 10⁹/L)
    • Prior to epidural anesthesia or lumbar puncture, procedures with expected blood loss > 500 mL, major nonneuraxial surgery (< 20 - 50 × 10⁹/L)
    • Significant bleeding (< 50 × 10⁹/L)
    • Guideline references: Transfus Med Rev 2015;29:3, Ann Intern Med 2015;162:205, J Clin Oncol 2018;36:283
  • Transfuse 1 dose (1 pool of whole blood derived platelets or 1 apheresis platelets unit) and reassess patient; 1 dose raises the platelet count by approximately 15 - 25 × 10⁹/L
    • Platelet life span in vivo is 8 - 10 days (J Biol Chem 2013;288:6826)
    • Platelet transfusions are associated with potential adverse events, the most common of which include febrile reaction, allergic reaction and bacterial sepsis
Terminology
  • Apheresis platelets: collected from single donors using automated cell separator devices (contains ≥ 3 × 1011 platelets per bag in 100 - 500 mL of plasma or plasma with platelet additive solution) (Transfusion 2016;56:2173)
  • Whole blood derived platelets: 4 - 6 random donor platelets are pooled to make an adult dose (contains ≥ 5.5 × 1010 platelets per bag in 40 - 70 mL of plasma) (Transfusion 2016;56:2173)
  • Pediatric platelet dosing: 5 - 10 ml/kg up to 300 ml (adult dose)
  • Neonates: 10 - 15 ml/kg
Pathophysiology
  • Platelets are activated upon exposure to extracellular matrix of injured endothelium to adhere and aggregate, which forms a hemostatic plug
  • This self amplifying mechanism maintains normal hemostasis and works in primary hemostasis to address injuries in bleeding (Blood Rev 2011;25:155)
    • Platelet membrane antigens include glycoconjugates of the ABO system, class I human leukocyte antigens (HLA) and human platelet antigens (HPA)
  • HLA matched platelets are indicated if the patient has anti-HLA antibodies reacting with antigens present on at least 20% of the donor population (i.e. PRA > 20%)
    • If the patient has poor increments to HLA matched platelets, an investigation for anti-HPA antibodies should be performed to determine if HPA matched platelets are indicated
    • HLA and HPA matched platelets are genotype matched products, HLA and HPA selected platelets lack HLA or HPA antigens to which the patient has formed HLA or HPA antibodies
  • Antibody formation against platelet antigens is responsible for alloimmune thrombocytopenia, platelet transfusion refractoriness, passive alloimmune thrombocytopenia, neonatal alloimmune thrombocytopenia and posttransfusion purpura (Wien Klin Wochenschr 2001;113:806)
    • Antiplatelet alloantibody - most prevalent in the obstetrical setting and in patients with history of multiple transfusions (see platelet antibodies)
    • Reduced posttransfusion platelet count increments can be seen with major ABO incompatible platelet transfusions, compared with minor ABO incompatible or ABO compatible platelet transfusions (Asian J Transfus Sci 2015;9:117)
    • While platelets themselves do not express RhD antigens, platelets from RhD positive donors are contaminated by RhD positive red blood cells that pose a risk of RhD alloimmunization to RhD negative recipients; prevention measures may be considered in women of childbearing age (Asian J Transfus Sci 2015;9:117)
Clinical features
  • Causes of thrombocytopenia include:
    • Reduced production by congenital and acquired causes of abnormal megakaryocytic development (drugs, hematologic malignancy, May-Hegglin syndrome, alcohol excess, infections, etc.)
    • Immune and nonimmune platelet consumption
    • Abnormal distribution of platelets (splenic sequestration)
    • Dilutional (in massive blood transfusion) (Medicine 2017;45:221)
Transmission
  • Platelet transfusions are associated with risks to recipients including the following adverse events (with approximate risk per platelet transfusion in the U.S.):
    • Febrile reaction (1/14)
    • Allergic reaction (1/50)
    • Bacterial sepsis (1/75,000)
    • Transfusion related acute lung injury (1/138,000)
    • Hepatitis B virus infection (1/2,652,580)
    • Hepatitis C virus infection (1/3,315,729)
    • HIV infection (0 - 1/1,461,888) (Ann Intern Med 2015;162:205)
  • Transmissible disease risk varies between jurisdictions based on donor population disease prevalence, donor screening criteria and donor unit testing methods
Symptoms and signs of thrombocytopenia
  • Range from asymptomatic to petechiae, bruises, mucosal bleeding (from nose, GU or GI tract) and rarely intracranial hemorrhage (Medicine 2017;45:221)
Screening
  • Platelet count should be measured pre and posttransfusion to help assess need for transfusion and the adequacy of response to a platelet transfusion, respectively
Blood donor screening
  • Donors must meet specific eligibility criteria outlined by regulators such as the Food and Drug Administration, laboratory accrediting organizations such as AABB and individual donation centers, including:
Blood donor testing
  • In addition to standard infectious disease testing as per whole blood donations (including testing for [some regional and seasonal] hepatitis B and C, HIV, West Nile virus, Chagas disease, Zika, Babesia, HTLV1), platelets undergo additional testing:
    • HLA antibody screening of donors with a history of transfusion or pregnancy to reduce the risk of transfusion related acute lung injury in recipients (Transfusion 2014;54:3036)
    • Strategies to reduce bacterial contamination of platelets for transfusion include skin decontamination, blood (and skin plug) diversion, bacterial culture testing, storage duration limitations and pathogen reduction / inactivation technologies (Crit Care 2018;22:271)
Donor deferral
  • In addition to standard deferrals for blood donation based on the donor health history questionnaire, patients with HLA antibodies are deferred from donating platelets since they pose a risk of transfusion related acute lung injury to recipients (Vox Sang 2012;103:10)
Laboratory
  • Platelets are stored at room temperature under constant agitation to prevent cold platelet storage lesion and aggregation, respectively
    • Cold platelet storage lesion describes a decrease in posttransfusion survival and hemostatic function (Curr Opin Hematol 2018;25:500)
    • Room temperature storage conditions increase risk of bacterial contamination, hence the short 5 - 7 day shelf life of platelets, which challenges blood bank inventory management due to rapid outdating (Blood Transfus 2019;17:321)
  • Measuring the pretransfusion count and posttransfusion platelet count approximately 1 hour after platelet transfusion can help distinguish between immune and nonimmune causes of platelet refractoriness, which is a complication most commonly encountered in the management of hypoproliferative thrombocytopenic patients
  • Various calculations can be used to define platelet refractoriness:
    • Platelet increment (PI) = P2 - P1, where P1 is the pretransfusion platelet count and P2 is the posttransfusion platelet count
    • Corrected count increment (CCI) = [(PI × BSA)/n] × 100, where BSA represents the body surface area in meters² and n is the number of platelets transfused
    • Percentage platelet recovery (PPR) = [(PI × body weight (kg) × 0.075 (l/kg))/n] × 100; body weight (kg) × 0.075 (l/kg) is an estimate of blood volume (Transfus Med 1992;2:35)
Case reports
Treatment
  • Clinical practice recommendations for platelet use in adult inpatients by diagnosis / indication (with recommended platelet count threshold):
    • Nonimmune thrombocytopenia, including prophylactic transfusion of hypoproliferative thrombocytopenic patients (< 10 × 10⁹/L)
    • Prior to procedures not associated with significant blood loss (including some percutaneous procedures) (< 20 × 10⁹/L)
    • Therapeutic anticoagulation that cannot be stopped (< 30 × 10⁹/L)
    • Prior to epidural anesthesia or lumbar puncture, procedures with expected blood loss > 500 mL, major nonneuraxial surgery (< 50 × 10⁹/L)
    • Patients with significant bleeding (< 50 × 10⁹/L)
    • Prior to neuraxial surgery (< 100 × 10⁹/L)
    • Head trauma, central nervous system hemorrhage, life threatening hemorrhage (< 100 × 10⁹/L)
    • Platelet dysfunction (secondary to aspirin or clopidogrel) and significant bleeding (with or without cardiopulmonary bypass) or prophylactic invasive procedure (any platelet count)
      • AABB does not recommend for or against platelet transfusion in the context of platelet dysfunction (secondary to aspirin or clopidogrel) in the context of intracranial hemorrhage due to low quality and conflicting evidence
    • Immune thrombocytopenia (case specific; only for life threatening bleeding in consultation with a hematologist)
    • Guideline references: Transfus Med Rev 2015;29:3, Ann Intern Med 2015;162:205, J Clin Oncol 2018;36:283
  • Transfuse 1 dose (1 pool of platelets or 1 apheresis platelets unit) and reassess patient; 1 dose raises the platelet count by approximately 15 - 25 × 10⁹/L
  • In patients with hypoproliferative thrombocytopenia, HLA matched platelets lead to better 1 hour posttransfusion count increments; however, the effect at 24 hours is inconsistent (Transfusion 2013;53:2230)
  • Contraindications to platelet transfusion - only use platelet transfusions to treat life threatening bleeding in patients with:
    • Thrombotic microangiopathies (e.g. thrombotic thrombocytopenic purpura) - increased risk of further thrombotic events
    • Congenital platelet functional disorders (e.g. Glanzmann thrombasthenia) - increased risk of alloimmunization leading to refractoriness, consider alternatives (recombinant factor VIIa, tranexamic acid, desmopressin) (Br J Haematol 2017;176:365)
  • Modifications to platelet products based on availability and indications:
    • Gamma irradiation: to prevent transfusion associated graft versus host disease (TA-GVHD) in patients by inactivating donor T lymphocytes that are present in platelet units in small numbers despite leukocyte reduction (Blood 2015;126:406)
    • Pathogen reduction technologies (such as amotosalen-ultraviolet A pathogen reduction) reduce the risk of transfusion-transmitted infection and TA-GVHD (Transfusion 2019;59:1953)
      • Disadvantages include reduced platelet activatability and increased / accelerated platelet apoptosis and clearance (Haematologica 2017;102:1650)
Sample assessment & plan
  • Assessment: John Doe is a 75 year old man undergoing induction chemotherapy for acute myeloid leukemia. He is pancytopenic with a platelet count of 2 × 10⁹/L and has bruising on his forearms.
  • Plan: The patient presentation and laboratory workup are consistent with a diagnosis of hypoproliferative thrombocytopenia.
    • Recommend: prophylactic transfusion of 1 dose of platelets
    • Perform platelet count 1 hour posttransfusion to assess response to platelet transfusion
Differential diagnosis
  • Hypoproliferative thrombocytopenia:
    • Decreased platelet production secondary to bone marrow dysfunction (hematological malignancy) or destruction (by metastatic infiltration)
  • Immune thrombocytopenia:
    • Most cases are autoimmune; some may be triggered by viral or bacterial infections
  • Drug induced thrombocytopenia:
    • Reported with drugs such as quinidine, trimethoprim-sulfamethoxazole, gold
  • Idiopathic thrombocytopenia:
    • Other causes of thrombocytopenia excluded
  • Platelet dysfunction:
    • Postcardiopulmonary bypass (via removal of GPIb from platelets and activated platelets from circulation)
    • Antiplatelet drugs (clopidogrel, aspirin)
    • Congenital (Bernard-Soulier, Glanzmann thrombasthenia, platelet storage pool disorders)
Board review style question #1

In patients with hypoproliferative thrombocytopenia and who have a platelet count increment less than 5 - 10 × 10⁹/L 1 hour posttransfusion on 2 occasions, what is the next best step in their transfusion management?

  1. Irradiated platelets
  2. Random donor whole blood derived platelets
  3. Apheresis platelets
  4. HLA or HPA selected platelets
  5. Fresh as possible platelets
Board review style answer #1
D. In HLA or HPA alloimmunized patients who are refractory to platelet transfusions with apheresis or whole blood derived platelets, HLA or HPA selected platelets are recommended. If these are unavailable, use ABO identical or crossmatched apheresis platelets. Never delay lifesaving platelet transfusions while waiting for HLA or HPA matched platelets.

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Reference: Platelet use
Board review style question #2
A 65 year old woman presents to the emergency department with a lower GI bleed and she is on dual antiplatelet therapy (DAPT). About 15 minutes into transfusion of 1 dose of platelets, she spikes a fever (temperature 38.8 °C = 101.8 °F) and experiences rigors. What adverse reaction do you suspect from her platelet transfusion?

  1. Mild allergic reaction
  2. Septic reaction
  3. Transfusion related acute lung injury
  4. Transfusion associated circulatory overload
  5. Hepatitis B virus infection
Board review style answer #2
B. Septic transfusion reactions occur at an approximate frequency of 1/100,000 platelet transfusions and present acutely with fever, chills, rigors, nausea, vomiting, diarrhea, abdominal and muscle pain or hypotension. Platelets are stored at room temperature, which makes them an ideal growth media for bacteria. Despite efforts to reduce bacterial contamination of platelets, including skin disinfection, volume diversion and microbiological culture of units, bacterial contamination leading to septic transfusion reactions still occurs. Pathogen reduction / inactivation technologies may help further prevent this adverse reaction.

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Reference: Platelet use
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