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Platelet transfusions A continuing challenge

Platelet transfusions A continuing challenge. Irene Sadek Head, Division of Hematopathology Department of Pathology and Laboratory Medicine QEII Health Sciences Centre Professor of Pathology Dalhousie University. Objectives. Indication for transfusion Platelet products

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Platelet transfusions A continuing challenge

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  1. Platelet transfusions A continuing challenge Irene Sadek Head, Division of Hematopathology Department of Pathology and Laboratory Medicine QEII Health Sciences Centre Professor of Pathology Dalhousie University

  2. Objectives • Indication for transfusion • Platelet products • Increased utilization • Platelet inventory challenges • Platelet refractoriness.

  3. Platelet role and function • Main function of platelets is to mediate primary hemostasis. They circulate in blood close to vessel walls until exposed to subendothelial matrix following injury to a blood vessel. http://physrev.physiology.org/content/93/1/327

  4. Thrombocytopenia Platelet count N=150.000-350.000 >50.000 20-50.000 10-20.000 5-10.000 <5.000 *Gaydos et al, N Engl J MEd 1962 Frequency of bleeding episodes asymptomatic rare, easy bruisability.... 38% of days 50% of days 65-92% of days.

  5. Relation of bleeding risk to blood platelet count: computed per 1000 days at risk *Gmur et al , Lancet 1991

  6. Thrombocytopenia

  7. Causes of thrombocytopenia

  8. Indications for Plt transfusion Canadian Blood Services Clinical Guide • There is limited high quality evidence to guide the use of platelet transfusions to treat bleeding. There is general agreement that the following patients should receive platelet transfusions. • Patients with thrombocytopenia or platelet dysfunction to; • Stop bleeding (therapeutic transfusion) • Prevent bleeding (prophylactic transfusion)

  9. Indications for Plt transfusion • Patients with thrombocytopenia or platelet dysfunction to; • Stop bleeding (therapeutic transfusion); consider cause! • Pts with non-immune thrombocytopenia and clinically significant bleeding with platelet count < 50 x109/L. • Immune mediated thrombocytopenia with severely reduced platelet count (<20 x 109/L) and significant bleeding. • Head trauma or life threatening hemorrhage with a platelet count <100 x 109/L. • Pltdysfunction from congenital or acquired causes (GABG, PHV, MDS, SLE, HCL) and clinically significant bleeding. • As part of a massive transfusion protocol in bleeding patients.

  10. Indications for Plt transfusion • Patients with thrombocytopenia or platelet dysfunction to; • Prevent bleeding (prophylactic transfusion) • Hospitalized patients with therapy-induced hypoproliferativethrombocytopenia with a platelet count of ≤10x109/L. • Elective central line with platelet count <20x109/L. • Elective LP with platelet count <50x109/L. • Major elective non-neuroaxial surgery with a platelet count <50x109/L. • Neuroaxialsurgery with a platelet count <100x109/L. • Consider transfusion for patients undergoing CABG who exhibit peri-op bleeding with thrombocytopenia and/or evidence of platelet dysfunction.

  11. Platelet Products • Buffy coat method providing pooled platelets from 4 donors. • Whole blood is collected, spun and platelets are separated from plasma and RBC. 4 units of platelets from same group donors are pooled and suspended in plasma from 1 of the male donors. • Platelet count: >240x109/unit in ≥75% of units tested. https://professionaleducation.blood.ca/en/transfusion/clinical-guide/platelet-transfusion-alloimmunization-and-management-platelet

  12. Platelet products • Apheresis method providing platelets from a single donor. • Platelet unit collected from a single donor using apheresis. • Blood is drawn and separated into components by centrifuge. Platelets are collected while RBC and plasma are returned to donor. • Platelet count: ≥300x109/unit in ≥75% of units tested https://simonsylvester.wordpress.com/

  13. Platelet products • Both products are used interchangeably • Both are leukoreduced (containing <5 x106 leukocytes in all units tested), • Contain <2mL RBC, • Tested for bacteria, and are equivalent in most patients. • Only absolute indication for apheresis platelets is the provision of matched platelets for patients with; • Documented anti-platelet antibodies (either anti-HLA or anti-HPA antibodies), AND • Allo-immune platelet refractoriness or post-transfusion purpura.

  14. Platelets products • 1 unit of platelets is expected to increase the platelet count by an average of 15-30 x 109/L. *Depends on underlying cause of thrombocytopenia, comorbidities and patient size. • Platelets express ABH antigens (often at very high levels), but not Rh antigens.

  15. 2014/2015 Total PLT: 91,937 2015-2016 Total PLT: 94,145

  16. Apheresis platelets are more frequently associated with adverse reactions than pooled platelets both in recipients and in donors: a study from French hemovigilance data.Daurat A et al Transfusion. 2016 Jun;56(6):1295-303 • 790,854 PLT transfusions during the study period • (477,747 [60%] with APCs, 313,107 [40%] with PPCs). • APCs were associated • with more adverse reactions (6244 vs. 2469 per 1,000,000, p < 0.001) and • more severe and life-threatening reactions (respectively, 241 vs. 131 per 1,000,000, p < 0.001; and 182 vs. 121 per 1,000,000, p = 0.04). • Mortality rates due to an adverse transfusion reaction were similar (15 vs. 6 per 1,000,000, p = 0.5). • Serious adverse reactions were more frequent for apheresis procedures than for WB donations (5445 vs. 803 per 1,000,000, p < 0.001).

  17. Platelet utilization in Canada

  18. Who receives platelets? The AABB Blood Survey Report 2013 Estcourt LJ. Transf Med 2014

  19. Increase platelet demand Aging population Increased prevalence of certain diseases (particularly hematologic malignancies) Improved survival of patients diagnosed with hematologic Malignancies Increase in numbers of patients undergoing stem cell transplantation

  20. Age of patient population receiving blood products

  21. Increase platelet demand • Canadian population: %>65 years, historical and projected.

  22. Platelet demand Healthcare spending is increasing • Platelets for transfusion are expensive to produce – Estimated cost of platelets – Apheresis platelet unit: $502 – Pooled whole blood platelet dose: $197

  23. Platelet challenges

  24. Platelet transfusion challenges • Short platelet shelf life • 5 days • Actually 3 days on hospital shelves • Two inventory • CMV negative and CMV unscreened • ABO specific platelets • Antibody titers testing • Platelet outdate • Platelet refractoriness

  25. Current revision and proposed recommendation • Recommendation #1 The National Advisory Committee recommends that CMV safe (leukoreduced) and CMV IgG seronegative products be considered equivalent except for Intrauterine transfusion.

  26. Dual inventory challenge • As of November 1, 2016. • The central zone Blood transfusion service do not carry CMV neg blood products • Only CMV safe / leukoreduced blood products • Provincial guideline development is on going.

  27. The Need for ABO Matched Platelet Transfusions: Why the Debate? • - Dr. Nadine Shehata, Hematologist, Mount Sinai Hospital Blood Matters 2014

  28. ABO mismatched platelets

  29. Central zone practice • ABO specific platelets in >90% transfusions. • Provision of low titer platelets by CBS?

  30. Longevity and Retransfusion Rates of Major ABO-Incompatible Platelets. Covello et al, AABB Oct 2016

  31. Time to 1stretransfusion, quartiles 2009-2015

  32. Freedom from retransfusion at 120h • 20.6% of patients receiving ABO-identical transfusions free from retransfusion at 120 hours • Compare 13.3% of those receiving major incompatible transfusions (p = 0.008 vs identical). • Minor incompatibility not associated with increased retransfusion rates at 120 hours (p = 0.57 vs. identical).

  33. Background Platelet outdates and rates—National Last year, 22.6% of all donated platelets expired without being transfused

  34. Hospital customer letter: Platelet utilization andinventory management best practices • Includes information about: – Blood Groups – Redistribution – Standing orders/inventory review – Clinical practice • CBS initiative

  35. CBS initiative 7 day platelets • This is in the proposal stage only • Requires submission to Health Canada • If approved, the project targets to go live by Spring or Summer 2017 • More to come on this!!!

  36. Decrease platelet outdate • Central zone will be working on a new platelet inventory tool similar to the red cell inventory tool.

  37. Platelet refractoriness

  38. Assessment of platelet transfusion response • 1 unit of platelets is expected to increase the platelet count by an average of 15-30 x 109/L. • Platelet increment: • 2 hours after transfusions, 62% of platelet are in the circulation. • Average patient expect plt increment of 7,000-10,000 • Corrected count increment plt increment/ml X BSA # of plt transfused (10 11) • CCI> 10.000 good response • CCI= 7.5-10.000 satisfactory response • CCI < 7.5 or 5.000 on 2 consecutive transfusions indicate platelet refractoriness

  39. Platelet refractoriness

  40. Alloimmunization to Platelets • Class I HLA ag are the most antigenic. • Antibodies • 75% develop HLA ab. • 20 % develop plt specific ab • 5% develop both • Require HLA matched platelets: • More expensive preparation • No available histocompatible donor • 40-60 % are unsuccessful transfusions

  41. Assessment of platelet transfusion response • 1hr post-ABO matched platelet transfusion platelet count distinguish. • Immune platelet destruction has greatest effect 10-120 min post-transfusion. Non-immune causes yield poor 16-24hr counts. • A 1hr post-transfusion Corrected Count Increment <7.5 x 109/L on 2 separate occasions is evidence of Allo-Immune refractoriness.

  42. Prevention of Alloimmunization to Platelets • Advantage: • Simplify transfusions • Increase safety of intensive chemotherapy • Decrease platelet utilization • Decrease Cost.

  43. Prevention of Alloimmunization to Platelets • Can SDP overcome refractoriness? • TRAP study in 1997 (NEJM) • Blinded, randomized trial of 530 patients • Patients receiving induction for AML • Randomized to receive • RDP • Leukocyte reduced RDP • Irradiated RDP • SDP

  44. Prevention of Alloimmunization to Platelets • Can SDP overcome refractoriness? • TRAP study in 1997 (NEJM) • No significant difference between leukocyte reduced groups • Leukocyte reduction as effective as the use of SDP for preventing refractoriness

  45. Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial. Vox Sanguinis 2016 • The platelet dose (PLADO) trial; largest prospective, randomized trial of prophylactic platelet therapy. Analyzing platelet allo-immunization and refractoriness. • 40 of 816 platelet-transfused patients became allo-immunized (5%). • Higher rates associated with prior pregnancy, chemotherapy, and low platelet dose • 102 of 734 patients who received at least 2 platelet transfusion, met criteria for refractoriness (14%), regardless of their allo-immunization status. • Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting non-immune causes are frequent • Incidence of new platelet allo-immunization was low (F/U only 30 days),

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