Blood Component Therapy Fundamentals in Acute Care Minh-Ha Tran Learning Objectives • After participating in this activity, participants will be able to: – Utilize newfound knowledge of transfusion risk to provide informed consent for blood transfusion – State evidence-based laboratory thresholds at which blood component transfusion may be considered in otherwise stable patients – Understand rationale behind proper labeling of specimens and of second specimen rule – Delineate between Type and Screen, Type and Hold, and Type and Crossmatch – Recognize and manage: • Febrile Non-Hemolytic and Allergic Transfusion Reactions – Distinguish between: • Transfusion Associated Circulatory Overload (TACO) and Transfusion Related Acute Lung Injury (TRALI) Frequency of Transfusion Reactions Informed Consent • Risks – Infectious vs Noninfectious • Infectious – quite rare • Noninfectious – much more common than infectious – Acute vs Delayed • Acute – Febrile, Allergic, Acute Hemolytic, Septic, Dyspnea • Delayed – Delayed Hemolytic or Delayed Serologic Transfusion Reactions, HLA alloimmunization and platelet refractoriness, Transfusional Siderosis Informed Consent • Use of Autologous Blood – not an option for most patients with acute transfusion needs • Preoperative Autologous Donation waning in popularity and use – Incites preoperative anemia, increasing transfusion risk – Adds patient inconvenience – Creates dual inventory and risk for inadvertent cross-over • Community donor generally regarded as safer than directed donor – Indications for Directed Donor: rare red cell phenotype or need for antigen negative maternal platelets in the setting of FNAIT • Red Cell Alternatives • EPO and IV Iron – – Unlikely to raise hemoglobin rapidly (ie, over the few days during acute inpatient stay) but reasonable if stable IDA • Red Cell Substitutes – – Not a readily available option, JAMA meta-analysis demonstrated higher risk for MI/Death, requires eIND from FDA • Plasma Alternatives • Selected scenarios in which PCC may be reasonable – Warfarin reversal in a volume sensitive individual Otherwise Stable Patients • Anemia – Physiologic Compensation • Thrombocytopenia – Non-bleeding, hem/onc patients – ITP with noncritical bleeding • Coagulopathy of Liver Failure – Benign Physical Examination, lab stability 5 1 3 A Donor Undergoing Plateletpheresis Platelet donors must pass all the Same rigorous criteria as whole blood donors. The donation interval for platelets is no more than twice in a 7 day period and up to 24 times a year. Each collection event takes up to 2.5 to 3 hours. 60% of our collections result in 2 apheresis platelet units – “doubles”. The centrifuge pack freed from the spool. On the left is the platelet Concentrate which will be resuspended in donor plasma to yield a plateletpheresis product. The resuspension process is partially automated. The instrument introduces donor plasma into the collection chamber and channels resuspended platelets into the storage bag. During this time, the operator can mix the product, ensuring complete resuspension. 6 2 4 A view of the platelet collection chamber (on the left) and the The operator readies the collection separation chamber (on the right) chamber for resuspension. at the completion of the plateletpheresis collection procedure. The platelet product is divided Between two gas-permeable storage bags to ensure adequate gas exchange and ‘rested’ for an hour prior to transport over to the Transfusion Services Laboratory for Further processing. Swirl Thresholds • Otherwise Stable Patients with: – Anemia • Assess duration of anemia and any clues provided by history, physical, and indices – Preceding volume challenges (hemodilution?), – stark deviation in results (wrong blood in tube?), – variation with HD cycles (hemodilution?), • Most large studies are supporting threshold levels in the 7 g/dL range in the absence of active myocardial ischemia • Two pilot RCTs of restrictive vs liberal thresholds acute in myocardial ischemia had conflicting results Medicine/Post-Operative In ICU, CAD post Hip Frx, UGIB, Restrictive OK – may have benefits Study TRICC Transfusion Requirements In Critical Care FOCUS Functional Outcomes in Cardiovascular patients Undergoing Surgical hip fracture repair Acute Upper GI Bleed Population ≥16 y/o (mean 57.5±18), Euvolemic, ICU, no active blood loss, Hb <9 ≥50 y/o (mean 81.6, 51-103) wCAD/CAD RFs, Post Hip Frx Repair, Hb <10 >18 y/o, Non Exsanguinating UGIB, excluding MI/PVD/ TIA/Stroke prev 90d Primary Outcome Results Restrictive Liberal Difference (95% CI, p value) 30 day mortality N=418; 7-9 78 (18.7%) N=420; 10-12 98 (23.3%) 4.7% (95% CI -0.84 to 10.2), p=0.11 (Cardiac Events – esp. pulmonary edema and MI) 55 (13.2%) 88 (21.0%) 7.8% (95% CI 2.7 to 12.9), p<0.01 Death or Inability to Walk across room without human assistance at 60 day follow up N=1009; <8 347/1001 34.7% N=1007; ≥ 10 351/998 35.2% 0.5% (95% CI -3.7 to 4.7), p=0.9 No difference All cause mortality at 45 days N=461; <7 Maintain 7-9 23/444 (5%) N=460; <9 Maintain 9-11 41/445 (9%) HR 0.55 (favoring restrictive) (95% CI 0.33 to 0.92), p=0.02 (Cirrhosis A-B) 5/113 (4%) 13/109 (12%) HR 0.30 (favoring restrictive) (95% CI 0.11 to 0.85), p=0.02 Transfusion in Coronary Ischemia Mixed Results – Use Judgement, Await Larger RCTs Study CRIT Study Pilot RCT Population 45 AMI (excluding active bleeding) Age Liberal: 76.4(13.5) Restrictive: 70.3 (14.3) 110 NSTEMI/ STEMI/ACS/ Carson J, et al Pilot RCT stable angina PCI; Hb < 10g/dL Excluded active bleeding. Age Liberal: 67.3 (13.6) Restrictive: 74.3 (11.1) Primary Outcome Results Restrictive Liberal Difference (CI,p) Composite: In-hospital death, recurrent MI, or new or worsening CHF N=24; <24 (24-27%) N=21; <30 (30-33) 3/24 13% 8/21 38% New or worsening CHF 3/24 8/21 Younger Older N=54; <8 N=55; Maintain ≥10 Comp: 15.0% Comp: 14/54 25.9% Comp: 6/55 10.9% (0.7 to 29.3) p=0.054 AgeAdj p=0.076 RR: 2.38 [0.99 to 5.73] D30d: 7/54 13% D30d: 1/55 1.8% D30d: 11.1% (1.5 to 20.8) RR 7.13 [0.91 to 56.02] Older Younger Composite: death, MI, unscheduled revascularization within 30d Composite P=0.046 CHF P=0.03 p=0.032 Thresholds • Otherwise Stable Patients with: – Thrombocytopenia • A 2012 Cochrane Review and 2 recent RCTs of Prophylactic vs Therapeutic strategy – Support continuation of prophylactic transfusions at ≤10 K/mcL – Preprocedurally • Most CVC, even tunneled catheters – When performed by experienced operators using US guidance » Low platelet counts and coagulation defects ok • For surgery, consider a 40-50 K/mcL threshold • Neurosurgery, consider 90-100 K/mcL threshold Where do the 50 and 100 K/mcL thresholds come from? • Gaydos, et al, NEJM 1962 Sum of days for all patients at each level 3K-5K <1K 92% 1K-3K 10K-20K 5K-10K III: 0.8% 50K-100K III: 0.07% 20K-50K III: 0.3% >100K Curve I: All hemorrhage Curve II: Other than skin/epistaxis Curve III:Grossly visible hemorrhage Gross hematuria, melena, hematemesis 33% 8% Thresholds • Otherwise Stable Patients with: – ESLD • Especially if fresh stigmata of bleeding… – assess for concomitant abnormalities (fibrinogen, uremia, etc) • Preprocedural FFP transfusion is controversial – Varies by institution: INR 1.7-2.0 • Platelet transfusion unlikely to result in major increment – Splenic pooling, volume – ‘Chasing’ a target preprocedural platelet count often futile Proper Specimen Labeling 1)Pink or Purple Top + 2)Patient Label with Name and MR# + 3)Legible Last Name of Phlebotomist + 4)Date and Time of Draw Properly Labeled: Proper Specimen: Patient Name Patient MR # Full Last Name of Phlebotomist Date and Time of Draw Plasma: Proteins Immunoglobulin Clotting Factors Soluble ABO Substance Lewis Substance Bilirubin Pigments Plasma Free Hemoglobin Lavender/Pink Top Doe, John 1234567 987654321 01/01/60 Blankenship 10/12/11 08:56 AM Example of Proper Labeling Label Label Centrifuge Pipette from here for IAT and Reverse Type Red Blood Cells: Red Cell Antigens May be bound in vivo with Immunoglobulin or Complement Pipette from here for DAT and Forward Type Second Specimen Rule Prevents mistransfusion event leading to Acute Hemolytic Transfusion Reaction • First-ever UCI Blood Bank Specimen • Types as non-Group O • Obtain and confirm ABO on second specimen – Prior to transfusion of type-specific RBCs • Please respect and heed blood bank’s request for a second specimen PreTransfusion Testing • Type and Screen • Type and Hold • Type and Crossmatch + + Plasma Containing Antibodies Red Blood Cells Expressing Antigens Anti-Human Globulin Blood Bank Test Serum/Plasma Red Cells AHG Phase Forward Type Anti-A1, Anti-B Patient or Donor Weak D Testing Reverse Type Patient or Donor A1 and B RBCs n/a Antibody Screen Patient or Donor Panel Cells PEG, LISS, Saline Direct Antiglobulin Test n/a Patient or Donor PEG, LISS, Saline Crossmatch Patient or Donor Donor RBCs IS vs AHG Phenotype Specific Anti-Sera Patient or Donor AHG Elution Eluate Panel Cells AHG Adsorption Patient Auto vs Allo AHG Transfusion Reactions • Febrile Nonhemolytic Transfusion Reaction – Elevation in blood pressure 1C above 37 – Changes in BP, HR, RR occurring during or within 4 hours of a transfusion – Negative (or unchanged) post-transfusion DAT, clerical check ok • Allergic Transfusion Reaction – – – – Most limited to cutaneous manifestations Pause, treat, resume Exception might be systemic rash or severe allergic Dose dependent, except for anaphylactic Transfusion Reactions • Transfusion Associated Circulatory Overload – Risk Factors: Any organ failure state, pre-existing cardiac disease, frail status – Cardiogenic pulmonary edema – Orders of magnitude more common than TRALI – Response to diuretics/ultrafiltration • Transfusion Associated Acute Lung Injury – Noncardiogenic pulmonary edema – Etiology is immunologic rather than volume related Transfusion Reactions • Acute Hemolytic – DIC, flank pain, hemoglobinemia, hemoglobinuria, sense of impending doom, fever, erythema tracking proximally along infusing vein – Post transfusion DAT positive, eluate most commonly with anti-A or anti-B, less commonly a non-ABO antibody (ie, Kidd) • Delayed Hemolytic – Decline in hemoglobin days after transfusion – Fall by number grams/dL correlating with number of antigen positive units – May be primary or secondary View the complete list at: http://www.choosingwisely.org/wp-content/uploads/2015/01/Choosing-Wisely-Recommendations.pdf Responsible Laboratory Utilization