1. Patient Blood Management Minh-Ha Tran, DO, FASCP UC Irvine Health Transfusion Medicine Service

2. Agenda State the guiding principles of Patient Blood Management Name the three phases of perioperative blood conservation Discuss examples of modalities relevant to each phase Define “restrictive” hemoglobin threshold Discuss transfusion risks Name three transfusion alternatives Become acquainted with basic principles of platelet and plasma transfusion practice

3. Patient Blood Management A series of ‘rights’ ◦ Right Patient  Right Product  Right Reason  Right Time Who defines ‘right’? ◦ Clinical decision informed by evidence  Not all hypotension is due to anemia  Not all hypoxia is due to reduced red cell mass  Not all who are anemic require red cell transfusion

4. Perioperative Management PreoperativeIntraoperativePostoperative Medication review and targeted bleeding history Acute normovolemic hemodilution when appropriate Iron supplementation Management plan for congenital bleeding disorders Use of antifibrinolytics when appropriate Reduction of iatrogenic blood loss Evaluation and treatment of preoperative anemia Application of minimally invasive surgical techniques Medical optimizationIntraoperative cell salvage Utilization of restrictive transfusion strategies throughout the perioperative period Anemia tolerance, utilization of transfusion alternatives when possible

5. A word about PAD Preoperative Autologous Donation ◦ Induces Preoperative Anemia  Increases risk for allogeneic transfusion  Generates waste as most units wind up discarded  A waning practice…

6. Restrictive Transfusion Strategies Emphasize clinical, not just laboratory indicators Whenever possible: single unit transfusion, then reassess Study Patient Population ArmsPrimary Outcome TRICC NEJM 1999 838 Critical Care patients [RCT] 7 g/dL (n=418) vs 9 g/dL (n=420) 30 Day ACM: (18.7% vs 23.3%, p = 0.11) TRACS JAMA 2010 502 Cardiac Surgery with Cardiopulmonary Bypass [RCT, NI study] 8 g/dL (n=249) vs 10 g/dL (n=253) NI margin for 30 day ACM predefined at -8%: Observed between group difference 1% [95% CI, -6% to 4%], p = 0.85. FOCUS NEJM 2011 2016 Patients with CAD/Risk of CAD after Hip Fracture Surgery [RCT] < 8 g/dL (n=1009) vs 10 g/dL (n=1007) Death or inability to walk across room unassisted at 60 days: Abs Risk Difference 0.5 percentage points [95% CI, -3.7 to 4.7] Acute UGI Bleed NEJM 2013 921 Patients with severe Upper GI bleeding [RCT] < 7 g/dL (n=461) vs < 9 g/dL (n=460) 45 Day ACM: 91% restrictive vs 95% liberal; HR for death with Restrictive Strategy 0.55 [95% CI: 0.33 to 0.92], p = 0.02.

7. Transfusion Risks (Allergic)

8. Anemia Management Strategies Anemia Tolerance – General Guidelines ◦ Acute bleeding, hypovolemic shock  Transfuse as needed  Surgical management ◦ Chronic anemia, stable patient  Assess for symptoms  …and comorbidities  Determine cause  …and anemia treatment options  Establish timeline for correction  …is the patient preoperative?

9. Iron Deficiency Anemia

10. Anemia severity ◦ Endogenous erythropoietic drive Likelihood of response ◦ Assess for malabsorption, continued losses, anemia of inflammation, renal anemia Slope of response ◦ Reduced if continued ongoing losses or malabsorption

11. Treatment Considerations Enteral Formulations Iron SaltsUnit Dose (mg)Elemental Iron (mg)Notes Ferrous Sulfate32565 Iron salts are similarly tolerated; adverse effects generally attributable to elemental iron content. Ferrous Gluconate32536 Ferrous Fumarate325106 Non-Salts Carbonyl Iron45 Carbonyl iron microspheres derived by heating gaseous iron pentacarbonyl; absorption dependent on solubilization by gastric acid Parenteral Formulations Dextran Stabilized Concentration (mg elemental iron/mL) VialNotes LMW Iron Dextran (INFed) 50100 mg/2 mLWatson Pharma, Inc, Corona, CA Iron Sucrose (Venofer) 20 100 mg/5 mL; 200 mg/10 mL American Regent, Inc, Shirley, NY Sodium Ferric Gluconate Complex in Sucrose solution (Ferrlecit) 12.562.5 mg/ 5 mLWatson Pharma, Inc, Corona, CA Ferumoxytol (Feraheme) 30510m g/17 mLAMAG Pharmaceuticals, Lexington, MA Ferric Carboxymaltose (Injectafer) 50750 mg/15 mLLuitpold Pharmaceuticals, Shirley, NY

12. Erythroid Stimulating Agents

13. SunMonTuesWedThursFriSat 300 U/Kg SunMonTuesWedThursFriSat 600 U/kg

14. Malabsorption Celiac Disease Inflammatory Bowel Disease Roux en Y Gastric Bypass [vegan/vegetarian]

15. General Comments Oral Iron ◦ Hb will rise slowly, beginning 1-2 weeks after initiation of treatment ◦ 2 g/dL over ensuing 3 weeks ◦ Hb deficit typically halved by 1 month, normal by 6-8 weeks Parenteral Iron ◦ In those unresponsive or intolerant to oral iron, or in those whose iron losses exceed absorptive capacity, IV iron is an option ◦ Calculate an iron deficit and replenish the deficit ESA ◦ If ESA’s are administered for renal anemia, coordinate care with the nephrologist ◦ In noncancer patients, ESA’s may be used to augment the erythropoietic response to iron – particularly in mild anemia or when IDA is complicated by inflammation ◦ Always co-administer with iron to avoid functional iron deficiency

16. Calculating Iron Deficit Example: 82 kg woman with heavy uterine bleeding presents with H/H of 6.3 g/dL and 18.9% Total Blood Volume ◦ 70 mL/kg x 82 kg = 5740 mL (57.4 dL) Hemoglobin Deficit ◦ 12 g/dL – 6.3 g/dL = 5.7 g/dL ◦ 5.7 g/dL x 57.4 dL = 327 g Iron Deficit ◦ 3.34 mg Fe/g Hb ◦ 327 g Hb x 3.34 mg Fe/g = ~1000 mg Fe

18. From the Literature IDA treatment: ◦ A higher and more rapid hemoglobin response with parenteral iron ◦ Risk of infection increased with parenteral iron Preoperative anemia: ◦ Oral iron alone ineffective for preoperative purposes, particularly when anemia is mild ◦ Treatment most effective with ESA containing regimen Critical Care Patients: ◦ ESA alone has minimal impact in transfusion avoidance among critical care patients, particularly when restrictive transfusion strategies are in place

19. The anemia we cause…

21. Platelets Usual Adult Dose is 1 Apheresis Platelet Unit

22. Platelets

23. Platelets

24. Plasma

25. Plasma

26. PCC – first view – Tran, et al. Tran MH, Gayatinea R, Albicker P, Baje M. PCC and NovoSeven for Critical Bleeds and Coagulopathy Reversal

27. PBM PI Project PMID: 24919540

28. EBM GI Bleed Protocol

29. Utilization Review

31. Summative Comments Patient Blood Management ◦ Protect the patient from unnecessary or excessive transfusions ◦ Inform transfusion decisions not simply by hemoglobin, but by patient symptoms and comorbidities ◦ Utilize restrictive transfusion strategies ◦ Reduce iatrogenic anemia through reduction in both the volume and frequency of blood draws ◦ Avoid arbitrary 2 unit transfusions ◦ Consider transfusion alternatives for anemia management