Anemia and transfusion guidelines in adults

1. Anemia and transfusion guidelines in adults Pablo M. Bedano M.D. Community Regional Cancer Care

2. Most common indications for red blood cell transfusion: • Treatment of symptomatic anemia • Prophylaxis of life threatening anemia • Restoration of oxygen-carrying capacity in the case of hemorrhage

3. Role of blood transfusion: • Oxygen delivery (DO2)= cardiac output x arterial O2 content • At rest in healthy adults delivery exceeds consumption x4 • Delivery can be raised by increasing cardiac output • Ill adults with other medical comorbidities may have impaired compensatory mechanisms

4. Effects of low Hgb in healthy adults: • 31 healthy adults had aliquots of blood (450-900 ml) removed to achieve Hgb 5 g/dL • Isovolemia was maintained • Statistically significant increases in heart rate and stroke volume (increased cardiac output) • Cognitive function impaired at Hgb 5-6 • No increase in plasma lactate concentration • 2 individuals developed reversible EKG changes consistent with ischemia Weiskopff et al JAMA. 1998 Jan 21;279(3):217-21.

5. Impact of anemia on morbitity and mortality: • A retrospective cohort study of 1958 patients who declined transfusion for religious reasons showed 30 day mortality 1.3% Hgb >12 g/dL, 33% if Hb <6, greater odds of death if underlying CV disease • A subset analysis of 300 post-operative patients postoperative risk of death increased progressively when Hb < 7 g/dL • Retrospective review of 310,311 patients undergoing non-cardiac surgery revealed 10% increase cardiac events Hct 36-38.9, 52% Hct 18-20.9 Carson et al Lancet 1996; 348:1055 Carson et al Transfusion 2002; 42:812 Wu et al JAMA 2007; 297:2481

6. Risks and complications of transfusions: • Infection • Allergic reactions • Volume overload • Iron overload • Cost

8. Transfusion thresholds AABB: • Hgb < 6 g/dL– Transfusion recommended except in rare circumstances • Hgb 6 to 7 g/dL – Transfusion likely to be recommended • Hgb 7-8 g/dL – Consider transfusion in postoperative surgical patients • Hgb 8-10 g/dL – Transfusion generally not indicated, consider in special situations (symptomatic anemia, ongoing bleeding, acute coronary syndrome with ischemia • Hgb > 10 g/dL – Transfusion generally not indicated

9. Cochrane review: • 19 randomized clinical trials identified including 6264 patients • All trials included used a transfusion threshold • Most trials used thresholds between 7-10 • 39% decrease in probability of receiving transfusion • Fewer units (1.19) transfused per patient • Trend towards lower 30 day mortality • Trend toward lower infection rate, no difference seen with pneumonia • No difference in functional recovery or length of stay Carson et al JAMA 2013; 309:83

10. Risk of myocardial infarction: • No increased risk of MI found on meta-analysis • TRICC 838 ICU patients with Hgb <9 within 72 hs. admission, randomized to liberal (Hgb>10) vs. restrictive (hgb>7). Lower overall mortality in restrictive group, lower risk of MI (0.7 vs 2.9%) • FOCUS 2016 patients >50 with history or risk factors for CAD and Hgb < 10 g/dL after hip surgery randomized to liberal (Hgb>10) or restrictive (Hgb>8) transfusion threshold. No-statistically significant increase of MI (3.8 vs 2.3). No difference in survival Hebert et al NEJM 1999; 340:409-417 Carson et al NEJM 2011; 365(26):2453-62

11. Acute coronary syndrome: • Most guidelines recommend transfusion when Hgb between 8-10 g/dL in the setting of active ischemia • Pilot trial 110 patients with ACS undergoing cardiac cath. with Hgb < 10 g/dL. Randomized to liberal (>10) vs restrictive (>8). Endpoint death, MI or revascularization <30 days. Trend to better outcome in liberal group (10.9% vs 25.5% P=0.54) Carson et al Am Heart J 2013; 165:964

12. Congestive heart failure: • AABB guidelines recommend transfusion threshold of 8 g/dL in asymptomatic patient and 7-10 g/dL in symptomatic patient • Fluid overload is a concern

13. Acute bleeding: • In case of massive bleeding transfusion should be guided by rate of bleeding and not Hgb • Hemodynamically stable patients restrictive strategy may be safe • Single center trial randomized 921 patients with acute upper GI bleed to restrictive (Hgb>7) vs liberal (Hgb >9) strategy, excluding massive bleeding, ACS or CVD. All patients underwent endoscopic treatment within 6 hs • Lower rate of transfusion (49 vs 89 percent) • Fewer deaths from bleeding (0.7 vs 3.1 percent) and from any cause (5 vs 9 percent)

14. Transfusion and surgery: • Based on FOCUS trial a transfusion threshold of Hgb 8 g/dL seems to be safe • Hgb threshold of 8 g/dL seems safe in patients undergoing cardiac surgery with cardiopulmonary bypass • 428 patients randomized to threshold 8 vs 9, no differences in outcome • TRACS 502 patients undergoing cardiac surgery with CP bypass, no differences in outcome. Independent of transfusion strategy, overall mortality correlated with number of transfusions Bracey et al Transfusion 1999;39:1070 Hajjar et al JAMA 2010; 304:1559

15. Cancer patients: • In patients undergoing active treatment maintain Hgb > 7-8 g/dL • No randomize studies to guide palliative benefit of blood transfusions in terminal patients

16. Conclusions: • Multiple clinical trials validate a restrictive transfusion strategy for most adults, with threshold Hgb 7-8 g/dL • In medically stable ICU patients Hgb threshold of 7 g/dL safe based on TRICC trial • Symptomatic patients with Hgb <10 g/dL should be transfused as clinically indicated • In patients with acute coronary syndrome, Hgb should be kept > 8 g/dL and > 10 g/dL in ongoing ischemia • Patients with massive bleeding cannot be managed based on Hgb thresholds • Transfusion on 1 unit of blood at a time is reasonable in the hemodynamicallystable patient