Red blood cell transfusions Risks, benefits, and surprises

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SIOP PODC Supportive Care Education Presentation Date: 19 th January 2016 www.cure4kids.

1 SIOP PODC Supportive Care Education Presentation Date: 19 th January Red blood cell transfusions Risks, benefits, and surprises Scott Howard, MD, MSc Professor, Universidad de Memphis, USA Director, World Child Cancer USA

2 Red blood cell transfusion Role of red blood cells (RBCs) Physiology of anemia Management of anemia RBC loss bleeding, hemolysis Decreased RBC production Risks of transfusion Recommendations

3 Red blood cell transfusion Role of red blood cells (RBCs) Physiology of anemia Management of anemia RBC loss bleeding, hemolysis Decreased RBC production Risks of transfusion Recommendations

4 Biconcave Red Blood Cell 3µ 1µ 8µ

5 What is the diameter of a typical capillary in humans? 1 micron 3 microns 8 microns 12 microns 15 microns

6 What is the diameter of a typical capillary in humans? 1 micron 3 microns 8 microns 12 microns 15 microns

7 What do you not see here?

8 Red blood cells traversing a capillary O O O O O 2 O 2

9 Importance of Oxygen Production of ATP Tricarboxylic acid cycle Electron transport chain Production of NADH/NADPH Comparison: energy produced by anaerobic metabolism

10 Glucose Metabolism Glycolysis, TCA cycle Glycolysis Glucose 2 Pyruvate + 2 ATP + 2 NADH 2 Acetyl CoA + 2 CO NADH Tricarboxylic acid (Krebs) cycle 2 GTP + 4 CO NADH + 4 NADH + 2 FADH 2

11 Glucose Metabolism Electron Transport System O 2 + NADH O 2 + FADH 2 Electron transport system 3 ATP + NAD + 2 ATP + FAD Glucose 2 ATP + 2 GTP + 10 NADH + 2 FADH 2 Glucose + O 2 38 ATP equivalents

12 Mitochondria Anatomy

13 The beautiful mitochondria

14 Mitochondria Anatomy

15 Glucose Metabolism Glycolysis, TCA cycle Glycolysis Glucose 2 Pyruvate + 2 ATP + 2 NADH 2 Acetyl CoA + 2 CO NADH Tricarboxylic acid (Krebs) cycle 2 GTP + 4 CO NADH + 4 NADH + 2 FADH 2 Electron transport system with O 2 36 ATP

16 Importance of Oxygen Production of ATP Tricarboxylic acid cycle Electron transport chain Production of NADH/NADPH Comparison: energy produced by anaerobic metabolism

17 Importance of Oxygen Aerobic versus anaerobic metabolism Aerobic metabolism 1 glucose molecule yields 38 ATP NADH, FADH are converted to ATP Complex enzyme system Requires O 2 Anaerobic metabolism 1 glucose molecule yields 2 ATP NADH must be re-oxidized to NAD Simple enzyme system No O 2 needed

18 Hemoglobin-oxygen dissociation curve Figure 1-3

19 Oxygen Transport Airways, alveoli Pulmonary arteries Pulmonary capillaries Pulmonary veins Left atrium, left ventricle Systemic arteries Systemic capillaries Interstitial fluid Cells Mitochondria

20 Pulmonary capillary Tissue capillary Interstitial fluid Lung Oxygen Transport From Lungs to Tissues Artery 98 Tissue Alveolus 100 Alveolus 100 Alveolus ???????? Cell? Mitochondrion? 40 Blue = po 2 Vein

21 Pulmonary capillary Tissue capillary Interstitial fluid Lung Oxygen Transport From Lungs to Tissues Artery 98 Tissue Alveolus 100 Alveolus 100 Alveolus ?? Cell? Mitochondrion? 40 Blue = po 2 Vein

22 Pulmonary capillary Tissue capillary Interstitial fluid Lung Oxygen Transport From Lungs to Tissues Artery 98 Tissue Alveolus 100 Alveolus 100 Alveolus Cell 1 Mitochondrion Blue = po 2 Vein

23 Oxygen Transport Site po 2 Pulmonary arteries 40 Pulmonary capillaries Pulmonary veins 100 Left atrium, left ventricle 98 Systemic arteries 98 Systemic capillaries Interstitial fluid 10 Cells 1 Mitochondria 0.1

Oxygen Content and Po 2 O 2 content = PO 2 x 0.

34 [cco 2 /g Hb]) Site Po 2 O 2 sat O 2 content Artery 100 100% 19.

24 Oxygen Content and Po 2 O 2 content = PO 2 x [cc O 2 /mmhg] + (O 2 sat x Hb [g/dl] x 1.34 [cco 2 /g Hb]) Site Po 2 O 2 sat O 2 content Artery % 19.1 cc O 2 /dl Vein 40 70% 13.2 cc O 2 /dl O 2 delivery = CO x (Cao 2 - Cvo 2 ) = 30dL/m 2 /min x 5.8 cc O 2 /dl = 174 cc O 2 /min/m 2 Blood volume = 70 cc/kg body weight Cardiac output (CO) = 44 dl/min/m 2

25 Po 2 and O 2 saturation (Assume Hb = 14 mg/dl) PPo2 O2 sat O2 content O2 Hb Dissolved O % % % % %

26 Pulmonary capillary Tissue capillary Interstitial fluid Lung Oxygen Transport Normal Hemoglobin Artery 98 Tissue Alveolus 100 Alveolus 100 Alveolus Cell 1 Mitochondrion 0.1 DO 2 = COx5.8 Blue = po 2 40 Vein Red = O 2 content

27 Red blood cell transfusion Role of red blood cells (RBCs) Physiology of anemia Management of anemia RBC loss bleeding, hemolysis Decreased RBC production Risks of transfusion Recommendations

28 Pulmonary capillary Tissue capillary Interstitial fluid Lung Oxygen Transport Anemia (Hb = 10) Artery 98 Tissue Alveolus Alveolus Alveolus Blue = po 2 Vein Cell 1 10 Mitochondrion 0.1 DO 2 = COx5.8 Red = O 2 content

29 Hemoglobin, 2,3-DPG, and Cardiac Index

30 Anemia that develops slowly in otherwise healthy adults Hemoglobin (g/dl) Symptoms 8 to 11 Generally none - pallor, slight tachycardia 7.5 Exertional dyspnea 6.0 Some weakness 3.0 Dyspnea at rest < 2.5 Cardiac failure

31 Response to Acute Hemodilution Before After % Change Hematocrit (%) Arterial O 2 (cc/dl) O 2 delivery (cc/kg/min) Heart Rate (beat/min) Cardiac Output (L/min) O 2 Extraction (%) From Levine, et.al. Transfusion 30:11, 1990

32 Red blood cell transfusion Role of red blood cells (RBCs) Physiology of anemia Management of anemia RBC loss bleeding, hemolysis Decreased RBC production Risks of transfusion Recommendations

33 Management of Anemia Determine the urgency of the situation Treat the underlying cause (bleeding, hemolysis, bone marrow failure) Transfuse RBCs when there is insufficient oxygen being delivered to tissues Transfuse the smallest amount possible (that is, the smallest number of donors) Minimize risks of transfusion

35 Major Define Types of Hemorrhage Fatal (CTCAE grade 5, WHO grade 4) Life-threatening (CTCAE grade 4) Requiring transfusion or other urgent intervention (CTCAE grade 3, WHO grade 3) Minor clinically significant but not urgent (CTCAE grade 2, WHO grade 2) Trivial petechiae, transient nose-bleed, microscopic hematuria, scleral hemorrhage

36 Causes of treatment failure for children with cancer in selected middle-income countries Abandonment = 16% Toxic death = 16% Relapse = 21.5%

39 Blood Transfusion and Survival Malaria as an example Lackritz, et al. The Lancet, 340: 524-8, Siaya District Hospital (Rural Western Kenya) October 1989 to October admissions for severe malaria 29% Hb<5.0 20% received transfusions

40 Malaria Hb>3.9 best to NOT transfuse

42 Red blood cell transfusion Role of red blood cells (RBCs) Physiology of anemia Management of anemia RBC loss bleeding, hemolysis Decreased RBC production Risks of transfusion Recommendations

48 Transfusion Requirements for Patients Receiving Critical Care (TRICC Study) Hebert, P., et.al. NEJM 340: , 1999 (Canadian Critical Care Trials Group). 838 ICU patients with Hb < 9.0 within 48 hours after ICU admission. Randomized to transfusion to maintain: Hemoglobin 7 to 9 g/dl (Restrictive) vs Hemoglobin 10 to 12 g/dl (Liberal)

49 TRICC Study - Subgroup Survival

51 Red blood cell transfusion algorithm for LMIC

52 Red blood cell transfusion Role of red blood cells (RBCs) Physiology of anemia Management of anemia RBC loss bleeding, hemolysis Decreased RBC production Risks of transfusion Recommendations

53 Conclusions Anemia is not important Lack of oxygen delivery to tissues is extremely important (38 ATP) and should guide transfusion decisions Benefits of increased Hb to carry oxygen to the mitochondria must be balanced against risk of transfusion It is RARE to need Hb > 7 g/dl The patient s social situation should be considered when providing prophylactic RBC transfusions

Red blood cell transfusions Risks, benefits, and surprises

Red blood cell transfusions Risks, benefits, and surprises SIOP PODC Supportive Care January 19, 2016 via www.cure4kids.org Scott Howard, MD, MSc Professor, Universidad de Memphis, USA Director, World