Basic and Advanced Apheresis Calculations – A Review

Huy P. Pham, MD, MPH Director, Apheresis Service Assistant Professor, Department of Pathology University of Alabama at Birmingham Disclosures

• Editor for Transfusion Medicine, Apheresis, and Hemostasis: Review Questions and Case Studies

• No other conflict of interest

• Email: [email protected] Apheresis Math and Calculations

• Apheresis math – Is usually performed by apheresis device – Apheresis operator and/or physician needs to understand the concepts

• Why is it important? – Ensure both efficacy and safety of the procedure

BASIC CALCULATIONS Question 1

• A 69 year-old woman with a history of acute myelogenous leukemia (AML) is brought to the emergency room by her husband. Because of severe shortness of breath, she is unable to give her own history. Her husband states that over the past 24 hours she has been experiencing increasing shortness of breath, lethargy, and headache.

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 1

• A CBC with differential is performed and she is noted to have an elevated WBC count of 180 x 109/L and 90% blasts. Her current hematocrit is 21%. The decision is made to initiate leukocytapheresis and the apheresis service is consulted. The patient has a weight of 50 kg and a height of 5 feet 0 inches (1.5 meters).

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 1

• Which of the following choices is the appropriate volume of whole blood that should be processed? A) 0.5 – 3 L B) 4.5 – 6 L C) 8 – 10 L D) 10 – 12 L E) 15 – 20 L

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• Various methods to estimate blood volume (BV) – Based on weight and body habitus

– Nadler’s formula = f(gender, height, weight)

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• May need adjustment for pediatric patients – Patient <9.1 kg  90 mL/kg – Patient between 9.1 and 25 kg  80 mL/kg – Patient > 25 kg  use Nadler’s formula • Except for prepubertal boys or boys weigh <30 kg  use “female” as gender for calculation

Kim HC. Chapter 21: Therapeutic Apheresis in Pediatric Patients. In McLeod (ed): Apheresis: Principles and Practice (3rd ed) Concept

• Other key calculations – 푅푒푑 푐푒푙푙 푣표푙푢푚푒 = 퐵푉 ∗ 퐻푐푡 – 푃푙푎푠푚푎 푣표푙푢푚푒 = 퐵푉 − 푅퐶푉 = 퐵푉 (1 − 퐻푐푡)

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

• Leukocytapheresis – Typically process 1.5 – 2 BVs

• Answer: B – Nadler’s formula  TBV  3 L  Need to process 4.5 – 6 L

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

• If this patient has myasthenia gravis and requires 1-plasma volume exchange – TBV  3 L and Hct 21%  푃푙푎푠푚푎 푣표푙푢푚푒 ≈ (3 퐿) 1 − 0.21 = 2.37 퐿 – Order to exchange approximately 2.5L • 5% albumin available at 250-mL or 500-mL bottle • If the patient is on multiple life supporting devices – 푇표푡푎푙 퐵푙표표푑 푉표푙푢푚푒 = 푃푎푡𝑖푒푛푡 퐵푙표표푑 푣표푙푢푚푒 + 푛 𝑖=1 퐵푙표표푑 푣표푙푢푚푒푑푒푣𝑖푐푒 𝑖

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 2

• A 4-year-old girl requires extracorporeal photopheresis (ECP) for the treatment of graft vs. host disease (GVHD). She weighs 28 kg, has a single lumen port for ECP, and her peripheral veins are not suitable for access. Your ECP device can perform ECP using both single- and double- needle access with the following limitations.

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 2

Hematocrit Maximum ECV Maximum ECV (%) (mL) – single (mL) – double needle access needle access 28 500 450 30 450 400 32 400 350 34 350 300 36 300 250 38 250 200

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 2 • Assuming that the Apheresis unit cannot do RBC priming for ECP, given that she can tolerate up to 15% blood outside of her body at a given time, what is the minimum Hct that this patient must have in order for her to safely undergo ECP? A) 30% with single needle access B) 32% with double needle access C) 34% with single needle access D) 36% with double-needle access E) 38% with single-needle access Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• Extracorporeal volume (ECV) 푛 – 퐸퐶푉 = 𝑖=1 퐸퐶푉푑푒푣𝑖푐푒 𝑖 – Within 10 – 15% TBV, depending on patient’s clinical and hemodynamic status

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• ECV depends on – Type of apheresis device – Usually fixed with TPE, RBC exchange, WBC depletion, and platelet depletion – Depends on patient’s access and Hct for ECP • Extracorporeal red cell volume (ERCV) – Ensure intra-procedural Hct is at a safe level 푅퐶푉 −퐸푅퐶푉  퐻푐푡 = 푝푎푡푖푒푛푡 푑푒푣푖푐푒 𝑖푛푡푟푎−푝푟표푐푒푑푢푟푒 푇퐵푉

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• For Spectra Optia (without blood warmer)

Procedure TPE RBC WBC Platelet MNC exchange depletion* depletion* collection

Typical 141 mL 141 mL 253 mL 253 mL 147 mL ECV (253 mL for CMNC) Maximum 185 mL 185 mL 297 mL 297 mL 191 mL ECV (297 mL for CMNC)

*Not FDA approved https://www.terumobct.com/spectra-optia/protocols Concept

• For the Amicus (without blood warmer)

Procedure TPE MNC collection

Maximum ECV 160 mL 163 mL

Maximum ERCV 73 mL 79 – 122 mL

Fresenius Kabi communication Concept

• Therakos UVAR Concept

• Therakos CELLEX Concept

• If ECVdevice>ECVtolerable or Hctintra-procedure

 Decision shall be made in conjunction with clinical team

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

푚퐿 • 푇퐵푉 ≈ 70 ∗ 28 푘푔 = 1960 푚퐿 푘푔 • Assuming the patient is stable

 퐸퐶푉푚푎푥𝑖푚푢푚 = 1960 ∗ 0.15 = 294 푚퐿

• Answer: E – Hct needs to be at least 38% to allow for a safe ECP procedure

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

Hematocrit Maximum ECV Maximum ECV (%) (mL) – single (mL) – double needle access needle access 28 500 450 30 450 400 32 400 350 34 350 300 36 300 250 38 250 200

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 3

• 45 year-old male undergoes therapeutic plasma exchange (TPE) for hyperviscosity due to Waldenstrom macroglobinemia.

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 3

• Assume the IgM monoclonal protein behaves as an ideal solute, after 1.2 plasma-volume exchange, what is the percentage of IgM monoclonal protein left in the patient’s body? A) 25% B) 30% C) 37% D) 63% E) 70% Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• Assumption: One compartmental model and the substance to be removed acts as an ideal solute −µ(푡)  푥 푡 ≈ 푥표푒 where • x(t) = concentration of substance X at time t

• xo = initial concentration of substance X • m(t) = number of plasma volume exchanged at time t

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

• Answer: B – 30% of IgM left after 1.2 PV exchanged – 푥 푡 ≈ 100% 푒−1.2 = 30.1%

• Apply the same formula – After 1 PV exchanged: 37% of initial IgM left – After 1.5 PV exchanged: 22% of initial IgM left – After 2 PV exchanged: 14% of initial IgM left

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

Pham HP and Schwartz J. Chapter 73: Therapeutic plasma exchange in Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects (2nd ed.) Answer

Pham HP and Schwartz J. Chapter 73: Therapeutic plasma exchange in Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects (2nd ed.) Question 4

• A 68 year-old man with multiple myeloma is preparing to undergo an autologous stem cell transplant. A request for hematopoietic progenitor cell (HPC) collection has been placed with a goal collection of 5 x 106 CD34+ cells/kg. The patient’s weight is 70 kg, his hematocrit is 36%, his pre- harvest CD34+ cell count is 20/μL, and the collection efficiency of the apheresis machine being used and the staff running it is 55%.

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 4

• What is the total volume of whole blood that needs to be processed in order to meet the collection target of 5 x 106 CD34+ cells/kg? A) 10 L B) 16 L C) 26 L D) 32 L E) 38 L

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• 퐶표푙푙푒푐푡𝑖표푛 푒푓푓𝑖푐𝑖푒푛푐푦 = 푃푟표푑푢푐푡 퐶퐷34+ 푑표푠푒

(푃푟푒 ℎ푎푟푣푒푠푡 푃퐵 퐶퐷34+(푚퐿−1))×(푉표푙푢푚푒 푝푟표푐푒푠푠푒푑 푚퐿 )  can be used for validation purpose • Predicted yield depends on – Pre-harvest CD34 – Volume of whole blood processed – Average collection efficiency from your institution

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• Rearrange equation

 푊ℎ표푙푒 퐵푙표표푑 푡표 푝푟표푐푒푠푠 = 퐷푒푠𝑖푟푒푑 퐶퐷34+푐푒푙푙/푘푔 ∗(퐵표푑푦 푤푒𝑖푔ℎ푡 𝑖푛 푘푔)

퐶표푙푙푒푐푡𝑖표푛 푒푓푓𝑖푐𝑖푒푛푐푦 ∗ (퐷표푛표푟 푝푟푒−ℎ푎푟푣푒푠푡 퐶퐷34+푐푒푙푙 푐표푢푛푡)

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

• 푊ℎ표푙푒 퐵푙표표푑 푡표 푝푟표푐푒푠푠 = 5 ∗106 퐶퐷34+/푘푔 ∗(70 푘푔) = 31.8 퐿 0.55 ∗ (20 ∗ 106 퐶퐷34+/퐿)

• Answer: D – 32L should be processed – Only an estimate, always need product CD34 count

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 5

• A 23 year-old male with sickle cell disease undergoes chronic RBC exchange. He is now in the outpatient apheresis clinic. His current labs show a Hct of 24% and HgbS level of 62%. Based on your institution protocol, the patient’s HgbS post-procedure should be less than 20% and final Hct should be ~27-30%.

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Question 5

• Please calculate the appropriate fraction cell remained (FCR) for this procedure. A) 32% B) 39% C) 48% D) 67% E) 310%

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Concept

• FCR – Part of the equation for replacement volume calculation for RBC exchange – Represent the ratio of “defected” RBCs at the end of the procedure comparing to the beginning • Sickle cell disease – HgbS% • Hemoglobin SC disease – HgbS% + HgbC% • Babesiosis, Malaria – % parasitemia 푇푎푟푔푒푡′푑푒푓푒푐푡푒푑′푅퐵퐶푠 푎푡 푡ℎ푒 푒푛푑 표푓 푡ℎ푒 푝푟표푐푒푑푢푟푒 – 퐹퐶푅 = ′퐷푒푓푒푐푡푒푑′푅퐵퐶푠 푎푡 푡ℎ푒 푏푒푔𝑖푛푛𝑖푛푔 표푓 푡ℎ푒 푝푟표푐푒푑푢푟푒 Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

20% • 퐹퐶푅 = = 0.32 표푟 32% 62%

• Answer: A – FCR of 32% should be used to achieve the exchange HgbS goal

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Answer

• To estimate Hct and HgbS after simple transfusion

푅퐶푉푖푛푖푡푖푎푙+(푉푡푟푎푛푠푓푢푠푒푑)(퐻푐푡푡푟푎푛푠푓푢푠푒푑) 퐻푐푡푓𝑖푛푎푙 ≈ 푇퐵푉+푉푡푟푎푛푠푓푢푠푒푑

– Hcttransfused depends on RBC storage solution • ~70-85% for CPDA-1 • ~55-65% for AS

퐻푔푏푆푓𝑖푛푎푙 ≈ (푅퐶푉∗퐻푔푏푆 ) 푖푛푖푡푖푎푙 푅퐶푉+(퐻푐푡푡푟푎푛푠푓푢푠푒푑∗푉표푙푢푚푒 푡푟푎푛푠푓푢푠푒푑)

Pham HP and Francis RO. Chapter 20: Practical and Advanced Calculations in Transfusion Medicine, Apheresis, and Hemostasis Thank You