Overview of Apheresis Overview of Apheresis and Sickle Cell Diseaseand Sickle Cell Disease

Raúl H. Morales-Borges, MD

Medical Director

American Red Cross

Blood Services

Puerto Rico Region

What is Sickle Cell What is Sickle Cell Disease?Disease?

• IncidenceIncidence• PathophysiologyPathophysiology• TreatmentTreatment• Apheresis ConsiderationsApheresis Considerations

– Patient HistoryPatient History– Amount and Type of blood Amount and Type of blood – Adverse ReactionsAdverse Reactions

Incidence

30 Years Ago- Infectious Disease- Stroke- Average Life Span

Today - Infectious Disease - Multiple Organs - Average Life Span

Peripheral Blood SmearPeripheral Blood SmearSickle CellsSickle Cells

From Raj, A. Sickle Cell Disease in Pediatrics. Emedicine.com/ped/topic2096.htm

Illustration of the formation of sickle cells

Organs Affected by SCD

Hereditary Genealogy of SCD

How does SCD cause How does SCD cause problems?problems?

• Increased blood viscosityIncreased blood viscosity– Limits blood flowLimits blood flow– Promotes red cell sicklingPromotes red cell sickling– Promotes cell-cell interactionsPromotes cell-cell interactions– Activation of coagulation systemsActivation of coagulation systems

• Increased cardiac outputIncreased cardiac output• Expanded plasma volumeExpanded plasma volume• Will likely have a lower Will likely have a lower

hemaglobin/hematocrithemaglobin/hematocrit

Sickled cells and their effect on blood flow

from

VelocityVelocity = = pi (pressure) (radius pi (pressure) (radius of tube)of tube)44

8 (length of tube) 8 (length of tube) (viscosity)(viscosity)

Classic Poiseuille equation for Classic Poiseuille equation for laminar flow of a fluid laminar flow of a fluid

through a straight tubethrough a straight tube

Lungs

Peripheral circulation

Deoxygenated RBCs

Oxygenated RBCs

What does this mean to my What does this mean to my patient?patient?

• By doubling the viscosity, the velocity is cut in By doubling the viscosity, the velocity is cut in half.half.

• Flow is slower in vessels of small radius.Flow is slower in vessels of small radius. – arterioles, venules, capillariesarterioles, venules, capillaries

• Flow is slower in vessels with lower pressures.Flow is slower in vessels with lower pressures. – VenulesVenules

• Vaso-occlusive events and Red Cell DestructionVaso-occlusive events and Red Cell Destruction

Treatment OptionsTreatment Options

• Prophylactic vaccines and antibioticsProphylactic vaccines and antibiotics• HydroxyureaHydroxyurea• AspirinAspirin• Iron Chelation TherapyIron Chelation Therapy• Simple TransfusionsSimple Transfusions• Red Cell ExchangeRed Cell Exchange

How do these issues impact my How do these issues impact my patient?patient?

• AcuteAcute– Vaso-occlusive strokeVaso-occlusive stroke– Acute chest syndromeAcute chest syndrome– Multiorgan failure syndromeMultiorgan failure syndrome– Right upper quadrant syndromeRight upper quadrant syndrome– Surgery/pregnancySurgery/pregnancy

• ChronicChronic– Primary and secondary stroke preventionPrimary and secondary stroke prevention– Multi-organ problemsMulti-organ problems

What are the potential What are the potential complications of SCD that may complications of SCD that may

be treated by apheresis?be treated by apheresis?• Acute infarctive strokeAcute infarctive stroke• Acute chest syndromeAcute chest syndrome• Multi-organ failure syndromeMulti-organ failure syndrome• Right upper quadrant syndromeRight upper quadrant syndrome• ? Priapism? Priapism• ? Acute pain episode? Acute pain episode• ? Pregnancy? Pregnancy

How does a RBC exchange How does a RBC exchange transfusion help my patient?transfusion help my patient?

• Removing sickle cells and replacing Removing sickle cells and replacing them with normal red cells will….them with normal red cells will….

– Improve the oxygen-carrying capacity of Improve the oxygen-carrying capacity of the bloodthe blood

– Decrease blood viscosityDecrease blood viscosity– Reduce vaso-occlusive eventsReduce vaso-occlusive events– Reduce hemolytic complicationsReduce hemolytic complications

Sickled cells and their effect on blood flow

from

What are your treatment What are your treatment options?options?

• Simple red blood cell (RBC) transfusionsSimple red blood cell (RBC) transfusions

• Partial RBC exchange transfusionPartial RBC exchange transfusion

• Automated RBC exchange transfusionAutomated RBC exchange transfusion– Partial exchange transfusionPartial exchange transfusion– Full exchange transfusionFull exchange transfusion

Advantages & Advantages & DisadvantagesDisadvantages

• Simple TransfusionSimple Transfusion• Sickle cells remainSickle cells remain• Increases viscosityIncreases viscosity• Increased iron loadIncreased iron load• Volume shiftVolume shift• Easier vascular Easier vascular

access access • TimeTime• Transfusion Transfusion

complicationscomplications

• Exchange TransfusionExchange Transfusion• Removes % of sickle Removes % of sickle

cellscells• Maintains viscosityMaintains viscosity• No increases in iron No increases in iron

loadload• Volume shift?Volume shift?• May need great accessMay need great access• TimeTime• Transfusion Transfusion

complicationscomplications

Procedural ConsiderationsProcedural Considerations

• HydrationHydration• MedicationMedication

– DiureticsDiuretics– ACE inhibitorsACE inhibitors

• AnemiaAnemia– Simple Simple

transfusiontransfusion– Blood primeBlood prime

• RBCsRBCs

• Extracorporeal Extracorporeal volumevolume

• Vascular AccessVascular Access– Indwelling line Indwelling line

or graftor graft– Temporary Temporary

femoral dialysis femoral dialysis catheterscatheters

– PortsPorts

Line Access Issues and Solutions

- Peripheral access

- Catheters

- Ports

Line Access Issues

Antibody

Red Cell

SENSITIZATION

Antigen – Antibody ReactionsAntigen – Antibody Reactions

ABO

Rh (D, C, c, E, e)

Kell (K, k)

Kidd (Jka, Jkb)

Duffy (Fya, Fyb)

Other: S, U, V, hrb

Goal: Less than 30%Goal: Less than 30%

• Final HematocritFinal Hematocrit– Raise it no more than 3% (why?)Raise it no more than 3% (why?)

• Final sickle cell % of less than 30 Final sickle cell % of less than 30 (why?)(why?)– Approximately 1.5 red cell volumes in Approximately 1.5 red cell volumes in

an untransfused patient.an untransfused patient.– Approximately 1 red cell volume in a Approximately 1 red cell volume in a

recently transfused patient.recently transfused patient.

What does this mean to my What does this mean to my patient?patient?

• By doubling the viscosity, the velocity is cut in By doubling the viscosity, the velocity is cut in half.half.

• Flow is slower in vessels of small radius.Flow is slower in vessels of small radius. – arterioles, venules, capillariesarterioles, venules, capillaries

• Flow is slower in vessels with lower pressures.Flow is slower in vessels with lower pressures. – VenulesVenules

• Vaso-occlusive events and Red Cell DestructionVaso-occlusive events and Red Cell Destruction

How much to exchange?How much to exchange?

• Prior to the exchange, need:Prior to the exchange, need:– Starting hematocritStarting hematocrit– Sickle cell percentageSickle cell percentage– Weight in kgWeight in kg– Total red cell volumeTotal red cell volume

Calculating the Red Cell Calculating the Red Cell VolumeVolume

Red cell volume = (*TBV) Red cell volume = (*TBV) (hematocrit)(hematocrit)

**TBV = estimated total blood volumeTBV = estimated total blood volume

- adult male: 60 – 75 (70)cc per kg- adult male: 60 – 75 (70)cc per kg

- adult female: 55 – 70 (65)cc per kg- adult female: 55 – 70 (65)cc per kg

- infant/child: 80/70cc per kg- infant/child: 80/70cc per kg

Procedural ConsiderationsProcedural Considerations

• Removal of Normal Plasma ConstituentsRemoval of Normal Plasma Constituents

• Lowers Plasma Cations – CalciumLowers Plasma Cations – Calcium

• Alteration of PharmacodynamicsAlteration of Pharmacodynamics

• May Alter Laboratory Test ResultsMay Alter Laboratory Test Results

Possible ComplicationsPossible Complications

• Acute transfusion reactionsAcute transfusion reactions• Vascular access complicationsVascular access complications• Procedural complicationsProcedural complications• Delayed transfusion reactionsDelayed transfusion reactions• OtherOther

Potential Apheresis Adverse Potential Apheresis Adverse ReactionsReactions

• AnxietyAnxiety– HyperventilationHyperventilation– VasovagalVasovagal

• ProceduralProcedural– HypocalcemiaHypocalcemia– HemolysisHemolysis– Hypo/Hypo/

HypervolemiaHypervolemia– MechanicalMechanical

• Transfusion Transfusion ReactionsReactions– Allergic reactionsAllergic reactions– ABO-incompatibilityABO-incompatibility– Bacterial sepsisBacterial sepsis– TRALITRALI– Anaphylactic Anaphylactic

ReactionsReactions• Thrombosis or Thrombosis or

HemorrhageHemorrhage

Paresthesia

Convulsions

Pause Procedure

Nausea &Vomiting

Slow pulse

Yes

Yes

YesConsider:

Hyperventilation,Citrate toxicity

Vasovagal

Consider:Oral calcium,

Knees above headSlow infusion rate

Consider:Citrate toxicityACE inhibitor

Consider:IV Calcium,

Cold compressesSlow infusion rate

Consider:Citrate Toxicity,

Vasovagal

Consider:Hyperventilation,

Citrate toxicityVasovagal

Consider:Oral calcium,

Slow infusion rate

Consider:IV Calcium,

Knees above headCall back-up

Erythema,Itching,Hives

Pause Procedure,Antihistamine

Steroids

RespiratorySymptoms

No YesNo

Mild, StopCall Backup

Resume,Redose if needed

Severe,Stop procedure,

ABCsCall Backup

Hypotension

fever

Pause Procedure,Check Vital Signs

dyspnea

Change in pulse rate

Yes

Yes

Yes

Hyperventilation,Vasovagal

Hyperventilation,Vasovagal

Hypovolemia,TRALI

Cardiogenic Shock

Sepsis,Bacterial contamination,

ABO incompatibilityTRALI

Dehydration,Vasovagal

Consider…

Issues of Exchange Issues of Exchange Transfusion in SCDTransfusion in SCD

• No clear cut guidelines for palliative No clear cut guidelines for palliative chronic exchange transfusion for painful chronic exchange transfusion for painful vaso-occlusive crisis in adults patients vaso-occlusive crisis in adults patients (Navaid M, Melvin T: Am J Hosp Palliat Care 2010 May; (Navaid M, Melvin T: Am J Hosp Palliat Care 2010 May;

27(3):215-218)27(3):215-218)..• Good results in the use of partial exchange Good results in the use of partial exchange

transfusion in the management of SCD in a transfusion in the management of SCD in a perioperative setting perioperative setting (Jaeckel R, Thieme M, Czezlick (Jaeckel R, Thieme M, Czezlick

E, Sablotzki A: Journal of Medical Case Reports 2010; 4:82)E, Sablotzki A: Journal of Medical Case Reports 2010; 4:82)..• Not effective in SCD with coexisting warm Not effective in SCD with coexisting warm

autoantibody haemolysis autoantibody haemolysis (Baron JM, Baron BW: (Baron JM, Baron BW:

Blood Transfus 2010; 8:303-306)Blood Transfus 2010; 8:303-306). .

SummarySummary

• What is SCD?What is SCD?

• What are some of the complications of SCD?What are some of the complications of SCD?

• What are some of the available treatment options?What are some of the available treatment options?

• How do RBC exchange transfusion help?How do RBC exchange transfusion help?

• What are some of the indications for treatment?What are some of the indications for treatment?

CommunicationCommunication

SummarySummary

• What are some of the factors to be considered What are some of the factors to be considered prior to beginning a RBC exchange procedure?prior to beginning a RBC exchange procedure?

• What are the goals of a RBC exchange?What are the goals of a RBC exchange?

• What are some of the possible complications What are some of the possible complications during and following a RBC exchange?during and following a RBC exchange?

• How do we recognize and manage these How do we recognize and manage these complications?complications?

ReferencesReferences

• Sharon, BI. Management of Congenital Hemolytic Sharon, BI. Management of Congenital Hemolytic Anemias. In Anemias. In Rossi’s Principles of Transfusion Rossi’s Principles of Transfusion MedicineMedicine. 4. 4thth ed. AABB Press, 2009. ed. AABB Press, 2009.

• Special Review Issue of the Journal of Clinical Special Review Issue of the Journal of Clinical Apheresis: Clinical Applications of Therapeutic Apheresis: Clinical Applications of Therapeutic Apheresis. 2010. ASFA website. Apheresis. 2010. ASFA website. http://apheresis.orghttp://apheresis.org..

• McLeod BC, Triulzi DJ. Therapeutic Apheresis. A McLeod BC, Triulzi DJ. Therapeutic Apheresis. A Physician’s Handbook, Bethesda, MD: American Physician’s Handbook, Bethesda, MD: American Association of Blood Banks, 2005.Association of Blood Banks, 2005.

• McLeod BC, Weinstein R, Winters, JL, McLeod BC, Weinstein R, Winters, JL, Szczepiorkowski, ZM eds. Apheresis: Principles and Szczepiorkowski, ZM eds. Apheresis: Principles and Practice. 3Practice. 3ndnd ed. Bethesda, MD: AABB Press, 2010. ed. Bethesda, MD: AABB Press, 2010.

• Popovsky MA, ed. Transfusion Reactions, 3Popovsky MA, ed. Transfusion Reactions, 3ndnd ed. ed. Bethesda, MD: AABB Press, 2007.Bethesda, MD: AABB Press, 2007.

• The Food and Drug Administration/Center for The Food and Drug Administration/Center for Biologics Evaluation and Research: Code of Federal Biologics Evaluation and Research: Code of Federal Regulations, Title 21 – Food and Drugs. Regulations, Title 21 – Food and Drugs. http://www.fda.govhttp://www.fda.gov..

ReferencesReferences• Technical manual, 16th ed. Bethesda, MD: American

Association of Blood Banks, 2008.• Standards for blood banks and transfusion services, 26-

27th ed. Bethesda, MD: American Association of Blood Banks, 2010-11.

• Swerdlow P. Red Cell Exchange. Hematology. 2006:48-53. http://asheducationbook.hematologylibrary.org/cgi/content/full/2006/1/48

• Lottenberg R & Hassell K. An evidence-based approach to the treatment of adults with sickle cell disease. Hematology. 2005: 58-65.

• Gladwin M & Kato G. Sickle cell disease: Advances in pathogenesis and management. Hematology. 2005:51-57.

• Immunohematology, American Red Cross.2006:22:101-148.

Dr. Raúl H. Morales BorgesDr. Raúl H. Morales BorgesHematólogo/OncólogoHematólogo/Oncólogo

• Cruz Roja Cruz Roja Americana de PRAmericana de PR– Servicios de Sangre Servicios de Sangre – Ubicados en el Ubicados en el

Centro Medico de Centro Medico de PRPR

– Tel. 787-759-8100Tel. 787-759-8100– Ext. 3873Ext. 3873– Cel. 787-505-5814Cel. 787-505-5814– MoralesBorgesR@usa.redcross.orMoralesBorgesR@usa.redcross.or

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• Ashford Medical Ashford Medical CenterCenter– Suite # 107Suite # 107– Condado, San JuanCondado, San Juan– Tel. 787-722-0412Tel. 787-722-0412– Fax 787-723-0554Fax 787-723-0554– ihoa@coqui.netihoa@coqui.net– www.ihoapr.comwww.ihoapr.com