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Abnormal Abnormal hemoglobinhemoglobin

By Dr. Ehab By Dr. Ehab KhairyKhairy

Abnormal HemoglobinAbnormal Hemoglobin

May be due to: May be due to:

1- Abnormal concentrations1- Abnormal concentrations

High or low concentrationsHigh or low concentrations

2- Abnormal Structures2- Abnormal Structures

Sickle cell disordersSickle cell disorders

3- Abnormal Synthesis 3- Abnormal Synthesis

ThalassemiasThalassemias

4- Abnormal Hemoglobin function4- Abnormal Hemoglobin function

Met hemoglobin Met hemoglobin

Abnormally low Hemoglobin Abnormally low Hemoglobin Concentration Concentration

• Iron deficiency Iron deficiency • Chronic diseaseChronic disease ThalassemiaThalassemia ThalassemiaThalassemia• Sickle cellSickle cell• A plastic anemiaA plastic anemia• AutoimmuneAutoimmune• Folic acid Folic acid deficiencydeficiency• Vit.B12 deficiencyVit.B12 deficiency• Distribution Of AnemiaDistribution Of Anemia

Physiological compensatory Physiological compensatory Mechanisms for Low HemoglobinMechanisms for Low Hemoglobin

Manifestations Of Sever Manifestations Of Sever Nutritional AnemiaNutritional Anemia

Iron deficiency anemiaIron deficiency anemia

• Respiratory distressRespiratory distress• Congestive heart failureCongestive heart failure• ThrombocytopeniaThrombocytopenia• Neurologic abnormalities Neurologic abnormalities

Vitamin B 12 deficiency Vitamin B 12 deficiency anemiaanemia

1- Neuropathy1- Neuropathy* Sensory : * Sensory : Bilateral symmetrical parasthesiaBilateral symmetrical parasthesiaLoss of propioceptive and vibratory sensationsLoss of propioceptive and vibratory sensations* Motor: * Motor: Diminished deep tendon reflexesDiminished deep tendon reflexesand un steady gaitand un steady gait* Mental: * Mental: Impaired memory and mentalImpaired memory and mentaldepressiondepression

2- Thyroid disorders: 2- Thyroid disorders: associated withassociated withpernicious anemiapernicious anemia

Folic acid deficiency anemiaFolic acid deficiency anemia

• Smooth tongueSmooth tongue• Hyper pigmentationHyper pigmentation• Mental depressionMental depression• Peripheral edemaPeripheral edema• Liver dysfunctionLiver dysfunction• With or without peripheral neuropathyWith or without peripheral neuropathy

Optimization Of Deficiency Optimization Of Deficiency Anemia Before Elective SurgeryAnemia Before Elective SurgeryIron Deficiency Anemia Iron Deficiency Anemia

# Oral preparations # Oral preparations 200 mg200 mg

# # ParenteralParenteral preparations preparations must be given must be given under close medical supervision under close medical supervision

# Human Erythropoietin# Human Erythropoietin

Vitamin B12 Deficiency AnemiaVitamin B12 Deficiency Anemia

1 mg hydroxo-cobolamin Im every three 1 mg hydroxo-cobolamin Im every three days for six injectionsdays for six injections

Folic Acid Deficiency AnemiaFolic Acid Deficiency Anemia

Oral 5 mg of folic acid for four monthsOral 5 mg of folic acid for four months

Preoperative Transfusion Preoperative Transfusion Decision makingDecision making

*Causes of anemia *Degree of anemia *Causes of anemia *Degree of anemia

*Duration of anemia *Urgency of surgery*Duration of anemia *Urgency of surgery

*Intravascular fluid volume*Intravascular fluid volume

*Likely hood of intra operative blood loss*Likely hood of intra operative blood loss

*Age of the patient*Age of the patient

**Co existing diseasesCo existing diseases- Ischemic heart disease - Ischemic heart disease

- Lung disease- Lung disease

- Cerebrovascular disease - Cerebrovascular disease

- - Peripheral vascular disease Peripheral vascular disease

Guide Line For Blood Guide Line For Blood TransfusionTransfusion

- Hb conc.> 10 g/dl - Hb conc.> 10 g/dl Transfusion rarely indicatedTransfusion rarely indicated

specially for chronic anemiaspecially for chronic anemia

- Hb conc. < 6g/dl - Hb conc. < 6g/dl Almost indicate bloodAlmost indicate blood

transfusion specially for acute anemiatransfusion specially for acute anemia

- Hb conc. Between 6 – 9 g/dl - Hb conc. Between 6 – 9 g/dl Decision ofDecision of

transfusion is determined by patient risk fortransfusion is determined by patient risk for

complications of decreased tissue oxygenation complications of decreased tissue oxygenation

( patient with ischemic heart)( patient with ischemic heart)

Adverse Effects Of Anesthesia On Adverse Effects Of Anesthesia On Anemia Anemia

Anesthesia depress sympathetic nervousAnesthesia depress sympathetic nervous

system and decrease C.O.P. and offsets system and decrease C.O.P. and offsets

An important physiological compensatoryAn important physiological compensatory

mechanism for anemiamechanism for anemia

Nitrous oxide can produce megaloblasticNitrous oxide can produce megaloblastic

changes even within a short period ofchanges even within a short period of

administrationadministration

Effects of Anemia On Anesthesia Effects of Anemia On Anesthesia and Its Choice and Its Choice

• Anemia theoretically reduces Mac of Anemia theoretically reduces Mac of Volatile AnestheticsVolatile Anesthetics

• Neurologic changes of vitamin B12 Neurologic changes of vitamin B12 deficiency detract the choice of Regional deficiency detract the choice of Regional anesthesia and peripheral nerve blockanesthesia and peripheral nerve block

Anesthetic Goals Anesthetic Goals

1-1- Adequate tissue Oxygen DeliveryAdequate tissue Oxygen DeliveryAvoid drug induce myocardial depressionAvoid drug induce myocardial depression

Avoid factors shifting oxygen dissociation curveAvoid factors shifting oxygen dissociation curve

to the left (Hyperventilation & Hypothermia) to the left (Hyperventilation & Hypothermia)

2-2- Minimizing blood LossMinimizing blood Loss

3-3- Adequate Monitoring Adequate Monitoring

Polycythemia Polycythemia

Pathologic excess of hematocrit with or withoutPathologic excess of hematocrit with or without

increased hemoglobin concentrationincreased hemoglobin concentration

1- Primary Polycythemia (vera)1- Primary Polycythemia (vera)

Increased hematocrit Iron deficiency anemiaIncreased hematocrit Iron deficiency anemia

2- Relative Polycythemia2- Relative Polycythemia

Increased hematocrit Normal Hb conc.Increased hematocrit Normal Hb conc.

3- Secondary Polycythemia3- Secondary Polycythemia

Increased hematocrit High Hb conc.Increased hematocrit High Hb conc.

Causes Of Secondary PolycythemiaCauses Of Secondary Polycythemia

1- Chronic anoxia1- Chronic anoxia* High Altitude * Smoker’s polycythemia* High Altitude * Smoker’s polycythemia

* Cardiopulmonary diseases * Cardiopulmonary diseases

* Obesity – hypoventilation & Sleep apnea* Obesity – hypoventilation & Sleep apnea

syndromesyndrome

2- Renal Diseases 2- Renal Diseases Calculi, Cysts, Hydronephrosis, CarcinomaCalculi, Cysts, Hydronephrosis, Carcinoma

3- Excessive Testosterone production3- Excessive Testosterone production

4- Iatrogenic 4- Iatrogenic Exogenous Testosterone and ErythropoietinExogenous Testosterone and Erythropoietin

Complications of Increased Complications of Increased Hb Conc. Hb Conc.

Increased Blood ViscosityIncreased Blood Viscosity

Increased peripheral resistanceIncreased peripheral resistance

ThrombosisThrombosis

Anesthetic Goals Anesthetic Goals

Reduction of Hb conc. < 15g/dl prior toReduction of Hb conc. < 15g/dl prior to

elective surgery byelective surgery by

1- Minimizing tissue anoxia and other factors1- Minimizing tissue anoxia and other factors

enhancing erythropoietin productionenhancing erythropoietin production

2- Normovolemic hemo- dilution just prior to2- Normovolemic hemo- dilution just prior to

surgery is much better than repeatedsurgery is much better than repeated

phlebotomy a week before…. Why?phlebotomy a week before…. Why?

Structure Of Hemoglobin Structure Of Hemoglobin

# Fetal Hemoglobin (Hb F)# Fetal Hemoglobin (Hb F)Consists of 2Consists of 2 chains & 2 chains & 2 Changes to adult Hemoglobin within 3 to 6 monthsChanges to adult Hemoglobin within 3 to 6 months

after birth to adult after birth to adult

# Adult Hemoglobin (Hb A)# Adult Hemoglobin (Hb A)Consists of 2Consists of 2 chains & 2 chains & 2 An other form of adult HbAn other form of adult Hb

# Adult hemoglobin (HB# Adult hemoglobin (HB A A22))

consists of 2consists of 2 chains & 2 chains & 2 δδ

•

Hereditary Disorder Of Hereditary Disorder Of Hemoglobin Hemoglobin

• Hemoglobinopathies consist of abnormal Hemoglobinopathies consist of abnormal structural variants of hemoglobin , the structural variants of hemoglobin , the most important is sickle disorders (Hb S) most important is sickle disorders (Hb S)

• Thalassemia reflects abnormal synthesis Thalassemia reflects abnormal synthesis of hemoglobin where chains of of hemoglobin where chains of hemoglobin are diminished or absenthemoglobin are diminished or absent

Sickle Cell Diseases Sickle Cell Diseases

Sickle cell disease is one of the most Sickle cell disease is one of the most prevalent genetic disorders affecting prevalent genetic disorders affecting millions through out the word millions through out the word

It is common in India, Saudia Arabia, It is common in India, Saudia Arabia, Mediterranean countries, South, and Mediterranean countries, South, and center of America center of America

Sickle cell disease denotes all Sickle cell disease denotes all genotypes that contain at least 1 sickle genotypes that contain at least 1 sickle gene in which hemoglobin S (HbS) makes gene in which hemoglobin S (HbS) makes up at least half of the hemoglobin present.up at least half of the hemoglobin present.

Mendelian Trait of Sickle Cell Mendelian Trait of Sickle Cell Disease Disease

Hb S is formed of 2 normal alpha-Hb S is formed of 2 normal alpha-and 2 abnormal beta-globin chainsand 2 abnormal beta-globin chains

• • Recessive (Hb S, Hb S)Recessive (Hb S, Hb S) Abnormal hemoglobin Abnormal hemoglobin

• • Heterozygous (Hb A, Hb S)Heterozygous (Hb A, Hb S) Normal and abnormal hemoglobinNormal and abnormal hemoglobin

Normal hemoglobin more abundantNormal hemoglobin more abundant

PathophysiologyPathophysiology# # chain of chain of Hb S differs form that of Hb A only inHb S differs form that of Hb A only in the substitution of valine for glutamic acid atthe substitution of valine for glutamic acid at the sixth position.the sixth position.# Hb S carries oxygen normally but it unloads# Hb S carries oxygen normally but it unloads

oxygen more easily as its Poxygen more easily as its P50 50 is 31mmHgis 31mmHg compared to 26 mmHg of normal Hbcompared to 26 mmHg of normal Hb# Once oxygen is unloaded to the tissues# Once oxygen is unloaded to the tissues It begins to form semisolid aggregateIt begins to form semisolid aggregate structures, structures, consequently RBCs acquire sickleconsequently RBCs acquire sickle shape.shape.

Results of Sickle CellsResults of Sickle Cells

• • ErythrostasisErythrostasis

• • Increased blood viscosityIncreased blood viscosity

• • Reduced blood flowReduced blood flow

• • HypoxiaHypoxia

• • Increased adhesion of red blood cellsIncreased adhesion of red blood cells

• • Vascular occlusionVascular occlusion

• • Further sicklingFurther sickling

Pathophysiology Pathophysiology of Sickle Cell of Sickle Cell DiseaseDisease

Clinical Signs and SymptomsClinical Signs and Symptoms

Vaso occlusive Painful crisisVaso occlusive Painful crisis

• • Acute chest syndrome (a life-Acute chest syndrome (a life-threatening pneumonia-like illness)threatening pneumonia-like illness)

• • Cerebrovascular accidentsCerebrovascular accidents

• • Splenic and renal dysfunctionSplenic and renal dysfunction

• • Chronic anemiaChronic anemia

• • Susceptibility to infectionsSusceptibility to infections

Cont.Cont.

• • JaundiceJaundice

• • PallorPallor

• • Hand and foot syndrome (warmth Hand and foot syndrome (warmth and tenderness)and tenderness)

• • Leg ulcersLeg ulcers

• • OrganomegalyOrganomegaly

• • Cardiac failureCardiac failure

• • Abdominal and bone pain (aseptic Abdominal and bone pain (aseptic necrosis)necrosis)

A plastic crisisA plastic crisis

Characterized by Characterized by profound anemia Hb is < 3g/dl, profound anemia Hb is < 3g/dl,

It may be Precipitated by It may be Precipitated by IInfection, hypoxia, systemic disease, nfection, hypoxia, systemic disease,

acidosis, dehydration, trauma, and acidosis, dehydration, trauma, and Folic acid deficiency Folic acid deficiency

Splenic Sequestration CrisisSplenic Sequestration Crisis

Characterized byCharacterized by Sudden pooling of blood in the spleen Sudden pooling of blood in the spleen

due to partial occlusion of its drainagedue to partial occlusion of its drainage

It can cause life threatening hypotension in It can cause life threatening hypotension in infants and young children…… Why?infants and young children…… Why?

Repeated splenic infarction result in Repeated splenic infarction result in fibrosis -auto spleenectomy.fibrosis -auto spleenectomy.

Managing a CrisisManaging a Crisis

A part of blood transfusionA part of blood transfusion

- High doses of folic acid- High doses of folic acid

- Analgesia for pain- Analgesia for pain

- Hydration- Hydration

- Enhance hemoglobin F production of - Enhance hemoglobin F production of by using hydroxyurea and by using hydroxyurea and erythropoietin …….. erythropoietin …….. Why?Why?

Anesthetic ManagementsAnesthetic Managements

Preoperative preparationPreoperative preparation- Adequate hydration- Adequate hydration

- Infection control- Infection control

- Prophylactic antibiotics- Prophylactic antibiotics- Optimization of quality and quantity of HbOptimization of quality and quantity of Hb

by partial exchange transfusionby partial exchange transfusion- The goal of such transfusion is to achieve The goal of such transfusion is to achieve

a hematocrit of 30-40% with > 50% a hematocrit of 30-40% with > 50% normal Hb Anormal Hb A

Intra operative ManagementsIntra operative Managements

Avoid 6H & 1SAvoid 6H & 1SHypoxia HypercarbiaHypoxia Hypercarbia

Hypotension Hypovolemia Hypotension Hypovolemia

Hypothermia HyperthermiaHypothermia Hyperthermia

StasesStases

Intra Operative MonitoringsIntra Operative Monitorings

CVPCVP is useful to monitor volume state is useful to monitor volume state

PAP PAP for monitoring of mixed venous for monitoring of mixed venous oxygen saturation oxygen saturation

Sickling changes do not occur if the Sickling changes do not occur if the VSOVSO22

above 40 mmHgabove 40 mmHg

Post operative ConsiderationsPost operative Considerations

Supplemental oxygenSupplemental oxygen

Pain ControlPain Control

Pulmonary physiotherapy Pulmonary physiotherapy

Early ambulationEarly ambulation

ThalassemiaThalassemia

Types Of ThalassemiaTypes Of Thalassemia

Alpha ThalassemiaAlpha Thalassemia

• NormalNormal // • Silent carrierSilent carrier - - // • MinorMinor --/-/-

--/--/• Hb H diseaseHb H disease --/---/-• Barts hydrops fetalisBarts hydrops fetalis --/-- --/--

Beta ThalassemiaBeta Thalassemia

• NormalNormal //• MinorMinor //00

//++

• IntermediaIntermedia 00//++

• Major Major 00//00

++//+ +

0 = no production of the chain0 = no production of the chain

+ = diminished production of the chain+ = diminished production of the chain

Clinical manifestationsClinical manifestations

1- Anemia : 1- Anemia :

Microcytic and hypochromicMicrocytic and hypochromic

2- Excessive 2- Excessive hemolysishemolysis

3- Hyperplasia of the bone marrow3- Hyperplasia of the bone marrow

and extramedullary erythropoiesisand extramedullary erythropoiesis

Excessive hemolysis:Excessive hemolysis:- Many RBCs fail to mature and early destroyed- Many RBCs fail to mature and early destroyed

By the reticuloendothelial systemBy the reticuloendothelial system

- Excess - Excess globins of globins of Thalassemia (Target cell) Thalassemia (Target cell)

- This Hb is poorly soluble, highly reactive and- This Hb is poorly soluble, highly reactive and

cause free radical cellular Injurycause free radical cellular Injury

- Excess hemolysis result in Excess hemolysis result in

Splenomegaly, Hepatomegaly, Cholelithiasis, Splenomegaly, Hepatomegaly, Cholelithiasis, and Jaundiceand Jaundice

3- Hyperplasia Of The Bone 3- Hyperplasia Of The Bone MarrowMarrow

Caused by Caused by vigorous secretion of erythropoietinvigorous secretion of erythropoietin

Result in Result in

* Skeletal abnormalities and facial* Skeletal abnormalities and facial

dysmorphism.dysmorphism.

*Development of extramedullary marrow in *Development of extramedullary marrow in

Pleura HemothoraxPleura Hemothorax

Sinuses EpistaxisSinuses Epistaxis

Epidural space Epidural hematomaEpidural space Epidural hematoma

Blood Transfusion Therapy for Blood Transfusion Therapy for ThalassemiaThalassemia

1- Palliative transfusion:1- Palliative transfusion:

It is just to keep patient surviving It is just to keep patient surviving

2- hypertransfusion:2- hypertransfusion:

Maintain a hemoglobin level of 9 to 10 g/dlMaintain a hemoglobin level of 9 to 10 g/dl

To reduce extramedullary erythropoiesisTo reduce extramedullary erythropoiesis

3- Supertransfusion: 3- Supertransfusion:

Maintain a hemoglobin level >12 g/dlMaintain a hemoglobin level >12 g/dl

in an effort to suppress all erythropoiesis.in an effort to suppress all erythropoiesis.

Complications of regular Complications of regular Blood Transfusion Blood Transfusion

HemosiderosisHemosiderosis

Cardiac and Hepatic iron toxicity Cardiac and Hepatic iron toxicity (cirrhosis)(cirrhosis)

Require Require

CChelation therapy with Deferoxaminehelation therapy with Deferoxamine

Expected Anesthetic Expected Anesthetic Difficulties Difficulties

1- Difficult Air Way:1- Difficult Air Way:Hyperplasia of facial bones and narrowing of Hyperplasia of facial bones and narrowing of

nasalnasal

passagepassage

2- 2- Hemosiderosis:Hemosiderosis:Resulting in cardiac dysfunction, supraResulting in cardiac dysfunction, supra

ventricular arrhythmias as well as hepaticventricular arrhythmias as well as hepatic

dysfunctions dysfunctions

Regional Anesthesia Regional Anesthesia

Epidural, spinal, and intrapleural anesthesiaEpidural, spinal, and intrapleural anesthesia

are relatively contraindicated as the presenceare relatively contraindicated as the presence

of extramedullary bone marrowof extramedullary bone marrow increases theincreases the

likelihood of bleeding and hematoma formationlikelihood of bleeding and hematoma formation

Patients receiving palliative transfusionPatients receiving palliative transfusion

therapy are at greatest risktherapy are at greatest risk

Met-hemoglobinMet-hemoglobinMet Met = beyond= beyond

Ferric iron Ferric iron (fe(fe+3+3) ) = one oxidation state = one oxidation state

beyond ferrous iron (Febeyond ferrous iron (Fe+2+2) )

Ferric form of ironFerric form of ironUnable to bind to OUnable to bind to O22, ,

Decreasing ODecreasing O22 carrying capacity carrying capacity

Shifts OShifts O22 dissociation curve to the dissociation curve to the

left Worsening tissue Oleft Worsening tissue O22 release release

EtiologyEtiology

HereditaryHereditaryCongenital absence of Congenital absence of

NADH methemoglobin reductaseNADH methemoglobin reductase

Acquired Acquired Drug inducedDrug induced

Chemical inducedChemical induced

Drugs Causing MethemoglobinDrugs Causing Methemoglobin

All begin with letter AAll begin with letter A

1- Anti hypertensive 1- Anti hypertensive Vaso dilator drugsVaso dilator drugs

2- Anesthetics2- Anesthetics

Benzocaine, Lidocaine, PrilocaineBenzocaine, Lidocaine, Prilocaine

3- Analgesics3- Analgesics

Phenacetin, PhenazopyridinePhenacetin, Phenazopyridine

4- Antiemetic 4- Antiemetic MetoclopramideMetoclopramide

5- Anti leprosy 5- Anti leprosy DapsoneDapsone

6- Anti malarial 6- Anti malarial ChloroquineChloroquine

7- Antibiotics 7- Antibiotics Sulfamethoxazole Sulfamethoxazole

Sign & Symptoms Associated Sign & Symptoms Associated with Methemoglobin blood Conc.with Methemoglobin blood Conc.

Met Hb conc. %total Hb Clinical Met Hb conc. %total Hb Clinical

< 1.5g/dl < 10% None< 1.5g/dl < 10% None

1.5-3 g/dl 10-20% Cyanosis1.5-3 g/dl 10-20% Cyanosis

3-4.5g/dl 20-30% Anxiety3-4.5g/dl 20-30% Anxiety

TachycardiaTachycardia

7.5-10.5 50-70% Acidosis7.5-10.5 50-70% Acidosis

g/dl Arrhythmiag/dl Arrhythmia

> 10.5g/dl >70% Death> 10.5g/dl >70% Death

DiagnosisDiagnosis1- Tachyphylaxis1- Tachyphylaxis

2- Cyanosis despite high FIo2- Cyanosis despite high FIo22

3- Low fixed reading of pulse oximetry3- Low fixed reading of pulse oximetry

4- Normal PO4- Normal PO22 of ABG, but higher of ABG, but higher calculated hemoglobin saturation than calculated hemoglobin saturation than that measured by pulse oximetrythat measured by pulse oximetry

5- Low PH of ABG5- Low PH of ABG

6- Higher than normal O6- Higher than normal O2 2 venous tensionvenous tension

7- Development of cardiac arrhythmias 7- Development of cardiac arrhythmias

Confirmation Of DiagnosisConfirmation Of Diagnosis

Co- oximetryCo- oximetryMasseurs light absorbance at fourMasseurs light absorbance at four

Different wave lengths so it is able toDifferent wave lengths so it is able to

quantify % ofquantify % of

Met Hb Co HbMet Hb Co Hb

Oxy Hb Deoxy Hb Oxy Hb Deoxy Hb

Management Of Acquired Management Of Acquired MethemoglobinMethemoglobin

Mild MethemoglobinemiaMild Methemoglobinemia

Withdrawal of the offending agentWithdrawal of the offending agent

Oxygen administrationOxygen administration

No specific therapyNo specific therapy

Methylene BlueMethylene Blue

Mechanism :Mechanism :Transfers electron to methemoglobinTransfers electron to methemoglobin

reducing it to normalreducing it to normal

Dosage :Dosage :1-2mg/kg iv over 3-5 minutes1-2mg/kg iv over 3-5 minutes

Can be repeated at a dose of 1mg/kg after 30 Can be repeated at a dose of 1mg/kg after 30

minutesminutes

Symptoms expected to diminish within 30-60Symptoms expected to diminish within 30-60

minutesminutes

Cautions: Cautions: Not effective in G6PD deficiency and Not effective in G6PD deficiency and

may cause hemolysis in these casesmay cause hemolysis in these cases