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ANEMIA

Anemias are a group of diseases characterized by a decrease in either the hemoglobin (Hgb) or the volume of red blood cells (RBCs), which results in decreased oxygen-carrying capacity of the blood.

Definition

Hb levels to diagnosa anaemia

Pregnant woman

Prevalence of anaemia

Adjustment to measured haemoglobine for smokers

Classification systems for anemias

MoRphology etiology

Algoritma Diagnosa Anemia

PATHOLOGY, SYMPTOMS, AND SIGNS OF ANEMIA

Normal ADB Anemia penyakit kronik

Thalasemia

MCV 80 – 90 fl Menurun <70 fl Menurun/N Menurun

MCH 27 – 31 pg Menurun Menurun/N Menurun

Besi serum 50 – 150 μg/dL Menurun <50 μg/dL

Menurun Normal

TIBC 240 – 360 μg/dL Meningkat >360 μg/dL

Menurun Normal/Meningkat

Saturasi transferin

30 – 35% Menurun < 15%

Menurun/N10-20%

Meningkat>20%

Besi sumsum tulang

Positif Negatif Positif Positif kuat

FEP 15 – 18 μg/dL Meningkat >100 μg/dL

Meningkat Normal

Feritin serum 20 – 250 μg/dL Menurun <20 μg/dL

Normal Meningkat>50 μg/dL

Elektrofoesis Hb

Normal Normal Hb A2meningkat

IRON DEFICIENCY ANEMIA

The anaemia of iron deficiency is caused by defective synthesis of haemoglobin, resulting in red cells that are smaller than normal (microcytic) and contain reduced amounts of haemoglobin (hypochromic).

Iron deficiency anemia

Nail changes in iron deficiency anaemia

ANGULAR CHEILITIS AND SMOOTH TONGUE IN IRON DEFICIENCY

Investigation of iron deficiency anaemia

CAUSES OF IRON DEFICIENCY ANEMIA

Causes of iron deficiency anemiaReproductive system : menorrhagiaGastrointestinal tract :Bleeding : Oesophagitis, Oesophageal varises, Hiatus hernia, peptic ulcer, Inflammatory bowel disease, Haemorrhoids, Carcinoma stomach and colorectalMalabsorption : Coeliac disease, Atrophic gastritis, gastrectomy, chronic diarrheaPhysiological : Growth spurts, pregnancy (increased iron needs)Dietary : vegans, elderly (inadequate dietary iron intake)

Wordwide commonest cause of iron deficiency is hookworm infection

Risk factors in iron deficiency

Prevalence of anaemia

Diagnostics:Iron levels Total iron-binding capacity (TIBC)Serum Ferritin

Diagnostic of Iron Deficiency anemia

MedicationsMedications:Iron supplements, oral or parenteralVit. C

Adverse reactions to therapeutic doses of iron are primarily gastrointestinal in nature and consist of a dark discoloration of feces, constipation or diarrhea, nausea, and vomiting

Gastrointestinal side effects are usually dose-related Patients most likely to experience adverse effects

with iron dextran include individuals with a history of allergies, asthma, or inflammatory diseases.

Iron sucrose injection should not be administered concomitantly with oral iron preparations, as it will reduce the absorption of oral iron and adverse effects include leg cramps and hypotension

Adverse reactions to therapeutic doses of iron

Many patients must take their iron with food, as they experience nausea and diarrhea when iron is administered on an empty stomach

Iron should be preferably administered at least 1 hour prior to meals, as food interferes with its absorption

A positive response to a trial of oral iron therapy would result in a modest reticulocytosis in 5 to 7 days, with an increase in Hgb at a rate of about 2 to 4 g/dL every 3 weeks until Hgb is normalized.

Evaluation of therapeutic outcome

Evaluation of therapeutic outcome

Patients with negative iron balances caused by bleeding may require iron replacement therapy for only 1 month after correction of the underlying lesion, whereas patients with recurrent negative balances may require long-term treatment. This latter group may require as little as 30 to 60 mg of elemental iron daily.Patients receiving regular IV iron should be

monitored for clinical or laboratory evidence of iron toxicity or overload. .Iron overload may be indicated by abnormal liver

function tests, serum ferritin greater than 800 ng/mL or a transferrin saturation greater than 50%

MEGALOBLASTIC ANEMIA

Megaloblastic anemia is a common disorder that may have several etiologies :Anemia associated with vit B12 deficiencyAnemia associated with folic acid deficiency

Megaloblastic anemias

CAUSES OF MEGALOBASTIC ANEMIA

Vit B12 and folic acid are both necessary for nucleic acid precursor used for DNA synthesis

DHF, dihydrofolate; 5-MTHF,5-methyl-tetrahydrofolate; 5,10-MTHF, 5,10-methyl tetrahydrofolate THF; THF, tetrahydrofolate

Vitamin B 12 deficiency may also result from overgrowth of bacteria in the bowel that utilizes vitamin B 12 ,or from injury or removal of ileal receptor sites where vitamin B 12 and the intrinsic factor complex are absorbed.

COMPARISON OF FEATURES OF VITAMIN B12 AND FOLIC ACIDDEFICIENCY STATES

Causes of megaloblastic anemia

Clinical features include pallor and jaundice. The onset is gradual, and a severely anaemic patient may present in congestive heart failure or only when an infection supervenes.

The blood film shows oval macrocytes and hypersegmented neutrophil nuclei (with six or more lobes). In severe cases, the white cell count and platelet count also fall (pancytopenia).

The bone marrow shows characteristic megaloblastic, erythroblasts and giant metamyelocytes

there is an increase in plasma of unconjugated bilirubin and serum lactic Dehydrogenase and presence in urine of haemosiderin.

The clinical features of megaloblastic anemia

Diagnostics:Schilling test (Urinating 8 - 40%

of the radioactive vitamin B12 within 24 hours is normal)

Medications:Vit. B12 parenteral

Vit. B12 deficiency anemia

Inadequate intake: Chronically malnourished Older adults Alcoholics Drug addicted persons

Increased need: Pregnant women: neural tube defects in fetus Persons experiencing rapid growth Malabsorption disorders: Celiac sprue Persons taking methotrexate and other

chemotherapy

Folic acid deficiency anemia

Good sources of folic acid

medicationsFolate deficiency is treated with folic acid, usually 5 mg daily orally for four months

HEMOLYTIC ANEMIA

Hemolytic anemia results from decreased survival time of RBCs secondary to destruction in the spleen or circulation.

Causes of hemolytic anemia in the younger patient differ from those in the elderly patient.

Most younger patients exhibit congenital disease, whereas older patients most often experience autoimmune hemolytic anemia .

Hemolytic anemia

Common Classes of Hemolytic Anemias

Causes: Mechanical trauma to RBC: prosthetic heart

valves Autoimmune disorders Bacterial or protozoan infection Immune system-mediated responses drugs, toxins, chemical agents

Manifestations: Anemia splenomegaly, jaundice, pathologic fractures

Acquired hemolytic anemia

Therapy for hemolytic anemia consists of managing the underlying cause of the anemia.

Steroids and other immunosuppressive agents have been used for management of autoimmune hemolytic anemias.

In some instances, a splenectomy is indicated in an attempt to reduce RBC destruction.

Treatment

THE HEREDITARY ANEMIA

Hereditary anaemias include disorders of the structure or synthesis of haemoglobin; deficiencies of enzymes that provide the red cell with energy or protect it from chemical damage; and abnormalities of the proteins of the red cell’s membrane.

The hereditary anemia

The structure of human haemoglobin (Hb) changes during development

Simplified representation of the genetic control of human haemoglobin. Because chains are shared by both fetal and adult Hb, mutations of the globin genes affect Hb production in both fetal and adult life; diseases that are due to defective globin production are only manifest after birth when Hb A replace Hb F

Normal Adult Blood

α2β2 = Hgb A (97%)α2δ2 = Hgb A2 (2%)α2γ2 = Hgb F (<1%)

http://sickle.bwh.harvard.edu/hbsynthesis.html

Haemoglobin structure

Haem consists of a protoporphyrin ring with an iron atom at its centre.

The protoporphyrin ring consists of four pyrrole groups which are united by methane bridges (=C-).

The hydrogen atoms in the pyrrole groups are replaced by four methylene (CH3-), two vinyl (-C=CH2) and two propionic acid (-CH2-CH2-COOH) groups.

There are mainly two types of abnormalities, these are :

Quantitative abnormalities: where there is reduction in the production of certain types of globins e.g. a thalassaemia

b thalassaemia Qualitative abnormalities: where there is

production of abnormal haemoglobin e.g. sickle cell anaemia.

Haemoglobin abnormalities

What Is Sickle Cell Disease? An inherited disease of red blood cells Affects hemoglobin Polymerization of hemoglobin leads to a

cascade of effects decreasing blood flow Tissue hypoxia causes acute and chronic

damage

Pathophysiology Inheritance of mutated hemoglobin β-globin chain Mutation GAG GTG at 6th codon Glutamic acid Valine at 6th AA α2βS = heterozygote = Sickle trait α2S2 = homozygote recessive = Sickle cell disease

Pathophysiology

1. Deoxygenation HgbS protein conformational change

2. Hydrophobic Valine exposed at molecular surface

3. Val6 of B2 chain of 1st Hgb S chain forms hydrophobic bond with Phe85 and Leu88 of a 2nd Hgb S B1 chain

4. Pairing Hgb S monomers polymerize to form Hgb S chains

5. Hgb S polymers precipitate in RBCs as long, rigid fibers

Sickling Mechanism

Wood AJ. NEJM, 340(13): 1021-1030, 1999.

Why Do Cells Sickle?

Glutamic acid is substituted for valine

Allowing the polymerization of sickle hemoglobin when deoxygenated

The origin of the disease is a small change in the protein

hemoglobin

The change in cell structure arises from a change in the structure of hemoglobin.

A single change in an amino acid causes hemoglobin to aggregate.

Normal Vs. Sickle Red Cells

Normal Disc-Shaped Deformable Life span of 120

days

Sickle Sickle-Shaped Rigid Lives for 20 days

or less

The function of hemoglobin is to carry oxygen

Biswal, B. K., Vijayan, M.: Structures of Human Oxy-and Deoxyhaemoglobin at Different Levels of Humidity: Variability in the T State Acta Crystallogr., Sect.D 58 pp. 1155 (2002)

Hemoglobin A

Normal hemoglobin hasfour subunits that eachcontain an oxygen bindingsite.

The origin of sickle cell anemia is a mutation in hemoglobin

Padlan, E. A., Love, W. E.: Refined crystal structure of deoxyhemoglobin S. I. Restrained least-squares refinement at 3.0-Å resolution. J Biol Chem 260 pp. 8272 (1985)

Hemoglobin S

A single mutation in hemoglobin results in abinding of one proteinto another.

Hemoglobin is a carrier protein

Lungs Tissues

O2

CO2

HbO2

deoxy Hb (CO2)

Hemoglobin changes structure for efficient oxygen uptake and delivery

HbO2

deoxy Hb (CO2)

Strong binding state R state

Weak binding state T state

The small change in hemoglobin structure leads to aggregation

Normal hemoglobin (Hb A) Sickle cell hemoglobin (Hb S)

ab

Subunits

Sickle Cells

Inheritance of Sickle Cell Anemia

If one parent has sickle cell trait (HbAS) and the

other does not carry the sickle

hemoglobin at all (HbAA) then none of the children will have

sickle cell anemia. There is a one in two (50%) chance that any given child will get one copy of the HbAS gene and therefore have the

sickle cell trait. It is equally likely that

any given child will get two HbAA genes and

be completely unaffected.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Inheritance of Sickle Cell Anemia

If both parents have sickle cell trait (HbAS)

there is a one in four (25%) chance that any given child

could be born with sickle cell anemia.

There is also a one in four chance that any given child

could be completely unaffected.

There is a one in two (50%) chance that any given child will get the sickle cell trait.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Inheritance of Sickle Cell Anemia

If one parent has sickle cell trait

(HbAS) and the other has sickle cell

anaemia (HbSS) there is a one in two (50%) chance that any given

child will get sickle cell trait and a one in two (50%) chance that any

given child will get sickle cell anemia.

No children will be completely unaffected.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Inheritance of Sickle Cell Anemia

If one parent has sickle cell anaemia (HbSS) and the other is completely unaffected (HbAA) then

all the children will have sickle cell trait.

None will have sickle cell anemia.

The parent who has sickle cell anemia (HbSS) can only pass the sickle hemoglobin

gene to each of their children.

Source from http://www.sicklecellsociety.org/education/inherit.htm#anchor298279

Screening Hemoglobin Electrophoresis: Once blood has been drawn, an blood

analysis is performed to determine the concentration of different hemoglobin molecules as percentages of the total hemoglobin count.

Normal Levels: Hgb A1: 95% to 98%

Hgb A2: 2% to 3% Hgb F: 0.8% to 2%

Hgb S: 0% Hgb C: 0%

Sickle-Cell Test: In this test, blood is extracted to determine if an individual possesses abnormal hemoglobin, labeling them either carriers (sickle-cell trait individuals) or affected (sickle-cell anemia individuals).

Complete Blood Count Test: Patients are screened for blood-cell counts, sizes, concentration, and hemoglobin content.

Manifestations: pallor, fatigue, jaundice, irritability Painful swelling hands and feet, large joints,

abdominal pain, stroke Aplastic anemia Blood pools in liver and spleen

Sickle cell crises

Complication of Sickle Cell Anemia

Hand-Food Syndrome

Splenic Crisis Infections Acute Chest

Syndrome Delayed growth

and puberty in children

Stroke Eye problem

Priapism Gallstone Ulcers on the legs Pulmonary Arterial

Hypertension (High blood pressure)

Multiple Organ Failure

Sickle Cell Disease

Health MaintenanceAnd

Management

Management Health maintenance Infection prevention Pain management Sickle emergencies Chronic disease management

Health Maintenance

Frequent visits: every 3 to 6 months Immunizations

◦ Routine immunizations◦ Hib- 6 months and older◦ 23 valent Pneumovax at five years

Penicillin prophylaxis beginning no later than two months

Nutrition and fluids◦ Folate supplementation is controversial

Health Maintenance Physical exam with attention to:

◦ Growth and development, jaundice, liver/spleen size, heart murmur of anemia, malocclusion from increased bone marrow activity, delayed puberty

Lab evaluations: ◦ CBC with differential and reticulocyte count,

urinalysis, renal & liver function

Treat precipitating factors

Folic acid supplementation

Blood transfusionsGenetic counseling

Interventions

New Treatments and Medicines Bone marrow transplants Gene therapy New medicine

◦ Butyric acid. This is a food additive that may increase normal hemoglobin in the blood.

◦ Clotrimazole. This is used now to treat fungus infections. This medicine helps prevent the loss of water from a red blood cell and can keep the cell from turning into a sickle cell.

◦ Nitric oxide. This may make sickle cells less sticky and keep blood vessels open. People with sickle cell anemia have low levels of nitric acid in their blood.

Prevention Identify what can trigger the

“Crisis” such as stress, avoid extremes of heat and cold weather, don’t travel airplane that is not cabin pressurized

Maintain healthy lifestyle habits

Eating healthy Avoid dehydration Exercise regularly Get enough sleep and rest Avoid alcohol and don’t smoke

Regular medical checkups and treatment are important

Treatment

Treatments For Splenic Sequestion Intravenous fluids

◦ Maintain vascular volume

Cautious blood transfusion◦ Treat anemia,

sequestered blood can be released from spleen

Spleen removal or splenectomy◦ If indicated

Pain Management

Mild-moderate pain Acetaminophen

◦ Hepatotoxic Non-steroidal anti-inflammatory

agents (NSAIDs)-Contraindicated in patients with gastritis/ulcers and renal failure -Monitor renal function if used chronically

Pain Management Moderate-severe pain

◦ Opioids are first-line treatment◦ Morphine sulfate or hydromorphone

Moderate or less severe pain◦ Acetaminophen or NSAID's in combination with

opioids◦ Other adjuvant medications (sedatives,

anxiolytics) May increase efficacy of analgesics

THALASEMIA

Genetic blood disorder resulting in a mutation or deletion of the genes that control globin production.

Normal hemoglobin is composed of 2 alpha and 2 beta globins

Mutations in a given globin gene can cause a decrease in production of that globin, resulting in deficiency

2 types of thalassemia: alpha and beta.Manifestations: Minor: asymptomatic; mild anemia,

splenomegaly, bronze skin, bone marrow hyperplasia

Major: severe anemia, heart failure, liver and spleen enlargement; fractures of long bones, ribs, vertebrae

What is thalassemia?

Pathophysiology of –Thalassemia/Hb E Disease

Thalasemia is hereditary disesase

mutation of 1 or more of the 4 alpha globin genes on chromosome 16

severity of disease depends on number of genes affected

results in an excess of beta globins

Alpha Thalassemia

Pathophysiology of α thalasemia

Result from gene deletions One deletion—Silent carrier; no clinical

significance Two deletions—a Thal trait; mild

hypochromic microcytic anemia Three deletions—Hgb H; variable

severity, but less severe than Beta Thal Major

Four deletions—Bart’s Hgb; Hydrops Fetalis; In Utero or early neonatal death

Alpha Thalassemias

• Normal / • Silent carrier - / • Minor -/-

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

Classification & TerminologyAlpha Thalassemia

1 functional globin gene results in very lightly coloured red blood

cells and possible severe anemia hemoglobin H is susceptible to oxidation,

therefore oxidant drugs and foods are avoided

treated with folate to aid blood cell production

Hemoglobin H Disease

Usually no treatment indicated 4 deletions incompatible with life 3 or fewer deletions have only mild anemia

Alpha Thalassemias

mutations on chromosome 11 Disease results in an overproduction of a-globin

chains, which precipitate in the cells and cause splenic sequestration of RBCs......(results in excess of alpha globins)

Severity depends on where the hit(s) lie◦ b0-no b-globin synthesis; ◦ b+ reduced synthesis

Erythropoiesis increases, sometimes becomes extramedullary

Beta Thalassemia

• Normal /• Minor /0

/+

• Intermedia 0/+

• Major 0/0

+/+

Classification & Terminology Beta Thalassemia

b-Thalassemia Minor◦ Minor point mutation◦ Minimal anemia; no treatment indicated

b-Thalassemia Intermedia◦ Homozygous minor point mutation or more severe

heterozygote◦ Can be a spectrum; most often do not require

chronic transfusions b-Thalassemia Major-Cooley’s Anemia

◦ Severe gene mutations◦ Need careful observation and intensive treatment

b-Thal--Clinical

It is characterize by severe anemia that can begin months after birth

Paleness Delays in growth and development Bone marrow expansion. Untreated Beta Thalassemia major can lead

to child death due to heart failure.

Symptoms of Beta Thalassemia

Beta Thalassemia Trait

lack of beta globin is more significant bony deformities due to bone marrow trying

to make more blood cells to replace defective ones

causes late development, exercise intolerance, and high levels of iron in blood due to reabsorption in the GI tract

if unable to maintain hemoglobin levels between 6 gm/dl – 7 gm/dl, transfusion or splenectomy is recommended

Beta Thalassemia Intermedia

complete absence of beta globin enlarged spleen, lightly coloured blood cells severe anemia chronic transfusions required, in conjunction

with chelation therapy to reduce iron (desferoxamine)

Beta Thalassemia Major

Reduced or nonexistent production of b-globin◦ Poor oxygen-carrying capacity of RBCs

Failure to thrive, poor brain development◦ Increased alpha globin production and precipitation

RBC precursors are destroyed within the marrow Increased splenic destruction of dysfunctional

RBCs◦ Anemia, jaundice, splenomegaly

Hyperplastic Bone Marrow◦ Ineffective erythropoiesis—RBC precursors

destroyed Poor bone growth, bone pain

◦ Increase in extramedullary erythropoiesis Iron overload—increased absorption and

transfusions◦ Endocrine disorders, Cardiomyopathy, Liver failure

Beta Thalassemia Major

Hypochromic, microcytic anemia◦ nucleated RBCs, anisocytosis

Reticulocytosis Hemoglobin electrophoresis shows

◦ Increased Hgb A2—delta globin production◦ Increased Hgb F—gamma globin production

Hyperbilirubinemia LFT abnormalities (late finding) TFT abnormalities, hyperglycemia (late

endocrine findings)

b-Thalassemia Major—Lab findings

Chronic Transfusion Therapy◦ Maximizes growth and development◦ Suppresses the patient’s own ineffective erythropoiesis and

excessive dietary iron absorption ◦ PRBC transfusions often monthly to maintain Hgb 10-12

Chelation Therapy◦ Binds free iron and reduces hemosiderin deposits◦ 8-hour subcutaneous infusion of deferoxamine, 5

nights/week or deferasirox 1x1◦ Start after 1year of chronic transfusions or ferritin>1000

ng/dl Splenectomy—indications

◦ PRBCs per year >250cc/kg◦ Severe leukopenia or thrombocytopenia◦ hipersplenomegali

Folic acid

b-Thalassemia Major--Treatment

Blood Transfusion0.3-0.5 mg iron/kg/day

In a 50kg person

15-25 mg/day

Iron Excretion(Urine & Feces)

1-2mg/day

IronAccumulation13-24 mg/day

Iron Accumulation in Transfusion-dependent Anemias

Hepatic Fibrosis --> Cirrhosis

Cardiac arrhythmia

Hypogonadism

Diabetes

Hypothyroidism

Hypoparathyroidism

Cardiac Failure

0

20

40

60

80

100

120

1 3 5 7 9 11 13 15 17 19

Age (years)

Iro

n (

g)

Tran

sfusi

onal

Iron Death

Transfusional Iron Overload in Thalassemia

Goals of iron chelation therapy Maintain iron balance/induce negative iron balance

Avoid accumulation of redox-active iron

Prevent/reverse organ dysfunction

Prolong survival

Avoid chelator toxicity

Maximise adherence to prescribed therapy

Maximize quality of life

Comparison of Currently Available Iron Chelators

Licensed

Licensed outside US/Canada

(approved in 46 countries)

LicensedStatus

FaecalUrinaryUrinary, faecalExcretion

12-16 hr3-4 hr20-30 minHalf-life

Oral (Once daily)

Oral(3 times daily)

SC, IV (8-12 hr, 5 d/wk)

Route

20-307525-60Usual dose(mg/kg/d)

DeferasiroxDeferiproneDesferrioxamineProperty

Chelators for managing iron overload

Chelator Advantages DisadvantagesDesferrioxamine 4 decades experience Parenteral route

Survival advantage Compliance problemsHeart failure prevented Dose dependent

toxicityHeart failure reversed -eye, ear, bone

Deferiprone Oral administration 3 x/day x7/weekCardiac protection Short plasma t 1/2

Unreliable control of body iron

AgranulocytosisArthropathyZinc deficiency

Deferasirox Oral administration Short clinical experience

Long plasma t1/2 Cardiac protection unknown

1/day administration Changes in creatinineControl of body iron

DESFERRIOXAMINE

Dose Schedule:

Ferriprox:70-80

mg/kg/d,7 days/week

Desferal:20-50 mg/kg/d,

2-6 days/week

DFO Desferrioxamine 20-50 mg/kg/day DFP Deferiprone 75-100 mg/kg/day DFX Deferasirox 20-30 mg/kg/day

Effects of Iron Chelators on Ferritin

MDS: myelodysplasticsyndrome; SCD: sickle cell disease.

Deferasirox 5 10 20 30Doses (mg/kg/day)

-1500

-1000

-500

0

500

1000

1500

2000

2500

Mean

Ch

an

ge in

Seru

m

Ferr

itin

(µg

/L)

SCD β-thalassaemia, MDS, other rare anaemias

β-thalassaemia

Desferrioxamine, deferiprone, and deferasiroxall decrease ferritin

Deferasiroxshown to maintain and reduce serum ferritinlevels in phase 2/3 clinical trials in adult and paediatricpatients (12 -month efficacy—serum ferritin )

Adverse events: Deferasirox

• GI events (15.2%): abdominal pain, nausea and vomiting, diarrhea, constipation

• Skin rash (10.8%)

• Mild, non progressive increases in serum creatinine. No reports of renal failure

• Increased transaminases (>5x ULN) in 5.7% Drug-induced hepatitis: Two cases both leading to discontinuation of Exjade

• Adverse effects on the ear/eye appear to be similar in frequency to those seen with DFO

Effects of Iron Chelators on Heart: Desferrioxamine(DFO) and Deferiprone (DFP)

MRI-T2*-LVEF

DFP more effective in reducing cardiac iron (27% vs 13%; P = .023) and increasing LVEF

(3.1% vs 0.3%; P= .003) than DFO3129Pennellet al.6

Clinical9/532 patients died of heart failure–532Ceciet al.5

Clinical-survival

5-year cardiac disease-free survival higher with DFP than DFO (P< .003)7554Pigaet al.1

MRI-T2*-LVEF

DFP is more effective than DFO in reducing cardiac iron

3015Anderson et al.2

MRI-ISRSimilar decrease in cardiac iron with

each drug7371Maggioet al.3

Clinical4/51 patients died of cardiac causes–51Hoffbrandet al.4

3,610*

DFO (n)

52 cardiac events on DFO; 0 on DFP

Data

Borgna-Pignattiet al.7

Author

Clinical750*

Estimated by

DFP (n)

*Patient-years. 1. PigaA et al. Haematologica. 2003;88:489.2. AndersonLJ et al. Lancet. 2002;360:516. 3. MaggioA et al. Blood Cells Mol Dis. 2002;28:196. 4. HoffbrandAV et al. Blood. 1998;91:295. 5. Ceci A et al. Br J Haematol. 2002;118:330. 6. Pennell DJ et al. Blood.

2006;107:3738. 7. Borgna-Pignatti C et al. Blood. 2006;107:3733.

Sepsis—Encapsulated organisms◦ Strep Pneumo

Cardiomyopathy—presentation in CHF◦ Use diuretics, digoxin, and deferoxamine

Endocrinopathies—presentation in DKA◦ Take care during hydration so as not to

precipitate CHF from fluid overload

b-Thalassemia Major Complications and Emergencies

Immunizations—Hepatitis B, Pneumovax Follow for signs of diabetes, hypothyroid,

gonadotropin deficiency Follow for signs of cardiomyopathy or

CHF Follow for signs of hepatic dysfunction Osteoporosis prevention

◦ Diet, exercise◦ Hormone supplementation◦ Osteoclast-inhibiting medications

Follow ferritin levels

Anticipatory Guidance and Follow Up

Family study Genetic counselling Prenatal diagnosis

Prevention

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