SEMINAR PRESENTATION ON APROACH
OF A PATIENT WITH ANEMIA
Niguse Desta, clerkship1
Yirgalem, MC 2014
OUTLINE
Objective
Introduction
Definition and major classification of anemia
Approach of a patient with anemia
Common...
OBIECTIVE
To Discuss Definition,Etiology,Manifestations
,Diagnosis And Management Of Common
Types Of Anemia
IRON DEFICIENCY ANEMIA
Introduction
Iron metabolism:
Daily 10-30mg iron ingested, 5-10% absorbed
to balance precisely the...
IRON DEFICIENCY ANEMIA
 Definition: - Iron deficiency anemia occurs
when body iron stores become inadequate for
the needs...
IRON DEFICENCY - STAGES
• Prelatent
– reduction in iron stores without reduced serum iron levels
• Hb (N), MCV (N), iron a...
IRON DEFICIENCY ANEMIA
 MCV
 MCH
 Fe
 TIBC
 TRANSFERIN SATURATION
 FERRITIN
Etiologies of Iron deficnecy Anemia
• Chronic blood loss
• Increased demands
• Mal absorption of iron
• Poor diet
Management
History and physical examination is sufficient
to exclude serious disease (e.g pregnant or
lactating women, ad...
Rx
• ORAL
– 200 mg of iron daily 1 hour before meal (e.g. 100
mg twice daily)
– How long?
• 14 days + (Hg required level –...
PARENTERAL IRON SUBSTITUTION
– Bad oral iron tolerance (nausea, diarrhoea)
– Negative oral iron absorption test
– Necessit...
Inadequate response may imply
 Continuing hemorrhage
non compliance to therapy
Wrong diagnosis
Mixed deficiency – asso...
Anemia of chronic disease
• ACD is a common type of anemia that occurs
in patients with infectious, inflammatory, or
neopl...
Etiologies
Chronic inflammatory diseases
- Infections e.g. pulmonary abscess, TB,
Osteomyelitis, pneumonia, bacterial
end...
Characteristic features are:
NCNC or mildly hypochromic indices and red
cell morphology
 Mild and non progressive anemia...
pathogenesis
• Shortened red cell life span, moderately 20-30%
(from 120 to 60-90 days)
• Relative bone marrow(erythropoie...
CON
• ABNORMAL IRON METABOLISM
• Activation of the reticuloendothelial system with
increased iron retention and storage wi...
Treatment of Anemia
Correction of underlying disease
Erythropoietin (40-80 % success rate)
Correction of reversible con...
MEGALOBLASTIC ANEMIAS
 The megaloblastic anemias are caused by a
deficiency of vitamin B12 or folates,or by
related condi...
Etiologies
Vitamin B12 deficiency
Folate deficiency
Abnormalities of vitamin B12 or folate
metabolism,transcobalamine
d...
B12: Cobalamin absorption
 Initially bound to protein in diet,
liberated by acid and pepsin,
then binds to R factors in s...
Causes of Vit. B12 deficiency
 Nutritional: especially in vegans
 Malabsorption
Gastric causes
-pernicious anemia
-Cong...
Pernicious Anemia
 Autoantibody to Intrinsic Factor detectable in <70%
– Highly specific, but insensitive
– 2 types of an...
B12 Deficiency Symptoms
• Atrophic glossitis (shiny tongue)
• Shuffling broad gait
• Anemia and related sx
• Vaginal atrop...
B12 Symptoms: Neurologic
 Paresthesias
 Memory loss
 Numbness
 Weakness
 Loss of dexterity due to loss
of vibration a...
B12 Lab findings
 Macroovalocytic anemia
with elevated serum bili and
LDH
Increased red cell
breakdown due to
ineffectiv...
Bone Marrow
Hypercellular marrow
Megaloblastic erythroid
hyperplasia
Giant metamyelocytes
Due to slowing of DNA synthesis
...
Shilling Test
1. PART 1: Oral labeled B12 and
IM unlabeled B12 at the
same time to saturate tissue
stores
2. 24h urine to ...
B12 Deficiency: Treatment
IM B12 1000mcg daily x 1 wk
– then 1000mcg weekly x 1 month
– Then 1000mcg monthly for life for...
Folate
• Animal products (liver), yeast and leafy
vegetables
• Normal requirement 400mcg/day
• Pregnancy/Lactation: 500-80...
Causes of Folate Deficiency
Folate deficiency symptoms
• The symptoms of severe folate deficiency are
similar to those in severe vitamin B12
deficienc...
Folate Deficiency Treatment
• Oral folate 1mg daily for 4 months or until
hematologic recovery
• Rule out B12 deficiency p...
SICKLE CELL ANEMIA
 A serious condition in which red blood
cells can become sickle-shaped
 Normal red blood cells are sm...
Normal and Sickled Red Blood Cells
in Blood Vessels
Mechanism
• Underlying mechanism of disease: sickle cell
anemia is a Glu->Val substitution in the sixth
amino acid of the ...
Sickle Cell Anemia vs. Sickle Cell Trait
• People who have sickle cell anemia are born with
it; means inherited, lifelong ...
Inheritance of Sickle Cell Anemia
Why Anemia?
• In sickle cell anemia, a lower-than-normal
number of red blood cells occurs because
sickle cells don’t last ...
Signs and Symptoms
Complication of Sickle Cell Anemia
• Splenic Crisis
• Infections
• Acute Chest Syndrome
• Delayed growth and
puberty in ch...
Treatments
 Effective treatments are available to help relieve the
symptoms and complications of sickle cell anemia, but
...
Prevention
 Identify what can trigger the “Crisis” such as
stress, avoid extremes of heat and cold weather
 Maintain hea...
Sideroblastic anemia
It is a refractory microcytic hypochromic anaemia (peripheral
blood) characterized by the presence of...
Classification
• Hereditary (sex linked recessive trait)
• Acquired
• Primary :Myelodysplasia
• Secondary :
-Malignant dis...
Diagnostic
• The bone marrow biopsy is
diagnostic: it reveals
erythroid dysplasia and
hyperplasia.
• Ringed sideroblasts
c...
Thalassemia
• Inherited hematologic disorders caused by
defects in the synthesis of one or more of the
haemoglobin chains
...
CON
• Alpha thalassemia is the result of deficient or
absent synthesis of alpha globin chains,
leading to excess beta glob...
CON
• It cause haemolysis and defective
erythropoiesis
• Silent carriers of alpha thalassemia and
persons with alpha or be...
CON
• Alpha Thalassemia intermedia, or hemoglobin
H disease, causes hemolytic anemia.
• Alpha Thalassemia major with hemog...
Diagnosis
• A very low MCV should lead to a suspicion
particularly if <70 MCV in any patient
• Ferritin level become norma...
Treatment
• Treatment include -life long transfution
-Bone marrow transplant
-Preconception councelling
• Prognosis -Perso...
Hemolytic anemia
 Anemia due to shortened survival of
circulating RBCs (Normal: 110-120 days)
– Hemolysis <100 days
 Wit...
Causes of Hemolysis - Intrinsic
• Generally, a hereditary disorder
• Remember, the mature RBC has lost its nucleus,
mitoch...
Causes of Hemolysis - Extrinsic
• Acquired disorder
• Causes include:
• Ab directed against RBC membrane components
-AIHA,...
Site of Hemolysis
• Dependant on the severity and type of cell
alteration (alteration in RBC membrane)
• Severe damage  i...
Intravascular Hemolysis
• Intravascular hemolysis  Release of Hgb into
the plasma
• Free Hgb binds to haptoglobin  Hgb-
...
Intravascular Hemolysis
• Causes:
• Direct trauma
• Shear stress
– Mechanical heart valve
• Heat damage
• Complement-induc...
Extravascular Hemolysis
• Damaged RBCs are destroyed by liver (receives a larger
portion of the cardiac output) and spleen...
Features of Hemolysis
 Rapid fall in Hgb
 Increased LDH, decreased Haptoglobin
 Jaundice (elevated indirect bilirubin)
...
Peripheral Smear
• Spherocytes
• Fragmented RBCs
– Schistocytes, helmet cells
• Microangiopathic hemolytic anemia
• Acanth...
con
• RBCs with inclusions
• Teardrop RBCs
• Red Cell “ghosts”
– Hemolyzed RBCs that reform, but have lost all
internal co...
Labs
 LDH: elevated
 Indirect bilirubin: elevated (due to catabolism of Hgb)
 Haptoglobin: decreased
 Binds to Hgb and...
Acquired hemolytic anemia
• They are classified as
-Immune hemolytic anemia
-Traumatic anemia
-Others like infectious agen...
Immune Hemolytic Anemia
• IgG and/or IgM bind to RBC surface Ag and
initiate RBC destruction via
– Complement system
– Ret...
Autoimmune Hemolytic Anemia
• Types
– Warm AIHA
– Cold Agglutinin Syndrome
– Paroxysmal Cold
Hemoglobinuria
– Mixed Type A...
Warm AIHA
48-79% of AIHA
Incidence increased at 40yrs
2:1 Female to Male ratio
No racial predilection
Idiopathic vs S...
Warm AIHA - Labs
• Elevated MCV (reflecting reticulocytosis)
• Mild leukocytosis with neutrophilia
• Blood smear:
– Polych...
Warm AIHA – DAT (direct Coombs)
Detects Ab on the RBC surface
Pt’s RBCs are washed then reacted with
monoclonal Ab again...
Warm AIHA - Treatment
Folic Acid
Further treatment depends on severity
Steroids – 1mg/kg/day
Splenectomy
Removes sour...
Cold Agglutinin Syndrome (CAS)
• 16-32% of AIHA
• after binding to RBCs, IgM activates complement
cascade - C3b binds, pha...
CAS - Treatment
• Avoidance of cold exposure
– Move to a warmer climate
• Immunosuppression (cyclophosphamide)
• Plasmaphe...
Drug induced immune hemolytic
anemia
• Penicillins
• Quinine, antihistamine, insulin
• Methyldopa
• Ibuprofein
• Sulfa dru...
Non immune Hemolytic anemia
• Fragmentation Hemolysis (Microangiopathy) –
result of mechanical shearing of RBCs from
damag...
Lead poisoning
• Inhibits both hem and globin synthesis
• Interferes with breakdown of RNA by inhibiting the
enzyme pyrimi...
SUMMARY
REFERANCE
• Reinhold Munker, MD ,ETAL:MODERN
HEMATOLOGY, SECOND EDITION
• HARRISON’S :PRINCIPLES OF INTERNAL
MEDICINE,18th
10Q! 4 UR ATTENTION!
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Aproach to anemia

  1. 1. SEMINAR PRESENTATION ON APROACH OF A PATIENT WITH ANEMIA Niguse Desta, clerkship1 Yirgalem, MC 2014
  2. 2. OUTLINE Objective Introduction Definition and major classification of anemia Approach of a patient with anemia Common types of anemia :diagnosis,management and complications of anemia
  3. 3. OBIECTIVE To Discuss Definition,Etiology,Manifestations ,Diagnosis And Management Of Common Types Of Anemia
  4. 4. IRON DEFICIENCY ANEMIA Introduction Iron metabolism: Daily 10-30mg iron ingested, 5-10% absorbed to balance precisely the amount lost (1mg) under physiologic condition  Amount absorbed can increases up to five fold if body iron store are depleted or erythropoiesis is accelerated.  Absorbed as hem and non hem iron in the duodenum and proximal jejunum
  5. 5. IRON DEFICIENCY ANEMIA  Definition: - Iron deficiency anemia occurs when body iron stores become inadequate for the needs of normal RBC production  On a worldwide basis, iron deficiency is among the most frequent causes of anemia.
  6. 6. IRON DEFICENCY - STAGES • Prelatent – reduction in iron stores without reduced serum iron levels • Hb (N), MCV (N), iron absorption ( ), transferin saturation (N), serum ferritin ( ), marrow iron ( ) • Latent – iron stores are exhausted, but the blood hemoglobin level remains normal • Hb (N), MCV (N), TIBC ( ), serum ferritin ( ), transferrin saturation ( ), marrow iron (absent) • Iron deficiency anemia – blood hemoglobin concentration falls below the lower limit of normal • Hb ( ), MCV ( ), TIBC ( ), serum ferritin ( ), transferrin saturation ( ), marrow iron (absent)
  7. 7. IRON DEFICIENCY ANEMIA  MCV  MCH  Fe  TIBC  TRANSFERIN SATURATION  FERRITIN
  8. 8. Etiologies of Iron deficnecy Anemia • Chronic blood loss • Increased demands • Mal absorption of iron • Poor diet
  9. 9. Management History and physical examination is sufficient to exclude serious disease (e.g pregnant or lactating women, adolescents) - treat ANEMIA History and/or physical examination is insufficient (e.g old men, postmenopausal women)
  10. 10. Rx • ORAL – 200 mg of iron daily 1 hour before meal (e.g. 100 mg twice daily) – How long? • 14 days + (Hg required level – Hg current level) x 4 – half of the dose - 6 – 9 months to restore iron reserve – Absorption • is enhanced: vit C, meat, orange juice, fish , Stomach acidity • is inhibited: cereals, tea, milk
  11. 11. PARENTERAL IRON SUBSTITUTION – Bad oral iron tolerance (nausea, diarrhoea) – Negative oral iron absorption test – Necessity of quick management (CHD, CHF) – 50 - 100 mg daily – I.v only in hospital (risk of anaphilactic shock) – I.m in outpatient department – iron to be injected (mg) = (15 - Hb/g%/) x body weight (kg) x 3
  12. 12. Inadequate response may imply  Continuing hemorrhage non compliance to therapy Wrong diagnosis Mixed deficiency – associated folate or vit.B12 deficiency Another cause for anemia e.g. malignancy, inflammation Malabsorption – rare cause  Use of slow release preparations
  13. 13. Anemia of chronic disease • ACD is a common type of anemia that occurs in patients with infectious, inflammatory, or neoplastic diseases that persist for more than 1 or 2 months. • It does not include anemias caused by marrow replacement, blood loss, hemolysis, renal insufficiency, hepatic disease, or endocrinopathy, even when these disirders are chronic.
  14. 14. Etiologies Chronic inflammatory diseases - Infections e.g. pulmonary abscess, TB, Osteomyelitis, pneumonia, bacterial endocarditis - Non infectious, e.g. Rheumatoid arthritis, SLE and other connective tissue diseases,sarcoidosis, Crohn’s disease  Malignant diseases E.g. carcinoma, lymphoma, sarcoma
  15. 15. Characteristic features are: NCNC or mildly hypochromic indices and red cell morphology  Mild and non progressive anemia (Hgb rarely < 9.0g/dl) : Severity being related to severity of underlying disease Both serum iron and TIBC are reduced  Serum ferritine is normal or raised and  Bone marrow storage iron is normal but erythroblast iron is reduced
  16. 16. pathogenesis • Shortened red cell life span, moderately 20-30% (from 120 to 60-90 days) • Relative bone marrow(erythropoiesis) failure - Cytokines released from inflammatory cells (TNF- , IL-1, IFN- ) affects erythropoiesis by inhibiting the growth of erythroid progenitors - Serum erythropoietin levels in patiens with ACD are normal when compared to healthy subjects but much lower than levels in non-ACD anemic patients
  17. 17. CON • ABNORMAL IRON METABOLISM • Activation of the reticuloendothelial system with increased iron retention and storage within it • Impaired release of iron from macrophages to circulating transferrin (impaired reutilization of iron) • Reduced concentration of transferrin (decreased production, increase sequestration in the spleen and in the foci of inflammation, increase loss)
  18. 18. Treatment of Anemia Correction of underlying disease Erythropoietin (40-80 % success rate) Correction of reversible contributors (iron, folate, cobalamine supplements if necessary)
  19. 19. MEGALOBLASTIC ANEMIAS  The megaloblastic anemias are caused by a deficiency of vitamin B12 or folates,or by related conditions that lead to impaired DNA synthesis.  MCV>100fL
  20. 20. Etiologies Vitamin B12 deficiency Folate deficiency Abnormalities of vitamin B12 or folate metabolism,transcobalamine deficiency,antifolate-drugs Other defects of DNA synthesis: congenital enzyme deficiency, alcohol, treatment with hydroxyurea
  21. 21. B12: Cobalamin absorption  Initially bound to protein in diet, liberated by acid and pepsin, then binds to R factors in saliva and gastric acids  Freed from R factors by pancreatic proteases them binds to Intrinsic Factor secreted by gastric parietal cells  Absorbed together (Cbl + IF) in ileum  Released from IF in ileal cell then exocytosed bound to trans-Cbl II  Cbl bound to transcobalamin II binds to cell surface receptors and is endocytosed
  22. 22. Causes of Vit. B12 deficiency  Nutritional: especially in vegans  Malabsorption Gastric causes -pernicious anemia -Congenital lack or abnormality of intrinsic factor -Total or partial gastrectomy Intestinal causes -Ileal resection and Crohn’s disease -Congenital selective malabsorption
  23. 23. Pernicious Anemia  Autoantibody to Intrinsic Factor detectable in <70% – Highly specific, but insensitive – 2 types of anti-IF antibody • Blocks attachment of Cbl to IF • Blocks attachment of Cbl-IF complex to ileal receptors  Chronic atrophic gastritis – Autoantibody against parietal cells (H-K-ATPase) though pathology indicates destruction by CD4+ T cells – Increased risk of gastric cancer (carcinoid and intestinal- type)
  24. 24. B12 Deficiency Symptoms • Atrophic glossitis (shiny tongue) • Shuffling broad gait • Anemia and related sx • Vaginal atrophy • Malabsorption • Jaundice • Personality changes • Hyperhomocysteinemia • Neurologic symptoms (next slide) • Copper deficiency can cause similar neurologic symptoms
  25. 25. B12 Symptoms: Neurologic  Paresthesias  Memory loss  Numbness  Weakness  Loss of dexterity due to loss of vibration and position sense  Symmetric neuropathy legs>arms  Severe weakness, spasticity, clonus, paraplegia and incontinence  Subacute combined degeneration of the dorsal (posterior) and lateral spinal columns  Due to a defect in myelination  NOT ALL PATIENTS WITH B12 DEFICIENCY RELATED NEUROLOGIC ABNORMALITIES ARE ANEMIA OR MACROCYTOSIS
  26. 26. B12 Lab findings  Macroovalocytic anemia with elevated serum bili and LDH Increased red cell breakdown due to ineffective hematopoiesis  Retic, WBC & platelets normal to low  Hypersegmented neurophils Also occur in renal failure, fe deficiency, inherited
  27. 27. Bone Marrow Hypercellular marrow Megaloblastic erythroid hyperplasia Giant metamyelocytes Due to slowing of DNA synthesis and delayed nuclear maturation Methionine deficiency may play a central role
  28. 28. Shilling Test 1. PART 1: Oral labeled B12 and IM unlabeled B12 at the same time to saturate tissue stores 2. 24h urine to assess absorption >5% normal <5% impaired 3. PART 2: Repeat w/oral IF if now normal =PA if abnormal = malabsorption 4. Can continue with antibiotics to look for bacterial overgrowth, pancreatic enzymes for exocrine insufficiency Part 1 test result Part 2 test result Diagnosis Normal - Normal or vitamin B12 deficiency Low Normal Pernicious anemia Low Low Malabsorption
  29. 29. B12 Deficiency: Treatment IM B12 1000mcg daily x 1 wk – then 1000mcg weekly x 1 month – Then 1000mcg monthly for life for PA Oral high dose 1-2 mg daily – As effective but less reliable than IM – Currently only recommended after full parenteral repletion Sublingual, nasal spray and gel formulations available
  30. 30. Folate • Animal products (liver), yeast and leafy vegetables • Normal requirement 400mcg/day • Pregnancy/Lactation: 500-800mcg/day • Increased requirement in hemolytic anemia and exfoliateive skin disease • Body stores: 5-10mg
  31. 31. Causes of Folate Deficiency
  32. 32. Folate deficiency symptoms • The symptoms of severe folate deficiency are similar to those in severe vitamin B12 deficiency. • However, there are no neurological signs and symptoms.
  33. 33. Folate Deficiency Treatment • Oral folate 1mg daily for 4 months or until hematologic recovery • Rule out B12 deficiency prior to treament as folic acid will not prevent progression of neurologic manifestations of B12 deficiency • Repeat testing for B12 deficiency may be reasonable for those on long-term folic acid therapy if hematologic (macrocytosis or ↑LDH) or neurologic sx persist
  34. 34. SICKLE CELL ANEMIA  A serious condition in which red blood cells can become sickle-shaped  Normal red blood cells are smooth and round. They move easily through blood vessels to carry oxygen to all parts of the body.  Sickle-shaped cells don’t move easily through blood. They’re stiff and sticky and tend to form clumps and get stuck in blood vessels.  The clumps of sickle cell block blood flow in the blood vessels that lead to the limbs and organs. Blocked blood vessel can cause pain, serious infection, and organ damage.
  35. 35. Normal and Sickled Red Blood Cells in Blood Vessels
  36. 36. Mechanism • Underlying mechanism of disease: sickle cell anemia is a Glu->Val substitution in the sixth amino acid of the β-globin gene
  37. 37. Sickle Cell Anemia vs. Sickle Cell Trait • People who have sickle cell anemia are born with it; means inherited, lifelong condition. • They inherit two copies of sickle cell gene, one from each parent. • Sickle cell trait is different from sickle cell anemia. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition. • People with sickle cell anemia and sickle cell trait can pass the gene on when they have children
  38. 38. Inheritance of Sickle Cell Anemia
  39. 39. Why Anemia? • In sickle cell anemia, a lower-than-normal number of red blood cells occurs because sickle cells don’t last very long. • Sickle cells die faster than normal red blood cells, usually after only about 10 to 20 days. • The bone marrow can’t make new red blood cells fast enough to replace the dying ones. The result is anemia.
  40. 40. Signs and Symptoms
  41. 41. Complication of Sickle Cell Anemia • Splenic Crisis • Infections • Acute Chest Syndrome • Delayed growth and puberty in children • Stroke • Eye problem • Priapism •Gallstone •Ulcers on the legs •Pulmonary Arterial •Hypertension • Organ Failure
  42. 42. Treatments  Effective treatments are available to help relieve the symptoms and complications of sickle cell anemia, but in most cases there’s no cure.  The goal is to relieve the pain; prevent infections, eye damage, strokes and control complications if they occur.  Pain medicine: acetaminophen, nonsteroidal anti- inflammatory drugs (NSAIDs), and narcotics such as meperidine, morphine, oxycodone, and etc.  Heating pads  Hydroxyurea, Folic Acid  Blood Transfusions
  43. 43. Prevention  Identify what can trigger the “Crisis” such as stress, avoid extremes of heat and cold weather  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
  44. 44. Sideroblastic anemia It is a refractory microcytic hypochromic anaemia (peripheral blood) characterized by the presence of sidroblasts in the bone marrow. Sidroblasts are:  Erythroblasts inside which iron accumulate into the mitochondria of erythroblasts owing to disordered haeme synthesis .  A ring of iron granules is formed around the nucleus.
  45. 45. Classification • Hereditary (sex linked recessive trait) • Acquired • Primary :Myelodysplasia • Secondary : -Malignant diseases of the marrow -Drugs e.g. cycloserin alcohol, lead -Others: hemolytic anemia, megaloblastic anemia, malabsorption
  46. 46. Diagnostic • The bone marrow biopsy is diagnostic: it reveals erythroid dysplasia and hyperplasia. • Ringed sideroblasts comprise more than 20% of the erythroid series
  47. 47. Thalassemia • Inherited hematologic disorders caused by defects in the synthesis of one or more of the haemoglobin chains • Two type - alpha Thalassemia - beta Thalassemia
  48. 48. CON • Alpha thalassemia is the result of deficient or absent synthesis of alpha globin chains, leading to excess beta globin chains. • Beta thalassemia is the result of deficient or absent synthesis of beta globin chains, leading to excess alpha chains
  49. 49. CON • It cause haemolysis and defective erythropoiesis • Silent carriers of alpha thalassemia and persons with alpha or beta thalassemia trait are asymptomatic and require no treatment
  50. 50. CON • Alpha Thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia. • Alpha Thalassemia major with hemoglobin Bart's usually results in fatal hydrops fetalis. • Beta Thalassemia major causes hemolytic anemia, poor growth, and skeletal abnormalities during infancy
  51. 51. Diagnosis • A very low MCV should lead to a suspicion particularly if <70 MCV in any patient • Ferritin level become normal • RDW normal • Mentzer index = MCV/RBC count become <13
  52. 52. Treatment • Treatment include -life long transfution -Bone marrow transplant -Preconception councelling • Prognosis -Persons with beta thalassemia major often die from cardiac complications of iron overload by 30 years of age.
  53. 53. Hemolytic anemia  Anemia due to shortened survival of circulating RBCs (Normal: 110-120 days) – Hemolysis <100 days  With intact bone marrow: • Anemia  Compensatory increase in Epo secretion  Enhances RBC production (reticulocytosis)  Reduces degree of anemia • This is most commonly seen with hemolytic anemia, but not specific to hemolysis (can also be seen with acute blood loss)
  54. 54. Causes of Hemolysis - Intrinsic • Generally, a hereditary disorder • Remember, the mature RBC has lost its nucleus, mitochondria, and RNA, leaving Hgb, RBC membrane • Intrinsic hemolysis is caused by defects in Hgb, RBC membrane or metabolic factors needed to generate ATP • Examples • Thalassemia (defect in alpha or beta globin chains) • Spherocytosis (missing RBC membrane proteins) • G6PD deficiency (abnormality in reducing power (NADPH))
  55. 55. Causes of Hemolysis - Extrinsic • Acquired disorder • Causes include: • Ab directed against RBC membrane components -AIHA, delayed transfusion reaction • Stasis/trapping/destruction in spleen (hypersplenism) • Trauma -Prosthetic heart valve • Exposure to compounds with oxidant potential -Sulfonamide in those with G6PD • Destruction of RBC by pathogens -Malaria, babesiosis
  56. 56. Site of Hemolysis • Dependant on the severity and type of cell alteration (alteration in RBC membrane) • Severe damage  immediate lysis in the circulation (INTRAVASCULAR) • Less severe damage  cell destruction is via the monocyte-macrophage system in the liver, spleen, BM, lymph node (EXTRAVASCULAR
  57. 57. Intravascular Hemolysis • Intravascular hemolysis  Release of Hgb into the plasma • Free Hgb binds to haptoglobin  Hgb- haptoglobin complex is taken up by liver  Decrease in plasma haptoglobin • Free Hgb breaks down to alpha-beta dimers  filtered by glomerulus  Hemoglobinuria
  58. 58. Intravascular Hemolysis • Causes: • Direct trauma • Shear stress – Mechanical heart valve • Heat damage • Complement-induced lysis – Paroxysmal cold hemoglobinuria • Osmotic lysis • Lysis from bacterial toxins • Clostridium
  59. 59. Extravascular Hemolysis • Damaged RBCs are destroyed by liver (receives a larger portion of the cardiac output) and spleen • Spleen contains cords of Billroth, which end blindly (unlike other vascular channels in body) • RBCs must deform to pass through 2-3 micron slits in the wall of the cords in order to get back into circulation • RBCs unable to pass are phagocytosed by the monocyte- macrophage system – Degraded into biliverdin, iron, carbon monoxide
  60. 60. Features of Hemolysis  Rapid fall in Hgb  Increased LDH, decreased Haptoglobin  Jaundice (elevated indirect bilirubin)  Splenomegaly  H/o pigmented gallstones  Abnormally shaped RBCs  Reticulocytosis
  61. 61. Peripheral Smear • Spherocytes • Fragmented RBCs – Schistocytes, helmet cells • Microangiopathic hemolytic anemia • Acanthocytes (spur cells) – Liver disease • Blister or “bite” cells – G6PD
  62. 62. con • RBCs with inclusions • Teardrop RBCs • Red Cell “ghosts” – Hemolyzed RBCs that reform, but have lost all internal components, leaving only the membrane – Indicates Intravascular Hemolysis
  63. 63. Labs  LDH: elevated  Indirect bilirubin: elevated (due to catabolism of Hgb)  Haptoglobin: decreased  Binds to Hgb and taken up by liver  In a series of reports:  Elevated LDH, low Haptoglobin was 90% specific  Normal LDH, Haptoglobin >25 was 92% sensitive for ruling out hemolysis  Reticulocyte Count: elevated  Normal is 0.5-1.5%  Anemia leads to increase Epo production leading to a reticulocytosis (4-5% increase above baseline)  Positive Direct Antiglobulin Test (Coombs)
  64. 64. Acquired hemolytic anemia • They are classified as -Immune hemolytic anemia -Traumatic anemia -Others like infectious agents,chemicals ,toxins,paraxismal nocturnal hemoglobin uria
  65. 65. Immune Hemolytic Anemia • IgG and/or IgM bind to RBC surface Ag and initiate RBC destruction via – Complement system – Reticuloendothelial system • AutoImmune Hemolytic Anemia – Production of Ab directed against self RBCs
  66. 66. Autoimmune Hemolytic Anemia • Types – Warm AIHA – Cold Agglutinin Syndrome – Paroxysmal Cold Hemoglobinuria – Mixed Type AIHA – Drug Induced AIHA Causes -Idiopathic Secondary causes -Lymphoproliferative disorders -Autoimmune disorders -Viral Infection -Immunodeficiency -Drugs
  67. 67. Warm AIHA 48-79% of AIHA Incidence increased at 40yrs 2:1 Female to Male ratio No racial predilection Idiopathic vs Secondary Causes CLL, Hodgkins, non-Hodgkins, Autoimmune, non-lymphoid neoplasms, immunodeficiency, viral illnesses Typically present with anemic signs and symptoms These symptoms may precede and underlying illness by months to years
  68. 68. Warm AIHA - Labs • Elevated MCV (reflecting reticulocytosis) • Mild leukocytosis with neutrophilia • Blood smear: – Polychromasia, macrocytosis, spherocytes, nucleated RBCs • Elevated LDH and indirect bilirubin • Haptoglobin typically low – Because it is an acute phase reactant, it can also be normal or elevated in mild disease
  69. 69. Warm AIHA – DAT (direct Coombs) Detects Ab on the RBC surface Pt’s RBCs are washed then reacted with monoclonal Ab against various Ig (IgG) and C3 Warm autoantibodies react at warmer temperatures (~37° C) 95% of Warm AIHA will have a positive DAT Negative tests due to: IgG quantity too low for detectable threshold IgA autoantibodies IgM autoantibodies
  70. 70. Warm AIHA - Treatment Folic Acid Further treatment depends on severity Steroids – 1mg/kg/day Splenectomy Removes source of extravascular hemolysis Removes a site of Ab production Cytotoxic drugs Cyclosporine Azathiaprine
  71. 71. Cold Agglutinin Syndrome (CAS) • 16-32% of AIHA • after binding to RBCs, IgM activates complement cascade - C3b binds, phagocytosis by hepatic macrophages (rather than splenic RES cells) • Most commonly in the 7th decade/60 ths • Idiopathic or secondary (most commonly infection or lymphoproliferative disorders) • RBC clumping (leads to artifactual elevation in MCV and decreased RBC count)
  72. 72. CAS - Treatment • Avoidance of cold exposure – Move to a warmer climate • Immunosuppression (cyclophosphamide) • Plasmapheresis can temporarily help • Compared to warm AIHI. . . – Steroids are not beneficial – Splenectomy is not beneficial • Extravascular hemolysis typically occurs in liver
  73. 73. Drug induced immune hemolytic anemia • Penicillins • Quinine, antihistamine, insulin • Methyldopa • Ibuprofein • Sulfa drugs • Cephalosporin
  74. 74. Non immune Hemolytic anemia • Fragmentation Hemolysis (Microangiopathy) – result of mechanical shearing of RBCs from damaged microvasculature, cardiac abnormalities, AV shunts, turbulent flow, drugs (cyclosporine, cocaine) • Hypersplenism – functionally hyperactive spleen too much sequestration of all blood cells • Infection – can be several mechanisms of hemolysis (direct attack, hypersplenism induction, immune, toxin release, altered RBC surface) • Burn ,liver disease
  75. 75. Lead poisoning • Inhibits both hem and globin synthesis • Interferes with breakdown of RNA by inhibiting the enzyme pyrimidine- nucleotidase ⇒ accumulation of denatured RNA in red cells giving rise to Basophilic stippling. • Hypo chromic/Hemolytic anemia with bone marrow ring sideroblasts • Free erythrocyte protoporphyrin is raised Management: • Pyridoxine, folic acid therapy : may bring some response • Repeated transfusion is ultimate choice
  76. 76. SUMMARY
  77. 77. REFERANCE • Reinhold Munker, MD ,ETAL:MODERN HEMATOLOGY, SECOND EDITION • HARRISON’S :PRINCIPLES OF INTERNAL MEDICINE,18th
  78. 78. 10Q! 4 UR ATTENTION!

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