Hemolytic Anemia and Sickle Cell Disease - ez-med.org fileHemolytic Anemia Introduction Etiology...

Hemolytic Anemia and Sickle Cell Disease

Dr. Wael Maher MD; PhD

A.Professor of Pathology

SRC, KU, FOMSCU

Hemolytic Anemia

Introduction Etiology

Corpuscular and Extra-corpuscular

Classification

Intra and Extra Vascular

Features

SSD

Introduction

• Blood composition: Plasma, blood cells

• Bone marrow: Red, Yellow

• Hematopoiesis:

• Pluripotent stem cell

• Unipotent stem cell

• Precursor cell

• Mature cell

• Properties of stem cell: PROLIFERATION, MATURATION

Introduction

• Erythropoiesis:• Pluripotent stem cell

• BFU-E, CFU-E

• Proerythroblast

• Erythroblast: Basophilic, Polychromatic, Orthochromatic

• Reticulocyte

• Eryhtrocyte

• Factors• Normal stem cells of BM

• Normal architecture of BM

• Regulatory hormones: Epo, Androgen, thyroxin, Cortisol, ACTH

• Nutritional elements: Ptns., Fe, Folic acid, Vit.B12, Vit.C

Normal Hematological values

1- RBCs• Hemoglobin concentration (Hb conc.)

• Red cell count

• Color index = Hb concentration / Red cell count=1

• Hematocrit/Packed cell volume (PCV)

• Red cell indices:

• MCV= PCV/Red cell count

• MCH=Hb conc./Red cell count

• MCHC=Hb conc./PCV

• Red cell distribution width (anisocytosis)

• Red cell diameter: Micro-Macro-Aniso

• Red cell morphology

• Reticulocytic count (Activity of BM)• +++ in Anemia due to destruction, MEGALOBLASTIC anemia under treatment, Recovery from BM supp.

• --- in Anemia due to --- RBCs production

Normochromic anemia

Hypochromic anemia

Anemia with increased color index

Anemia with increased MCH

Hyperchromic anemia

Normocytic anemia

Microcytic anemia

Macrocytic anemia

2- WBCs• TLC

• Differential count

3- Platelet count

Normal Hematological values

AnemiaGeneral

• Definition

• Pathophysiology:

• +++Oxygen delivery to tissue

• +++Plasma volume

• +++CO

• Redistribution of blood

• +++Epo

• Classification

• Etiological

• Morphological

AnemiaGeneral

• Etiological classification

• Decrease production

• Decrease proliferation (Hypoproliferative)

# BM stem cells # BM architecture Organ failure Chronic disease

• Decrease maturation (Dyshematopoietic)

Hypochromic Megaloblastic Myelodysplastic

• Increase destruction

Hemolytic Acute post-Hemorrhagic

• Dilutional

• Morphological

• Hypochromic microcytic Anemia: Fe #, Thaless

• Normochromic normocytic Anemia: Hemolytic, Hgic

• Macrocytic Anemia: Megaloblastic

Hemolytic Anemia

IntroductionDefinition and

general featuresEtiology


Classification


Features

SCD

Hemolytic Anemia

• Definition

• Anemia due to shortened red cell life span (normal = 120 days); that is, premature destruction of red cells

• Hemolytic anemias share the following features:

• --- life span below the normal 120 days

• +++ Epo levels and a compensatory increase in erythropoiesis

• Accumulation of Hb degradation products

Hemolytic Anemia




Classification


Features

SCD

Hemolytic AnemiaEtiology

• Corpuscular:• Membrane defects: HS, PNH• Hemoglobin defect ( Hemoglobinopathies)

• Thalessemia (Defect in chain synthesis)• Others (Defect in aa sequence in chain)

Sickle cell anemia (HbS) HbC, HbD, HbE

• Enzyme defect• G6PD deficiency

• Extracorpuscular: • Immune hemolytic anemia

• Alloimmune: Incompatible blood transfusion, Hemolytic disease of the newborn• Autoimmune hemolytic anemia

• Hypersplenism• Infection: ( eg, Malaria, Clostridium welchii)• Traumatic: DIC, March hemoglobinuria, Artificial and Calcific valves• Chemicals: Snake venom, Copper

Hemolytic Anemia




Classification


Features

SCD

Hemolytic AnemiaManifestations

• Anemia

• Increased numbers of normoblasts in the marrow

• Increased Reticulocytic count

• Increased serum LDH

• Hepatosplenomegaly

• Hemolytic Jaundice

• Pigment stones and Obstructive Jaundice

HemeUnconjugatedIndirect

CholeConjugatedDirect

Hemolytic Anemia• Crisis:

• Hemolytic crisis

• RES hyperplasia( e.g. with infection)

• Aggravation of anemia and Jaundice:

• Fever, Rigors, Abdominal and bone pains

• Marked pallor, Deepening of jaundice and Dark urine

• Marked increased Reticulocytic count

• Aplastic crisis

• Viral infection ( Parvovirus B19)

• Aggravation of anemia without deepening of Jaundice

• Decreased reticulocytic count

• Megaloblastic crisis: Aggravation of anemia due to relative folate deficiency

• Sequestrational crisis: Aggravation of anemia due to pooling of RBCs in spleen.

• Painful veno-occlusive crisis: Sickle cell anemia

• Other features:

Iron Overload : Thalessemia Iron deficiency: PNH

Skin pigmentation and leg ulcers: Sickle Cell Anemia..


• Intravascular Hemolysis

• Hemoglobinemia

• Hemoglobinuria

• Hemosiderinuria

• Reduced serum Haptoglobin

• Reduced serum Hemopexin

• Methemalbuminemia and Methemoglobinurea

• Anemia and Jaundice


• Extravascular hemolysis

• Hemolytic Jaundice

• RES hyperplasia (work-related hyperplasia marked by splenomegaly)

• Hemoglobinemia and hemoglobinuria are not observed

Hemolytic Anemia




Classification


Features

SCD

Hemoglobinopathies

• Hb is formed of:

• Haem: Fe +prtotporphyrin

• Globin: 4 polypeptide chains

• Normally, Hb in adult is of 3 types:

• HB A: 2 alpha (141 aa), 2 beta (146 aa) (4 alpha genes on chrom.16, 2 beta genes on chrom. 11)

• Hb A2: 2 alpha, 2 delta (2 delta genes on chromosome 11)

• Hb F: 2 alpha, 2 gamma (4 gamma genes on chromosome 11)

• Hemoglobinopathies are abnormalities in the structure of globin molecule giving rise to abnormal types of Hb.

Hemoglobin Synthesis

a

a

a

a a

a

b g d

b dg

HbA HbF HbA2

98% ~1% <3.5%

Hemoglobins in normal adults

Sickle cell anemia

• Hereditary disorder…Abnormality in structure of beta chain of globin…..Abnormal Hb…HbS• Point mutation in beta globin chain: HYDROPHILIC aa Glutamine is substituted with

HYDROPHOBIC aa VALIINE at 6th position

• Sickle cell RBCs live only 10-20 days

• Homozygous (Sickle cell anemia= βS/βS) and Heterozygous (Sickle cell trait= βS/β)

• On exposure to hypoxia, HbS :• Polymerization…. +++ K+ efflux… +++ cell density/dehydration….Sickle shaped

• ---Deformability…+++ Rigidity….Destruction

• Vascular occlusion ( may be due to abnormal interactions between sickle cells and the vascular endothelium or the coagulation system)

Pathophysiology of Sickle Cell Anemia

(Modified from Steinberg, M., Cecil Medicine 2007)

HbS Polymer

Vaso-occlusion

Hemolysis

Arginine NO

Genetic and Laboratory Features of Sickle Hemoglobinopathies

Sickle cell anemia• Clinical features

• Common in blacks• Sickle cell trait: Asymptomatic. Partial protection from malaria• Features of hemolytic anemia• Attacks ppt. by temperature changes, stress, dehydration and high altitude• Painful veno-occlusive crisis: Attacks of severe pain in back, abdomen and extremities.• Splenic sequestration crisis• Acute chest syndrome

• At least two: chest pain, fever, pulmonary infiltrate, respiratory symptoms, or hypoxemia.• Second-most common complication• Accounts for 25% of deaths in patients with SCD.

• Vascular occlusion:• Splenic infarction

• Renal infarction

• Bone infarction: Avascular necrosis of femur head.

• Pulmonary vascular occlusion and cor pulmonale

• Cerebral vascular occlusion

• Retinal detachment

• Priapism and impotence

• Leg ulcers

• Increased susceptibility to infections especially• Pneumococcal infections

• Salmonella and St.aureus osteomyelitis

Sickle Cell Anemia - Investigations

• Blood film

• Hb electrophoresis (Hb S > 90%)

Sickle Cell Anemia - treatment

• Opiates and hydration for painful crises

• Pneumococcal vaccination

• Retinal surveillance

• Transfusion for serious manifestations (eg stroke); exchange transfusion

• Hydroxyurea

• Stem cell transplant

Hemolytic Anemia




Classification


Features

SCD

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