ANEMIA

By Dr Bashir Ahmed Dar

Chinki pora sopore kashmir

Associate professor of Medicine

Classification of Anemia I. Etiologic Classification 1. Impaired RBC production 2. Excessive destruction 3. Blood lossII. Morphologic Classification 1. Macrocytic anemia 2. Microcytic hypochromic anemia 3. Normochromic normocytic anemia

Impaired RBC Production1. Abnormal bone marrow 1.1 Aplastic anemia 1.2 Myelophthisis : Myelofibrosis, Leukemia, Cancer metastasis 2. Essential factors deficiency 2.1 Deficiency anemia : Fe, Vit. B12, Folic acid, etc 2.2 Anemia in renal disease : Erythropoietin3. Stimulation factor deficiency 3.1 Anemia in chronic disease 3.2 Anemia in hypopituitarism 3.3 Anemia in hypothyroidism

Excessive Destruction of RBC(cont.)

Hemolytic anemia

1. Intracorpuscular defect

1.1 Membrane : Hereditary spherocytosis

Hereditary ovalocytosis, etc.

1.2 Enzyme : G-6PD deficiency, PK def., etc.

1.3 Hemoglobin : Thalassemia, Hemoglobino- pathies

Excessive Destruction of RBC

2. Extracorpuscular defect

2.1 Mechanical : March hemolytic anemia

MAHA (Microangiopathic HA)

2.2 Chemical/Physical

2.3 Infection : Clostridium tetani

2.4 Antibodies : HTR, SLE

2.5 Hypersplenism

Blood Loss

1. Acute blood loss : Accident, GI bleeding

2. Chronic blood loss : Hypermenorrhea

Parasitic infestation

Macrocytic Anemia MCV > 94 MCHC > 311. Megaloblastic dyspoiesis 1.1 Vit. B12 deficiency : Pernicious anemia 1.2 Folic acid deficiency : Nutritional megaloblas-

tic anemia, Sprue, Other malabsorption 1.3 Inborn errors of metabolism : Orotic aciduria, etc. 1.4 Abnormal DNA synthesis : Chemotherapy, Anticonvulsant, Oral contraceptives

Microcytic Hypochromic Anemia MCV < 80 MCHC < 311. Fe deficiency anemia : Chronic blood loss, Inadequate diet, Malabsorption, Increased demand, etc.2. Abnormal globin synthesis : Thalassemia with or without Hemoglobinopathies3. Abnormal porphyrin and heme synthesis : Pyridoxine responsive anemia, etc.4. Other abnormal Fe metabolism :

Normocytic Normochromic Anemia MCV 82 - 92 MCHC > 301. Blood loss2. Increased plasma volume : Pregnancy, Overhydration3. Hemolytic anemia : depend on each cause4. Hypoplastic marrow : Aplastic anemia, RBC aplasia5. Infiltrate BM : Leukemia, Multiple myeloma, Myelofibrosis, etc.6. Abnormal endocrine : Hypothyroidism, Adrenal insufficiency, etc.7. Kidney disease / Liver disease / Cirrhosis

Hemolytic Anemia

What is Hemolysis

- Premature destruction of dead cells.

- Causes hereditary and acquired disorders.

- Hemolysis occurs at two sites:

Intravascular

- Hemolysis occurs within systemic circulation.

- Hemoglobin is released into plasma.

- Hemoglobin is lost through kidneys or catabolized in the liver.

Extravascular

- Trapping of red cells in spleen or liver sinuses.

- Lyses of trapped red cells.

- Release of lysed hemoglobin and catabolism within the sequestering organ.

Classification of Hereditary Hemolytic Anemia

• Based on side effect:

- Metabolic defect

- Membrane defect

- Hemoglobin defect

A) Metabolic defect:

- Defect in hexose monophosphate shunt: G-6-PD deficiency.

- Defects of glycolysis; pyrovate kinase def., glucose phosphate isomerase def.

- Defects in red cell nucleotide metabolism: pyramidine-5-nucleotidase def.

B) Membrane defect:

- Heriditary spherocytosis

- Heriditary elliptocytosis

- Hereditary pyropoikilocytosis

C) Hemoglobin defect:

- Thalassemias

- Sickle cell anemia

- Hemoglobin C disease

- Hemoglobin E disease

- Unstable hemoglobin

Laboratory Findings

• Chemistry

Hyperbilirubinemia, predominantly unconjugated bilirubin due to breakdown of heme ring by reticuloendothelial cells in the liver.

elevated LDH: released from destroyed cells.

Hemoglobinemia: free hemoglobin level increases in hemolysis esp. intravascular hemolysis: levels of 10-20 mg/dl gives plasma amber color and 50-100 gm/dl reddish color.

Hemoglobinuria: red-brown color of urine due to free hemoglobin and methamoglobin.

Decreased Heptaglobin level: it is a alpha-2-globin produced in the liver. It binds free hemoglobin thus level is reduced in hemolysis.

Hemosidrinuria: it reflects extensive hemolysis for a prolonged period of time. When hemoglobin is filtered by nephron, proximal tubular cells metabolize hemoglobin and iron accumulate in the cells. Cells then exfoliate in the urine and iron can be detected by Prussian blue reaction.

Drug-Induced Acute Hemolysis

• Drugs that have been linked to G6PD:• Primaquine (an antimalarial) • Sulphonamide antibiotics • Sulphones (e.g. dapsone, used against leprosy) • Other sulphur-containing drugs: glibenclamide (an anti-diabetic drug) • Nitrofurantoin (an antibiotic often used for urinary tract infections) • Vitamin K analogues • Several others• Henna can cause a hemolytic crisis in G6PD deficient infants

Acquired hemolytic anaemia

Immune haemolytic anaemias

Are caused by AB production by the body

against its own red cells.

Divided into 1) warm 37c

2) cold 4 c

Warm AIHA

• IgG alone ,Bind at 37c

Cold AIHA

• Usually IgM

• Bind to red cell at 4c

Coombs TestCoombs TestAntiglobulin TestAntiglobulin Test

RBCRBC

Red cell withRed cell withbound antibody tobound antibody tomembrane antigenmembrane antigen

++

Anti-immunoglobulinAnti-immunoglobulin

Coombs TestCoombs TestAntiglobulin TestAntiglobulin Test

RBCRBC RBCRBC

AgglutinationAgglutination

Non-Immune Hemolytic AnemiasNon-Immune Hemolytic AnemiasHemolytic anaemias due to mechanisms or agentsHemolytic anaemias due to mechanisms or agentsother than antibodies +/or complement e.g.:other than antibodies +/or complement e.g.:• Mechanical (traumatic)Mechanical (traumatic)• ToxinsToxins• Infections Infections • Splenomegaly (hypersplenism)Splenomegaly (hypersplenism)• Burn (physical)Burn (physical)• Renal failure and liver failureRenal failure and liver failure• ChemicalChemical

Mechanical (Traumatic) Mechanical (Traumatic) (Fragmentation)(Fragmentation)This is due to direct trauma (stress) to the RBCs This is due to direct trauma (stress) to the RBCs

causing fragmentation of the RBCs & intra-causing fragmentation of the RBCs & intra-vascular hemolysis. The fragmented cells can be vascular hemolysis. The fragmented cells can be seen on peripheral blood smears & are called seen on peripheral blood smears & are called (schistocytes).(schistocytes).

Due to:Due to:1.1. Prosthetic valvesProsthetic valves2.2. PatchesPatches3.3. Valvular diseasse e.g., stenosisValvular diseasse e.g., stenosis

Cont…

Mechanical (Traumatic) (Fragmentation)

(cont…)2.2. Microangiopathic:Microangiopathic: mechanical hemolysis due to mechanical hemolysis due to

contact between the RBCs & the abnormal intema contact between the RBCs & the abnormal intema of thrombosed, narrowed, necrotic small vessels or of thrombosed, narrowed, necrotic small vessels or fibrin strand formation.fibrin strand formation.Caused by many diseases e.g., DIC (disseminated Caused by many diseases e.g., DIC (disseminated intravascular coagulation), malignant hypertension, intravascular coagulation), malignant hypertension, disseminated malignancies especially mucin disseminated malignancies especially mucin secreting adenocarcinomas, TTP secreting adenocarcinomas, TTP (thrombocytopenic purpura), hemolytic uremic (thrombocytopenic purpura), hemolytic uremic syndrome (HUS).syndrome (HUS).

THE END

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