RBC Disorders 3 Flashcards
Immunohemolytic Anemias (IHA)
• Caused by Abs that binds to RBC antigens
• Subdivided according to the characteristics of the offending antibodies into:
– Warm Antibody IHA – Cold Antibody IHA
• Cold Agglutinin Type • Cold Hemolysin Type
-extrinsic
Nonimmune Hemolytic Anemias
– Mechanical trauma to red cells
– Infections (e.g. Malaria parasite)
Warm Antibody Immunohemolytic Anemia
• Most antibodies are IgG class (active at 37°C)
• Antibody-coated RBCs are removed from the circulation
by phagocytes in the spleen (Extravascular Hemolysis)
• Most patients have chronic mild anemia and moderate
splenomegaly
Cold Antibody Immunohemolytic Anemia: Cold Agglutinin Type
Are IgM antibodies that do not interact with RBCs at body temperature but react strongly at lower temperatures
Pathological cold agglutinins are produced either in : – Infections: Mycoplasma, EBV, HIV, CMV, influenza – Neoplastic growth: B-cell lymphomas
Immune Hemolytic Anemias: Laboratory Diagnosis- Direct Coombs test
– Patient RBCs are incubated with antibodies against human immunoglobulin or complement
– Positive test result→RBC agglutination
Immune Hemolytic Anemias -indirect coombs test (Indirect Antiglobulin Test- IDAT)
– Patient serum is tested for its ability to agglutinate test RBCs bearing defined surface antigens.
- Hemolysis due to Mechanical RBC damage
-Cardiac valve prostheses: more in mechanical than bioprosthetic valves
-Microangiopathic hemolytic anemia:
*Occurs following partial microvascular obstruction
*Seen in: DIC, malignant hypertension, TTPHUS, SLE and disseminated cancer
-March hemoglobinuria
Malaria
– Intracellular red cell parasite that causes hemolysis of variable severity
Anemias of Impaired RBC Production
• Failure of proliferation and/or maturation of committed RBC precursors
• Failure of stem cells(aplastic anemia )
• Unknown/multiple mechanisms(anemias of chronic disease)
Failure of proliferation and/or maturation of committed RBC precursors
– Defective DNA synthesis – Megaloblastic anemias
– Defective Heme synthesis – Iron deficiency anemia
– Defective Globin synthesis – Thalassemias
Causes of megaloblastic anemia are:
• Vitamin B12 deficiency (cobalamin)
• Folic acid deficiency (Folate)
Pathogenesis of megaloblastic anemia:
• Vitamins B12 and folate are both co-enzymes, necessary for the synthesis of thymidine, one of the four bases in DNA
• Deficiency results in inadequate DNA synthesis→ defective nuclear maturation, with relatively normal RNA and protein synthesis→nuclear/cytoplasmic asynchrony
Peripheral blood film-Megaloblastic Anemias
• Patients may have pancytopenia
• RBCs are macrocytic (MCV >100 fl), with increased reticulocyte count
• Neutrophils are hypersegmented (with ≥5
Megoblastic bone marrow
-Hypercellular (but ineffective) hematopoiesis
-Megaloblastic changes: large red cell and white cell precursors, large megakaryocytes, with large immature nuclei or increased
nuclear lobes
Causes of vitamin B12 Deficiency:
-Decreased Intake
-impaired GI absorption (pernicious anemia)
-genetic disorders affecting vitamin B12
Pernicious anemia
• Is an autoimmune disease where there is destruction of the gastric mucosa particularly parietal cells→failure of IF production→failure of B12 absorption→B12 deficiency→megaloblastic anemia
-Histologically:chronicatrophicgastritis
B12 Deficiency anemia- clinical features
-symptoms of anemia
-mild jaundice
-beefy tongue : due to megaloblastic changes in the oropharyngeal epithelium
-paraparesis, sensory ataxia, lower limb paresthesia
B12 Deficiency anemia- lab findings
• CBC: Low Hb with high MCV, pancytopenia
• Peripheral blood film and bone marrow examination show features of megaloblastic anemia, with low reticulocyte counts
• Other lab investigations:
– Serum B12 and Folate levels: Low B12 with normal folate – Serum homocysteine level: Elevated
– Serum methylmalonic acid: Elevated
– Serum antibodies to IF(very specific)
-Schilling test – inability to absorb an oral dose of B12
Causes of Folic acid Deficiency:
- Decreased intake
– Diet inadequate for green vegetables (e.g. alcoholics) - Impaired gastrointestinal absorption
- Increased requirements
– Pregnancy
– Infancy
– disseminatedcancer
– Drugs:e.g.methotrexate,Trimethoprim
Clinical features of Folic acid Deficiency:
-Are like B12 deficiency but no CNS involvement
Folate deficiency anemia : lab findings
• CBC: Low Hb with high MCV, pancytopenia
• Peripheral blood film and bone marrow examination
shows features of megaloblastic anemia with low reticulocyte counts
• Other lab investigations:
– Serum Folate and B12 levels: Low folate with normal B12 – Serum homocysteine level: Elevated
– Serum methylmalonic acid: Normal
– Red cell folate level: Low (v. specific & not affected by diet)
Causes of iron Deficiency:
- Dietary deficiency
– commonest cause of IDA in developing countries - Impaired absorption
- Increased requirements
– growing infants/children, premenopausal women, pregnancy - Chronic blood loss
– commonest cause of IDA in the Western world (mainly due to chronic GI blood loss)
Hepcidin
a peptide synthesized in the liver in response to high levels of liver iron stores, inhibits iron uptake from duodenal mucosal cells into the
bloodstream
Storage Iron:
– Ferritin: which is an iron-protein complex
– Hemosiderin: partly degraded aggregates of ferritin
Iron Transport:
• Iron is transported in the plasma bound to a protein called Transferrin
• The capacity of the transferrin to bind iron is referred to as Total Iron Binding Capacity (TIBC)
• Normally 33% of the transferrin is satur
Symptoms of IDA
-symptoms of anemia
-pica and ice craving
Signs of IDA
• Pallor
• Dry or rough skin
• Atrophic glossitis, with loss of tongue papillae
• Angular cheilitis
• Koilonychia (spoon shaped nails)
Lab findings of IDA
• CBC: Low Hb, low MCV, low MCH and High RDW
• Peripheral Blood smear: – Microcytic hypochromic
anemia
– In severe cases “poikilocytosis” and “pencil cells”
• Reticulocytes count: Low
IDA : serum iron studies
-low ferritin
-low serum iron
-high TIBC
-low transferrin
Anemia of Chronic Disease (ACD)
mainly seen in patients with:
–Chronic bacterial infections:
• e.g. lung abscess, osteomyelitis, endocarditis
–Chronic immune disorders: • e.g. Rheumatoid Arthritis
–Malignant tumors:
• e.g. lymphomas, lung or breast cance
Pathogenesis of Anemia of chronic disease
• There is impairment of iron utilization and reduction in RBC production
• During inflammation, there is increased production of hepcidin and decreased production of erythropoietin→decrease transfer of iron from the BM storage pool (macrophages) to RBC precursors→decrease erythropoiesis, with inappropriately low erythropoietin
Lab findings of ACD
• Clinical history: chronic medical condition
• CBC: Low Hb, low/normal MCV
• Peripheral Blood smear:
– Normocytic normochromic anemia, but sometimes hypochromic microcytic
• Erythropoietin (EPO) levels: Inappropriately low
• Bone marrow examination for iron stores
– There are normal or increased levels of stainable iron (Prussian blue stain).
Serum iron studies:ACD
Ferritin : normal/increased
Serum iron : reduced
Transferrin saturation: normal
TIBC : reduced
Aplastic Anemia
-Is a disorder characterized by a defect in the multipotent hematopoietic stem cells (HSCs) leading to bone marrow failure and pancytopenia
Causes of aplastic anemia
1) genetic causes / idiopathic
2) acquired : drugs (dose related or Idiosyncratic e.g. chloramphenicol, chlorpromazine, phenytoin) /irradiation / viral infections /
Clinical features of Aplastic Anemia:
• Recurrent infections
– due to Leukopenia
• Mucosal hemorrhage or menorrhagia
– due to thrombocytopenia
• Characteristically No Organomegaly
Aplastic anemia general investigations
Pancytopenia (↓Hb, WBC, platelet)
PB: Normocytic hypochromic
Low reticulocytes count BM: Hypocellular( only fat cells, few lymphocytes, plasma cell
