RBC disorders 3 Flashcards
What is autoimmune hemolytic anemia
hemolytic anemia with a defect extrinsic to RBCs caused by antibodies that recognize red cells and lead to their premature destruction
Pathogenesis of AIHA
Antibodies can either opsonize the RBC themselves or initiate a complement activation→can form opsonins or membrane attack complex→hemolysis
How to diagnose AIHA
Coombs antiglobulin test
- reagent used is anti human globulin— an antibody against human antibodies/ complement
Explain direct Coombs test
Autoantibodies against RBCs on patient RBCs + Coombs reagent = agglutination/clumping —> positive
Explain indirect Coombs test
Patient serum with autoantibodies+ commercially available test RBCs + Coombs reagent = agglutination/clumping—> positive
Warm antibodies are _____ antibodies that bind to RBCs at ______C. It opsonize RBCs → splenic macrophages → _________ hemolysis. This causes warm hemolysis disease
Warm antibodies are IgG antibodies that bind to RBCs at 37C. IgG opsonize RBCs → splenic macrophages → extravascular hemolysis. This causes warm hemolysis disease
What happens with IgM antibodies that bind at cold temperatures
IgM binds to RBCs in exposed fingers, toes, ears etc.→fixes complement→C3b forms
Blood recirculates to warmer areas→IgM falls off before MAC is formed
C3b opsonizes RBCs→ splenic macrophages→ extravascular hemolysis
Pentameric IgM causes agglutination: Cold agglutinin disease
What happens with IgG antibodies that bind at cold temperatures
IgG binds to RBCs in exposed fingers, toes, ears etc.→fixes complement →doesn’t fall off when blood recirculates to warmer areas→MAC (membrane attack complex) formed → intravascular hemolysis
Cold hemolysin disease/ paroxysmal cold hemoglobinuria (PCH)
Warm hemolysin
Target antigen – most commonly Rh
IgG coated RBCs bind to Fc receptor on phagocytes→ remove a bit of membrane→ spherocytes formed→lysed in spleen
- Chronic anemia, splenomegaly
AIHA associated with SLE, drugs like alpha methyl dopa and B- cell neoplasms like chronic lymphocytic leukemia
Warm hemolysin
AIHA associated with Mycoplasma, EBV (Epstein Barr virus), CMV (cytomegalovirus), HIV and B-cell neoplasms
Cold agglutinin
Cold agglutinin
Clumped/ agglutinated RBCs seen in peripheral smear with some spherocytes
Raynaud phenomenon when exposed to cold
Which AIHA associated with viral infections in children
Cold hemolysin
Cold hemolysin
Usually normocytic RBCs with evidence of intravascular hemolysis
Acute, self limiting. Can be fatal is severe
Megaloblastic anemia
Impairment of dna synthesis due to vitamin b 12 and folic acid deficiency. Needed for synthesis of thymidine
- leads to ineffective hematopoiesis
- abnormally large erythroid precursors and red cells
Causes of vitamin b12 deficiency
Decreased intake
• Inadequate diet
• Strict vegans Impaired absorption
Impaired absorption • Pernicious anemia (autoimmune attack on gastric mucosa) • Gastrectomy • Malabsorption • Fish tapeworm infestation
Cause of folic acid deficiency
- Decreased intake of green vegetables (eg.alcoholics)
- Impaired absorption
- Increased requirement like in pregnancy
- Folic acid antagonist drugs like methotrexate
Vitamin b12 absorption
- After ingestion of B12-containing diet, gastric pepsin releases the B12 from the food allowing it to bind with a salivary protein (Haptocorrin)
- By the action of pancreatic proteases in the duodenum, B12 is released from the B12-Haptocorrin complex
- The free B12 then attaches to intrinsic factor (IF) produced from the gastric parietal cells
- The B12-IF complexes pass to the distal ileum and get absorbed via a receptor of IF into the enterocytes.
- The absorbed B12 is then transported in the blood by Transcobalamin to the liver
Outcomes of B12 deficiency
- increased homocysteine and tetrahydrofolate
- folate trap—> decrease folate —>cannot do thymidylate synthesis—> megaloblastic anemia
Neurological symptoms due to increased methyl malonyl CoA
Findings in megaloblastic anemia
- ineffective hematopoiesis —> pancytopenia
- low reticulocyte count
- As a result to make more cells→precursors increase→bone marrow becomes hypercellular
- In all cells→ delayed nuclear maturation + normal cytoplasmic maturation and Hb accumulation→nuclear cytoplasmic asynchrony
- An-iso-poikilo-cytosis (variation in shape and size of RBCs)
- erythroid family—> megaloblasts making mature RBCs called macrocytes
- Granulocyte family—> Giant metamyelocytes making mature neutrophils that are larger and show nuclear hypersegmentation
What makes a neutrophil hypersegmented?
There are >5 nuclear lobes instead of normal 3-4 lobes
What else is seen in megaloblastic anemia
• Intramedullary hemolysis → mild jaundice
• Beefy tongue
• Neurological symptoms in vitamin B12 deficiency
- paraparesis, sensory ataxia, lower limb paresthesia
• Start with serum vitamin B12 and Folate levels
• Schilling test- not done anymore → inability to absorb an oral dose of B12
What should be done before starting treatment for folate deficiency?
Very important to exclude B12 deficiency before starting treatment for folate deficiency. It might transiently correct the anemia, however, while depleting the little remaining B12 and lead to worsening of the neurological symptoms
Pernicious anemia
Autoantibodies against parietal cells which make intrinsic factor which is required for b12 absorption
chronic atrophic gastritis → prominent infiltrate of lymphocytes and plasma cells
Clinical features: particularly autoimmune thyroiditis and adrenalitis
