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PCM1 Exam 3 > RHS20 - Red Cell Disorders 3 > Flashcards

RHS20 - Red Cell Disorders 3 Flashcards

1
Q

What is warm antibody immunohemolytic anemia? What causes it?

A

A type of immunohemolytic anemia (IHA) in which an IgG (active at 37C hence the name) antibody coats the RBCs leading to their total or partial phagocytosis in the spleen (extravascular hemolysis). If they are only partially phagocytosed, they will transform into spherocytes which will be later destroyed.

  • 50% of cases are idiopathic (primary)
  • 50% are secondary to:
    • Autoimmune diseases (lupus)
    • B-cell neoplasms (CLL, lymphoma)
    • Drug reactions
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2
Q

What are the clinical features of Warm Antibody IHA? What is the treatment?

A
  • Most patients present with a chronic mild anemia and moderate splenomegaly
  • Most do not require treatment but treatments include
    • Supportive + removal of the offending agent
    • Immunosuppression
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3
Q

What is Cold Antibody IHA: Cold Agglutinin Type?

A
  • Cold Agglutinins are pathologic IgM antibodies that bind RBCs at lower temperatures (in the peripheral circulation) causing them to agglutinate and get fixed with complements.
  • This can cause Raynaud’s Syndrom (episodes of reduced blood flow in the peripheries, aka - acrocyanosis).
  • It also causes deposition of C3b (an potent opsonin) onto the RBC which lead to their phagocytosis in the spleen (extravascular hemolysis)
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4
Q

What is the cause of Cold Agglutinin anemia?

A

Cold agglutinins are produced in response to either:

  • Infections - mycoplasma spp, EBV, HIV, CMV, influenza
  • Neoplastic B-Cell growth - CLL, lymphomas
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5
Q

What is and what causes Cold Antibody IHA: Cold Hemolysin Type?

A

Cold Hemolysins are IgG autoantibodies that fix complements to RBCs in the cold peripheries, causing intravascular hemolysis upon rewarming. This leads to a symptom called “Paroxysmal Cold Hemoglobinuria” which is the sudden appearance of hemoglobinuria in the cold (due to the intravascular hemolysis)

Usually the result of a viral infection in children or as an autoimmune phenomenon.

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6
Q

How are IHAs usually diagnosed?

A
  • Direct Coombs Test (aka - direct antiglobulin test (DAT)) is used to detect antibodies/complements on RBC surface
    • RBCs are incubated with antibodies against the immunoglobulin or complement. Agglutination is a positive test result
  • Indirect Coombs test (IDAT) is used to detect antibodies/complements on RBC surface
    • Serum is tested for its ability to agglutinate test RBCs bearing defined surface antigens
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7
Q

List the most common causes of nonimmune hemolytic anemias

A
  • Hemolysis due to mechanical damage
    • Cardiac valve prostheses
    • Microangiopathic hemolytic anemia which occurs following partial microvascular obstruction
    • March hemoglobinuria
  • Infections (mostly malaria)
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8
Q

What is this?

A

Peripheral blood smear from someone with microangiopathic hemolysis. Schistocytosis (mechanical fragmentation of RBCs) causes the appearance of different cell shapes (schistocytes).

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9
Q

List and briefly describe the different impaired RBC production anemias.

A
  • Megaloblastic anemias - defective DNA synthesis
  • Iron deficiency anemias - defective heme synthesis
  • Thalassemias - defective globin synthesis
  • Aplastic anemias - stem cell failure
  • Anemias of chronic disease - unknown/multiple mechanisms
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10
Q

Give the etiologies and pathogenesis of megaloblastic anemias.

A
  • Etiologies - Vitamin B12 (cobalamin) or Folic Acid (folate) deficiency

B12 and Folate are co-enzymes necessary for the synthesis of thymidine. Without thymidine there is inadequate DNA synthesis with normal RNA/Protein synthesis.

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11
Q

What are the peripheral blood findings of megaloblastic anemias?

A
  • Macrocytic RBCs with decreased reticulocyte count
  • Neutrophils are hypersegmented
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12
Q

What are the bone marrow findings for megaloblastic anemias?

A

Megaloblastic changes

  • large red and white cell precursors
  • large megakaryocytes
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13
Q

Give an overview of how Vit B12 is absorbed

A
  1. Gastric pepsin released B12 from the food
  2. B12 binds with salivary protein, Haptocorrin
  3. In the duodenum, pancreatic protease separates B12 from Haptocorrin
  4. B12 binds to intrinsic factor (IF) produced by the gastric parietal cells
  5. An IF receptor in the distal ileum binds to the B12-IF complex and it is absorbed into the enterocytes
  6. A serum carrier protein, Transcobalamin, then carries B12 in the blood throughout the body
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14
Q

List the primary causes of vitamin B12 deficiency

A
  • Decreased intake - usually only seen in vegans (since B12 is present only in animal products)
  • Impaired GI absorption
    • Pernicous anemia
    • Malabsorption syndromes (Crohn’s, Coeliac disease)
    • GI surgery (gastrectomy, ileal resection)
    • Fish tapeworm infestation
    • Drug interactions
  • Genetic disorders that affect one of the factors involved in the absorption or metabolism of B12 (very rare)
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15
Q

What is the most frequent cause of B12 deficiency? How does it usually present?

A

Pernicious Anemia - an autoimmune disease that damages the gastric mucosa, particularly the parietal cells, leading to decreased IF production.

It has an insidious onset but patients often have severe anemia by the time they come to the clinic

  • Typical anemia symptoms
  • Mild jaundice
  • Beefy tongue
  • CNS involvement since B12 is involved in myelination - paraparesis, sensory ataxia, lower limb paresthesia
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16
Q

What are the lab findings associated with megaloblastic anemias caused by B12 deficiency? How is it treated?

A
  • CBC - low Hb and high MCV
  • Blood and Bone Marrow show megaloblastic changes
  • Increased plasma and urine methylmalonyl-CoA and methyl malonic acid (methylmaolonate)(because B12 is needed to convert methyl malonyl CoA to succinyl-CoA)
  • Increased plasma and urine homocysteine (because B12 is needed to convert homocysteine to methionine)

Treat with B12 injections

17
Q

Is B12 deficiency of Folate deficiency more common? Why?

A

Folate Deficiency

B12 is in most animal products while folate is really only found in raw fruits and vegetables. Also, body stores for folate are only modest.

18
Q

Describe the absorption of folate.

A
  1. Polyglutamylated dietary folate is cleaved to the monoglutamate by a brush border enzyme in the jejunum
  2. Folate enters plasma via both active and passive mechanisms
  3. In peripheral tissues, folate is polygultamated back to its active form which cannot diffuse back out of cell
19
Q

Where is folate mostly stored and how long does it take to deplete those stores?

A

Liver

4-5 months

20
Q

What are the leading causes of folate deficiency?

A
  1. Decreased intake (common in alcoholics)
  2. Impaired GI absorption
  3. Alcohol abuse impairs the enterohepatic circulation (liver>bile>small intestine>enterocyte>liver) of folate
  4. B12 deficiency - B12 is required to convert inactive dietary folate into active folate
  5. Increased requirements
    1. pregnancy
    2. infancy
    3. advanced age
    4. Chronic hemolytic anemias
    5. disseminated cancer
    6. Drug Interaction
21
Q

What are the clinical features of folate deficiency?

A

Similar to B12 deficiency except:

  • No CNS involvement. Except for neural tube defects seen in the first trimester of pregnancy
22
Q

What are the lab findings in folate deficiency?

A

Same as for B12 deficiency except:

  • Serum/Plasma methylmalonic-CoA and methylmalonic acid levels are normal. Homocysteine is still increased
  • Decrease in serum red cell folate
23
Q

What is the treatment for folate deficiency?

A

Very important to exclude B12 deficiency before treating

  • Identify and treat cause
  • Folate replacement
24
Q

Describe where and how iron is absorbed.

A
  • Dietary Fe2+ is absorbed into a duodenal enterocyte via DMT1 (divalent metal transporter 1). It then follows one of two pathways
  1. Storage in mucosal ferritin (an iron protein complex) or hemosiderin (partly degraded aggregates of ferritin) in the enterocytes
  2. Transport into the plasma by ferroportin, oxidization by ferroxidase to Fe3+, and binding by transferrin which then carries it to either the bone marrow or liver where it is converted back into Fe2+ and stored in ferritin
25
Q

What signals dietary iron for absorption or storage?

A
  • When liver iron stores are high, the liver releases Hepcidin, a peptide that inhibits the activity of ferroportin in the duodenal enterocytes. This inhibits release of iron stored in the enterocyte and inhibits iron absorption from the diet
26
Q

What is total iron binding capacity (TIBC)?

A

It is a measure of how much transferrin is available in the blood to bind iron.

27
Q

What are the primary causes of iron deficiency?

A
  • Dietary deficiency (commonest cause in developing countries)
  • Impaired absorption
  • Increased requirements - growing children, premenopausal women, pregnancy
  • Chronic blood loss (commonest cause in western world)
28
Q

What are the stages of iron deficiency?

A
  • Iron deficiency without anemia
  • Iron deficiency with mild anemia
  • Severe iron deficiency with severe anemia
    • Starts with decreased serum ferritin and absent bone marrow iron
    • Progresses to decreased transferrin saturation
29
Q

What are the clinical features of iron deficiency anemia (IDA)?

A
  • Typical anemia symptoms
  • Pica Cravings - cravings to eat or chew things with no nutritional value like ice, paper, clay, chalk, etc.
  • Pallor
  • Dry or rough skin
  • Atrophic glossitis (bald tongue from papillae atrophy)
  • Angular cheilitis (inflammation of one or both corners of the mouth)
  • Koilonychia (nails bent up like spoons)
30
Q

What are the lab findings for IDA?

A
  • CBC - low Hb, low MCV, low MCH, high RDW
  • Microcytic hypochromatic anemia (see image)
  • Low reticulocyte count
  • Low ferritin (could be false negative since ferritin rises during inflammatory conditions)
  • High TIBC (lots of empty transferrin)
  • Bone marrow exam
    • No stainable iron (prussian blue stain)
31
Q

What is the treatment plan for IDA?

A
  • Treat underlying cause
  • Iron replacement therapy
    • Oral or IV iron
    • Treatment should continue for 3 months after Hb normalization to replenish body stores

PCM1 Exam 3 (31 decks)

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