RBC Disorders - Anemia Lecture Flashcards
Aplastic Anemia
Characterized by loss of hematopoietic cells, fatty replacement of marrow, and pancytopenia
May be congenital (Fanconi’s anemia) with or without visceral/bony malformations
Secondary causes of aplastic anemia
Infection—viral hepatitis, EBV, Erythrovirus (parvovirus), HIV
Radiation—therapeutic, diagnostic
Drugs—chloramphenicol, quinacrine…risk is 1:30,000
Primary causes of aplastic anemia
Chemicals - Toluene, glue - occupational or abuse
Immunologic - autoimmune mediated, paroxysmal nocturnal hemoglobinuria (PNH)
Chronic Kidney dz in erythroid progenitor proliferation defects
Degree of anemia roughly proportional to degree of renal insufficiency
Due to several factors:
- Shortened RBC survival time
- Decreased EPO levels resulting in decreased RBC production
- Decreased RBC production independent of EPO
Clinical manifestations:
Normochromic normocytic anemia
Acanthocytes on peripheral smear
Evidence of renal failure
Causes of megaloblastic anemias
95% due to deficiency of either vitamin B12 or folic acid
Rest: drugs (sulfonamides, chemotherapeutic agents, anticonvulsants, contraceptives) or toxins (arsenic)
Megaloblastic anemia with neurologic symptoms
B12 deficiency—posterior column degeneration, combined degeneration of dorsal/lateral columns (subacute combined system disease)
Megaloblastic madness—severe B12 deficiency resulting in psychosis with macrocytic anemia
Folic acid deficiency
Body stores minimal, must have continuous supply in diet
May be due to decreased dietary intake for body demands (pregnancy, hemolytic anemias) or impaired absorption (sprue, enteritis, Whipple’s disease, diabetes)
Lab: decreased serum folate and RBC folate
Tx: supplement folate 1mg po qd
Cobalamin deficiency
impaired absorption—pernicious anemia, gastrectomy, Zollinger-Ellison syndrome, blind loop syndrome, tapeworm infestation)
- Some cases of poor intake (vegetarianism)
- Body stores significant, usually takes years to develop
Lab tests—decreased serum B12
Treatment—supplemental B12 (1000mcg IM monthly for maintenance, may need to dose more often if deficient)
Refractory megaloblastic anemia
May occur in myelodysplasia—bone marrow usually helps identify frankly dysplastic cells from more benign megaloblastic cells in classic megaloblastic anemia
Iron deficiency anemia - causes
most common anemia
Cause:
- decreased intake, increased iron loss, hemolysis, or combo
- infants - inadequate iron in milk
GI bleeding - men and postmenopausal women - PUD, angiodyplasia, inflammatory states, tumors
Pulmonary/GU losses
Hemolysis/hemoglobinuria - PNH
Post gastrectomy - insufficient acid to maintain iron in Fe2+ state
Malabsorption - intestinal resection, altered nRAMP2 gene (DCT1 aka DMT1) - facilitates Fe2+ transport across brush border
Factitious anemia
d/t auto phlebotomy
Affected patients have underlying psychiatric problems; treatment of underlying disease results in resolution of practice
Iron Deficiency anemia - clinical presentation, labs
Clinical presentation
Microcytic hypochromic anemia (may be normocytic in ~35%)
Constitutional symptoms
Lab features
Decreased serum iron and ferritin (a measure of total body iron stores)
Increased total iron binding capacity— transferrin is less saturated with iron and increased capacity for transporting iron exists
Anemia of chronic disease
Usually occurs in chronically ill, debilitated patients or patients with multiple medical problems
Etiology:
Decreased RBC survival time Decreased erythropoiesis Disturbed iron metabolism
Lab features:
Decreased serum iron and TIBC Normal or increased serum ferritin
Normocytic normochromic anemia with normal reticulocyte count
Therapy:
Iron supplementation is NOT effective in most cases Supportive care only if anemia is mild (Hb 10-12 gm)
If anemia severe, transfusions may be helpful to keep Hb > 9gm
Marrow infiltration causing anemia
May occur secondary to malignancy (leukemia, lymphoma, myeloma, breast, lung, prostate, etc.)
May occur with benign disease Myelofibrosis Gaucher's disease Histiocytosis Sarcoidosis
G6PD deficiency
Pyruvate kinase (PK) deficiency
Hereditary nonspherocytic hemolytic anemia
Clinical features:
Hemolysis with anemia
-Food/Drug induced in case of G6PD (fava beans, sulfa containing medicines)
-Some may have chronic jaundice or neuromuscular disease due to absence of enzyme
-Family history of disease (X-linked)
Lab features:
Heinz bodies—collections of denatured hemoglobin
“Bite cells”—RBCs which have had denatured hemoglobin removed in the spleen
Anemia—normochromic normocytic
Elevated reticular count
Tx:
Avoid food/drugs known to predispose to hemolysis
Splenectomy helpful for some, especially if disease aggressive
Replacement therapy?
Lab features of hemolysis
Decreased haptoglobin
Increased LDH and bilirubin
Urine hemosiderin may be elevated in some
Plasma hemoglobin may be elevated if hemolysis severe
March hemoglobinuria
Feet striking the ground repeatedly causes damage/lysis of RBCs in capillaries on plantar surface of feet
Common in marathon runners
Treat with well padded footwear and reassurance
aka sports anemia, footstrike hemolysis, others
Cardiac anemia
Patients with severe aortic stenosis (valve gradient > 50mmHg) and patients with prosthetic valves may have ongoing lysis of RBCs - shearing forces
Anemia is usually mild
Treatment usually supportive unless anemia severe, resolves when a new prosthesis is inserted
Iron replacement helpful as iron loss can be significant with time
Chemical induced hemolytic anemias
Lead:
Interferes with cation pump—results in shortened RBC survival time
Lead slows production of RBCs in marrow
Copper: - complex mechanisms
Oxygen: pure O2 atmosphere - astronauts
Insect venoms:
Bee/wasp
Spider - brown recluse spiders
Malaria
Most common cause of hemolytic anemia in the world
Hemolysis can be severe, urine can contain significant amounts of hemoglobin and color can be very dark (“blackwater fever”)
Treat with antimalarial agents and supportive care
Bartonellosis
Due to Bartonella baciliformis (Carrión’s disease)
Does not infect, but adheres to RBC membrane
Hemolysis is the initial stage of the infection (“Oroya fever”)
Transmitted by sand flea
Treatment with antibiotics and supportive care
Babesiosis
From Babesia microti
Intraerythrocytic protozoa
Normally a parasite in rodents
Mechanism of hemolysis unclear
“Maltese cross” appearance in RBCs with Giemsa-stained peripheral smears
Warm- immune mediated hemolytic anemia
warm reacting antibodies (occurs at body temperature [37°C] and is mediated by IgG)
Complement involvement unusual
Tx:
Most not in imminent danger
Transfusions may be helpful—trouble with crossmatching, watch for signs of hemolysis
Steroids—mainstay, use high doses
Remissions are usually long-lasting
Immunosuppressives—of some benefit, cyclophosphamide and azathioprine most favored; considered in refractory cases
Splenectomy—used for patients in whom chronic steroid use is required
“Georgia’s warm”
Cold- immune mediated hemolytic anemia
cold reacting antibodies (occurs below body temperature and is mediated by IgM)
Complement may directly lyse RBCs or opsonize RBCs for lysis in the spleen
Etiology:
Lymphoproliferative disorders
Cold agglutinin disease (Mycoplasma)
–Hemolysis from Mycoplasma very rare—need titers at least 1:10,000 which don’t usually occur with infection
Tertiary syphilis (Donath-Landsteiner hemolytic anemia)— cause of paroxysmal cold hemoglobinuria (PCH)
Features:
Chronic anemia or severe episodic anemia following cold exposure
Veno-occlusive phenomena d/t sludging of RBCs in affected capillaries
Tx: Supportive, avoid cold, tx infections
“Minnesota’s cold”
