intravascular normocytic anemia Flashcards
paroxysmal nocturnal hemoglobinuria: pathophysiology
acquired defect in myeloid stem cells that causes an abscent glycophosphatidylinositol (GPI). this renders the cells susceptible to destruction by complement.
(remember: blood cells coexist with complement; decay accelerating factor (DAF) on the surface of bloos cells protects acatinst complement mediated damage by inhibiting C3 convertase. DAF is secured to the cell membrane by GPI. wihtout GPI, there isn’t DAF- cells are susceptible to complement mediated damage).
intravscular hemolysis occurs at night because sleep causes a mild respiratory acidosis, which activates complement. RBCs, WBCs, and platelets are all lysed.
intravascular hemolysis causes hemoglobinemia and hemoglobinuria; hemosiderinuria is seen days after hemolysis.
paroxysmal nocturnal hemoglobinuria: dx, manifestations, complications,
sucros test used to screen for disease. acidified serum test or flow sytometry to detect lack of CD55 (DAF) on cells.
main cause of death is thrombosis of hepatic, portal, or cerebral veins. destroyed platelets release cytoplasmic contents into the circulation, inducing thrombosis.
complications: iron deficiency anemia (chronic loss of hemoglobin in the urine), acute myeloid leukemia (10% of pts)
glucose-6-phosphatase deficiency: pathophysiology
X-linked recessive disorder causes a reduced half-life of G6PD. cells are suceptible to oxidative stress. RBCs are normally exposed to oxidative stress, esp H2O2. Glutathion neutralizes H2O2 but becomes oxidized in the process. NADPH, a byprodicut of G6PD, is needed to regenerate glutathione. decr. G6PD means decr. NADPH means decr. glutathion means oxidative injury and intravascular hemolysis.
glucose-6-phosphatase deficiency: variants; findings, diagnosis, presentation
African: mildly reduced half life leading to mild intravascular hemolysis with oxidative stress.
mediterranean variant: markedly reduced half life leading to makred intravascular hemolysis with oxidative stress.
Oxidative stress precipitates Heinz bodies (Hb precipitates).
causes of oxidative stress: infection, drugs like primaquine, sulfa drugs, dapsone, fava beans.
Heinz bodies are removed from RBCs by splenic macrophages- bite cells. leads to intravascular hemolysis.
presentation: hemoglobinuria and back pain hrs after exposure to oxidative stress.
diagnosis: heinz preparation, enzyme studies confirm deficiency (performed weeks after episodes- during acute episode, all the cells that lack the enzyme are already dead).
immune hemolytic anemia and warm hemagluttinin
antibody mediated (IgG or IgM) desctuction of RBCs. 1. IgG mediated disase usually involves extravascular hemolysis. IgG binds RBCs in the warm temp of the central body. membrane of antibody-coated RBC is consumed by splenic macrophages, resulting in spherocytosis. associated with SLE, CLL, and some drugs (penicillin, cephalopsorins). drugs may attach to the RBC membrane with subsequent bidning of ab to drug-membrane complex, or drugs may induce production of autoabs (alpha-methyldopa) that bind self-antigens)
cold hemagluttinin
IgM mediated disease. usually involves intravascular hemolysis. IgM binds RBC and fixes complement in the cold extremities. associated with mycoplasma pneumoniae and infection mononucleosis.
micorangiopathic hemolytic anemia
intravascular hemolysis that results from vascular pathology. RBCs are destroyed as they pass through the circulation. Iron deficiency anemia occurs with chronic hemolysis. seen with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, aortic stenosis.
aplastic anemia
damage to hematopoietic stem cells, resulting in a pancytopenia with low retic count. may be drugs, chemicals, viral infections, autoimmunity. biopsy reveals an empty, fatty marrow. tx: cessation of causative drugs, supportive care.
myelophthisic process
pathologic process like mets that preplaces the bone marrow. hematopoiesis is impaired, resulting in pancytopenia.
