Hemolytic Anemias

Causes of Hemolytic Anemia by Mechanism

Location

Mechanism

Examples

Mode

Intrinsic

Enzyme deficiency

G6PD deficiency

Hereditary

Hemoglobinopathies

Sickle cell anemia, thalassemia

Membrane abnormalities

Hereditary spherocytosis

PNH

Immune-mediated

Autoimmune; drug-induced, tx rxn

Extrinsic

Traumatic

MAHA: prostheses

Acquired

Direct infections.

Malaria, babesiosis; snake & spider

toxins

venoms; Wilson's; hypotonic infusions

Entrapment

Hypersplenism

(Lancet 2000:355:1169 & 1260)

(Lancet 2000:355:1169 & 1260)

Diagnostic evaluation

• 7 reticulocyte count (Rl >2%). t LDH. 1 haptoglobin (83% Se. 96% Sp). 7 indirect bili

• Autoimmune hemolysis: Coombs' test direct antiglobulin test (DAT) -» © if agglutination occurs when antisera against Ig or C3 are applied to patient RBCs

• Intravascular: It LDH. 11 haptoglobin; hemoglobinemia. hemoglobinuria, hemosiderinuria

• Extravascular: splenomegaly

• Family h o anemia; personal or family h o cholelithiasis

Glucose-6-phosphate dehydrogenase (G6PD) deficiency inejm 1991:324 169)

• X-linked defect of metabolism causing T susceptibility to oxidative damage

• Most common in males of African or Mediterranean descent

• Hemolysis precipitated by drugs (dapsone. primaquine, sulfamethoxazole, doxorubicin.

methylene blue), infection. DKA. or foods (fava beans in children)

• Diagnosis: smear may show RBC Heinz bodies (oxidized Hb) that result in bite cells once removed by spleen; 1 G6PD levels (may be normal after acute hemolysis as older RBCs have already lysed and young RBCs may still have near normal levels)

Sickle cell anemia (HEjm 1999:340:1021)

• Recessive fi-globin mutation — structurally abnl hemoglobin (HbS)

8% of African-Americans are heterozygotes and 1 in 400 are homozygotes

• Deoxygcnated HbS polymerizes — RBC sickles and 1 RBC deformability • hemolysis and microvascular occlusion

• Anemia: chronic hemolysis • acute aplastic (parvo. B19) or splenic sequestration crises

• Vaso-occlusion and infarction: painful crises, acute chest syndrome. CVA. splenic sequestration, hand-foot syndrome, renal papillary necrosis, aseptic necrosis, priapism

• Infection: splenic infarction -» overwhelming infection by encapsulated organisms;

infarcted bone osteomyelitis (Salmonella, Staph, aureus)

• Diagnosis: sickle-shaped RBCs and Howell-Jolly bodies on smear: Hb electrophoresis

• Treatment: hydroxyurea causes ' HbF i painful crises, acute chest episodes (N£}M

1995:3311317) and may i mortality (/AMA 2003:289 1645); allogeneic HSCT may have a role in young Pts with severe disease (Wood 200055:1918)

• Supportive care: folic acid qd; pneumococcal, meningococcal. H. fiu & HBV vaccination;

pain crises treated with hydration, oxygen, and analgesia: simple or exchange transfusion for CVA. severe acute chest syndrome, and preop (goal Hb 10 g dl)

Hereditary spherocytosis (HS) & j Hematology 2004 126 455)

• Defect in a cytoskeletal protein of RBC membrane — membrane loss mutations in ankyrin.u- and {J- spectrin, band 3. and pallidin have been identified

• Most common in N. European populations (1 in 5000 births): • FHx (75% of Pts)

• Anemia, jaundice, splenomegaly, pigmented gallstones

• Diagnosis: spherocytes on smear. V osmotic fragility test ( 80% Se). I eosin-5-maleimide

• Treatment: folate, splenectomy for moderate and severe HS

Paroxysmal nocturnal hemoglobinuria (see above)

Autoimmune hemolytic anemia (AIHA)

• Acquired, antibody-mediated RBC destruction

• Warm AIHA: IgG Abs opsonize RBCs at body temp — removal by spleen

Etiologies: idiopathic, lymphoproliferative disorders (CLL). autoimmune diseases (SLE). drugs (see below)

• Cold AIHA: IgM Ab bind to RBCs at temp ■ 37°C — complement fixation

-* intravascular hemolysis and acrocyanosis upon exposure to cold Etiologies: idiopathic, lymphoproliferative disorders (monoclonal). Mycoplasma pneumoniae infection and infectious mononucleosis (polyclonal)

• Diagnosis: spherocytes on smear. Coombs'; / cold agglutinin titer

• Treatment: treat underlying disease; warm AIHA: corticosteroids • splenectomy. IVIg, cytotoxic agents, rituximab; cold AIHA: cold avoidance, steroids often ineffective, rituximab (BW 2004:103:2925)

Drug-induced hemolytic anemia

• Acquired, antibody-mediated. RBC destruction precipitated by a medication:

abx: cephalosporins, sulfa drugs, rifampin

CV: methyldopa. procainamide, quinidine. thiazides other: TCAs. phenothiazines, NSAIDs. sulfonylureas. MTX. 5-FU

• Diagnosis: Coombs' usually negative

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