Hemolytic Anemia Flashcards
Lab markers of hemolysis
- all hemolysis: increased LDH, increased UNCONJUGATED bilirubin, increased reticulocytes (unless other underlying production issues)
- intravascular hemolysis: decreased haptoglobin, increased plasma Hb, hemoglobinuria
2 types of hemolytic anemia
- intravascular: within blood vessels
2. extravascular: within RES (spleen)
Clinical manifestations of hemolytic anemia. Be sure to associate which symptoms are due to anemia and which are due to hemolysis.
- referable to anemia: pallor, fatigue, decrease exercise tolerance, shortness of breath
- referable to hemolysis: jaundice, hemoglobinuria (esp with intravascular hemolysis), gallstone disease
6 notable causes of intravascular hemolysis.
- MAHA
- Acute hemolytic transfusion rxn (ABO mismatch)
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Paroxysmal Cold Hemoglobinuria (PCH)
- Infections
- Snake venom
Notable causes of extravascular hemolysis
- Intrinsic RBC defects: hemoglobinopathies, membrane defects (HS), enzyme deficiency (G6PD deficiency, PK deficiency)
- Extracorpuscular defects: immune-mediated hemolytic anemia (drug-induced, autoimmune), liver disease, infections, toxins
Discuss what Hereditary Spherocytosis is and what type of anemia is can lead to.
- genetic defect usually in ankyrin, spectrin or band 3 that causes RBC to become spheroidal and lose its deformity
- extravascular hemolysis due to intrinsic RBC defect
HS: inheritance, clinical manifestations, diagnosis, treatment, and morphology
- 75% AD, 25% AR; people from N. europe
- range of symptoms from asymptomatic to severe hemolysis w. splenomegaly
- diagnosis: confirmed by osmotic fragility test
- Rx: splenectomy for symptomatic patients
- Morphology:round cells without central pallor
Describe the osmotic fragility test and what it is useful in diagnosing.
- expose RBCs to progressively hypotonic solution of saline and see when cells burst. Usually, RBCs are elastic and can change volume quite a bit, but HS RBCs cannot due to membrane defects
- see HS RBCs lyse at less severe changes in hypotonicity
Describe why G6PD deficiency is pathologic and key characteristics that go along with this disorder, including what kind of anemia it can cause.
- G6PD is crucial to form glutathione within RBCs. Glutathione acts to reduce ROS. Those deficient for G6PD do not generate enough glutathione and Hb within the RBC is susceptible to oxidative damage by ROS
- Heinze Bodies and bite cells are signatures: damaged and denatured Hb aggregates form intracellular Heinz Bodies, which are removed by macrophages in the spleen to form “bite cells” and hemolysis
- extravascular hemolytic anemia due to intrinsic RBC defect
G6PD: inheritance, common variants
- Inheritance: G6PD is on X chromosome, so mostly affects males but some females due to unfavorable lyonization in RBC
- G6PD A-: in ~10% AAs males; decreased G6PD only in AGED RBCs
- G6PD B: 5% of mediterranean and asian ancestry; decreased G6PD in all RBCs
G6PD: clinical manifestations, diagnosis and rx.
-CM: hemolysis is usually precipitated by an acute event inducing oxidant stress like 1. acute illness (infection) 2. exposure to certain drugs or chemicals (napthalene, sulfa drugs) 3. fava bean ingestion (favism)
-Dx: G6PD biochemical assay, best tested months after acute event
Rx: avoidance of triggers, RBC transfusion as needed for acute episodes
Cold vs. Warm AIHA mechanism
- Warm: IgG-mediated and bind to antigens on RBCs (usually Rh complex) optimally at 37 degrees C. Ab-coated RBCs are cleared by FcR-expressing macrophages in spleen. Partial phagocytosis= microspherocytes
- Cold: IgM-mediated and bind to antigens on RBCs (usually carbs) optimally at less than 37 degrees C. IgM fixes complement, which remains bound even after IgM leaves RBC. Complement coated RBCs cleared by C3bR-expressing Kuppfer cells in liver.
How to make the AIHA diagnosis?
- Patient’s RBCs are washed and incubated with Coomb’s reagent (anti human IgG or anti human C3)
- if RBCs are coated with IgG or C3b, the corresponding Coomb’s reagent will cause the RBCs to agglutinate. This is visible to the naked eye.
Clinical manifestations, causes, and Rxs for warm vs. cold AIHA
- Warm: hemolytic anemia; common causes are idopathic, autoimmune disorder, lymphoproliferative disorder; Rx with corticosteroids, splenectomy, rx underlying condition if present, immunosuppressants
- Cold: hemolytic anemia, triggered by cold exposure, acrocyanosis in extremities bc colder here; causes are idiopathic, infection (EBV, mycoplasma), lymphoproliferative disorders; Rx: avoid cold, rx underlying condition, Rituximab (anti-CD20), plasma exchange as temporizing measure
Would a splenectomy work for Cold AIHA?
-no, bc the pathologic clearance for these cells occurs in the liver
