248. Acquired Hemolytic Anemias Flashcards
What are 3 big categories of intracorpuscular hemolysis?
- Hemoglobinopathies
- Sickle Cell Anemia
- Hb C, E - Enzyme Defects
- G6PD Deficiency
- PK Deficiency - Membrane Abnormalities
- Hereditary Spherocytosis, Elliptocytosis
- Acanthocytosis (spur cell anemia)
- Paroxysmal nocturnal hemoglobinuria
What are 4 big categories of extracorpuscular hemolysis?
- Immunologic
- Warm Ab
- Cold Ab - Mechanical
- MAHA (microangiopathic)
- March Hemoglobinuria
- Traumatic cardiac hemolytic anemia - Infectious
- Malaria
- Babesiosis - Hypersplenism
What are 7 lab features of hemolytic anemia?
- Anemia
- Reticulocytosis and polychromasia
- Decreased haptoglobin (binds up more free Hb and cleared)
- Hemoglobinuria or later hemosiderinuria
- Indirect (Unconjugated) hyperbilirubinemia
- Elevated LDH
- Abnormal RBCs on smear (spherocytes, elliptocytes, acanthocytes)
What are the differences between intravascular and extravascular hemolysis?
Intravascular
- direct mechanical damage to RBCs
- immune-mediated hemolytic anemias with complement-mediated destruction
- more haptoglobin decrease/absense
- higher Hb in blood (more breakdown noticeable)
- more hemosiderinuria
Extravascular
- in reticuloendothelial system (spleen liver)
What is the difference between Direct and Indirect Coombs Test?
Direct
- test for Ab’s already bound to host RBC
- add Anti-Igs to host RBC and look for clumping
Indirect
- test for any type of non-bound/bound Abs (ex: alloimmune Ab’s) to RBCs
- add host serum to RBC sample with Anti-Igs and look for clumping
Warm Antibody Hemolytic Anemia
- Epi
- Etiology
- Pathophys
- Lab findings
- tx
Epi: any age, usually W > M
Etio: 25% assoc with underlying disease (lymphoma, SLE, drugs, post-viral)
PPhys: IgG Ab’s coat RBC, get removed by macrophages in spleen, form spherocytes
Lab: spherocytes, microspherocytes, anemia, reticulocytosis, indirect hyperbilirubin, elevated LDH, decreased haptoglobin
DAT IgG POSITIVE
Tx
- Folate, vitamin deficiency tx
- RBC transfusion if symptomatic (but Abs may hemolyze this blood)
- cessation of suspect drugs
- IMMUNOSUPPRESSION - CS FIRST LINE
- splenectomy if refractory (decrease Ab production and macrophage recognition)
Drug induced Hemolytic Anemia
- types and examples
- warm or cold ab?
WARM ANTIBODY hemolytic anemia
- Hapten-induced HA: drug binds RBC and Ab is anti-drug (PCN)
- Immune Complex (neoantigen) HA: drug binds RBC and Ab is anti-RBC/drug complex (Quinine)
- Autoimmune Drug-induced HA: drug stimulates production of anti-RBC Ab (alpha methyldopa, procainamide) - drug cessation may not be self-limiting!
Cold Agglutinin Disease
- type of Ab
- factors that cause hemolysis (4)
- type of hemolysis
- epi
- CP
- labs
IgM Abs usually reacting to polysaccharides on RBC surface
Increased hemolysis with
- Antibody titer (high)
- Thermal amplitude of Ab-Ag interaction (high)
- Enviro temp (low)
- Complement fixation (high) - usually needs high Ab titer
Intravascular hemolysis
Ages 50-70
CP: RBC agglutination, necrosis of hangs/feet
Labs: RBC agglutination with disaggregation on RBC warming; signs of hemolysis, DAT positive with anti-C3 (complement), negative for IgG, Cold agglutinin titers
Tx: ONLY if hemolysis!
- supportive (warm pt and fluids, must only give warm RBCs or risk worsening disease)
- treat underlying disorder (infection, lymphoproliferative disorders)
- therapeutic plasma exchange (remove Ab temporarily)
- Rituximab (anti-CD20 on B lymphs, may decrease cold agglutinin production) and other IMMUNOSUPPRESSIVES (CS not as effective)
Alloimmune Hemolytic Disease
- Rh hemolytic disease (how does it occur, CP, labs, prevention)
- ABO Hemolytic disease (how does it occur, tx, prevention)
Rh Hemolytic Disease
- Rh- mother with previous Rh+ pregnancy develops anti-D IgG, next pregnancy results in hydrops fatalis or neonatal severe anemia, jaundice, hepatosplenomegaly, labs with nucleated RBCs, reticulocytes, Positive DAT
- prevention: anti-D Ig to mom at 28 weeks and any blood exchange occurs
ABO Hemolytic Disease
- O Mom with A or B fetus causes hemolysis in fetal blood, may occur in INITIAL pregnancy (preformed Abs), causes less severe hemolysis and anemia, Positive Indirect Cooms, Weakly positive Direct Coombs
- Tx: phototherapy for mild jaundice, transfuse if severe anemia
- PREVENTION: mother-child transfusions in utero peri-delivery
Paroxysmal Nocturnal Hemoglobinuria
- cause
- labs/CP
- major complications
- dx
- tx
Acquired stem cell disorder, mutation in PIG-A = deficient GPI protein anchors
- cells lose CD55, CD59 = complement-mediated lysis of RBCs
- nightly acute hemolysis, red urine
- labs: normochromic normocytic anemia, Coomb’s negative
- complications: venous thrombosis (PV, cerebral vein, cutaneous veins), Iron deficiency (Hb loss in urine)
- dx: Flow Cytometry (no CD55/59), Sucrose Hemolysis Test (Ham’s Test: sucrose activates complement to enhance hemolysis)
- tx: supportive (replace iron, folate)
ECULIZUMAB: inhibit complement = decrease hemolysis, risk of thrombosis
Anticoagulation prophylaxis for thrombosis
CURATIVE = allogenic stem cell transplant!
Spur Cell Anemia
- cause
- labs
- tx
Membrane defect of excess cholesterol with normal phospholipids, seen in liver disease
Labs: acanthocytes (asymmetric projections), prone to hemolysis (severe anemia, splenomegaly)
Tx: liver tx (>90% die from liver disease within a year)
