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NORMOCYTIC ANEMIA: Hemolytic Anemia (HA) - Coggle Diagram
NORMOCYTIC ANEMIA:
Hemolytic Anemia (HA)
classifications
Site of RBC destruction
Intravascular hemolysis
Extravascular hemolysis
Nature of defect
Acquired Hemolytic Anemia
Immune hemolytic anemias
Non-immune hemolytic anemias
Microangiopathic HA (MAHA)
Schistocytes
Thrombotic microangiopathy (TMA)
Thrombotic thrombocytopenic purpura (TTP)
ADAMTS-13
von Willebrand factor-cleaving protease (vWFCP)
vWF
2 types:
Inherited >> Upshaw-Schulman syndrome
Acquired >> body makes Ab (proteins) that block ADAMTS-13 activity
Hemolytic-uremic Syndrome (HUS)
Mostly caused by E. coli O157:H7 infection
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Clonal hematopoietic stem cell disorder
Deficient glycophosphatidylinositol
Primary PNH: develop on its own
Secondary PNH: develop in the context of other BM disorders e.g. aplastic anemia
Clinical features
Mild to severe anemia
Hemoglobinuria
Hemosiderinuria
Lab evaluations
Normochromic normocytic RBC
Slight macrocytosis (polychromasia increase)
BM shows RBC hyperplasia
Increased erythropoiesis → usually normoblastic
Flow cytometry → detect complement regulators CD55 and CD59 on RBC
Hemosiderin in urine
Hereditary Hemolytic Anemia
Membranopathies
Structural defects
Hereditary elliptocytosis (HE)
Hereditary pyropoikilocytosis (HPP)
Hereditary spherocytosis (HS)
Hereditary ovalocytosis (Southeast asian ovalocytosis; SAO)
Altered permeability of RBC membrane
Hereditary stomatocytosis (HSt)
Xerocytosis or dehydrated (DHSt)
Overhydrated (OHSt)
Abnormal cells associated w/ alterations in RBC membrane
Target cells
Acanthocytes
Echinocytes
Spherocytes
Elliptocytes
Stomatocytes
Poikilocytes/fragments
Proteins in defect
Ankyrin
𝜶-Spectrin
Band-3
𝜷-Spectrin
Protein 4.2
GPC
Protein 4.1
Enzymopathies
congenital nonspherocytic HA
G6PD deficiency (or favism)
Gene located on X chromosome
icterus neonatorum
PK deficiency
RBC death by shrinking (dehydrated)
cell shape deformation
Abnormal Hb synthesis
Site of etiologic defect
Intracellular RBC
Extracellular RBC
Specific clinical features
Jaundice*
Dark urine*
Cholelithiasis
Potential aplastic crisis
Iron overload w/ extravascular hemolysis
Iron deficiency w/ intravascular hemolysis
Laboratory investigations
Screening tests
Increased RET count
Increased unconjugated bilirubin
Increased urobilinogen
Increased LDH
Decreased haptoglobin
Tests specific for intravascular hemolysis
Schistocytes on blood smear
Free Hb in serum
Methemoglobinemia (heme + albumin)
Hemoglobinuria (immediate)
Hemosiderinuria (delayed)
Tests specific for extravascular hemolysis
DAT (direct antiglobulin test)
IAT (indirect antiglobulin test)
Causes of Hemolysis
Intracorpuscular defect
Extracorpuscular defect
Non-immune HA
Immune HA
IgG mediated hemolysis
active at > 37C
Warm Ab HA
IgM mediated hemolysis
react at <37C
Complement mediated hemolysis
Classification
AIHA
Warm autoimmune HA (WAIHA)
Cold autoimmune HA (CHD)
Drug-induced HA
Mechanism:
Drug adsorption (Hapten model)
Immune complex formation
Auto-ab induction
Membrane modification
Alloimmune HA
Hemolytic disease of newborn (HDN)
Hemolytic transfusion reaction
Delayed type: 2-14 days
Immediate type: within 24 hrs
Laboratory Investigation
Agglutination test
Direct anti-human globulin (DAT)
Indirect anti-human globulin (IAT)