Hereditary spherocytosis
Pathologic Cells
RBCs, destroyed via hemolysis
Hereditary spherocytosis
Patients
1:2,000 individuals from Northern European Ancestry
Hereditary spherocytosis
Unique Features
Autosomal dominant
mutations in RBC membrane proteins, weak RBCs are
removed by spleen, manifests with anemia & splenomegaly, jaundice, RBCs lack central pallor
Hereditary spherocytosis
Prognosis
Variable severity, most have minor anemia, possibly complicated by
parvovirus B19 infection (aplastic crisis), splenectomy may be Tx. for severely affected patients
Sickle cell anemia
Pathologic Cells
RBCs, destroyed by hemolysis
Sickle cell anemia
Patients
8% of African Americans are heterozygotes (trait), 1:600 are homozygotes (have anemia)
Sickle cell anemia
Unique Features
Autosomal recessive betaglobin mutation in the RBC hemoglobin, makes RBCs prone to thrombosis, exacerbated by: blood is sluggish (spleen, marrow), dehydration, inflammation
Sickle cell anemia
Prognosis
Heterozygotes are asymptomatic and homozygotes express the condition, 50% of homozygotes live past their 50s, death is most commonly from a stroke or acute chest syndrome
α-thalassemia
Pathologic Cells
RBCs, destroyed
via hemolysis
α-thalassemia
Patients
Individuals from:
Mediterranean,
Africa, Southeast
Asia
α-thalassemia
Unique Features
Both cause early RBC hemolysis and damage RBC precursors in marrow. α-thalassemia results from α-globin mutation and damages RBCs due to unpaired β-globin
α-thalassemia
Prognosis
lethal in utero (4/4 mutations) or
asymptomatic carrier (1/4
mutations)
β-thalassemia (Minor/Major)
Pathologic Cells
RBCs, destroyed
via hemolysis
β-thalassemia (Minor/Major)
Patients
Individuals from:
Mediterranean,
Africa, Southeast
Asia
β-thalassemia (Minor/Major)
Unique Features
Both cause early RBC
hemolysis and damage RBC precursors in marrow. α-thalassemia results from α-globin mutation and damages
RBCs due to unpaired β-globin
(vice versa for β-thalassemia).
β-thalassemia
(Minor vs Major)
Prognosis
β-thal. minor: asymptomatic or
minor anemia, normal lifespan.
β-thal. major: severe, hair-on-end skull, growth restrictions, lethal
during 20s, hemochromatosis
(heart/liver failure) secondary to
repeated blood transfusion
Glucose-6-phosphate
dehydrogenase (G6PD)
deficiency
Pathologic Cells
RBCs, destroyed
via hemolysis
Glucose-6-phosphate
dehydrogenase (G6PD)
deficiency
Patients
Individuals from
Mediterranean or
the Middle East,
10% of U.S. blacks
Glucose-6-phosphate
dehydrogenase (G6PD)
deficiency
Unique Features
X-linked, RBCs are susceptible to damage because glutathione can’t be produced without G6PD, hemolysis is exacerbated by oxidants: infections, aspirin, fava beans
Glucose-6-phosphate
dehydrogenase (G6PD)
deficiency
Prognosis
Many patients are asymptomatic or
have very mild anemia, many go undiagnosed due to the lack of obvious features, avoidance of precipitating oxidants is
recommended.
Paroxysmal nocturnal
hemoglobinuria (PNH)
Pathologic Cells
RBCs, destroyed
via hemolysis
Paroxysmal nocturnal
hemoglobinuria (PNH)
Patients
Individuals from Southeast Asia or the Far East, frequently diagnoses among middle-aged adults
Paroxysmal nocturnal
hemoglobinuria (PNH)
Unique Features
X-linked, PIGA gene mutations in myeloid stem cells, RBCs are susceptible to damage from complement fixation, which is exacerbated at night a pH drops slightly
Paroxysmal nocturnal
hemoglobinuria (PNH)
Prognosis
This conditions is very rare, may be managed with antibodies that
inhibit the MAC of the complement system
Immunohemolytic anemias (Warm/Cold) Pathologic Cells
RBCs, destroyed
via hemolysis
Immunohemolytic anemias (Warm/Cold) Patients
Individuals with leukemia/lymphoma
and other or other
autoimmune disorders: SLE, RA, systemic sclerosis, or inflammatory bowel disease (Crohn, U.C.)
Immunohemolytic anemias (Warm vs Cold) Unique Features
Opsonization of antibodies against one’s own RBCs, commonly results is removal of
RBCs in the spleen,
complement activation is also involved to a lesser degree
a) Warm: IgG, rarely IgA
b) Cold: IgM
Immunohemolytic anemias (Warm/Cold) Prognosis
Mild-moderate anemia when the condition is isolated, may be associated with reduced lifespan in patients with serious comorbidities
(e.g. leukemia, SLE)
Malaria (tertian malaria)
Pathologic Cells
RBCs, destroyed
via hemolysis
Malaria (tertian malaria)
Patients
Anyone infected
with malaria:
Southeast Asia, Africa
Malaria (tertian malaria)
Unique Features
Plasmodium falciparum
destroys RBCs as part of its lifecycle, merozoite showers every 48 hours, blackwater fever, fatigue, vomiting, jaundice, headaches, convulsions, loss of consciousness
Malaria (tertian malaria)
Prognosis
Patient with malaria have a shortened lifespan and die from cerebral malaria, liver or kidney failure