Hereditary Hemolytic Anemias

Hereditary Hemolytic Anemias

an inherited, genetic abnormality that resuls in premature and often rapid destruction of RBCs resulting in anemia

autosomal dominant

hereditary spherocytosis mode of inheritance

hereditary spherocytosis defect in the membrane

mutatied spectrin beta gene and others → decreased spectrin/others → membrane instability → increased membrane loss → decreased surface:volume → decreased cell deformability → splenic removal → increased glucose → decreased pH → increased macrophages → more membrane loss → hemolysis

jaudice, anemia, splenomegaly

triad of symptoms associated with hereditary spherocytosis

hereditary spherocytosis clinical features

triad of symptoms
asymptomatic to severe symptoms
pigment gallstones

hereditary spherocytosis CBC

mile, moderate, or sever anemia
normal MCV and MHC
increased MCHC in 50% of cases

hereditary spherocytosis differential

anisocytosis, Poikilocytosis, spherocytes
increased poly/retics/NRBC/RPI

increased

hereditary spherocytosis osmotic fragility test

hereditary spherocytosis treatment

splenectomy in moderate and sever cases
transfusion as needed

hereditary spherocytosis prognosis

generally good
normal lifespan with treatment
mild forms do not require treatment

autosomal dominant

hereditary elliptocytosis mode of inheritance

hereditary elliptocytosis clinical features

mild in heterozygotes to sever in homozygotes
can be inherited with spherosytosis and stromatocytosis

hereditary elliptocytosis defect in membrane

sytoskeletal defect → spectrin and others → microvascular passage → permanent deformation → forms elliptocytes → cell fragmentation

hereditary elliptocytosis CBC

mild, moderate, or severe anemia
normal MCV, MCH, and MCHC
MCV can be increased if many retics

hereditary elliptocytosis differectial

poikilocytosis, elliptocytes (>30% mild and >75% severe)
Schistocytes and microshperocytes in severe disease
strmatocytes and spherocytes in appropriate variants
increased poly/retics/NRBC

hereditary elliptocytosis laboratory findings

decreased haptoglobin, increased bilirubin
increased osmotic fragility only in sever disease and infancy

hereditary elliptocytosis treatment

splenectomy if severe
treat symptoms in infancy
transfusions as needed

hereditary elliptocytosis prognosis

good
most do not need treatment

autosomal recessive

Hereditary Pyropoikilocytosis mode of inheritance

Hereditary Pyropoikilocytosis defect in membrane

cytoskeletal defect → spectrin and others → microvascular passage → RBC instability → fragmentation → decreased surface:volume ratio → spherocytes → schistocytes

Hereditary Pyropoikilocytosis clincal features

severe anemia, splenomegaly, jaundice

Hereditary Pyropoikilocytosis CBC

anemia
decreased MCV due to schistocytes
normal MCH and MCHC

Hereditary Pyropoikilocytosis differential

sever poikilocytosis, RBC budding, Schistocytes, Micropherocytes, Elliptocytes
Bone marrow response (increased poly, NRBC, and retics)

Hereditary Pyropoikilocytosis laboratory findings

decreased thermal stability
increased osmotic fragility

Hereditary Pyropoikilocytosis treatment

transfusions as needed, splenectomy (severe), folate

Hereditary Pyropoikilocytosis prognosis

poorest of membrane disorders

hereditary stomatocytosis mode of inheritance

autosomal dominant
autosomal recessive in more severe cases

hereditary stomatocytosis membrane defect

defect in the sodium/potassium pump
increased permeability to very increased Na+ and increased K+ → influx of water → RBC swelling → splenic sequestration → hemolysis

hereditary stomatocytosis clinical features

mild anemia

hereditary stomatocytosis CBC

Anemia
increased MCV
normal MCH
decreased MCHC

hereditary stomatocytosis differential

stomatocytes, macrocytes

hereditary stomatocytosis laboratory findings

increased RBC sodium and decreased potassium
increased osmotic fragility

hereditary stomatocytosis treatment

splenectomy

hereditary stomatocytosis prognosis

generally good depending on severity

autosomal dominant

hereditary xerocytosis mode of inheritance

hereditary xerocytosis membrane defect

sodium/potassium pump defect
increased permeability to Na+ and Increased K+ → loss of water → dehydration → RBC shrinkage → RES sequestration (not spleed) → hemolysis

hereditary xerocytosis clinical features

mild anemia

hereditary xerocytosis CBC

mild anemia
normal MCV, MCH, MCHC

hereditary xerocytosis differential

blister cells (increased surface:volume ratio), target cells
bone marrow response (increased poly, NRBC and retics)

hereditary xerocytosis laboratory findings

decreased osmotic fragility
increased RBC potassium

hereditary xerocytosis treatment

transfussions as necessary
splenectomy is nto beneficial
icreased risk of thromboemobilsm

hereditary xerocytosis prognosis

good, depending of severity

X linked incomplete dominant

G-6-DP Deficiency mode of inheritance

Gd B+

G-6-DP Deficiency genotype
normal

Gd A+

G-6-DP Deficiency genotype
african

Gd A-

G-6-DP Deficiency genotype
all blacks

Gd Met

G-6-DP Deficiency genotype
mediterranean

Gd Canton

G-6-DP Deficiency genotype
Asian

G-6-DP Deficiency

asymptomatic till trigger

G-6-DP Deficiency clinical features

sudden and severe hemolytic crisis
Jaundice, Malaise, Back pain, hemoglobinuria

G-6-DP Deficiency CBC

normo/normo anemia

G-6-DP Deficiency differential

schistocytes
poly/retics/NRBC
bite cells or helmet cells

G-6-DP Deficiency laboratory findings

Heinz bodies
hemoglobinuria
chemistry testing (increased bilirubin and LD with decreased haptoglobin)

Methemoglobin reductase test

G-6-DP Deficiency
MetHb + RBC + Methylene blue
MB activated G6PD → reverses metHb → color change
G6PD deficiency = no color change from brown to red

acorbate cyanide test

G-6-DP Deficiency
ascorbate/cyanide + RBC → denatures Hb → heinz
G6PD prevents denaturation
G6PD deficiency = Heinz body formation

Fluorescent Spot test

G-6-DP Deficiency
G6P + NADP + Saponin + blood → NADPH
increased fluoresence
G6PD deficiency - reduced fluoresence

G-6-DP Deficiency Treatment

remove cause
transfusions if severe

G-6-DP Deficiency prognosis

good if patients avoid triggers

Autosomal recessive

Pyruvate Kinase Deficiency mode of inheritance

Pyruvate Kinase Deficiency pathogenesis

decreased ATP → membrane instability

Pyruvate Kinase Deficiency clinical features

varying severity depending on mutation
splenomegaly
jaundice

Pyruvate Kinase Deficiency CBC

Normo/normo anemia 

Pyruvate Kinase Deficiency differential

retics, no heinz bodies

Pyruvate Kinase Deficiency chemistry

increased bilirubin and LD, decreased haptoglobin and hemoglobinuria

Pyruvate Kinase Deficiency orocresyl Rest test

as lactate is produced → decreased ph → Red → yellow

Pyruvate Kinase Deficiency treatment

blood transfusions as needed
splenectomy in severe cases

Pyruvate Kinase Deficiency prognosis

generally good depending on prognosis