S18C231 - Sickle Cell Disease and Other hereditary hemolytic anemias

Question 1

Life span of a sickle cell

Answer 1

20 days

Question 2

Sickle cell abnormal shape

Answer 2

-distorted sickle cell increases viscosity of blood leading to obstruction w/in microvasculature causing tissue ischemia

Question 3

Sickle cell trait

Answer 3

• heterozygous, one normal beta-globin chain and one sickle mutation gene
• normal life span
• usually asymptomatic
• increased risk of renal medullary carcinoma, hematuria, renal papillary necrosis, hyposthenuria, splenic infarcts, exercise related deaths
• probable risk for: VTE, pregnancy complications, complicated hyphema
• possible risk for: retinopathy, ACS, asymptomatic bacteria

Question 4

SCD: ED presentation

Answer 4

• vaso-occlusive crisis
• stroke
• aplastic crisis
• Acute chest syndrome
• sepsis

Question 5

SCD: vaso-occlusive pain crisis

Answer 5

• painful sickle cell crisis
• stressors: infxn, cold, dehydration, altitude
• intravascular sickling leads to : infarction of bone, viscera, soft tissues
• have diffuse bone, muscle, joint pain
• mgmt: pain control, hydration
• can be common to have a low-grade temp and icnreased WBC (however >20 would be abnormal and infxn should be considered)
• hydroxyurea reduces frequency and severity of painful crises by increasing production of HbF which are protective against sickling
• daily prophylactic Pen V reduces infxn in children, not as much benefit in adults
• admit if WBC >30, platelets

Question 6

SCD: bone pain

Answer 6

• usually in back and extremities
• should be no physical findings unless infxn present
• 30% of SCD pts develop femoral head damage, be aware of aseptic necrosis
• young children can get dactylitis (hand foot syndrome), fever and painful swelling of hands/feet

Question 7

SCD: Acute chest syndrome

Answer 7

• defn: new infiltrate on CXR + one of fever (>38.5), cough, wheeze, tachypnea, chest pain
• usually 2-4yo, declines wtih age
• common precipitants: infxn, fat emobli, rib infarction, VTE
• aggressive hydration for SC crisis can lead to pulm edema
• tx: oxygen, analgesia, Abx, bronchodilators, exchange tvn, hydration
• give abx irrespective of cultures
• exchange tfn for PaO2

Question 8

SCD: Abdominal crisis

Answer 8

• should not have peritonitis
• hepatic infarct will cause jaundice
• biliary dz common b/c pigment related choletlithiasis is seenin 40-70% of SCD pts

Question 9

SCD: GU

Answer 9

• vaso-occlusive events of kidney can occur but often are asymptomatic
• may have flank pain, renal colic, CVA tender
• papillary necrosis may cause gross or micro-hematuria but rarely RBC casts
• renal medulla infarction and papillary necrosis are treated with IV fluids
• priaprism occurs in 30% of males, tx with hydration, analgesia, tfn
• UTI are common

Question 10

SCD: splenic infarct

Answer 10

• microinfarcts lead to a non-functional spleen
• risk of infxn from encapsulated organisms
• immunization, and PCN are important

Question 11

SCD: splenic sequestration

Answer 11

• sudden enlargement of spleen with drop in Hb
• Sx: tachy, HoTN, pallor, lethargy, may have LUQ pain, enlarged firm spleen
• platelets are also sequestered
• reticulocyte coutn remains elevated
• tx: volume restriction to mobilize RBC trapped in spleen, RBC tfn, exchange tfn, rarely splenectomy

Question 12

SCD: hemolytic anemia

Answer 12

• baseline hb often 60-90 with retic count 5-15%
• will drop further with infxn
• fatigue pallor and scleral icterus

Question 13

SCD: Aplastic crisis

Answer 13

• occurs when production of RBCs declines significantly producing rapid drop in Hb level with reticulocytopenia
• cause: infxn esp parvovirus
• more common in children
• will have increased fatigue and pallor with no evidence of increased hemolysis
• retic

Question 14

SCD: infections

Answer 14

• functionally asplenic after early childhood

- risk of encapsulated organisms: h flu, strep pneumo

Question 15

Thalassemia

Answer 15

• defect in globin chains resulting in inabililty to produce normal adult Hb
• microcytic, hypochromic hemolytic anemia
• mediterranean, middle eastern, african, southeat asian descent
• protective against malaria?
• alpha-thalassemia have excess beta-globin chains that accumulate and cuase increased cell destruction
• beta-thalassemia have decreased production of beta-globin resulting in ealry cell death, have decreased Hb

Question 16

alpha-thalassemia carrier and trait

Answer 16

• no clinical symptoms or physical findings

- trait is detected by finding microcytic RBC and a normal Hb level

Question 17

hemoglobin H disease

Answer 17

• one alpha-globin chain gene is still functional
• presents in neonates as severe hypochromic anemia
• hypochromic, microcytic anemia with jaundice and hepatosplenomegaly
• may require transfusion when under stress (infxn)

Question 18

beta-thalassemia minor (trait)

Answer 18

• heterozygous for beta-globin mutation
• mild microcytic anemia
• may have splenomegaly
• smear: microcytosis, hypochromia, basophilic stippling
• elevated HbA2 level confirms dx

Question 19

beta-thal major (cooley anemia)

Answer 19

• both beta-globin genes are defective
• newborns are well b/c of HbG
• sx occur at 6mo when HbF decreases
• HSM, jaundice, osteoporosis, increased infxns
• severe anemia, regular blood TFNs leading to iron overload
• low MCV, microcytic, hypochromic cells, incrased RDW

Question 20

all 4 alpha-globin mutations?

Answer 20

-incompatible with life

Question 21

G6PD deficiency

Answer 21

• risk: african, asian, mediterranean
• x-linked (mostly affects males)
• spectrum from asymptomatic to chronic hemolysis
• Hb precipitates in cells, seen as Heinz bodies
• class I-V, most G6PD variants have self-limited hemolytic events
• many will not know they have the mutation
• precipitants: favism, drugs, infxn
• may present as neonatal jaundice in 1st wk of life, bilirubin can cause kernicterus
• drugs to avoid: sulfonamides, cipro, chloramphenical, vit K analgogues, antimalarials, macrobid

Question 22

hereditary spherocytosis

Answer 22

• inherited in autosomal dominant, 20% will be spontaneous
• mild-severe dz
• complications: aplastic or megaloblastic crises, hemolytic crisis, cholecystitis/cholelithiasis, neonatal hemolysis with jaundice
• moderate dz: mild anemia, modest splenomegaly, periodic hemolysis with jaundice, gallstones
• severe dz: blood tfn, chronic jaundice, enlarged spleen
• tx: splenectomy can reverse most anemia except in rare cases, TFNs