Sickle cell anemia

Blood film showing many features of SCD: sickles (blue arrow), Howel-Jolly body (black arrow), targets (red arrow), and nucleated RBC (top left)





Today we discussed sickle cell anemia. Some important points:

Pathophysiology is point mutation on Beta globin gene. Results in Hb polymerization and rigid, elongated RBC.

Sickling is promoted by hypoxia, low temp, low pH, volume depletion.

Notes on diagnosis:
1) Hemoglobin electrophoresis- shows 40% HbS in carriers (~60-40 split), and 90%+ HbS in homozygotes.
2) "Sickledex" screening test does not distinguish carriers vs. homozygotes vs hemoglobin SC. Looks for presence of sickling on hypoxic conditions.
3) Blood film will often show no sickles in carriers, but there should always be some sickles in SS. If you see predominantly targets, ddx includes hyposplenism and SC disease (shows almost all targets)

Heterozygotes are usually asymptomatic, with occasional sickles on PBF, but normal Hb levels.

Homozygotes have moderate to severe hemolytic anemia, and have crises and complications

Crises and complications:

Vaso-occlusive crisis: in bone, muscle (very painful). Also at increased risk for stroke even in children (on ddx of stroke in young). May develop 'Moya Moya' (hypervascularity from chronic hypoxia- increased hemorrhage risk)
Resp- chest crisis- defined by infiltrates and hypoxemia (not due to CHF).
Renal- hematuria, tubular defects (acidic, hypoxic environment causes sickling).
Marrow- aplastic crisis- Keep close eye on Hgb in patients with low retics (can drop rapidly) Pts may get parvo and have severe aplastic crisis (can't keep up with increased baseline demand).
ID- hyposplenic- susceptible to encapsulated microorganisms. Risk of osteomyelitis (esp with Salmonella)
Others: priapism, retinopathy/retinal occlusion, leg ulcers

Crisis management:
1) O2 whether hypoxemic or not
2) Fluids
3) Correct precipitating factor (infection, volume depletion, etc)
4) Analgesia
5) Consider transfusion strategy

Transfusions in SCD:
In general be sparing with transfusions because these patients develop antibodies and it's difficult to find units when really needed. Fe overload is also a problem with frequent "sub-necessary" transfusions. Simple pain crisis does not require a transfusion.

Conventional transfusion guidelines:
-aplastic crisis (i.e. below baseline hgb with low or inappropriately normal retics)
-Hb below 50 (may accept lower than usual because baseline may be low)
-active bleeding, etc
STOP TRANSFUSING WHEN hematocrit >0.35 (hyperviscosity and stroke risk)

When to exchange transfuse (i.e. ~14 units exchange)

1) Chest crisis (FiO2 over 40%, infiltrate, no pulmonary edema)
2) Stroke (ischemic or hemorrhagic)
3) Pre-operatively for major surgery to HGB S below 30%
4) Severe sepsis, multiorgan failure
5) Retinal occlusion
6) Fetal distress
7) Priapism (relative indication)

Hydroxyurea in sickle cell disease

Adults with 3 or more painful crises/year; increases proportion of HbF
reduces frequency of painful crises and chest crises. Also mortality benefit (secondary outcome).
Need to monitor hepatic fcn and counts carefully.


References:

Click here for BMJ review of sickle cell disease management

Click here for NEJM review of hydroxyurea in SS disease