Sickle Cell

Phenotypes

2 Main and Overlapping Phenotypes:

  • Vaso-occlusive – Presents w/ pain, higher resting Hgb, at risk for acute chest
  • Hemolytic –  Lower resting Hgb (5-6). Less pain crises but anemia leads to risk of pulmonary HTN, leg ulcers, sudden death

Pathophys of Vaso-occlusion

2 Problems:

  • “Sticky Blood” – Activation of thrombotic, platelet and inflammatory cascades
  • Endothelial dysfunction – Free Hgb scavenges NO and leads to inability of capillaries to dilate

Vaso-occlusive Crisis

  • No objective evidence of acute pain crises
  • No need to oxygen unless SpO2<92% (hyperoxia doesn’t actually help and may cause bone marrow suppression)
  • Dehydration may precipitate crisis but no evidence volume repletion reverses it – avoid excess isotonic fluids d/t risk for atx->ACS
  • Fluid resus per usual if needed, then D51/2NS maintenance for hypotonic fluid (theoretic benefit)
  • Aggressive opioid titration
  • Avoid NSAIDS b/c pts are at high risk for occult renal dysfunction

 

Acute Chest Syndrome

  • Pulmonary infiltrate and sxs of PNA in pt w/ sickle cell
  • Should be considered ACS if 2 of these 5:
    • 1. CP
    • 2. Fever >38.5
    • 3. Infiltrate
    • 4. Infiltrate
    • 5. Resp sxs or hypoxia
  • Unknown underlying pathophysiology (not necessarily infxn – could be fat embolism, pulm infarction, sickle crisis in lung parenchyma); leading cause of death for adults w/ sickle cell
  • Tx:
    • Pain control and IS to decr. splinting
    • antibiotics (e.g ceftri + azithro), supportive care, NEED EXCHANGE TRANSFUSION
  • Exchange transfusion: remove pts Hgb, transfuse non-sickle donor RBC’s w/ goal to get HbS ~30%
  • Simple transfusion less ideal d/t elevated Hb->increased viscocity->CVA
  • Can gently do simple transfusion if exchange is unavailable and Hgb < 10

 

Anemia in Sickle Cell

Defined as DROP from baseline Hgb

Consider same etiologies as for any anemic pt (e.g blood loss, IDA, folate/B12 etc.) PLUS:

  • Hemolytic crisis
  • Splenic Sequestration
  • Transient Red Cell Aplasia

W/u: CBC, retic count, LFTs

Preferable to transfuse cross-matched, leukocyte depleted, irradiated RBCs but do not delay in case of sequestration crisis

Splenic Sequestration

  • Most sickle pts infarct their spleen by puberty but not always so both children and adults are at risk
  • 2 Phases of Disease course
    • Acute – Essentially hemorrhaging to death into spleen; acute onset and critically ill
    • Remobilization – sequestered blood remobilizes causing hyperviscosity and stroke risk
  • Dx:
    • Elevated retic (eg 5-12)
    • Enlarged spleen
    • Without markers of accelerated hemolysis that would suggest this is a hemolytic crisis (eg AST, indirect bili, LDH that are increased from baseline)
  • Acute phase tx:
    • Transfuse first and ask questions later – at least 2 units to start regardless of their hemoglobin
    • May need splenectomy
    • Admit to ICU

Hemolytic Crisis

  • Generally indolent course d/t increase in baseline hemolysis
  • Can transfuse in ED if needed for symptomatic anemia
  • Otherwise admit for transfusion
  • Often d/t underlying condition e.g. sepsis – need to identify and treat

Transient Red Cell Aplasia

  • Parvovirus infxn stops RBC production for few days, causes anemia in sickle cell pts d/t dependence on rapid RBC turnover
  • Reticulocyte ct of 0 rules in the dx
  • Tx:
    • Droplet isolation (can cause fetal hydrops in pregnant women)
    • Call a hematologist (Tx  will be IVIG)
    • Only need to transfuse if unstable (rare)

Other Sickle Cell Emergencies

Stroke

  • By age 20, 11% have clinically apparent CVA, 20% by MRI
  • Adults: Tx=TPA and maybe exchange transfusion
  • Children: Tx= Emergent Exchange Transfusion!

Hyphema

  • Trauma->hyphema->vaso-occlusion->angle closure glaucoma->vision loss
  • Invisible “micro hyphema” can cause same sequelae
  • Send sickle cell prep in any pt w/ hyphema, maybe any pt w/ significant blunt trauma to eye
  • Check IOP’s in any sickle cell pt w/ ocular trauma
  • Tx:
    • Elevate HOB
    • Consult ophtho
    • BB and clonidine okay
    • No Diamox, diuretics, or topical B-agonists
    • Admit

Priapism

  • ~90% of sickle pts get it by age 20
  • Treatment is slightly dif’t than other priapism:
    • If < 2hrs of sxs – analgesics and IVF
    • If > 2hrs intracavernosal epi or phenylephrine
    • If  >12 hrs or if still symptomatic after initial management next steps are exchange transfusion, epidural anesthesia, shunt w/ urology
  • After detumescence can usually go home after period of ED obs

Fever

  • Impaired antibody production = high encapsulated org infection risk
  • Kids < 5 yo should be on daily PCN
  • Any child w/ fever needs full sepsis w/u, abx (ceftri) and admission
  • Low threshold for similar w/u for adults

Sudden Death after Exercising

  • At risk for sudden death at high altitude or after exhausting exercise
  • Unknown etiology

Complications By Age

Age 0-3 yo

  • Splenomegaly
  • Sequestration
  • Infection
  • Pain

Age 3-20 yo

  • Pain
  • ACS
  • CVA

20-30 yo

  • Pain
  • CKD
  • Osteonecrosis
  • Retinopathy
  • Leg ulcers
  • Pulm HTN
  • CHF
  • CKD
  • Pain