Sickle Cell Disease

Vaso-occlusive pain crisis, acute chest syndrome, and severe anemia — the most common life-threatening complications of SCD

Symptoms / Associated Sx

  • Vaso-occlusive crisis (VOC): Severe bone pain (long bones, back, chest, abdomen); bilateral symmetry; acute onset; no fever typically unless infection

  • Acute chest syndrome (ACS): New pulmonary infiltrate + fever + respiratory symptoms (cough, chest pain, hypoxia) — most common cause of death in SCD

  • Severe anemia: Acute fatigue, pallor, tachycardia (aplastic crisis — parvovirus B19; splenic sequestration crisis)

  • Jaundice (chronic hemolysis); splenomegaly in young children; functional asplenia in adults

  • Priapism (prolonged painful erection >4h — urologic emergency)

Denies

  • Prior episodes with different character (any atypical features warrant additional workup)

  • Fever without pain (raises infection as primary diagnosis — SCD patients are functionally asplenic)

  • Productive cough + fever without new infiltrate (rules out ACS — requires new chest X-ray finding)

  • Bilateral lower extremity edema (rules out DVT — though SCD patients have elevated DVT risk)

Social History (SHx)

Known SCD genotype (HbSS most severe; HbSC milder; HbS-β thalassemia), baseline Hgb and Hct, frequency of prior crises and hospitalizations, prior transfusions and alloimmunization history, hydroxyurea compliance, penicillin prophylaxis, vaccination history (asplenic), prior ACS, stroke, or priapism.

Main Etiology

  • HbS polymerization under deoxygenation → sickling → microvascular occlusion → ischemia and pain

  • VOC triggers: cold, dehydration, infection, stress, hypoxia, high altitude, alcohol

  • ACS triggers: fat embolism from bone marrow (during VOC), infection (S. pneumoniae, Mycoplasma, Chlamydia, viral), pulmonary sequestration

  • Aplastic crisis: parvovirus B19 infection (transient arrest of erythropoiesis)

  • Splenic sequestration: acute trapping of blood in spleen → acute anemia; usually in children

Most Common DDx

  • Infection / sepsis (SCD patients are functionally asplenic → encapsulated organism sepsis: S. pneumoniae, H. influenzae, N. meningitidis — fever in SCD = infection until proven otherwise; blood cultures + broad antibiotics)

  • Pneumonia (ACS mimic — new infiltrate + fever + cough; often indistinguishable from ACS; treat both simultaneously)

  • Pulmonary embolism (SCD patients have elevated VTE risk; dyspnea + hypoxia + pleuritic pain without infiltrate; CTPA if ACS not confirmed by CXR)

  • Acute abdomen — cholecystitis, appendicitis (SCD patients develop gallstones from chronic hemolysis; abdominal pain can be VOC or surgical — differentiate with ultrasound, CT, serial exams)

  • Acute stroke (SCD patients have elevated stroke risk — ischemic stroke; sudden neurologic deficits; CT head + MRI brain; exchange transfusion urgently)

  • Aplastic crisis from parvovirus B19 (acute Hgb drop without reticulocytosis; parvovirus B19 IgM positive; bone marrow recovery after 7–10 days; transfusion supportive)

DATA

  • CBC with differential (Hgb vs. baseline — compare to patient's known baseline; reticulocyte count)

  • Reticulocyte count (low in aplastic crisis; elevated in hemolytic crisis)

  • BMP (creatinine — SCD nephropathy common; electrolytes)

  • LFTs (hepatic sickling, sickle cell intrahepatic cholestasis, cholelithiasis)

  • LDH, indirect bilirubin, haptoglobin (hemolysis markers)

  • Blood cultures × 2 (fever in asplenic patient = sepsis workup mandatory)

  • UA + urine culture (papillary necrosis, UTI common)

  • CXR (new infiltrate → ACS; must compare to prior; obtain on admission for any respiratory or chest symptoms)

  • ABG or pulse oximetry (ACS — hypoxia assessment)

  • Type and screen (transfusion readiness; alloimmunization history critical)

  • Parvovirus B19 IgM (if aplastic crisis suspected — low Hgb + very low reticulocytes)

  • HbS/HbF% (if hydroxyurea patient — monitor HbF level)

Home Meds

  • Hydroxyurea (assess dose and compliance — increases HbF, reduces sickling frequency; continue)

  • Penicillin VK or amoxicillin prophylaxis (asplenic — ensure compliance; continue)

  • Folate 1 mg PO daily (continue — high turnover state)

  • Iron chelation (if on chronic transfusion program with iron overload)

  • Opioid regimen (assess baseline home opioid doses — essential for appropriate dosing in crisis)

Plan

  • Vaso-occlusive crisis (VOC):

    • IV fluids: D5 ½NS at 1–1.5× maintenance (avoid aggressive saline — promotes sickling; glucose helps)

    • Opioid analgesia: individualize based on patient's baseline regimen — hydromorphone 0.2–0.4 mg IV q3–4h PRN or PCA; morphine 0.1 mg/kg IV q3–4h; reassess pain q30–60 min

    • DO NOT under-dose opioids — pain crises are severe; undertreated pain is a major issue in SCD

    • NSAIDs: ketorolac 15–30 mg IV q6h × 5 days (useful adjunct if no renal contraindication)

    • Incentive spirometry (prevents hypoventilation → ACS)

    • Supplemental O2 only if hypoxic (SpO2 <95%)

    • Antihistamines (Benadryl) if opioid-induced pruritus; avoid in high doses (sedation)

  • Acute chest syndrome (ACS) — medical emergency:

    • Supplemental O2 to maintain SpO2 ≥95%; escalate to non-invasive ventilation or intubation if needed

    • Bronchodilators: albuterol nebulizer q4–6h (bronchospasm common)

    • Antibiotics (cover typical + atypical pulmonary pathogens): Ceftriaxone 1 g IV daily + Azithromycin 500 mg IV daily

    • Simple transfusion (Hgb <9 or mild ACS): transfuse to Hgb ~10 g/dL; match phenotypically to reduce alloimmunization

    • Exchange transfusion (severe ACS — rapidly worsening, Hgb ≥9, bilateral infiltrates, ICU): reduce HbS% to <30%; hematology + apheresis

    • Incentive spirometry; aggressive pain control (splinting → hypoventilation → ACS progression)

    • ICU if O2 requirement escalating or hemodynamically unstable

  • Severe anemia (aplastic or sequestration crisis):

    • Transfusion: pRBCs phenotypically matched; goal Hgb ~10 (aplastic) or raise to baseline +2 g/dL (sequestration)

    • Parvovirus B19 isolation precautions (aplastic crisis — immunocompromised contacts at risk)

  • Priapism (>4h): Urologic emergency — IV hydration + analgesia + aspiration/irrigation by urology; exchange transfusion if unresponsive; NOT ice or compression

  • Continue hydroxyurea throughout admission; do not hold

  • Continue folic acid; penicillin prophylaxis

  • Hematology consult for ACS, exchange transfusion decisions, or severe/refractory VOC

  • Trend CBC q12–24h; BMP; reticulocytes; LDH; CXR if ACS

  • PT/OT; incentive spirometry; ambulation when able

  • Discharge: Resume hydroxyurea; ensure adequate home analgesic plan; penicillin prophylaxis; folic acid; outpatient hematology within 1–2 weeks; ensure vaccinations current (pneumococcal, meningococcal, Hib, influenza); hydroxyurea dose optimization discussion

Red Flags

  • Fever in SCD = sepsis emergency → blood cultures + broad antibiotics immediately (ceftriaxone); do not delay for workup

  • ACS with O2 sat <90% or bilateral infiltrates → exchange transfusion urgently + ICU

  • Acute neurologic deficits (stroke) → CT head → MRI → exchange transfusion to HbS% <30% urgently; stroke team

  • Priapism >4h → urologic emergency → aspiration/irrigation; irreversible erectile dysfunction if untreated

  • Hgb acutely <5 or drop >2 below baseline → aplastic or sequestration crisis → transfuse phenotypically matched pRBCs immediately

Senior IM Resident Pearls

  • ACS is the leading cause of death in SCD — can develop during or after VOC due to hypoventilation from pain; incentive spirometry and adequate pain control are preventive

  • Hydroxyurea increases HbF production → reduces sickling frequency and severity; reduces ACS rate by ~50%, hospitalization rate, and mortality; compliance is the most modifiable factor

  • Phenotypic matching of transfused pRBCs (C, E, Kell antigens at minimum) reduces alloimmunization — critical because SCD patients receive many transfusions over their lifetime

  • Functional asplenia begins in the first years of life in HbSS — adults have NO spleen function; S. pneumoniae sepsis can be fulminant within hours; prophylactic penicillin and pneumococcal vaccination are life-saving

  • Common mistake: Under-treating pain in VOC — institutional opioid hesitancy leads to undertreated pain; patients often know their own pain regimen; use PCA and patient-reported outcomes

  • Common mistake: Stopping hydroxyurea during admission — continue throughout hospitalization; abrupt discontinuation worsens disease

Labs

  • CBC with differential

  • Reticulocyte count

  • CMP

  • Mg, Phos

  • LDH

  • Total/direct bilirubin

  • Haptoglobin

  • Type & Screen

  • HbS%

If Fever

  • Blood cultures x2

  • UA

  • Urine culture

  • RVP/COVID/Flu

Trending

  • CBC q12–24h

  • Retic daily

  • CMP daily

  • LDH daily

  • Bilirubin daily

Imaging

  • CXR on admission

  • Repeat CXR PRN for ACS

  • CT PE if PE suspected

  • CT head ± MRI brain if neurologic deficits

Meds – VOC

  • D5½NS 75–125 mL/hr (or 1–1.5× maintenance)

  • Hydromorphone 0.2–0.4 mg IV q3–4h PRN
    OR

  • Morphine 0.1 mg/kg IV q3–4h PRN

  • Ketorolac 15–30 mg IV q6h × 5 days

  • Ondansetron 4 mg IV/PO q6h PRN

  • Diphenhydramine 25 mg IV/PO q6h PRN

  • O₂ only if hypoxic (goal SpO₂ ≥95%)

Meds – ACS

  • Ceftriaxone 1 g IV q24h

  • Azithromycin 500 mg IV/PO daily

  • Albuterol neb q4–6h PRN

  • O₂ to maintain SpO₂ ≥95%

Blood Products

  • pRBC transfusion if symptomatic, Hgb <7, ACS, or acute drop >2 below baseline

  • Goal Hgb ~10

  • Exchange transfusion for severe ACS, stroke, worsening hypoxia, MOF

Consults

  • Hematology

  • ICU (if severe ACS)

  • Apheresis/Transfusion Medicine

  • Urology (priapism >4 hr)

  • Neurology/Stroke Team (neurologic deficits)

Monitoring

  • Telemetry

  • Continuous pulse ox

  • Strict I&O

  • Daily weights

  • Incentive spirometry q2h while awake

  • Ambulate TID

VTE Prophylaxis

  • Enoxaparin 40 mg SQ daily
    OR

  • Heparin 5000 units SQ q8h

Therapy

  • PT/OT eval and treat

  • RT for pulmonary hygiene

Discharge

  • Pain controlled on PO regimen

  • No oxygen requirement

  • Stable Hgb

  • Continue hydroxyurea

  • Folic acid 1 mg daily

  • Hematology follow-up 1–2 weeks

Red Flags

  • Fever → cultures + ceftriaxone immediately

  • ACS + worsening hypoxia → exchange transfusion

  • Stroke symptoms → exchange transfusion emergently

  • Priapism >4 hr → Urology STAT

  • Do not stop hydroxyurea