Sickle Cell Disease and Complications

AJ Winer

Sickle Cell Anemia – the Basics 

  • Pathogenesis: Recessive mutation in β-globulin of hemoglobin => substitution of Val for Glu => structurally abnormal Hgb (HbS).
  • Homozygosity for HbS (Hb SS) is the classic form of sickle cell disease, but compound heterozygosity with other pathogenic beta globulin (HbSC, HbS Beta0-thal, HbS Beta+- thal)
  • Epidemiology:
    • Often linked to Sub-Saharan Africa, but also in other regions with high malaria burden (Central/South America, Caribbean, Middle East, Mediterranean, India)
    • 8% of African Americans are heterozygotes (“sickle trait”)
    • ~1/400 of African Americans are homozygotes (sickle cell disease)
  • Pathogenesis of sickling: Decreased O2 => HbS polymerization => RBC sickling & decreased RBC deformability => hemolysis and microvascular occlusion
  • Most common complications of SCD: acute chest syndrome, CVA, VTE (DVT, PE), pain crisis, ARF, sickle cell nephropathy, renal papillary necrosis, acute on chronic anemia, avascular necrosis, priapism, PH, hepatobiliary complications
  • Diagnosis: Anemia on CBC, Hgb electrophoresis, periph blood smear

Evaluation

  • Labs: LDH (high), Hgb/Hct (low; check vs baseline), retic, smear, WBC - If febrile: UA + Blood cultures
  • Send Hgb S level, and compare to baseline w/ other hospital admissions
  • Imaging: CXR, MRI for hip pain, Abdominal U/S or CT abdomen
  • Maintain active type and cross given probability of antibodies

Management

  • Health Maintenance:
    • BP goal <130/80 o consider hydroxyurea (reduces pain crises and ACS, improves QOL)
    • proteinuria screens (for Sickle cell nephropathy), screen for s/s of respiratory symptoms (PH)
    • Ensure uptodate on asplenia vaccinations: (SHiN) strep pneumo, H Flu, N meningitidis, COVID, flu
  • See table below for specific pathways for most common complications
  • General management plans for almost all patients:
    • O2:
      • maintain high O2 goals (goal sat ~95% (higher O2 goal will help to prevent further sickling!)
  • Anemia:
    • Transfuse:
    • If Hgb <10, simple transfusion is appropriate to goal >10 (no higher than 11 due to risk of hyperviscosity)
      • Avoid transfusions when able, given risk of antibody formation
      • Order RBC extended phenotype for minor RBC antigens to avoid immunization and Ab development to these proteins
      • Match for Rh and K antigens
      • Maintain low HbS% to reduce stroke
  • Continue folic acid 1 mg qDay
  • Continue hydroxyurea if uncomplicated pain crisis
    • Hold if counts suppressed or concern for infection
  • Pain: Aggressively treat pain
    • Look for a care coordination yellow note in the Summary Tab; (heme clinic will have specific management preferences for individual patients)
    • Will generally require opiates, likely initiation of PCA
    • All SS patients should have pain plans; inpatient pain plans are in the problem list under sickle cell disease or in the care coordination section of Epic
    • Outpatient plans (to which you will transition pts back prior to discharge) are not standardized in location, but can be under Media (with a pain contract) or found in notes *Recommendations by ASH (2019)

Complication

Signs/Sx

Pathogenesis

Workup

Management
Acute Chest Syndrome (PNA, intrapulm onary sickling, pulmonary fat embolism) ACS = new radiodensity on chest imaging AND either fever +/- respiratory symptoms (hypoxia, tachypnea, cough, chest pain) - of note, infiltrate on CXR may initially be negative, absence does not eliminate possibility Vaso-occlusion in pulmonary microvasculature. Precipitants: infection (PNA - chlamydia, bacteria, mycoplasma), pulmonary infarction, PE, fat embolism, and pain crisis => deoxygenation => sickling => vaso-oclusion CBC, CXR, assess pain, examine for bone pain in back or chest, assess for s/s DVT, assess for indwelling catheter
Other: consider CTAPE, ECG
  1. C/s heme
  2. Supplemental O2 (>95%)
  3. D5 ½ NS @ 150-250cc/hr (caution to avoid pulmonary edema)
  4. Transfuse to Hgb 10
  5. Pain control: see pt’s pain plan, consider PCA
  6. Immediate Abx – CAP coverage (vs HAP if risk factors) [3rd gen cephalosporin + macrolide]
TIA Or Stroke Focal seizures, hemiparesis, speech deficit, any new neurologic insult Chronic vasooclusion => endothelial damage => Intimal hyperplasia => vascular stenosis + occlusion of vasculature by sickle cells. Vascular + oxidative injury => activation of coagulation cascade.
*O2 delivery to the brain is dependent on total Hgb concentration and % of HbS (transfusion goal of Hgb 10, HbS 15-20%)
  1. STAT non-con CTH to assess for hemorrhag e vs moyamoy a vasculopat hy vs LVO
  2. CBC
  3. MRI
 Sx onset <4-5h:
  1. Prompt blood transfusion (simple, exchange, or apheresis) within 2 hours*. If Hgb <8.5, simple transfusion to goal >10 (followed by apheresis). If Hgb >8.5, consider apheresis (decrease possibility of hyperviscosity syndrome*)
  2. If hemorrhage on CTH => c/s heme and NSG
  3. If no moyamoya vasculopathy, but LVO present => eval for thrombectomy + simple transfusion to achieve Hgb 10, exchange transfusion to reach Hgb S level 15-20%*
  4. If moyamoya vasculopathy, simple transfusion to achieve Hgb 10, exchange transfusion to reach Hgb S level 15-20%* For 24-72H onset: O2, transfuse for Hgb >10 and exchange transfusion for Hb S 15-20%
Aplastic crisis Sx: Dyspnea, weakness, fatigue Signs: tachycardia, pallor, acute drop in Hgb low reticulocyte count, nonpalpable spleen, functional systolic murmur Parvovirus B19 infection => transient arrest of erythropoiesis (lasts 2-14 days) Trend CBC (often <6) and reticulocyt e count (often <1.0%)
  1. C/s benign heme
  2. Blood transfusion
Splenic sequestrat ion crisis LUQ pain, hypotension, acute-onset severe hemolytic anemia Occlusion of splenic vessels => pooling of RBC within spleen Reticulocy te count (high vs in aplastic crisis would be low)
  1. C/s benign heme
  2. IVF
  3. Consider simple blood transfusion
Pain crisis/vaso-occlusive Crisis Typically acute, localized, severe pain, can be gradual Triggers: stress, exposure to cold, infectious illness VS, CBC, is pain typical or in new area, CXR Rule out can’t miss diagnoses (acute chest, multiorgan failure, CVA, PE)
  1. 1.Aggressive, prompt pain mx: opioids, NSAIDs (reference pain plan in EPIC)
  2. Encourage PO intake, if cannot consider IVF
  3. supplemental O2
  4. consider transfusion if Hgb drop >2 and low RC
Osteonecr osis/Avasc ular necrosis (most often hip, sometimes shoulder) Chronic groin/hip/buttock/thigh pain with weight bearing that progresses to occurring at rest Sickling => disruption of bone microcirculation and increased intraosseous pressure due to bone marrow hyperplasia => end artery occlusion => necrosis PEx: pain and limited ROM with internal rotation and abduction of hip Labs: normal WBC ct, ESR, CRP Imaging: Xray (may appear normal early on), MRI
  1. Pain control
  2. Consider outpatient ortho referral
  3. hydroxyurea if not already on
Osteomyelitis Fever, leg pain (often in pt w hx of bone infarction, avascular necrosis, or gastroenteritis) Low blood flow => microinfarctions => nidus for infection Asplenia => staph aureus and salmonella CBC, CT/MRI, blood/bone cultures
  1. Cultures
  2. Antistaph therapy + 3rd-gen cephalosporin for salmonella coverage
Splenic infarct Acute LUQ pain Stressor (high altitude, hypoxia, dehydration) => splenic artery occlusion CBC, Retic Ct, Tbili and DBili Abdomina l U/S
  1. Hydration, supplemental 2, analgesia
  2. Consider future splenectomy (may recur), monitor for development of splenic abscess
Priapism Sustained unwanted painful erection lasting >4 hours Most often due to low-flow priapism (thought due to sickling of RBCs in venous sinuses => high pressure and prevention of outflow) History (precipitati ng factors: dehydratio n or medicatio ns), Physical exam, CBC and retic count, possible duplex U/S
  1. emergent urology c/s for sympathomimeti c injection vs aspiration vs shunt
  2. analgesia
  3. IVF if dehydrated, O2 if hypoxic
  4. Hydroxyurea outpatient
Renal papillary necrosis Macroscopic hematuria +/- flank pain Often patient has sickle cell nephropathy Decreased O2 in renal medulla => sickling => RPN => hematuria U/A with microscopy, Creatinine, renal imaging
  1. microscopic hematuria => hydration
  2. Macroscopic hematuria – bedrest and aggressive hydration
  3. consider exchange blood tx to lower %HbS
  4. Outpatient start hydroxyurea for SCN (reduce proteinuria, delay/prevent CKD)

Sickle Cell Pain Crisis

Background

  • Present with severe pain in bone, joints, chest, abdomen
  • Causes: (HIDISC) Hypoxia, Ischemia, Dehydration, Infection, Stress, Cold
  • Can’t miss:
    • Acute chest: new infiltrate on CXR + another clinical symptom (fever, chest pain, hypoxia). Consult Benign Hematology immediately. Do not wait until the next day.
    • PE (ACS less likely in these pts), avascular necrosis of hip, priapism, stroke

Evaluation

  • Labs: ↑ LDH, Hgb/Hct (low; check versus baseline), retic, smear, WBC
  • If febrile: UA + blood cultures
  • Hgb S level only in certain circumstances (e.g. guides treatment in acute chest)
  • Imaging: CXR, MRI for hip pain, abdominal U/S or CT abdomen
  • Maintain active type and cross given probability of alloimmunization

Management

  • General
    • Look for a care coordination yellow note in the Summary Tab
      • Heme clinic will have specific management preferences for individual pts
    • Maintain hydration, IVF at 150-200 cc/hr (if no contraindication)
    • Oxygen: goal sat ~95% (higher O2 goal will help to prevent further sickling)
    • Continue folic acid 1 mg QD o Continue hydroxyurea if uncomplicated pain crisis
      • Hold if counts suppressed or concern for infection
    • If in the MICU: consider discussion for plasma exchange (if Hgb SS or SC or S-Thal)
    • Transfuse: Simple transfusion if Hgb lower than baseline and/or complications
      • Avoid transfusions when able, given risk of antibody formation
  • Pain
    • Will generally require opiates, often initiation of PCA
    • All SS pts should have pain plans. Inpt pain plans are in the problem list under sickle cell disease or in the care coordination section of Epic
    • Outpt plans (to which you will transition pts back prior to discharge) are not standardized in location, but can be under Media (with a pain contract) or found in notes
  • Acute chest:
    • Consult Hematology at time of admission
    • Obtain HbS level
    • Avoid dehydration. Consider LR @ 125-200 cc/hr but caution with overhydration (may worsen pulmonary edema)
    • Incentive spirometry: atelectasis and hypoxia drive V/Q mismatching and further sickling
    • Transfuse hgb to goal of 10 (do not exceed to avoid hyperviscosity)
    • Pain control per pain plan
    • Consider Abx for CAP (vs HAP if risk factors)
    • Plasma exchange for moderate-severe cases (driven by hematology)
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