Eduovisual
Blood & Lymphoreticular
Hereditary spherocytosis: diagnosis and management
— Loss of membrane surface area → spheroidal RBCs with reduced deformability → splenic sequestration and extravascular hemolysis.
— Most common inherited hemolytic anemia in people of Northern European descent (~1 in 2,000–5,000).
— Autosomal dominant in ~75% (most often ANK1 ankyrin mutations); ~25% recessive or de novo.
— Severity ranges from asymptomatic compensated hemolysis to transfusion-dependent disease.
— Adult or child with chronic or intermittent jaundice + splenomegaly + anemia and a family history of "anemia," "gallstones at a young age," or splenectomy.
— Incidental MCHC > 36 g/dL with elevated RDW on a routine CBC.
— Neonatal jaundice requiring phototherapy or exchange transfusion, especially with positive family history.
— Pigmented (calcium bilirubinate) gallstones in a young adult — classic stem trigger.
— Sudden severe anemia after a viral illness (parvovirus B19 aplastic crisis) in someone with previously mild compensated hemolysis.
— Membrane instability → vesiculation → ↓ surface-to-volume ratio → spherocytes → spleen culls them → extravascular hemolysis → unconjugated hyperbilirubinemia, ↑ LDH, ↓ haptoglobin, reticulocytosis.
Board pearl: The triad of anemia + jaundice + splenomegaly with a positive family history and spherocytes on smear should make HS your top diagnosis before ordering any confirmatory test. Coombs-negative spherocytic hemolytic anemia in a Northern European patient = HS until proven otherwise; Coombs-positive spherocytic anemia = warm autoimmune hemolytic anemia (AIHA) — this is the single highest-yield distinction in this topic on the boards.
— Mild (20–30%): Hgb 11–15, retics 3–6%, bilirubin 1–2 mg/dL; often diagnosed incidentally or via family screening.
— Moderate (60–70%): Hgb 8–12, retics ≥6%, bilirubin >2; intermittent transfusions, gallstones common.
— Severe (~5%): Hgb 6–8, transfusion-dependent, growth failure in children; usually recessive.
— Neonate: Hyperbilirubinemia in first 48 hours, often needs phototherapy; can mimic ABO incompatibility.
— Child: Pallor, fatigue, scleral icterus, splenomegaly noted on well-child exam; school-age gallstones.
— Adult: Pigment cholelithiasis, splenomegaly found on imaging, or unexplained mild anemia with elevated MCHC.
— Family history of anemia, jaundice, gallbladder surgery at <40 years, or splenectomy.
— Episodic worsening of jaundice or fatigue (suggests hemolytic crisis).
— Recent viral illness with abrupt pallor and reticulocytopenia → parvovirus B19 aplastic crisis.
— Folate intake (chronic hemolysis depletes folate → megaloblastic/megaloblastoid crisis).
— Pregnancy history (anemia worsens; folate demand ↑).
— Hemolytic crisis: Triggered by infection; ↑ jaundice, ↑ retics, ↓ Hgb modestly.
— Aplastic crisis: Parvovirus B19; reticulocytopenia with profound Hgb drop — the dangerous one.
— Megaloblastic crisis: Folate deficiency during pregnancy or chronic illness.
Key distinction: Aplastic crisis has LOW reticulocytes despite severe anemia — opposite of every other HS exacerbation. A stem describing a child with HS, recent "slapped cheek" rash exposure, and a retic count of 0.2% is parvovirus B19 until proven otherwise; manage with transfusion support and isolate from pregnant contacts (risk of hydrops fetalis).
— Pallor (conjunctival, palmar creases).
— Scleral icterus and mild generalized jaundice — fluctuates with hemolytic activity.
— Splenomegaly — palpable in 50% of children and ~75% of adults; usually mild-to-moderate (2–6 cm below costal margin), rarely massive.
— Frontal bossing, maxillary hyperplasia, "chipmunk facies" in severe untreated childhood disease (marrow expansion) — less common than in thalassemia but tested.
— Leg ulcers (chronic hemolysis), rare.
— Growth delay in moderate-severe pediatric cases.
— Right upper quadrant tenderness or Murphy sign if cholecystitis from pigment stones.
— Normal cardiac exam unless severely anemic: tachycardia, flow murmur at LSB.
— Check HR, BP (orthostatics), capillary refill, mental status.
— Aplastic crisis: Patient can decompensate quickly because Hgb falls without compensatory reticulocytosis — look for tachycardia, narrow pulse pressure, exertional dyspnea.
— Hemolytic crisis with infection: Fever + jaundice + splenic tenderness — assess for sepsis (qSOFA, lactate).
— Vitals q15 min, continuous SpO₂, 2 large-bore IVs.
— Type & crossmatch (notify blood bank — antibodies common from prior transfusions).
— CBC with retic, peripheral smear, LDH, haptoglobin, total/direct bilirubin, DAT, BMP.
— Transfuse if Hgb <7 or symptomatic; aim Hgb 8–9, avoid over-transfusion.
CCS pearl: In a CCS case of suspected HS aplastic crisis, order reticulocyte count and DAT early — a Coombs-negative result with reticulocytopenia and a known family history clinches the diagnosis and justifies transfusion. Don't forget to isolate the patient (droplet precautions) if parvovirus B19 is suspected, particularly to protect pregnant staff and immunocompromised co-patients on the ward.
— Anemia (variable severity), ↑ MCHC (>36 g/dL) — the most specific routine CBC clue.
— ↑ RDW reflecting reticulocytosis and spherocyte heterogeneity.
— MCV usually normal or low-normal.
— Reticulocyte count elevated (>3%), often 5–20% — except in aplastic crisis.
— ↑ Unconjugated bilirubin, ↑ LDH, ↓ haptoglobin.
— Urine urobilinogen ↑, but urine hemosiderin/hemoglobin negative (extravascular, not intravascular).
— Normal PT/PTT.
— Spherocytes: Small, dense, hyperchromic RBCs without central pallor.
— Polychromasia (reflects reticulocytosis).
— No schistocytes (rules out MAHA), no bite cells (rules out G6PD), no sickle forms.
— Must be negative to call it HS. A positive DAT redirects you to autoimmune hemolytic anemia (AIHA), which also shows spherocytes.
— Iron studies (often elevated ferritin from chronic hemolysis and transfusions — risk of iron overload).
— Folate, B12.
— Hepatitis serologies, HIV (baseline before splenectomy and immunosuppression considerations).
— Right upper quadrant ultrasound to screen for pigmented gallstones — even in asymptomatic patients with confirmed HS.
Board pearl: The combination of MCHC >36 + reticulocytosis + negative DAT + spherocytes on smear + family history is sufficient on Step 3 to diagnose HS without confirmatory testing — confirmatory studies (next chunk) are reserved for ambiguous cases, atypical presentations, or pre-splenectomy planning. Always check the DAT first — missing AIHA and proceeding to splenectomy for presumed HS is a major board (and real-world) error.
— Flow cytometry measuring fluorescent EMA binding to band 3 protein on RBC membranes.
— Sensitivity ~93%, specificity ~98%; rapid, small blood volume, works in neonates.
— Decreased fluorescence confirms HS (especially band 3 and ankyrin defects).
— Has largely replaced the osmotic fragility test in modern US labs.
— Spherocytes lyse at higher salt concentrations than normal RBCs.
— Incubated (24-hour) version more sensitive than fresh.
— Can be falsely negative in compensated HS with many reticulocytes; falsely positive in AIHA.
— Next-generation sequencing panels (ANK1, SPTB, SPTA1, SLC4A1, EPB42) — reserved for:
— Atypical or recessive cases, severe neonatal disease, ambiguous EMA results, or family planning/genetic counseling.
— Negative family history + spherocytes + hemolysis → confirm with EMA before committing to chronic management or splenectomy.
— Unclear differential between HS and AIHA when DAT is weakly positive.
— Preoperative confirmation in pediatric severe disease before splenectomy.
— RUQ ultrasound at diagnosis and every 3–5 years (or sooner if symptoms) for gallstones.
— Spleen size documented (sometimes useful pre/post-splenectomy decision).
Key distinction: EMA binding test is now the preferred confirmatory study — osmotic fragility is an older Step 1/2 favorite but Step 3 expects you to know that EMA + flow cytometry is the modern standard. Genetic testing is NOT routinely required for diagnosis; reserve it for atypical, recessive, or severe neonatal cases where management or counseling depends on the result.
— Mild HS: Hgb >11, retics <6%, bilirubin <2, no transfusions → observation + folate.
— Moderate HS: Hgb 8–11, retics 6–10%, bilirubin 2–3, occasional transfusion → folate + monitor + consider splenectomy if symptomatic.
— Moderate-severe: Hgb 6–8, regular transfusion need → splenectomy candidate after age 6.
— Severe: Transfusion-dependent, growth failure → splenectomy after age 6 (rarely earlier), vaccinations, iron monitoring.
— Daily folic acid 1 mg PO — prevents megaloblastic crisis; lifelong for moderate/severe disease, often for mild as well.
— Avoid iron supplementation unless documented iron deficiency (most patients are iron-overloaded, not iron-deficient).
— Annual CBC, retic, bilirubin, LDH, ferritin.
— RUQ ultrasound at diagnosis and periodically; symptomatic gallstones → cholecystectomy (often combined with splenectomy if both indicated).
— Recurrent aplastic or hemolytic crises.
— Symptomatic anemia (fatigue limiting school/work, growth failure).
— Transfusion dependence or iron overload (ferritin >1000).
— Refractory hyperbilirubinemia or pigment stone complications.
— Vaccinate ≥2 weeks before surgery: pneumococcal (PCV20 or PCV15+PPSV23), meningococcal (MenACWY + MenB), H. influenzae type b.
— Counsel on lifelong infection risk and need for prompt antibiotic access.
Step 3 management: For an adult with mild HS and an incidental finding, the answer is almost always folate + observation + RUQ ultrasound, not splenectomy. Splenectomy is reserved for moderate-to-severe disease, growth failure, or recurrent crises, and is deferred until at least age 6 (ideally older) to preserve immune function and reduce overwhelming post-splenectomy infection (OPSI) risk.
— 1 mg PO daily for moderate-severe HS; 0.4–1 mg for mild disease.
— Prevents megaloblastic crisis during periods of high erythropoietic demand (pregnancy, growth spurts, infection).
— Cheap, well-tolerated; essentially universal in chronic hemolytic disease.
— Initiate when ferritin >1000 ng/mL or after ~20 transfusions or with cardiac/hepatic iron evidence on MRI T2*.
— Deferasirox (oral, first-line in US) — monitor renal/hepatic function, GI side effects.
— Deferoxamine (subQ infusion) — used in pregnancy and severe overload.
— Deferiprone — agranulocytosis risk; weekly CBC required.
— Indications: symptomatic anemia, Hgb <7, aplastic crisis, hemodynamic compromise.
— Use leukoreduced, irradiated products if possible; phenotype-match to reduce alloimmunization (common in chronically transfused patients).
— Transfuse to Hgb ~8–9, not normal — over-transfusion accelerates iron loading.
— Pneumococcal: PCV20 alone, or PCV15 followed by PPSV23 ≥8 weeks later; PPSV23 booster at 5 years.
— Meningococcal: MenACWY (2-dose primary, boosters q5 years) + MenB (2-dose series).
— Hib: Single dose.
— Annual influenza and routine COVID-19 vaccination.
— Administer ≥2 weeks before elective splenectomy; if emergent, give ≥14 days after.
— Penicillin V 250–500 mg BID (or amoxicillin) for children for ≥5 years post-splenectomy and until at least age 5 — often continued lifelong in high-risk patients.
— Adults: individualized; many guidelines support at least 1–2 years post-op or lifelong if prior OPSI.
— Standby emergency antibiotic (amoxicillin-clavulanate or levofloxacin) at home for febrile illness.
Board pearl: NEVER give iron to an HS patient unless deficiency is biochemically proven — chronic hemolysis recycles iron, and patients are typically iron-loaded. Mistakenly prescribing iron is a classic distractor on board questions about chronic hemolytic anemias.
— Severe HS: Transfusion-dependent, growth failure → splenectomy generally recommended.
— Moderate HS: Symptomatic anemia, fatigue, recurrent crises, gallstone formation → splenectomy reasonable.
— Mild HS: Generally NOT indicated — risks outweigh benefits.
— Concurrent symptomatic cholelithiasis → combined splenectomy + cholecystectomy.
— Delay until age ≥6 years whenever possible to minimize OPSI risk; ideally older if clinically tolerable.
— Avoid in infancy except in life-threatening transfusion dependence.
— Laparoscopic total splenectomy preferred (lower morbidity, faster recovery).
— Partial splenectomy (subtotal) — emerging option in pediatrics to preserve immune function while reducing hemolysis; risk of regrowth and need for completion splenectomy.
— Concurrent cholecystectomy if gallstones are present.
— Search for and remove accessory spleens intraoperatively (10–30% of patients) — missed accessory spleens cause hemolysis recurrence.
— Hgb normalizes or near-normalizes in >90%.
— Reticulocyte count drops, bilirubin falls, hemolysis markers improve.
— Spherocytes persist on smear (the membrane defect remains) — don't be fooled.
— Howell-Jolly bodies, target cells, and Pappenheimer bodies appear — confirm functional asplenia.
— Overwhelming post-splenectomy infection (OPSI): encapsulated organisms (S. pneumoniae, N. meningitidis, H. influenzae); mortality up to 50%.
— Venous thromboembolism (especially portal/splenic vein thrombosis), arterial events, pulmonary hypertension long-term.
— Persistent thrombocytosis (often >1,000,000) — usually asymptomatic but monitor.
CCS pearl: For a CCS scenario of a child with moderate HS and gallstones requiring elective splenectomy, the high-yield order set includes: vaccinations ≥2 weeks preop, type & screen, baseline CBC/retics/LDH/bilirubin, RUQ ultrasound, surgery and anesthesia consults, postoperative penicillin V prophylaxis, VTE prophylaxis, and patient/family education on febrile-illness emergency plan.
— Many have compensated mild HS undiagnosed for decades; presents with new gallstones, anemia after illness, or incidental MCHC elevation.
— Coexisting comorbidities (CAD, CKD) lower the threshold for transfusion (target Hgb ~8 with cardiac disease).
— Splenectomy in elderly patients carries higher perioperative risk; weigh symptoms against OPSI risk in a population with less robust immune response to vaccines.
— Deferasirox is nephrotoxic — avoid if CrCl <40, monitor SCr at baseline, week 2, then monthly.
— Adjust other meds (e.g., levofloxacin emergency prophylaxis) for CrCl.
— CKD patients have blunted erythropoietin response — chronic hemolysis is poorly tolerated; consider lower transfusion threshold.
— Chronic hemolysis + transfusion iron loading → secondary hemochromatosis with cirrhosis risk.
— Monitor LFTs, ferritin, and hepatic MRI T2* in chronically transfused patients.
— Pigment gallstones common — low threshold for cholecystectomy even when mildly symptomatic to prevent cholangitis in cirrhotic patients.
— Deferasirox and deferiprone both hepatotoxic — monitor LFTs, dose-adjust.
— Elderly HS patient undergoing non-splenectomy surgery: ensure adequate Hgb, type & screen, communicate with anesthesia about hemolysis risk from drugs that stress RBCs.
— VTE prophylaxis important — chronic hemolysis is a hypercoagulable state.
— Older adults have weaker vaccine responses → may need more aggressive revaccination schedules post-splenectomy.
Step 3 management: For an elderly HS patient with new symptomatic gallstones and CKD stage 3, prioritize elective cholecystectomy with type & screen, optimize hemoglobin preoperatively, and reserve splenectomy unless hemolysis is significantly contributing to morbidity. Always reassess vaccination status in older patients — many missed adult booster doses for pneumococcal and meningococcal vaccines, and they need to be current before any elective splenectomy.
— Anemia often worsens due to increased plasma volume, folate demand, and erythropoietic stress.
— Increase folic acid to 4–5 mg daily (vs standard 0.4–0.8 mg) starting preconception.
— Monitor CBC each trimester; transfuse for symptomatic anemia or Hgb <7.
— Avoid deferasirox and deferiprone (teratogenic/limited safety data); deferoxamine is preferred chelator if needed.
— Splenectomized mothers: ensure vaccinations up to date; counsel on infection risk; continue penicillin prophylaxis through pregnancy.
— Neonatal hyperbilirubinemia common in affected newborns — coordinate with neonatology.
— Presents with jaundice in first 24–48 hours, often requiring phototherapy and occasionally exchange transfusion.
— Anemia may emerge over weeks as fetal hemoglobin declines.
— EMA binding test reliable even in neonates.
— Avoid splenectomy in neonatal period; transfuse as needed; some severe cases require monthly transfusions during infancy.
— Growth velocity is a key clinical parameter — growth delay is a splenectomy indication.
— Folate 1 mg daily, school accommodations during crises.
— Parvovirus B19 exposure — counsel families that "fifth disease" outbreaks in school may trigger aplastic crisis; seek care for sudden pallor/fatigue.
— Routine immunizations on schedule; add splenectomy-specific vaccines if applicable.
— Subtotal/partial splenectomy preferred in young children when feasible to preserve some immune function.
— Autosomal dominant: 50% transmission risk; recessive forms require both parents to carry.
— Offer family screening (CBC + smear) to first-degree relatives — many have undiagnosed mild disease.
Board pearl: A pregnant patient with known HS needs high-dose folate (4–5 mg/day), trimester CBC monitoring, deferoxamine if chelation required, and continued penicillin prophylaxis if previously splenectomized — and remember to screen the newborn for HS and hyperbilirubinemia. Parvovirus B19 in a pregnant household contact is a dual threat: aplastic crisis in mother + hydrops fetalis in fetus.
— Develop in 50%+ of HS patients by adulthood from chronic bilirubin turnover.
— Risk increases with co-inheritance of Gilbert syndrome (UGT1A1 polymorphism) — important pearl.
— Complications: biliary colic, cholecystitis, choledocholithiasis, gallstone pancreatitis, cholangitis.
— Parvovirus B19 infects erythroid progenitors → transient red cell aplasia.
— Severe anemia with reticulocytopenia for 7–10 days.
— Self-limited but requires transfusion support; IVIG if immunocompromised.
— Triggered by intercurrent infection or stress; jaundice and anemia worsen with brisk reticulocytosis.
— Folate deficiency during pregnancy, malnutrition, or chronic illness → ineffective erythropoiesis.
— Prevented by daily folate supplementation.
— From chronic transfusion and increased GI absorption.
— Causes cardiomyopathy, cirrhosis, endocrinopathy (diabetes, hypogonadism).
— Monitor ferritin, hepatic and cardiac MRI T2*.
— OPSI (overwhelming sepsis with encapsulated organisms) — lifelong risk, highest in first 2 years.
— VTE / portal vein thrombosis — postoperative incidence 5–10%.
— Persistent thrombocytosis, pulmonary hypertension (long-term, more in hemolytic anemias).
— Atherosclerotic risk modestly elevated.
Key distinction: Aplastic crisis = reticulocyte LOW, parvovirus B19; hemolytic crisis = reticulocyte HIGH, infection-triggered; megaloblastic crisis = folate-deficient, MCV up. Three crises, three reticulocyte patterns — board favorite. The single most preventable HS complication is OPSI — vaccination, prophylactic antibiotics, and patient education are the trio you must always recommend.
— Hemodynamic instability from severe acute anemia (Hgb <6 with shock physiology).
— Aplastic crisis with cardiopulmonary compromise.
— Post-splenectomy sepsis / OPSI — septic shock with encapsulated organism bacteremia.
— Iron-overload cardiomyopathy with decompensated heart failure.
— Massive splenic infarction or splenic rupture (rare).
— Hgb <7 with symptoms (chest pain, syncope, dyspnea, severe fatigue).
— Suspected aplastic crisis with retic <1%.
— Acute cholecystitis, cholangitis, or gallstone pancreatitis.
— Febrile illness in a splenectomized patient (presume OPSI until proven otherwise).
— Postoperative complications (bleeding, thrombosis, infection).
— Hematology: All confirmed HS cases; severity stratification, splenectomy decision, transfusion planning.
— General/pediatric surgery: Splenectomy and/or cholecystectomy planning.
— Infectious disease: Post-splenectomy febrile illness, recurrent infections, OPSI.
— Maternal-fetal medicine: Pregnant HS patient, especially if transfusion-dependent or splenectomized.
— Genetic counseling: Family planning, atypical phenotypes.
— Gastroenterology: Cholangitis, choledocholithiasis requiring ERCP.
— Stable, mild anemia, no crisis → outpatient hematology follow-up.
— Acute symptomatic anemia or febrile splenectomized patient → ED + admission.
— Pregnant patient with worsening anemia → MFM + hematology, often outpatient transfusion.
— Blood cultures × 2, lactate, CBC, comprehensive metabolic panel.
— Empiric IV ceftriaxone within 1 hour (add vancomycin if shock or resistant pneumococcus suspected).
— Aggressive fluid resuscitation; ICU consult if hypotensive.
CCS pearl: A splenectomized HS patient presenting with fever — even if "well-appearing" — must receive empiric IV ceftriaxone within 60 minutes and be admitted for observation. Do not wait for cultures. This is a classic CCS time-pressure scenario where delayed antibiotics will lower your score and harm the patient. Patients should be taught to seek emergency care for any temperature ≥101°F (38.3°C).
— Spherocytes on smear, hemolysis labs identical to HS — but DAT POSITIVE (IgG ± C3).
— Often idiopathic or associated with lupus, CLL, lymphoma, viral infections, drugs (methyldopa, cephalosporins).
— Treat with corticosteroids, not splenectomy first-line.
— Bite cells and Heinz bodies on smear (not spherocytes).
— X-linked, episodic intravascular hemolysis triggered by oxidants (sulfa, nitrofurantoin, fava beans, dapsone, primaquine).
— Diagnosed by G6PD activity assay (false-negative during acute hemolysis — repeat 2–3 months later).
— Spectrin defects; elliptocytes dominate smear; usually milder than HS.
— Autosomal recessive; non-spherocytic hemolytic anemia with burr cells/echinocytes.
— Diagnosed by enzyme assay.
— GPI-anchor defect (PIGA mutation); intravascular hemolysis with hemoglobinuria (dark morning urine), thrombosis, cytopenias.
— Diagnosed by flow cytometry for CD55/CD59 deficiency; treated with eculizumab/ravulizumab.
— Microcytic, target cells, basophilic stippling; iron studies normal/elevated; Hgb electrophoresis abnormal.
— Sickle forms on smear, vaso-occlusive crises, Hgb electrophoresis.
— Schistocytes, thrombocytopenia; clinical context (renal failure, neuro signs, coagulopathy).
Key distinction: DAT separates HS from AIHA — both have spherocytes and hemolysis labs, but only AIHA is Coombs-positive. Don't splenectomize a presumed HS patient until DAT has confirmed it is negative. Spherocytes are nonspecific — context, family history, and DAT decide the diagnosis.
— Isolated unconjugated hyperbilirubinemia during fasting or illness.
— No anemia, no reticulocytosis, normal smear, normal LDH/haptoglobin.
— Coexists with HS in some patients and accelerates gallstone formation — important association.
— Jaundice with elevated AST/ALT, conjugated bilirubin predominant.
— No spherocytes, no hemolysis labs.
— Conjugated hyperbilirubinemia, elevated alkaline phosphatase and GGT, dilated ducts on imaging.
— May coexist with HS via pigment stones — but distinguish from primary hemolysis.
— Cirrhosis with portal hypertension, lymphoma, infections (malaria, kala-azar) — splenomegaly with pancytopenia.
— Smear and clinical context distinguish.
— Acute thermal injury denatures spectrin → transient spherocytes; clinical history is obvious.
— Spherocytic intravascular hemolysis; acute toxin-mediated; very different clinical context.
— Coombs-negative hemolytic anemia + liver disease + neuropsychiatric symptoms; low ceruloplasmin, Kayser-Fleischer rings.
— Iron overload without hemolysis; HFE gene; differs from transfusion-related secondary iron overload of HS.
— Excluded by normal hemolysis labs, smear, and appropriate iron studies/levels.
Board pearl: A young patient with isolated unconjugated hyperbilirubinemia, normal Hgb, and normal smear has Gilbert syndrome, not HS. But Gilbert + HS together dramatically increases pigment gallstone risk — a favorite distractor stem. Always check a smear and retic count before attributing jaundice to "just Gilbert's."
— Folic acid 1 mg PO daily (4–5 mg if pregnant or actively planning).
— Iron studies every 6–12 months; avoid iron supplementation unless deficient.
— RUQ ultrasound at diagnosis, then every 3–5 years or with symptoms.
— Annual CBC, retic count, LDH, bilirubin, ferritin.
— Hgb-targeted transfusion for severe disease; iron chelation if ferritin >1000 or organ overload.
— Penicillin V 250–500 mg PO BID (or amoxicillin) — pediatric: ≥5 years and until at least age 5; adult: at least 1–2 years, often lifelong if high-risk.
— Penicillin allergy: erythromycin or azithromycin.
— Standby emergency antibiotic (amoxicillin-clavulanate or levofloxacin) — patient takes at home with first dose of fever and proceeds immediately to ED.
— PPSV23 booster 5 years after first dose post-splenectomy.
— MenACWY booster every 5 years, MenB primary series + boosters per ACIP.
— Annual influenza, COVID-19 updates, and routine adult vaccines (Tdap, zoster, HPV as appropriate).
— Medical alert bracelet noting asplenia.
— Travel counseling: malaria prophylaxis (asplenic patients have severe malaria), babesiosis avoidance, animal bite caution (Capnocytophaga from dog bites is lethal in asplenia).
— Avoid contact sports for 4–6 weeks post-splenectomy; lifelong awareness of trauma risk to retroperitoneum.
— Dental hygiene — endocarditis risk slightly elevated.
— Offer CBC + smear + family history review to first-degree relatives — pick up undiagnosed mild HS that may need folate and monitoring.
Step 3 management: The discharge checklist for a newly splenectomized HS patient is a high-yield CCS sequence: penicillin prophylaxis, vaccination completion, emergency antibiotic prescription, medical alert ID, travel and animal-bite counseling, hematology follow-up in 2–4 weeks, and family screening offered. Missing any item — especially the emergency antibiotic — costs points.
— Newly diagnosed mild HS: Hematology visit at diagnosis, then annually with CBC/retic/LDH/bilirubin/ferritin.
— Moderate HS: Every 6 months; closer monitoring during illness, growth, or pregnancy.
— Severe / transfusion-dependent: Every 1–3 months with transfusion planning, iron monitoring, organ assessment.
— 2–4 weeks postop: Wound check, CBC (expect thrombocytosis and Howell-Jolly bodies), review vaccinations and prophylaxis.
— 3 months: CBC, hemolysis labs (should normalize); confirm spherocytes persist but retic count drops.
— Annual: CBC, vaccination status, infection history, prophylaxis adherence.
— Ferritin q3 months.
— Cardiac MRI T2 annually when ferritin >1000 or >10 transfusions; hepatic MRI T2 for liver iron quantification.
— Endocrine screening: A1c, TSH, gonadal function (testosterone, FSH/LH), DEXA.
— Growth curves at every visit — growth failure is a key splenectomy trigger.
— School coordination for fatigue, infection-related absences.
— Developmental milestones.
— Recognize crisis symptoms (severe fatigue, dark urine, abdominal pain, scleral icterus worsening).
— Avoid known triggers (dehydration, missed folate, oxidant stress is not a concern in HS but worth distinguishing from G6PD).
— Genetic counseling — 50% transmission in dominant forms; offer to relatives.
— Reproductive counseling: pregnancy is generally safe but requires planning.
— Chronic illness burden, body image post-splenectomy scar, school/work impact — screen and refer.
Board pearl: After splenectomy, expect persistent spherocytes but normalized hemoglobin and retic count, plus new Howell-Jolly bodies confirming functional asplenia. If hemolysis recurs months to years later, suspect a missed accessory spleen — confirm with technetium-99m labeled heat-damaged RBC scan, and resect.
— Must explicitly cover OPSI lifetime risk (~1–5% lifetime, mortality up to 50%), VTE, surgical complications, alternatives (observation, partial splenectomy, transfusion).
— In pediatric patients, assent of the child and informed consent of parents/guardians — document both.
— For severe disease in a minor, if parents refuse splenectomy and the child is dying despite transfusions, ethics consult and possibly legal involvement; courts have generally supported life-saving intervention.
— Adolescents with HS deserve developmentally appropriate explanation of vaccines, prophylaxis, and lifelong risks.
— Reproductive counseling for sexually active teens with HS — folate adequacy, contraception, future pregnancy planning.
— Autosomal dominant inheritance means 50% transmission risk; offer family screening but respect patient autonomy about informing relatives.
— Cannot disclose genetic information to relatives without consent (HIPAA, GINA protections).
— Document the conversation, OPSI risk, alternatives; engage motivational interviewing; do not withhold splenectomy if absolutely indicated but ensure patient understands amplified infection risk.
— Pediatric-to-adult hematology transition (ages 16–22) is a high-risk period — patients often lapse on prophylaxis and vaccinations.
— Use a structured transition checklist: vaccination records, emergency antibiotic prescription, hematology handoff, primary care notification.
— Penicillin prophylaxis adherence drops with cost barriers — verify formulary coverage.
— Ensure access to emergency antibiotic at home; many patients live far from EDs.
— Document asplenia in the EHR problem list and allergies/alerts section so any future provider sees it.
— Not typically relevant; however, in severe pediatric disease with suspected medical neglect (missed transfusions, no vaccinations despite counseling), child protective services consultation may be warranted.
Step 3 management: The single most actionable patient-safety intervention for a splenectomized patient is prominent EHR documentation of "functional/anatomic asplenia" with a linked best-practice alert for any febrile presentation triggering empiric ceftriaxone within 60 minutes. Transition-of-care lapses are the most common preventable cause of OPSI in young adults — build a structured handoff.
— Aplastic (parvovirus B19, low retic).
— Hemolytic (infection, high retic).
— Megaloblastic (folate deficiency, high MCV).
Board pearl: "Northern European child + jaundice + splenomegaly + family history of gallstones + spherocytes on smear + negative Coombs + MCHC 37" = HS. Memorize that vignette; it appears in dozens of variations.
— 8-year-old with intermittent jaundice, palpable spleen, fatigue. CBC: Hgb 9.5, MCV 86, MCHC 37, retic 10%. Smear: spherocytes. DAT negative. Mom had splenectomy at 20.
— Answer: Hereditary spherocytosis; next best test: EMA binding (or osmotic fragility); management: folate, monitor, RUQ ultrasound.
— Known HS child returns from school where "fifth disease" is going around; now profoundly fatigued. Hgb 4.5, retic 0.3%.
— Answer: Parvovirus B19 aplastic crisis; transfuse PRBCs, supportive care, isolate from pregnant contacts.
— 30-year-old splenectomized at age 8 for HS; presents with fever 39.5°C, BP 95/55, HR 120.
— Answer: Suspected OPSI; IV ceftriaxone within 1 hour, blood cultures, ICU admission.
— Adult with new anemia, jaundice, spherocytes, retic 8%, DAT positive for IgG.
— Answer: Warm AIHA, not HS; treat with prednisone, evaluate for lymphoproliferative disorder.
— 22-year-old with biliary colic; ultrasound shows multiple small stones. CBC reveals MCHC 36.8, mild anemia, family history of "yellow skin."
— Answer: HS with pigmented gallstones; combined laparoscopic cholecystectomy and splenectomy after vaccination.
— Splenectomy 3 years ago; now mild anemia recurring with retic 5%.
— Answer: Accessory spleen; Tc-99m heat-damaged RBC scan to localize.
— Pregnant HS patient at 28 weeks with Hgb 8.5.
— Answer: Increase folate to 4–5 mg/day, monitor monthly, transfuse if symptomatic; avoid deferasirox.
— HS patient scheduled for splenectomy in 1 week without vaccines.
— Answer: Vaccinate now (≥2 weeks ideal); if surgery is urgent and given <14 days prior, complete vaccines ≥14 days postoperatively.
Key distinction: Step 3 vignettes typically force you to choose between HS vs AIHA (DAT), aplastic vs hemolytic crisis (retic count), and splenectomy timing (age ≥6, vaccination ≥2 weeks prior). Anchor on these three forks and you'll get the right answer >90% of the time.
Hereditary spherocytosis is a Coombs-negative extravascular hemolytic anemia caused by RBC membrane protein defects (most often ankyrin), diagnosed by spherocytes on smear + reticulocytosis + elevated MCHC + negative DAT confirmed with EMA binding, managed with folate and observation in mild disease and splenectomy (after age 6, with pre-op pneumococcal/meningococcal/Hib vaccination, post-op penicillin prophylaxis, and lifelong OPSI vigilance) in moderate-to-severe disease — with pigmented gallstones, parvovirus B19 aplastic crisis, and iron overload as the major complications to anticipate.
— Aplastic (parvovirus B19, low retic — the dangerous one).
— Hemolytic (infection-triggered, high retic).
— Megaloblastic (folate-deficient — prevent with daily folate).
— Spherocytes + MCHC >36 + reticulocytosis.
— Negative DAT (distinguishes from AIHA — the #1 board distractor).
— EMA binding flow cytometry as modern confirmatory test.
— Folate 1 mg/day lifelong (4–5 mg in pregnancy).
— Vaccinate ≥2 weeks before elective splenectomy (PCV, MenACWY+MenB, Hib).
— Empiric IV ceftriaxone within 60 minutes for any febrile splenectomized patient — OPSI is a time-critical emergency.
— Giving iron supplements (patients are usually overloaded).
— Splenectomy before age 6 (OPSI risk).
— Calling it HS without checking DAT (missing AIHA).
Board pearl: When in doubt on a Step 3 HS question, ask: What does the DAT show, what is the reticulocyte count, and is the patient splenectomized? Those three data points resolve nearly every HS vignette and direct correct management.