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symptom.leukocytosis-workup.v1

Leukocytosis symptom-triage (outpatient ddx + ED escalation for blasts / hyperleukocytosis)

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Detailed

WBC magnitude (mild 11-15K / mod 15-30K / severe >30K / leukemoid >50K / hyperleukocytosis >100K); dominant lineage (neut / lymph / mono / eos / baso); acuity (transient vs persistent); peds vs adult (Leucocytosis BJH 2019 PMID 33237040 verify)

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magnitude + lineage anchored

Patient inputs (27)

Age shifts priors: peds (<3 mo) → congenital infection / TAM; child → pertussis / viral mono; adolescent / young adult → ALL; middle-age → CML; elderly → CLL / CMML / AML / lymphoma

Sex shifts: pregnancy → physiologic neutrophilia 12-15K; gestational/lactational; pediatric trisomy 21 → TAM

Recent steroid (prednisone, IV methylpred) → demargination neutrophilia (benign); G-CSF / GM-CSF → drug-induced leukocytosis; lithium → benign neutrophilia

New medication (aromatic AED phenytoin/carbamazepine, allopurinol, vancomycin, sulfa, lamotrigine, dapsone) 2-8 wk prior + rash + fever + eosinophilia → DRESS; stop drug + supportive

Fever + leukocytosis → infection (route id.sepsis.core.v1 if criteria); fever + rash + LAD + eos → DRESS

Tachycardia + leukocytosis + fever → sepsis; high WBC + fever + hypotension → sepsis route

Hypotension + leukocytosis → sepsis; hypertension + smoking/cocaine → substance-related; route id.sepsis.core.v1 if criteria met

Fever + focal sx (cough/dysuria/cellulitis/abdominal pain) → reactive infection; B-sx (fever + drenching sweats + weight loss) → lymphoma/leukemia

Drenching night sweats + weight loss >10% + fever + fatigue → lymphoma / CLL / CMML; pruritus → MPN / Hodgkin

WBC absolute + differential (neut, lymph, mono, eos, baso, bands, blasts) — central; magnitude (mild 11-15K, mod 15-30K, severe >30K, leukemoid >50K, hyperleukocytosis >100K) + dominant lineage drives differential

Smear review CRITICAL: blasts → leukemia STAT; smudge cells → CLL; atypical lymphs → viral mono; bands + toxic granulation + Döhle → bacterial; dysplasia → MDS/CMML; basophils → MPN; left shift severity

Hyperleukocytosis with leukostasis: dyspnea/hypoxia + AMS + retinal hemorrhage + priapism + visual changes → EMERGENT (AML M4/M5 + blast crisis CML/ALL) → leukapheresis + hydroxyurea + STAT hematology

LAP (leukocyte alkaline phosphatase) HIGH → leukemoid reaction; LAP LOW → CML; key pivot in WBC >50K (LAP score historical PMID 23391835 verify; now BCR-ABL preferred)

BCR-ABL PCR (Philadelphia chromosome) — diagnostic for CML; replaces LAP in modern workup; route heme.acute-leukemia.core.v1

Flow cytometry CD5+ CD19+ CD23+ → CLL diagnosis (Matutes score ≥4); FISH for prognostic markers (17p-, 11q-, +12, 13q-)

JAK2 V617F mutation + CALR + MPL → PV/ET/PMF (MPN); EPO low → PV; thrombopoietin elevated → ET; route heme.acute-leukemia.core.v1

Stool O&P + Strongyloides serology + filaria + schistosoma + hookworm — parasitic eosinophilia workup; MUST exclude Strongyloides BEFORE steroids (hyperinfection)

ANCA (p-ANCA / MPO) + asthma + sinusitis + eos + multifocal neuropathy → EGPA (Churg-Strauss); only 40-60% ANCA+

Serum tryptase + bone marrow + KIT D816V → mastocytosis with eos; HES workup (FIP1L1-PDGFRA, T-cell clonality, idiopathic)

Monospot / EBV VCA IgM / CMV IgM / HIV / toxoplasma → atypical lymphocytosis viral; pertussis → swab PCR if suspected

BMBx if persistent unexplained leukocytosis, suspected leukemia (blasts), suspected CMML (monocytosis + dysplasia), HES (>6 mo + organ damage), MDS, MPN

Smoking → mild chronic; cocaine → catecholamine demargination; pregnancy → 12-15K physiologic; post-partum / lactational → transient

Travel / immigration (Strongyloides, schistosoma, filaria, hookworm, malaria) + eosinophilia → parasitic; check stool O&P, serology, Strongyloides before steroids

RA / IBD / vasculitis / sarcoidosis → reactive leukocytosis; HIV → atypical lymphocytes; malignancy → paraneoplastic leukemoid / chemo-induced

Splenomegaly → CML, CLL, lymphoma, MPN, sickle/thal; lymphadenopathy → lymphoma, CLL, viral, TB; both → hematologic malignancy workup

Asthma + sinusitis + multifocal neuropathy + eosinophilia → EGPA (formerly Churg-Strauss); rash + drug → DRESS; allergic dx → atopic eosinophilia

CRP / ESR / procalcitonin → bacterial infection prediction; procalcitonin >0.5 ng/mL favors bacterial; CRP very high (>100) → severe inflammation/infection

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Severity triggers (8)

8 need judgement
  • informationallife_threateninghyperleukocytosis_with_leukostasis_blast_crisis
    WBC >100K + blasts on smear + leukostasis symptoms (dyspnea/hypoxia, AMS, retinal hemorrhage, priapism, visual changes) — hyperleukocytosis with leukostasis (AML M4/M5, blast crisis CML, ALL) → ED STAT + hematology + hydroxyurea 50-100 mg/kg + leukapheresis + cytoreductive chemo (route heme.acute-leukemia.core.v1)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecml_bcr_abl_diagnostic_pivot
    WBC >50K + chronic + basophilia + eosinophilia + splenomegaly + LAP score LOW + BCR-ABL/Philadelphia chromosome positive — CML; tyrosine kinase inhibitor (imatinib 400 mg PO daily / dasatinib / nilotinib / bosutinib / ponatinib); route heme.acute-leukemia.core.v1 (NCCN CML PMID 30796100 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereleukemoid_reaction_LAP_high_pivot
    WBC >50K + extreme left shift (bands + metas + myelos) + LAP score HIGH (>100) + identifiable trigger (severe infection, sepsis, paraneoplastic, post-G-CSF, severe burns) — leukemoid reaction (NOT CML); treat underlying; pivot vs CML (LAP score historical PMID 23391835 verify; BCR-ABL preferred modern)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehes_with_organ_damage
    Persistent eosinophilia >1500/µL × >6 mo + organ damage (cardiac restrictive cardiomyopathy/Löffler endocarditis, pulm infiltrates, neuro embolic, skin angioedema, GI gastroenteritis) — hypereosinophilic syndrome (HES); FIP1L1-PDGFRA → imatinib; idiopathic → corticosteroid + hydroxyurea + mepolizumab (HES PMID 26573041 verify)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveredress_with_organ_involvement
    New medication (aromatic AED phenytoin/carbamazepine, allopurinol, vancomycin, sulfa, lamotrigine, dapsone) 2-8 wk prior + rash + fever + lymphadenopathy + eosinophilia + multi-organ (LFT >5x, AKI, myocarditis, pneumonitis) — DRESS syndrome; STOP offending drug + supportive + steroid 1 mg/kg if severe organ involvement
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresepsis_bacterial_neutrophilic_route
    WBC neutrophilic leukocytosis + bands + toxic granulation + Döhle + fever + SIRS/qSOFA/lactate >2 + identified source — bacterial sepsis; route id.sepsis.core.v1 for full Surviving Sepsis Campaign bundle; empiric antibiotics within 1 h
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepediatric_leukemoid_or_TAM_in_down_syndrome
    Pediatric (<3 mo) WBC >25-50K + bandemia + congenital infection (sepsis, parvovirus, HSV, syphilis) OR Down syndrome neonate with TAM (transient abnormal myelopoiesis) — pediatric leukemoid; rule out leukemia (10-20% TAM → AML/AMKL); pediatric hematology consult
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatecll_with_autoimmune_cytopenia
    CLL + AIHA (DAT+, retic high, LDH high, indirect bili high) OR ITP (plt <100K, megakaryocytes preserved on BMBx) — autoimmune complication of CLL; prednisone 1 mg/kg + rituximab; ibrutinib for refractory; Hallek PMID 24600289 verify
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

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Recommended regimen

Hyperleukocytosis with leukostasis: emergent cytoreduction + leukapheresis + tumor-lysis prophylaxis + definitive induction (Blood Rev 2012; leukostasis is an oncologic emergency)
axis: hyperleukocytosis_leukostasis_bundlestep 1 - Recognize leukostasis (oncologic emergency)
Selected step "Recognize leukostasis (oncologic emergency)" — WBC >100k (esp. AML) or >400k (ALL/CLL) with respiratory (dyspnea/hypoxia) or neurologic (AMS, visual change, headache) signs
  • STAT heme/onc consult + peripheral smear + flow cytometry; IV isotonic fluids; AVOID RBC transfusion before cytoreduction (raises viscosity); cautious correction of anemia
    first line
    recognition / supportive
    triggers: hyperleukocytosis, leukostasis_symptoms
    Leukostasis carries high early mortality; transfusing packed cells before cytoreduction worsens hyperviscosity (Blood Rev 2012)

outpatient playbook — drug actions (10)

  1. 1. reassurance + repeat CBC (physiologic / mild reactive)
    N/A • observation • one-time
    trigger: WBC <15K + transient + identifiable benign trigger (stress, smoking, pregnancy, post-partum, exercise)
    Most mild leukocytosis is physiologic; repeat CBC in 2-4 weeks; reassure if normal
  2. 2. empiric antibiotics (suspected bacterial infection)
    Source-directed empiric (e.g., ceftriaxone 1 g IV q24h, levofloxacin 750 mg PO/IV q24h, amox-clav 875/125 mg PO BID) • IV or PO • per protocol
    trigger: Neutrophilia + bands + fever + identified focus (pneumonia, UTI, cellulitis, abdominal source) + sepsis criteria → route id.sepsis.core.v1
    Identify focus + targeted antibiotics; blood cultures before antibiotics; route to id.sepsis.core.v1 if SIRS/qSOFA criteria met; de-escalate after culture data
  3. 3. discontinue offending drug (DRESS, drug-induced eos, steroid, G-CSF)
    N/A • medication management • one-time
    trigger: Identified drug trigger: DRESS (AED 2-8 wk, allopurinol, vancomycin, sulfa), G-CSF-induced extreme leukocytosis, steroid demargination (reassure)
    Critical for DRESS — stop offending drug + supportive ± steroid 1 mg/kg if severe organ injury; counsel cross-reactivity (aromatic AEDs phenytoin/carbamazepine/lamotrigine); monitor recovery 2-8 weeks
  4. 4. imatinib (CML first-line TKI)
    400 mg PO daily (CP-CML); 600-800 mg if AP/BC • PO • daily
    trigger: CML confirmed (BCR-ABL+ + Philadelphia chromosome + CP-CML); NCCN PMID 30796100 verify
    First-generation TKI; molecular response monitored q3 mo with BCR-ABL PCR; 2nd-gen (dasatinib, nilotinib, bosutinib) for resistance/intolerance; ponatinib for T315I; lifelong therapy unless deep MR achieved + trial of TKI cessation
  5. 5. ibrutinib (CLL — BTK inhibitor)
    420 mg PO daily • PO • daily
    trigger: CLL symptomatic (Rai II-IV or rapid lymphocytosis doubling or B-sx) + first-line for unfit / del17p / TP53; per Hallek PMID 24600289 verify
    BTK inhibitor; AF + bleeding risk; bone marrow + lymph node response; alternative: venetoclax + obinutuzumab; FCR for fit young patients without 17p-
  6. 6. hydroxyurea (cytoreduction for MPN / hyperleukocytosis)
    500-1000 mg PO BID (titrate); 50-100 mg/kg/d for hyperleukocytosis emergency • PO • BID-daily
    trigger: MPN cytoreduction (PV/ET high-risk); hyperleukocytosis with leukostasis (bridge to chemo/leukapheresis)
    Oral cytoreduction; rapid WBC + platelet reduction; monitor CBC weekly initially; ulcer risk; secondary leukemia rare risk; teratogen (avoid pregnancy)
  7. 7. systemic corticosteroid (DRESS / EGPA / HES)
    Prednisone 1 mg/kg PO daily × 2-4 wk taper (DRESS); methylprednisolone 1 g IV × 3 d for severe; mepolizumab 300 mg SC q4w for EGPA/HES • PO / IV / SC • daily / monthly
    trigger: DRESS with organ involvement (LFT >5x, AKI, myocarditis); EGPA (vasculitis); HES with organ damage
    CRITICAL: rule out Strongyloides BEFORE high-dose steroids (hyperinfection risk); PCP prophylaxis (TMP-SMX or atovaquone) for chronic steroids >4 wk
  8. 8. imatinib (HES with FIP1L1-PDGFRA)
    100-400 mg PO daily • PO • daily
    trigger: HES with FIP1L1-PDGFRA fusion (M-HES); HES PMID 26573041 verify
    TKI for myeloid HES variant; rapid response within weeks; lifelong maintenance; monitor cardiac (rare cardiomyopathy)
  9. 9. antiparasitic (ivermectin / albendazole)
    Ivermectin 200 µg/kg PO × 1-2 doses (Strongyloides); albendazole 400 mg PO BID × 3-7 d (filaria, hookworm); praziquantel for schistosoma • PO • one-time / short course
    trigger: Confirmed parasitic eosinophilia (Strongyloides, hookworm, schistosoma, filaria); travel/immigration history; eosinophilia NEJM PMID 25060842 verify
    Treat Strongyloides BEFORE any steroid initiation (hyperinfection / disseminated mortality); empiric ivermectin if eos + travel + planned steroids
  10. 10. pertussis vaccine + macrolide (pediatric pertussis)
    Azithromycin 10 mg/kg/d × 5 days (peds) or 500 mg × 1 then 250 mg × 4 days (adults); Tdap vaccination • PO • short course
    trigger: Pediatric lymphocytosis + whoop cough + apnea + cyanosis → pertussis swab PCR confirmation
    Macrolide reduces transmission; supportive (oxygen, hydration, hospital if <3 mo or apnea); Tdap booster for contacts

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: WBC 11-15K + transient (post-exercise, stress, pregnancy, post-partum, smoking) + normal differential — physiologic stress demargination; reassure + repeat CBC in 2-4 weeks (Leucocytosis BJH 2019 PMID 33237040 verify); WBC 12-25K + neutrophilia + bands >10% + left shift + toxic granulation + Döhle bodies + fever — acute bacterial infection; identify source + empiric antibiotics; route id.sepsis.core.v1 if sepsis criteria met; WBC mild-mod elevation + neutrophilia + chronic inflammation (RA, IBD, vasculitis, gout flare, MI, pancreatitis, post-op) — inflammatory leukocytosis; treat underlying.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Leukocytosis symptom-triage (outpatient ddx + ED escalation for blasts / hyperleukocytosis)** (symptom.leukocytosis-workup.v1).
Phenotype framing: Reactive (physiologic stress, pregnancy, post-partum, exercise, smoking, cocaine, steroid, G-CSF, lithium); infectious (bacterial neut + bands, viral lymphocytic, parasitic eos, fungal); inflammatory (RA, IBD, vasculitis, post-MI, post-op, gout); allergic/drug (DRESS, asthma, atopic); hematologic malignancy (CML, AML, ALL, CLL, CMML, MPN, lymphoma); HES; mastocytosis; paraneoplastic; pediatric (TAM, congenital infection)
Scope: WBC magnitude (mild 11-15K / mod 15-30K / severe >30K / leukemoid >50K / hyperleukocytosis >100K); dominant lineage (neut / lymph / mono / eos / baso); acuity (transient vs persistent); peds vs adult (Leucocytosis BJH 2019 PMID 33237040 verify)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Hyperleukocytosis with leukostasis: emergent cytoreduction + leukapheresis + tumor-lysis prophylaxis + definitive induction (Blood Rev 2012; leukostasis is an oncologic emergency)** — step "Recognize leukostasis (oncologic emergency)".
1. STAT heme/onc consult + peripheral smear + flow cytometry; IV isotonic fluids; AVOID RBC transfusion before cytoreduction (raises viscosity); cautious correction of anemia (recognition / supportive, first line) — Leukostasis carries high early mortality; transfusing packed cells before cytoreduction worsens hyperviscosity (Blood Rev 2012)

Setting playbook (outpatient) — Stratify elevated WBC (reactive vs infectious vs inflammatory vs drug-induced vs hematologic malignancy) + identify red flags (blasts, leukostasis, hyperleukocytosis, severe sepsis, DRESS with organ injury) + initial workup + route to dedicated engines for confirmed malignancy or sepsis (Leucocytosis BJH 2019 PMID 33237040 verify; NCCN CML PMID 30796100 verify)
2. reassurance + repeat CBC (physiologic / mild reactive) N/A observation one-time — WBC <15K + transient + identifiable benign trigger (stress, smoking, pregnancy, post-partum, exercise) (Most mild leukocytosis is physiologic; repeat CBC in 2-4 weeks; reassure if normal)
3. empiric antibiotics (suspected bacterial infection) Source-directed empiric (e.g., ceftriaxone 1 g IV q24h, levofloxacin 750 mg PO/IV q24h, amox-clav 875/125 mg PO BID) IV or PO per protocol — Neutrophilia + bands + fever + identified focus (pneumonia, UTI, cellulitis, abdominal source) + sepsis criteria → route id.sepsis.core.v1 (Identify focus + targeted antibiotics; blood cultures before antibiotics; route to id.sepsis.core.v1 if SIRS/qSOFA criteria met; de-escalate after culture data)
4. discontinue offending drug (DRESS, drug-induced eos, steroid, G-CSF) N/A medication management one-time — Identified drug trigger: DRESS (AED 2-8 wk, allopurinol, vancomycin, sulfa), G-CSF-induced extreme leukocytosis, steroid demargination (reassure) (Critical for DRESS — stop offending drug + supportive ± steroid 1 mg/kg if severe organ injury; counsel cross-reactivity (aromatic AEDs phenytoin/carbamazepine/lamotrigine); monitor recovery 2-8 weeks)
5. imatinib (CML first-line TKI) 400 mg PO daily (CP-CML); 600-800 mg if AP/BC PO daily — CML confirmed (BCR-ABL+ + Philadelphia chromosome + CP-CML); NCCN PMID 30796100 verify (First-generation TKI; molecular response monitored q3 mo with BCR-ABL PCR; 2nd-gen (dasatinib, nilotinib, bosutinib) for resistance/intolerance; ponatinib for T315I; lifelong therapy unless deep MR achieved + trial of TKI cessation)
6. ibrutinib (CLL — BTK inhibitor) 420 mg PO daily PO daily — CLL symptomatic (Rai II-IV or rapid lymphocytosis doubling or B-sx) + first-line for unfit / del17p / TP53; per Hallek PMID 24600289 verify (BTK inhibitor; AF + bleeding risk; bone marrow + lymph node response; alternative: venetoclax + obinutuzumab; FCR for fit young patients without 17p-)
7. hydroxyurea (cytoreduction for MPN / hyperleukocytosis) 500-1000 mg PO BID (titrate); 50-100 mg/kg/d for hyperleukocytosis emergency PO BID-daily — MPN cytoreduction (PV/ET high-risk); hyperleukocytosis with leukostasis (bridge to chemo/leukapheresis) (Oral cytoreduction; rapid WBC + platelet reduction; monitor CBC weekly initially; ulcer risk; secondary leukemia rare risk; teratogen (avoid pregnancy))
8. systemic corticosteroid (DRESS / EGPA / HES) Prednisone 1 mg/kg PO daily × 2-4 wk taper (DRESS); methylprednisolone 1 g IV × 3 d for severe; mepolizumab 300 mg SC q4w for EGPA/HES PO / IV / SC daily / monthly — DRESS with organ involvement (LFT >5x, AKI, myocarditis); EGPA (vasculitis); HES with organ damage (CRITICAL: rule out Strongyloides BEFORE high-dose steroids (hyperinfection risk); PCP prophylaxis (TMP-SMX or atovaquone) for chronic steroids >4 wk)
9. imatinib (HES with FIP1L1-PDGFRA) 100-400 mg PO daily PO daily — HES with FIP1L1-PDGFRA fusion (M-HES); HES PMID 26573041 verify (TKI for myeloid HES variant; rapid response within weeks; lifelong maintenance; monitor cardiac (rare cardiomyopathy))
10. antiparasitic (ivermectin / albendazole) Ivermectin 200 µg/kg PO × 1-2 doses (Strongyloides); albendazole 400 mg PO BID × 3-7 d (filaria, hookworm); praziquantel for schistosoma PO one-time / short course — Confirmed parasitic eosinophilia (Strongyloides, hookworm, schistosoma, filaria); travel/immigration history; eosinophilia NEJM PMID 25060842 verify (Treat Strongyloides BEFORE any steroid initiation (hyperinfection / disseminated mortality); empiric ivermectin if eos + travel + planned steroids)
11. pertussis vaccine + macrolide (pediatric pertussis) Azithromycin 10 mg/kg/d × 5 days (peds) or 500 mg × 1 then 250 mg × 4 days (adults); Tdap vaccination PO short course — Pediatric lymphocytosis + whoop cough + apnea + cyanosis → pertussis swab PCR confirmation (Macrolide reduces transmission; supportive (oxygen, hydration, hospital if <3 mo or apnea); Tdap booster for contacts)

Non-pharmacologic actions:
- Repeat CBC + smear at 2-4 weeks for mild/transient reactive leukocytosis
- Smoking cessation counseling (chronic mild neutrophilia from smoking)
- Travel medicine consult for parasitic workup
- Drug counseling for DRESS (cross-reactivity aromatic AEDs phenytoin/carbamazepine/lamotrigine; allopurinol HLA-B*5801; abacavir HLA-B*5701)
- Hematology consult: persistent unexplained leukocytosis, suspected leukemia/CML/CLL/MPN, HES, CMML, hyperleukocytosis
- Bone marrow biopsy for definitive diagnosis (leukemia, CMML, MPN, HES)
- Flow cytometry for CLL diagnosis + prognostication
- BCR-ABL PCR + cytogenetics for CML
- JAK2/CALR/MPL panel for MPN
- Cardiac monitoring during HES/EGPA treatment (eosinophilic cardiomyopathy)
- PCP prophylaxis for chronic steroid >4 wk
- Strongyloides screening BEFORE empiric steroid in eosinophilia patients with travel/immigration

AVOID / contraindication checks:
- Do NOT transfuse packed RBCs before cytoreduction in leukostasis — increases blood viscosity
- Avoid leukapheresis in acute promyelocytic leukemia (APL) — can exacerbate DIC
- Screen G6PD before rasburicase (hemolysis risk)
- Most leukocytosis is reactive — treat the cause, not the number; reserve cytoreduction for blastic hyperleukocytosis/leukostasis

Monitoring

Regimen monitoring:
- serial WBC/blast count + peripheral smear
- TLS labs (K, phosphate, calcium, uric acid, LDH, creatinine) q6-12h during cytoreduction
- respiratory + neurologic status for leukostasis progression

Setting (outpatient) monitoring:
- CBC + differential at 1-2 weeks (reactive); 4 weeks (medication-induced post-discontinuation)
- BCR-ABL PCR q3 months for CML on TKI; major molecular response (MMR = BCR-ABL ≤0.1%) at 12 mo target
- CLL: CBC q3 mo (Rai 0-I watch-and-wait); FISH + IGHV mutational status at diagnosis
- DRESS: weekly LFT + Cr + CBC + clinical sx; rash recovery 4-12 weeks
- HES: eos count + organ function (cardiac echo, pulm, neuro) + tryptase
- EGPA: ANCA + asthma control + neurologic exam + steroid taper
- MPN (PV/ET/PMF): hematocrit (target <45% PV), platelet, JAK2 allele burden
- Hyperleukocytosis: serial WBC + lytes + uric acid + LDH for TLS during cytoreduction

Follow-up plan: Hematology referral for persistent unexplained / suspected malignancy / HES / CMML / MPN. Smoking cessation. Travel medicine for parasitic. Drug counseling (DRESS cross-reactivity for AEDs). Pertussis vaccination booster. CLL surveillance with Rai/Binet staging q3-6 mo. CML on TKI lifelong + BCR-ABL PCR q3 mo first year. Recurrence prevention.
- Close-out criterion: long-term plan + follow-up scheduled

Monitoring phase: CBC + differential at 1-2 weeks (reactive); 4 weeks (medication-induced post-discontinuation); 3 months (CLL); BCR-ABL PCR for CML response (major molecular response MMR target); peripheral blast clearance for AML on chemo; eos count + organ function for HES on therapy; TLS panel during induction

Disposition

Current setting: outpatient — Stratify elevated WBC (reactive vs infectious vs inflammatory vs drug-induced vs hematologic malignancy) + identify red flags (blasts, leukostasis, hyperleukocytosis, severe sepsis, DRESS with organ injury) + initial workup + route to dedicated engines for confirmed malignancy or sepsis (Leucocytosis BJH 2019 PMID 33237040 verify; NCCN CML PMID 30796100 verify)

Disposition criteria:
- Continue outpatient: mild reactive, identified benign trigger, chronic CLL Rai 0-I, resolved DRESS
- ED escalation: blasts, hyperleukocytosis, leukostasis, severe sepsis, severe DRESS with organ involvement
- Inpatient: new acute leukemia, CML diagnosis stabilization, severe DRESS, EGPA induction, sepsis
- Telemetry: leukapheresis monitoring, severe DRESS with myocarditis
- ICU: hyperleukocytosis on leukapheresis, sepsis, DRESS multi-organ
- Route to: heme.acute-leukemia.core.v1; id.sepsis.core.v1

Escalation triggers (move to higher acuity):
- Blasts on smear → STAT hematology + BMBx + flow cytometry + cytogenetics + route heme.acute-leukemia.core.v1
- Hyperleukocytosis >100K + leukostasis sx (dyspnea, AMS, retinal hemorrhage, priapism, hypoxia) → ED + leukapheresis + hydroxyurea (route heme.acute-leukemia.core.v1)
- Sepsis criteria met → route id.sepsis.core.v1
- DRESS with severe organ involvement (LFT >5x, AKI, myocarditis, encephalitis) → admit + IV steroid
- Tumor lysis syndrome features (hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia) → ED + allopurinol/rasburicase + IVF
- CML in blast crisis or accelerated phase → emergent hematology + cytoreductive chemo + TKI switch
- CLL with autoimmune cytopenia (AIHA + ITP) → steroid + rituximab
- Eosinophilic pneumonia / cardiomyopathy → admit + steroid
- Refractory hyperleukocytosis despite leukapheresis → ICU
- Pediatric leukocytosis with TAM (transient abnormal myelopoiesis in Down syndrome) → pediatric hematology STAT

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] WBC >100K + blasts on smear + leukostasis symptoms (dyspnea/hypoxia, AMS, retinal hemorrhage, priapism, visual changes) — hyperleukocytosis with leukostasis (AML M4/M5, blast crisis CML, ALL) → ED STAT + hematology + hydroxyurea 50-100 mg/kg + leukapheresis + cytoreductive chemo (route heme.acute-leukemia.core.v1)
- [SEVERE] WBC >50K + chronic + basophilia + eosinophilia + splenomegaly + LAP score LOW + BCR-ABL/Philadelphia chromosome positive — CML; tyrosine kinase inhibitor (imatinib 400 mg PO daily / dasatinib / nilotinib / bosutinib / ponatinib); route heme.acute-leukemia.core.v1 (NCCN CML PMID 30796100 verify)
- [SEVERE] WBC >50K + extreme left shift (bands + metas + myelos) + LAP score HIGH (>100) + identifiable trigger (severe infection, sepsis, paraneoplastic, post-G-CSF, severe burns) — leukemoid reaction (NOT CML); treat underlying; pivot vs CML (LAP score historical PMID 23391835 verify; BCR-ABL preferred modern)

Citations

- 2019 Leucocytosis BJH + 2018 NCCN CML + ASH CLL Hallek + ICH-eosinophilia + AGA DRESS + Surviving Sepsis Campaign [PMID:26760415](https://pubmed.ncbi.nlm.nih.gov/26760415/)
- Cited evidence (PMID 22364832) [PMID:22364832](https://pubmed.ncbi.nlm.nih.gov/22364832/)

Last reconciled with current guidelines: 2026-05-31.
References
  • 2019 Leucocytosis BJH + 2018 NCCN CML + ASH CLL Hallek + ICH-eosinophilia + AGA DRESS + Surviving Sepsis Campaign — PMID:26760415
  • Cited evidence (PMID 22364832) — PMID:22364832