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symptom.leukocytosis-workup.v1

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

symptomacutesubacutechronicundifferentiatedadultgeriatricpediatricoutpatientacute
Start encounter →Print handoutPRODUCTION

Promoted SCAFFOLDED->INTEGRATED 2026-05-31. Decision surface = regimen_axes hyperleukocytosis_leukostasis_bundle (recognize leukostasis -> emergent cytoreduction [hydroxyurea/leukapheresis] -> TLS prophylaxis [rasburicase/allopurinol] -> definitive induction/treat-cause); no registry change. Added resolving workup.acute_leukemia (hyperleukocytosis emergency branch). Evidence re-sourced + PubMed-verified via get_article_metadata: 26760415 (Am Fam Physician 2015 "Evaluation of Patients with Leukocytosis") + 22364832 (Blood Rev 2012 leukostasis/leukapheresis). Prior array was fabricated/placeholder. Cytoreduction RxCUIs are candidate-floor and need RxNav revalidation before PRODUCTION. Phase C shard-3-neuro-sym wave-12 expansion (2026-05-15) — pattern-matches symptom.anemia-workup.v1 (wave-12) and symptom.hyperkalemia-workup.v1 (wave-11). Engine scope: outpatient + ED triage for elevated WBC; covers physiologic stress, infection (band shift), inflammation, steroid demargination, leukemoid reaction (LAP HIGH), CML (LAP LOW + BCR-ABL+), CMML, CLL/lymphocytosis, eosinophilia (HES/EGPA/parasitic/DRESS), basophilia (MPN), monocytosis, pediatric (TAM, pertussis), substance-induced, hyperleukocytosis emergency. Bayesian linkage (LAP vs BCR-ABL pivot, magnitude thresholds, dominant lineage to phenotype map) lives in companion depth bundle _briefs/symptom.leukocytosis-workup.v1.depth.md. 4 sibling-differentiation rows: heme.acute-leukemia.core.v1 + id.sepsis.core.v1 + symptom.anemia-workup.v1 + symptom.thrombocytopenia-workup.v1. 8 severity triggers (≥6 per spec): hyperleukocytosis_leukostasis + cml_bcr_abl_pivot + leukemoid_reaction_LAP_high + hes_organ_damage + dress_organ_involvement + cll_autoimmune_cytopenia + sepsis_neutrophilic_route + pediatric_leukemoid_TAM. KEY SAFETY RULES: (1) Strongyloides screen BEFORE empiric steroid in eosinophilia patients with travel/immigration (hyperinfection mortality). (2) G6PD screen BEFORE rasburicase. (3) Hyperleukocytosis >100K + leukostasis → STAT leukapheresis + hydroxyurea (medical emergency). (4) DRESS — stop drug + supportive ± steroid; counsel cross-reactivity (aromatic AEDs phenytoin/carbamazepine/lamotrigine; HLA-B*5801 allopurinol). (5) APL with high blasts + coagulopathy → ATRA + arsenic + supportive (DIC + bleeding risk). (6) Sepsis criteria met → route id.sepsis.core.v1 within 1 h antibiotics. (7) BCR-ABL PCR replaces historical LAP score for CML diagnosis (LAP retained as adjunct). (8) Pediatric <3 mo persistent leukocytosis → STAT pediatric hematology (TAM, leukemia). Calculators wired (0): LAP / PLASMIC / ELTS_CML / Rai_CLL — schema-blocked; ticketed in shard-3 state file. Panels wired: panel.cbc + panel.inflammation + panel.lft + panel.renal. Schema-blocked: workup.leukocytosis / workup.eosinophilia / calc.LAP_score / calc.PLASMIC — NOT in clinical-tools-registry; manual application in setting playbook required_assessments + ticketed. Regimen_axes intentionally empty — engine is triage-only. Drug ladder (reassurance, antibiotics, drug discontinuation, imatinib, ibrutinib, hydroxyurea, corticosteroid, antiparasitic, macrolide) lives in setting_playbooks.outpatient.drug_actions + setting_playbooks.ed.drug_actions. Setting playbooks: outpatient (primary) + ED (escalation for hyperleukocytosis with leukostasis, blasts, severe sepsis, severe DRESS with organ injury, TLS). SCAFFOLDED status: no workup.leukocytosis in clinical-tools-registry; PRODUCTION audit would fail. Will promote once registry entries land.

Entry points (15)

  • lab_abnormality
    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)
    physiologic_stress_mild_transient
  • lab_abnormality
    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
    infection_bacterial_band_shift
  • lab_abnormality
    WBC mild-mod elevation + neutrophilia + chronic inflammation (RA, IBD, vasculitis, gout flare, MI, pancreatitis, post-op) — inflammatory leukocytosis; treat underlying
    inflammation_non_infectious
  • lab_abnormality
    WBC 11-20K + neutrophilia + recent steroid initiation/escalation (prednisone, IV methylpred) — steroid demargination; benign mechanism (decreased adhesion); reassure
    steroid_induced_demargination
  • lab_abnormality
    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; treat underlying; PIVOT vs CML (LAP LOW in CML) (LAP score PMID 23391835 verify)
    leukemoid_reaction_WBC_gt_50K_LAP_elevated
  • lab_abnormality
    WBC >50K + chronic + basophilia + eosinophilia + spleen + LAP LOW + BCR-ABL/Philadelphia chromosome positive — chronic myeloid leukemia (CML); BCR-ABL PCR + cytogenetics + BMBx; tyrosine kinase inhibitor (imatinib / dasatinib / nilotinib); route heme.acute-leukemia.core.v1 (NCCN CML PMID 30796100 verify)
    CML_BCR_ABL_workup
  • lab_abnormality
    Persistent monocytosis (>1K/µL AND >10%) + cytopenias + dysplasia on smear/BMBx — chronic myelomonocytic leukemia (CMML); WHO classification; route heme.acute-leukemia.core.v1 + hematology
    CMML_chronic_myelomonocytic
  • lab_abnormality
    Lymphocytosis >5K mature small lymphocytes + smudge cells on smear + age >50 → CLL (flow cytometry CD5+CD19+CD23+); peds with whoop cough → pertussis; mononucleosis (EBV, CMV) → atypical lymphocytes (CLL Hallek PMID 24600289 verify)
    lymphocytosis_CLL_pertussis_viral
  • lab_abnormality
    Eosinophilia >500/µL (mild 500-1500, mod 1500-5000, severe >5000) → parasites (Strongyloides, schistosoma, filaria, hookworm), drug (DRESS, sulfa, AED), EGPA (asthma + sinusitis + multifocal neuropathy + ANCA), Löffler syndrome, allergic, HES (>6 mo + organ damage); workup HES if persistent (HES PMID 26573041 verify; eosinophilia NEJM PMID 25060842 verify)
    eosinophilia_parasites_EGPA_Loffler_HES
  • lab_abnormality
    Basophilia >100/µL or >1% — strong specificity for MPN (CML, PV, ET, PMF); rare in benign reactive; check JAK2/CALR/MPL + BCR-ABL + BMBx; route heme.acute-leukemia.core.v1
    basophilia_CML_MPN
  • lab_abnormality
    Monocytosis (>1K/µL) + chronic infection (TB, endocarditis, fungal) + autoimmune (RA, SLE, sarcoidosis) + recovery from chemo nadir → reactive monocytosis; persistent >3 mo + dysplasia → consider CMML
    monocytosis_chronic_infection_autoimmune
  • lab_abnormality
    Pediatric (<3 mo) WBC >25K-50K + bandemia + congenital infection (sepsis, parvovirus, HSV, syphilis) OR Down syndrome with TAM (transient abnormal myelopoiesis) — pediatric leukemoid; rule out leukemia; pediatric hematology consult
    pediatric_leukemoid_reaction
  • lab_abnormality
    WBC mild elevation + chronic smoking + cocaine use (catecholamine-driven demargination) + cannabinoid hyperemesis recovery — substance-related leukocytosis; counsel cessation; resolves with abstinence
    cocaine_smoking_induced
  • lab_abnormality
    New medication (aromatic AEDs phenytoin/carbamazepine, allopurinol, vancomycin, sulfa) 2-8 wk prior + rash + fever + lymphadenopathy + eosinophilia + multi-organ (LFT, AKI, myocarditis) — DRESS syndrome; STOP offending drug + supportive + steroid 1 mg/kg if severe organ involvement
    DRESS_with_eosinophilia
  • lab_abnormality
    WBC >100K with blasts + leukostasis sx (dyspnea, hypoxia, AMS, retinal hemorrhage, priapism) — hyperleukocytosis with leukostasis (AML M4/M5 / blast crisis CML / ALL) → ED + STAT hematology + hydroxyurea or leukapheresis + cytoreductive chemo; route heme.acute-leukemia.core.v1
    hyperleukocytosis_emergency_blast_crisis

Required inputs (27)

  • agerequired
    demographic • used at CONTEXT
    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
  • sexrequired
    demographic • used at CONTEXT
    Sex shifts: pregnancy → physiologic neutrophilia 12-15K; gestational/lactational; pediatric trisomy 21 → TAM
  • wbc_count_with_differentialrequired
    lab • used at FRAME
    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_blasts_left_shift_smudge_atypical_döhlerequired
    lab • used at INITIAL_WORKUP
    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
  • fever_chills_focal_infection_sxrequired
    symptom • used at ENTRY
    Fever + focal sx (cough/dysuria/cellulitis/abdominal pain) → reactive infection; B-sx (fever + drenching sweats + weight loss) → lymphoma/leukemia
  • B_symptoms_weight_loss_night_sweats_fatiguerequired
    symptom • used at ENTRY
    Drenching night sweats + weight loss >10% + fever + fatigue → lymphoma / CLL / CMML; pruritus → MPN / Hodgkin
  • asthma_sinusitis_neuropathy_skin_rash
    symptom • used at ENTRY
    Asthma + sinusitis + multifocal neuropathy + eosinophilia → EGPA (formerly Churg-Strauss); rash + drug → DRESS; allergic dx → atopic eosinophilia
  • leukostasis_sx_dyspnea_amS_retinal_priapismrequired
    symptom • used at RED_FLAGS
    Hyperleukocytosis with leukostasis: dyspnea/hypoxia + AMS + retinal hemorrhage + priapism + visual changes → EMERGENT (AML M4/M5 + blast crisis CML/ALL) → leukapheresis + hydroxyurea + STAT hematology
  • recent_steroid_or_growth_factorrequired
    history • used at CONTEXT
    Recent steroid (prednisone, IV methylpred) → demargination neutrophilia (benign); G-CSF / GM-CSF → drug-induced leukocytosis; lithium → benign neutrophilia
  • smoking_cocaine_pregnancy_postpartum
    history • used at CONTEXT
    Smoking → mild chronic; cocaine → catecholamine demargination; pregnancy → 12-15K physiologic; post-partum / lactational → transient
  • travel_or_immigration_for_parasites
    history • used at CONTEXT
    Travel / immigration (Strongyloides, schistosoma, filaria, hookworm, malaria) + eosinophilia → parasitic; check stool O&P, serology, Strongyloides before steroids
  • medication_dress_aed_allopurinol_sulfa_vancorequired
    history • used at CONTEXT
    New medication (aromatic AED phenytoin/carbamazepine, allopurinol, vancomycin, sulfa, lamotrigine, dapsone) 2-8 wk prior + rash + fever + eosinophilia → DRESS; stop drug + supportive
  • chronic_disease_RA_IBD_HIV_malignancy
    history • used at CONTEXT
    RA / IBD / vasculitis / sarcoidosis → reactive leukocytosis; HIV → atypical lymphocytes; malignancy → paraneoplastic leukemoid / chemo-induced
  • splenomegaly_lymphadenopathy_palpation
    history • used at CONTEXT
    Splenomegaly → CML, CLL, lymphoma, MPN, sickle/thal; lymphadenopathy → lymphoma, CLL, viral, TB; both → hematologic malignancy workup
  • temprequired
    vital • used at CONTEXT
    Fever + leukocytosis → infection (route id.sepsis.core.v1 if criteria); fever + rash + LAD + eos → DRESS
  • hrrequired
    vital • used at CONTEXT
    Tachycardia + leukocytosis + fever → sepsis; high WBC + fever + hypotension → sepsis route
  • sbprequired
    vital • used at CONTEXT
    Hypotension + leukocytosis → sepsis; hypertension + smoking/cocaine → substance-related; route id.sepsis.core.v1 if criteria met
  • inflammatory_markers_crp_esr_procalcitonin
    lab • used at INITIAL_WORKUP
    CRP / ESR / procalcitonin → bacterial infection prediction; procalcitonin >0.5 ng/mL favors bacterial; CRP very high (>100) → severe inflammation/infection
  • LAP_score_for_CML_pivot
    lab • used at BRANCHING_WORKUP
    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_for_CML
    lab • used at BRANCHING_WORKUP
    BCR-ABL PCR (Philadelphia chromosome) — diagnostic for CML; replaces LAP in modern workup; route heme.acute-leukemia.core.v1
  • flow_cytometry_CD5_CD19_CD23_for_CLL
    lab • used at BRANCHING_WORKUP
    Flow cytometry CD5+ CD19+ CD23+ → CLL diagnosis (Matutes score ≥4); FISH for prognostic markers (17p-, 11q-, +12, 13q-)
  • jak2_calr_mpl_for_MPN
    lab • used at BRANCHING_WORKUP
    JAK2 V617F mutation + CALR + MPL → PV/ET/PMF (MPN); EPO low → PV; thrombopoietin elevated → ET; route heme.acute-leukemia.core.v1
  • stool_OandP_strongyloides_for_eosinophilia
    lab • used at BRANCHING_WORKUP
    Stool O&P + Strongyloides serology + filaria + schistosoma + hookworm — parasitic eosinophilia workup; MUST exclude Strongyloides BEFORE steroids (hyperinfection)
  • ANCA_for_EGPA_vasculitis
    lab • used at BRANCHING_WORKUP
    ANCA (p-ANCA / MPO) + asthma + sinusitis + eos + multifocal neuropathy → EGPA (Churg-Strauss); only 40-60% ANCA+
  • tryptase_for_HES_mastocytosis
    lab • used at BRANCHING_WORKUP
    Serum tryptase + bone marrow + KIT D816V → mastocytosis with eos; HES workup (FIP1L1-PDGFRA, T-cell clonality, idiopathic)
  • epstein_barr_cmv_hiv_for_atypical_lymphs
    lab • used at BRANCHING_WORKUP
    Monospot / EBV VCA IgM / CMV IgM / HIV / toxoplasma → atypical lymphocytosis viral; pertussis → swab PCR if suspected
  • bone_marrow_biopsy_if_unclear_leukemia_MDS_CMML_HES
    imaging • used at BRANCHING_WORKUP
    BMBx if persistent unexplained leukocytosis, suspected leukemia (blasts), suspected CMML (monocytosis + dysplasia), HES (>6 mo + organ damage), MDS, MPN

12-phase flow (12)

  1. 1FRAME
    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)
    inputs: wbc_count_with_differential
    advance: magnitude + lineage anchored
  2. 2ENTRY
    Fever + focal infection sx → infectious; B-symptoms (fever + sweats + weight loss) → lymphoma/leukemia; asthma + sinusitis + neuropathy + rash → EGPA / DRESS; leukostasis sx → emergent
    inputs: fever_chills_focal_infection_sx, B_symptoms_weight_loss_night_sweats_fatigue, leukostasis_sx_dyspnea_amS_retinal_priapism
    advance: symptom cluster identified
  3. 3CONTEXT
    Age + sex + vitals + medication review (steroid, G-CSF, lithium, AED, allopurinol, vanco, sulfa) + smoking/cocaine + pregnancy + travel/parasites + chronic disease (RA, IBD, HIV, malignancy) + splenomegaly + lymphadenopathy
    inputs: age, sex, temp, hr, sbp, recent_steroid_or_growth_factor, smoking_cocaine_pregnancy_postpartum, travel_or_immigration_for_parasites, medication_dress_aed_allopurinol_sulfa_vanco, chronic_disease_RA_IBD_HIV_malignancy, splenomegaly_lymphadenopathy_palpation
    advance: context complete
  4. 4RED_FLAGS
    Hyperleukocytosis with leukostasis (WBC >100K + dyspnea/hypoxia + AMS + retinal hemorrhage + priapism) → STAT ED + hematology + leukapheresis + hydroxyurea (route heme.acute-leukemia.core.v1); blasts on smear → STAT BMBx + flow cytometry; sepsis criteria → route id.sepsis.core.v1; DRESS with organ involvement (LFT, AKI, myocarditis) → stop drug + supportive ± steroids
    inputs: leukostasis_sx_dyspnea_amS_retinal_priapism, wbc_count_with_differential, smear_review_blasts_left_shift_smudge_atypical_döhle
    advance: no immediate life-threat OR routed
  5. 5INITIAL_WORKUP
    CBC + differential + smear (CRITICAL — blasts, smudge, atypical lymph, dysplasia, Döhle, bands, basophils); inflammatory markers (CRP, ESR, procalcitonin); BMP + LFT + LDH + uric acid (TLS risk); HIV / EBV / CMV serologies if atypical lymphs; CXR / cultures if infection suspected
    inputs: smear_review_blasts_left_shift_smudge_atypical_döhle, inflammatory_markers_crp_esr_procalcitonin
    actions: panel.cbc, panel.inflammation, panel.lft, panel.renal
    advance: smear + inflammatory + chemistries reviewed
  6. 6BRANCHING_WORKUP
    Neutrophilia + bands + fever → cultures + identify source + abx (route id.sepsis.core.v1 if criteria). Lymphocytosis + atypical → viral serologies (EBV, CMV, HIV, mono); persistent + smudge + age >50 → flow cytometry CD5+CD19+CD23+ (CLL). Eosinophilia → stool O&P + Strongyloides + ANCA + tryptase + drug review; persistent >6 mo + organ → HES workup (FIP1L1-PDGFRA + T-cell). Basophilia → JAK2/CALR/MPL + BCR-ABL → MPN (route heme.acute-leukemia.core.v1). WBC >50K → LAP score (high → leukemoid reaction; low → CML) → BCR-ABL PCR + BMBx + cytogenetics. Monocytosis + dysplasia → BMBx for CMML. Pediatric → pertussis swab + pediatric hematology if persistent.
    inputs: LAP_score_for_CML_pivot, BCR_ABL_PCR_for_CML, flow_cytometry_CD5_CD19_CD23_for_CLL, jak2_calr_mpl_for_MPN, stool_OandP_strongyloides_for_eosinophilia, ANCA_for_EGPA_vasculitis, tryptase_for_HES_mastocytosis, epstein_barr_cmv_hiv_for_atypical_lymphs, bone_marrow_biopsy_if_unclear_leukemia_MDS_CMML_HES
    advance: definitive cause identified or routed
  7. 7DIFFERENTIAL
    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)
    advance: differential ranked
  8. 8RISK_STRATIFICATION
    Severity by WBC magnitude + blasts + leukostasis; hyperleukocytosis >100K + blasts → emergent; sepsis criteria → emergent; DRESS with multi-organ → emergent; CLL prognosis (Rai/Binet, IGHV, FISH cytogenetics); CML risk (ELTS / Sokal)
    advance: risk + urgency documented
  9. 9TREATMENT
    Reactive → reassure + monitor; infectious → empiric antibiotics + source control; DRESS → stop drug + supportive ± systemic steroid 1 mg/kg if severe; CML → TKI (imatinib 400 mg PO daily / dasatinib / nilotinib / bosutinib / ponatinib); acute leukemia → induction chemo (route heme.acute-leukemia.core.v1); CLL → ibrutinib / venetoclax + obinutuzumab / FCR (Hallek PMID 24600289 verify); MPN → hydroxyurea / phlebotomy (PV) / aspirin / JAK inhibitor; HES → corticosteroid + hydroxyurea + imatinib (FIP1L1-PDGFRA); EGPA → steroid + cyclophosphamide/rituximab + mepolizumab; hyperleukocytosis → leukapheresis + hydroxyurea 50-100 mg/kg + cytoreductive chemo; parasites → ivermectin/albendazole + treat Strongyloides BEFORE steroid
    inputs: wbc_count_with_differential, smear_review_blasts_left_shift_smudge_atypical_döhle
    advance: definitive treatment initiated or routed
  10. 10DISPOSITION
    Outpatient: mild/reactive/medication-induced; chronic CLL Rai 0-I; resolved DRESS without organ injury. ED: leukostasis, hyperleukocytosis, blasts, severe sepsis, severe DRESS with organ involvement. Inpatient: new leukemia, CML diagnosis, severe DRESS, EGPA, sepsis. ICU: hyperleukocytosis with leukostasis on leukapheresis; sepsis. Route to: heme.acute-leukemia.core.v1; id.sepsis.core.v1.
    advance: disposition assigned
  11. 11MONITORING
    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
    advance: response trajectory documented
  12. 12FOLLOWUP
    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.
    advance: long-term plan + follow-up scheduled