12-phase flow (12)

1. 1FRAME
   Establish the VTE phenotype (DVT vs PE vs combined; proximal vs distal DVT; upper-extremity vs lower-extremity; provoked vs unprovoked; cancer-associated; pregnancy-associated) — ASH 2020 PMID 33007077
   inputs: leg_swelling_pain, dyspnea_chest_pain_hemoptysis, pregnancy_status, active_cancer_status
   advance: VTE location and population context defined — ASH 2020
2. 2ENTRY
   Document chief complaint and time course; capture incidental imaging findings; document setting (ED vs outpatient vs inpatient surveillance) — ASH 2018 dx PMID 30482764
   inputs: leg_swelling_pain, dyspnea_chest_pain_hemoptysis
   advance: Suspected DVT or PE pattern documented; setting recorded — ASH 2018 dx
3. 3CONTEXT
   Capture VTE risk factors (recent surgery, hospitalization, trauma, immobilization, hormonal therapy, prior VTE, family history, thrombophilia), bleeding risk factors, age, weight, CrCl, pregnancy status, active cancer, antiphospholipid features — CHEST 2021 PMID 34352278
   inputs: age, body_weight, pregnancy_status, active_cancer_status, recent_major_surgery_immobilization, prior_vte, bleeding_history, heart_rate, oxygen_saturation
   advance: Patient-specific risk factors and population context documented — CHEST 2021
4. 4RED_FLAGS
   Screen for HIGH-RISK PE (ESC 2019 — sustained hypotension SBP <90 for ≥15 min OR requiring vasopressors OR cardiac arrest) → directly to systemic thrombolysis pathway (alteplase 100 mg / 2 h or 0.6 mg/kg max 50 mg over 15 min if arrest; tenecteplase weight-based). Phlegmasia cerulea dolens (massive ileofemoral DVT with venous gangrene) → catheter-directed thrombolysis or thrombectomy. Pregnancy with hypoxia → emergent CTPA/V-Q + LMWH bolus. Active major bleeding contraindicating anticoagulation → IVC filter (PREPIC2 PMID 25919526 — only when anticoagulation absolutely contraindicated)
   inputs: blood_pressure, oxygen_saturation, heart_rate
   actions: workup.pe_full
   advance: High-risk PE excluded or treated; massive DVT addressed; absolute contraindication to anticoagulation evaluated — ESC 2019
5. 5INITIAL_WORKUP
   Pretest probability with Wells DVT or Wells PE / Geneva; PERC rule in low-PTP PE; age-adjusted D-dimer (age x 10 ng/mL if >50; ADJUST-PE PMID 24643601) if low/intermediate PTP; compression ultrasound (DVT) or CTPA (PE first-line; V-Q scan if contrast allergy or pregnancy with normal CXR); CBC + creatinine + LFT + INR for anticoagulation baseline — ASH 2018 dx PMID 30482764
   inputs: d_dimer, cbc_platelets, creatinine_crcl, lft, compression_ultrasound, ctpa
   actions: calc.wells_dvt, calc.wells_pe, calc.perc, panel.cbc, panel.coag, panel.renal, panel.lft, workup.le_edema, workup.pe_full
   advance: Pretest probability documented; D-dimer interpreted appropriately for PTP; confirmatory imaging obtained or excluded — ASH 2018 dx
6. 6BRANCHING_WORKUP
   For PE: assess RV strain (echo, troponin, BNP) to refine ESC 2019 risk category; calculate sPESI (calc.spesi) and BOVA. For unprovoked VTE: age-appropriate cancer screening (NOT whole-body CT — limited yield per SOME trial); antiphospholipid antibody testing (LAC + anticardiolipin + anti-beta2-GP1; triple-positive = warfarin per TRAPS PMID 30002145). For pregnancy: D-dimer unreliable; compression ultrasound or low-dose perfusion scan / CTPA per ATS/STR. For thrombophilia: defer hereditary thrombophilia testing ≥3 mo off anticoagulation (cost/utility limited; LAC may be tested anytime)
   inputs: troponin, bnp_ntprobnp, echo, antiphospholipid_syndrome
   actions: calc.spesi, panel.cardiac
   advance: RV strain assessed; antiphospholipid syndrome status documented; cancer status assessed if unprovoked — ESC 2019 + ASH 2020
7. 7DIFFERENTIAL
   For DVT: differentiate from cellulitis (warmth + erythema + leukocytosis), ruptured Baker cyst (sudden onset + posterior calf), superficial thrombophlebitis (palpable cord), lymphedema (chronic, bilateral, no pitting late), hematoma. For PE: differentiate from pneumonia (fever + infiltrate), ACS (ECG changes + troponin pattern), aortic dissection (tearing pain + widened mediastinum), pneumothorax (CXR), CHF exacerbation (BNP + bilateral edema) — ASH 2018 dx
   advance: VTE confirmed and alternatives excluded — ASH 2018 dx
8. 8RISK_STRATIFICATION
   PE per ESC 2019 — HIGH RISK (hemodynamic instability / shock — direct to thrombolysis); INTERMEDIATE-HIGH RISK (sPESI ≥1 + RV dysfunction on imaging + elevated cardiac biomarker — close ICU/step-down monitoring; consider catheter-directed thrombolysis or rescue systemic thrombolysis if decompensation); INTERMEDIATE-LOW (sPESI ≥1 + ONE of RV dysfunction or biomarker — ward anticoagulation); LOW RISK (sPESI 0 — HESTIA-screen for outpatient management). DVT proximal vs distal: proximal = treat full course; isolated distal in low-risk patient = surveillance ultrasound with selective anticoagulation per CHEST 2021 PMID 34352278
   inputs: blood_pressure, troponin, bnp_ntprobnp, echo
   actions: calc.spesi, calc.wells_pe, calc.wells_dvt
   advance: PE risk class assigned; DVT anatomic location documented; outpatient vs inpatient decision made — ESC 2019
9. 9TREATMENT
   Anticoagulation: DOAC first-line for most adults — apixaban 10 mg BID × 7 d → 5 mg BID (AMPLIFY PMID 23808982); rivaroxaban 15 mg BID × 21 d → 20 mg daily with food (EINSTEIN-PE PMID 22449293); dabigatran 150 mg BID after ≥5 d parenteral lead-in (RE-COVER PMID 19966341); edoxaban 60 mg daily after ≥5 d parenteral lead-in (Hokusai). Cancer-associated VTE: apixaban (Caravaggio PMID 32223112) for most; LMWH (enoxaparin 1 mg/kg SC BID or dalteparin 200 IU/kg → 150 IU/kg) preferred for luminal-GI / GU primaries (SELECT-D PMID 29746227 + Hokusai cancer PMID 29231094 showed higher GI bleeding with rivaroxaban / edoxaban). Pregnancy: LMWH ONLY; switch to UFH at ≥37 wk for neuraxial. Triple-positive APS: warfarin INR 2-3 (TRAPS PMID 30002145). HIGH-RISK PE: systemic thrombolysis with alteplase 100 mg / 2 h IV (or 0.6 mg/kg max 50 mg over 15 min for arrest) OR tenecteplase by weight; catheter-directed thrombolysis as alternative if high bleeding risk. INTERMEDIATE-HIGH PE: anticoagulation + close monitoring; rescue thrombolysis only on decompensation (PEITHO PMID 24716681 — primary thrombolysis reduces decompensation but increases major bleeding + ICH). IVC filter ONLY if absolute contraindication to anticoagulation in acute VTE (PREPIC2 negative for added filter benefit; PMID 25919526)
   inputs: creatinine_crcl, body_weight, pregnancy_status, active_cancer_status, antiphospholipid_syndrome, bleeding_history
   advance: Anticoagulant selected with dose adjusted for weight/renal/age/population; thrombolysis decision made for PE; patient education delivered — ASH 2020 PMID 33007077
10. 10DISPOSITION
    OUTPATIENT for HESTIA-negative low-risk PE (sPESI 0 + hemodynamically stable + no high bleeding risk + social/follow-up arranged) and most proximal DVT without phlegmasia. WARD for most intermediate-low-risk PE on anticoagulation, symptomatic patients needing supportive care, and patients with comorbidity-driven concerns. ICU for high-risk PE, intermediate-high PE under observation for decompensation, post-thrombolysis monitoring, massive DVT with phlegmasia, or hemodynamic instability — ESC 2019
    advance: Disposition selected and handoff documented — ESC 2019
11. 11MONITORING
    On DOAC: CBC + creatinine annually (q6 mo if CrCl 30-60; q3 mo if 15-30); LFT annually; bleeding surveillance at each visit. On warfarin: INR q1-2 weeks during initiation, q4 weeks when stable; TTR target >65%; CBC at least annually. On LMWH in pregnancy: anti-Xa monitoring is OPTIONAL outside extremes of weight / renal impairment; CBC for HIT surveillance. Compliance review; drug-interaction review; symptom-recurrence and bleeding-symptom review at every visit — ASH 2020
    inputs: creatinine_crcl, cbc_platelets, lft
    advance: Monitoring schedule active; no breakthrough or bleeding events — ASH 2020
12. 12FOLLOWUP
    Duration at 3 mo per CHEST 2021 PMID 34352278: PROVOKED VTE (transient major risk factor — surgery, hospitalization, trauma within 3 mo) → STOP at 3 mo; UNPROVOKED VTE → consider INDEFINITE (especially male, recurrent, persistent D-dimer positivity); CANCER-associated → continue until cancer resolved or anticoagulation no longer tolerated; RECURRENT unprovoked → INDEFINITE; ANTIPHOSPHOLIPID syndrome triple-positive → INDEFINITE warfarin. AMPLIFY-EXT PMID 23216615 supports apixaban 2.5 mg BID for extended treatment with similar efficacy and lower bleeding vs 5 mg BID. Annual reassessment of indication, bleeding risk (HAS-BLED), renal function. Patient education on bleeding precautions, dietary consistency (warfarin), missed-dose handling, medical-alert ID
    advance: Duration plan documented; annual reassessment scheduled; chronic-management handoff to heme.anticoagulation-management.core.v1 if extended treatment — CHEST 2021