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heme.vte.core.v1PRODUCTION
heme.vte.core.v1

Venous thromboembolism — DVT + PE (diagnosis, anticoagulation, duration)

hematologyacutesubacuteadultpregnancygeriatric
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

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

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Actions
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Advance rule
Set
Advance when

VTE location and population context defined — ASH 2020

Patient inputs (22)

Tachycardia is a Wells PE criterion (HR >100); persistent tachycardia post-anticoagulation suggests RV failure or recurrent PE

Hypoxia (SpO2 <94% on room air) supports PE pretest probability; persistent hypoxia post-anticoagulation suggests submassive PE — ESC 2019

Age >50 invalidates PERC; age drives age-adjusted D-dimer cutoff (age x 10 ng/mL if >50) — ADJUST-PE (PMID 24643601)

Weight <60 kg triggers apixaban dose-reduction criteria; extreme obesity (>120 kg or BMI >40) limits DOAC PK data — ISTH 2021 guidance

Pregnancy MANDATES LMWH (DOAC crosses placenta; warfarin teratogenic 6-12 wk + fetal anticoagulation throughout) — CHEST 2021 PMID 34352278

Active cancer changes regimen to apixaban (Caravaggio) or LMWH (luminal GI/GU primary, dalteparin/enoxaparin); duration becomes indefinite while cancer active

Transient major risk factor within 3 mo (surgery, hospitalization, trauma) defines PROVOKED VTE — anticoagulation typically stops at 3 mo

Prior unprovoked VTE shifts toward indefinite anticoagulation; prior provoked VTE allows 3-mo course if same transient trigger

Prior major bleeding (GI, intracranial) drives agent selection (apixaban has lowest GI bleed) and may shift to lower-dose extended treatment — CHEST 2021

Baseline platelets needed for bleeding-risk assessment and HIT surveillance; thrombocytopenia <50 may contraindicate anticoagulation

Cockcroft-Gault CrCl (not eGFR — DOAC labels use C-G) drives DOAC dose-adjustment: dabigatran avoid <30, apixaban dose-reduce per criteria, rivaroxaban avoid <15, edoxaban not in AF if CrCl >95

Child-Pugh B/C is a relative contraindication to rivaroxaban and apixaban; hepatic dysfunction also affects warfarin PD via CYP2C9

Sustained hypotension (SBP <90 for ≥15 min, or requiring vasopressors) defines high-risk PE per ESC 2019 — triages directly to systemic thrombolysis pathway

Triple-positive antiphospholipid syndrome (lupus anticoagulant + anticardiolipin + anti-beta2-GP1) MANDATES warfarin (DOAC inferior — TRAPS PMID 30002145)

Unilateral leg swelling, pain, warmth, erythema drives Wells DVT score and compression ultrasound trigger — ASH 2018 dx (PMID 30482764)

Dyspnea, pleuritic chest pain, hemoptysis, syncope are core PE entry symptoms; absence drops PE pretest probability via PERC — ASH 2018 dx

D-dimer is the cornerstone of low-PTP rule-out; age-adjusted cutoff (age x 10 if >50) raises specificity without losing sensitivity — ADJUST-PE PMID 24643601

Compression ultrasound is the first-line imaging for suspected DVT in all settings; sensitive for proximal DVT, less for calf-only DVT (consider repeat in 1 wk)

CTPA is the first-line imaging for suspected PE in most settings; V/Q scan if contrast allergy, pregnancy with normal CXR, or CKD/AKI

Elevated hsTroponin in PE indicates RV strain; combined with elevated BNP and RV dysfunction = intermediate-high-risk PE (ESC 2019)

BNP elevation in PE supports RV strain; combined with troponin and echo defines intermediate-high-risk PE category

Bedside echo assesses RV strain and dilation in hemodynamically unstable patients; supports high-risk PE diagnosis when CTPA unavailable

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Severity triggers (6)

6 need judgement
  • informationallife_threateninghigh_risk_pe_hemodynamic_instability
    Confirmed PE with sustained SBP <90 for ≥15 min, vasopressor requirement, or cardiac arrest — ESC 2019
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningphlegmasia_cerulea_dolens
    Massive ileofemoral DVT with cyanotic ischemic limb (phlegmasia cerulea dolens) — limb-threatening
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningmajor_bleeding_on_anticoagulation
    Major bleeding (GI, ICH, retroperitoneal, hemodynamically significant) on anticoagulation for VTE — ANNEXA-4 + RE-VERSE AD
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereintermediate_high_risk_pe_with_decompensation
    Intermediate-high-risk PE (sPESI ≥1 + RV dysfunction + elevated cardiac biomarker) with clinical decompensation (worsening hypotension, hypoxia, tachycardia) — ESC 2019
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_pe_with_hypoxia
    Pregnant patient with suspected or confirmed PE and SpO2 <94% or hemodynamic compromise — CHEST 2021
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecancer_associated_vte_with_gi_bleed_on_doac
    GI bleeding in patient with cancer-associated VTE on DOAC (especially rivaroxaban or edoxaban with luminal-GI primary) — SELECT-D + Hokusai cancer
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

INITIAL_WORKUPrequiredDrives risk stratification
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Recommended regimen

Anticoagulation initiation for VTE — non-cancer, non-pregnancy — ASH 2020 PMID 33007077; CHEST 2021 PMID 34352278
axis: anticoagulation_initiation_non_cancerstep 1 - Apixaban — single-drug strategy (no parenteral lead-in) — AMPLIFY PMID 23808982
Selected step "Apixaban — single-drug strategy (no parenteral lead-in) — AMPLIFY PMID 23808982" — Adult VTE without active cancer, pregnancy, mechanical valve, triple-positive APS, severe renal failure (CrCl <15), or extreme weight (>120 kg); preferred for GI bleeding history (lowest GI bleed of DOACs)
  • apixaban
    first line
    direct_factor_Xa_inhibitor
    10 mg PO BID x 7 days, then 5 mg PO BID • PO • BID (max: 10 mg BID induction then 5 mg BID)
    triggers: vte_treatment, no_active_cancer, no_pregnancy, crcl_ge_15, no_triple_positive_aps
    AMPLIFY (Agnelli NEJM 2013 PMID 23808982): apixaban non-inferior to enoxaparin/warfarin for recurrent VTE/death with significantly less major bleeding (0.6% vs 1.8%, RR 0.31). No parenteral lead-in. Lowest GI bleed of DOACs.
    rxcui 1364430

outpatient playbook — drug actions (3)

  1. 1. apixaban
    rxcui 1364430
    5 mg PO BID (after 7-day 10 mg BID induction) • PO • BID
    trigger: Maintenance for adult VTE — AMPLIFY
    First-line maintenance; lowest GI bleed of DOACs
  2. 2. apixaban
    rxcui 1364430
    2.5 mg PO BID • PO • BID
    trigger: Extended treatment after ≥6 mo full-dose — AMPLIFY-EXT PMID 23216615
    Reduced-dose extended treatment for unprovoked VTE with lower bleeding risk
  3. 3. warfarin
    rxcui 11289
    INR-adjusted to 2-3 • PO • daily
    trigger: Triple-positive APS or mechanical valve — TRAPS PMID 30002145
    Warfarin retained for APS and mechanical valves where DOACs inferior or contraindicated

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Unilateral leg swelling + calf pain suggesting DVT — Wells DVT score + compression ultrasound (ASH 2018 dx PMID 30482764); Pleuritic chest pain + dyspnea ± hemoptysis suggesting PE — Wells PE / PERC / age-adjusted D-dimer / CTPA (ASH 2018 dx; ESC 2019 PE PMID 31504429); Syncope with hypoxia / tachycardia / RV strain — high-risk PE workup with bedside echo (ESC 2019 PMID 31504429).

Objective

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

Assessment

**Venous thromboembolism — DVT + PE (diagnosis, anticoagulation, duration)** (heme.vte.core.v1).
Phenotype framing: 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
Scope: 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

No severity triggers fired against current inputs.

Plan

Regimen axis: **Anticoagulation initiation for VTE — non-cancer, non-pregnancy — ASH 2020 PMID 33007077; CHEST 2021 PMID 34352278** — step "Apixaban — single-drug strategy (no parenteral lead-in) — AMPLIFY PMID 23808982".
1. apixaban 10 mg PO BID x 7 days, then 5 mg PO BID PO BID (direct_factor_Xa_inhibitor, first line) — AMPLIFY (Agnelli NEJM 2013 PMID 23808982): apixaban non-inferior to enoxaparin/warfarin for recurrent VTE/death with significantly less major bleeding (0.6% vs 1.8%, RR 0.31). No parenteral lead-in. Lowest GI bleed of DOACs.

Setting playbook (outpatient) — Initial outpatient management for HESTIA-negative VTE and longitudinal management of stable VTE on anticoagulation through ≥3-12 months — CHEST 2021 PMID 34352278
2. apixaban 5 mg PO BID (after 7-day 10 mg BID induction) PO BID — Maintenance for adult VTE — AMPLIFY (First-line maintenance; lowest GI bleed of DOACs)
3. apixaban 2.5 mg PO BID PO BID — Extended treatment after ≥6 mo full-dose — AMPLIFY-EXT PMID 23216615 (Reduced-dose extended treatment for unprovoked VTE with lower bleeding risk)
4. warfarin INR-adjusted to 2-3 PO daily — Triple-positive APS or mechanical valve — TRAPS PMID 30002145 (Warfarin retained for APS and mechanical valves where DOACs inferior or contraindicated)

Non-pharmacologic actions:
- Patient education: bleeding precautions, missed-dose handling, medical alert ID — ASH 2020
- Compression stockings for proximal DVT (modest evidence; CHEST 2021 conditional) — CHEST 2021
- Pregnancy / contraception counseling for women of reproductive age — CHEST 2021
- Anticoagulation clinic referral if on warfarin — ASH 2020
- Annual reassessment of duration — CHEST 2021

AVOID / contraindication checks:
- Active_major_bleeding_anticoagulation_held — CHEST 2021
- Platelets_lt_50_relative_ci_anticoagulation — ASH 2020
- DOACs_CI_with_mechanical_heart_valves_RE_ALIGN — Eikelboom NEJM 2013
- DOACs_inferior_to_warfarin_in_triple_positive_APS — TRAPS Pengo Blood 2018 PMID 30002145
- Dabigatran_CI_if_CrCl_lt_30_US_labeling — ASH 2020
- Rivaroxaban_must_be_taken_with_food_bioavailability — Patel NEJM 2011
- Apixaban_dose_reduce_2_of_3_criteria_age_ge_80_weight_le_60_Cr_ge_1_5 — Granger NEJM 2011
- Strong_dual_P_gp_CYP3A4_inhibitors_ketoconazole_ritonavir_CI_with_DOACs — ASH 2020
- Warfarin_requires_5d_parenteral_bridge_until_INR_ge_2_for_24h — CHEST 2021

Monitoring

Regimen monitoring:
- DOAC CBC creatinine LFT annually q6mo if CrCl 30 60 q3mo if 15 30 — ASH 2020
- warfarin INR q1 2weeks during initiation q4weeks stable TTR target gt 65pct — CHEST 2021
- symptom recurrence and bleeding assessment every visit — ASH 2020
- medication compliance review every visit — ASH 2020

Setting (outpatient) monitoring:
- CBC + creatinine per schedule (q3-12 mo) — ASH 2020
- LFT annually — ASH 2020
- INR if on warfarin (q1-2 weeks initiation, q4 weeks stable, TTR > 65%) — CHEST 2021
- Annual recurrence and bleeding-risk reassessment — ASH 2020

Follow-up plan: 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
- Close-out criterion: Duration plan documented; annual reassessment scheduled; chronic-management handoff to heme.anticoagulation-management.core.v1 if extended treatment — CHEST 2021

Monitoring phase: 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

Disposition

Current setting: outpatient — Initial outpatient management for HESTIA-negative VTE and longitudinal management of stable VTE on anticoagulation through ≥3-12 months — CHEST 2021 PMID 34352278

Disposition criteria:
- Continue outpatient if stable on anticoagulation without complications — CHEST 2021
- Refer to hematology for recurrent VTE on therapeutic AC, APS, or complex perioperative management — ASH 2020
- Transition to heme.anticoagulation-management.core.v1 for chronic optimization at ~3 mo — CHEST 2021

Escalation triggers (move to higher acuity):
- Suspected recurrent VTE → imaging + assess compliance + consider LMWH switch — ASH 2020
- Major bleeding → ED for reversal — ANNEXA-4
- CrCl decline below dosing threshold → switch agent — ASH 2020
- Pregnancy detected → switch DOAC/warfarin to LMWH immediately — CHEST 2021

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Confirmed PE with sustained SBP <90 for ≥15 min, vasopressor requirement, or cardiac arrest — ESC 2019
- [LIFE_THREATENING] Massive ileofemoral DVT with cyanotic ischemic limb (phlegmasia cerulea dolens) — limb-threatening
- [LIFE_THREATENING] Major bleeding (GI, ICH, retroperitoneal, hemodynamically significant) on anticoagulation for VTE — ANNEXA-4 + RE-VERSE AD

Citations

- ASH 2018 VTE diagnosis (Lim Blood Adv 2018) + ASH 2020 VTE treatment (Ortel Blood Adv 2020) + CHEST 2021 antithrombotic update (Stevens Chest 2021) + ESC 2019 PE guidelines (Konstantinides Eur Heart J 2020) [PMID:30482764](https://pubmed.ncbi.nlm.nih.gov/30482764/)
- Cited evidence (PMID 33007077) [PMID:33007077](https://pubmed.ncbi.nlm.nih.gov/33007077/)
- Cited evidence (PMID 34352278) [PMID:34352278](https://pubmed.ncbi.nlm.nih.gov/34352278/)
- Cited evidence (PMID 31504429) [PMID:31504429](https://pubmed.ncbi.nlm.nih.gov/31504429/)
- Cited evidence (PMID 32223112) [PMID:32223112](https://pubmed.ncbi.nlm.nih.gov/32223112/)

Last reconciled with current guidelines: 2026-05-26.
References
  • ASH 2018 VTE diagnosis (Lim Blood Adv 2018) + ASH 2020 VTE treatment (Ortel Blood Adv 2020) + CHEST 2021 antithrombotic update (Stevens Chest 2021) + ESC 2019 PE guidelines (Konstantinides Eur Heart J 2020) — PMID:30482764
  • Cited evidence (PMID 33007077) — PMID:33007077
  • Cited evidence (PMID 34352278) — PMID:34352278
  • Cited evidence (PMID 31504429) — PMID:31504429
  • Cited evidence (PMID 32223112) — PMID:32223112