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cardio.dvt.recurrent-on-anticoagulation.v1

Recurrent DVT on therapeutic anticoagulation (treatment failure)

cardiologyacuteadultacuteinpatienttransitionoutpatient
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Phase E variant of cardio.dvt.core.v1 — narrowed to recurrent DVT on therapeutic AC (treatment-failure phenotype). Inherits diagnostic arc from parent via routing; specializes for the breakthrough-VTE root-cause analysis: adherence + drug-level testing FIRST, then occult cancer screen + APS panel + AC switch/intensification per cause. Manifest pointer reuses cardio.dvt.core.v1 manifest. Design-brief pointer reuses parent (treatment-failure differences documented inline). Critical pathway: (1) confirm therapeutic level — anti-Xa for DOAC/LMWH, INR for warfarin; subtherapeutic level reframes case as adherence/dosing rather than treatment failure. (2) If true breakthrough — switch AC class (DOAC → LMWH default; warfarin → DOAC if subtherapeutic INR was cause). (3) Triple-positive APS confirmed at 12 weeks → warfarin INR 2-3 mandatory (TRAPS PMID 30196097, RAPS PMID 27932287, ISTH 2024). (4) Occult cancer found → transition to cancer-VTE pathway. (5) IVC filter ONLY if absolute AC contraindication (PREPIC2 PMID 25919526). Status INTEGRATED. Authored 2026-05-14 by shard-06-cardio-acute as recurrent-DVT-on-AC variant.

Entry points (4)

  • symptom
    New unilateral leg swelling/pain in patient on therapeutic-dose AC ≥4 weeks → confirm DVT and classify as breakthrough VTE
    new_dvt_symptoms_on_therapeutic_ac
  • imaging
    Compression US confirms new DVT (different segment or new thrombus extension) in patient on documented therapeutic AC
    us_new_thrombus_on_ac
  • history
    Documented breakthrough VTE while on therapeutic AC ≥4 weeks — treatment failure pathway initiated; root cause analysis mandatory
    breakthrough_vte_documented
  • lab_abnormality
    Subtherapeutic anti-Xa or INR in patient with confirmed VTE on prescribed AC — adherence vs interaction vs malabsorption vs dose insufficiency differential
    subtherapeutic_anti_xa_or_inr

Required inputs (9)

  • agerequired
    demographic • used at CONTEXT
    Older patients higher cancer risk and more likely to have absorption + drug-interaction issues
  • current_ac_regimenrequired
    medication • used at CONTEXT
    Specific agent (apixaban/rivaroxaban/edoxaban/warfarin/LMWH), dose, frequency, duration must be confirmed; many "failures" are actually subtherapeutic doses for weight or renal function
  • adherence_historyrequired
    history • used at CONTEXT
    Adherence is the single most common cause of "breakthrough" VTE; must be documented before invoking treatment failure
  • anti_xa_or_inrrequired
    lab • used at INITIAL_WORKUP
    Drug-level testing: anti-Xa for DOAC/LMWH (chromogenic anti-Xa calibrated for the specific agent), INR for warfarin; subtherapeutic level reframes the case as adherence/dosing rather than treatment failure
  • creatininerequired
    lab • used at TREATMENT
    eGFR for AC dose adjustment; cancer + chemotherapy + age can produce occult AKI affecting DOAC clearance
  • cbcrequired
    lab • used at INITIAL_WORKUP
    Anemia or thrombocytopenia complicate AC; new anemia may signal occult cancer or bleeding
  • compression_usrequired
    imaging • used at INITIAL_WORKUP
    Confirm new DVT location and burden; differentiate new thrombus from chronic residual
  • cancer_screening_statusrequired
    history • used at BRANCHING_WORKUP
    Recent age-appropriate screening status drives decision for low-threshold CT chest/abdomen/pelvis (occult cancer is a leading driver of breakthrough VTE)
  • antiphospholipid_historyrequired
    history • used at BRANCHING_WORKUP
    Prior APS dx, miscarriages, livedo, or unexplained arterial events shift suspicion toward APS — highest-yield thrombophilia workup

12-phase flow (11)

  1. 1FRAME
    Recurrent DVT on therapeutic AC = breakthrough VTE; mandatory adherence + drug-level workup + occult cancer screen + targeted thrombophilia (APS focus); treatment options include AC class switch, intensity escalation, or IVC filter only if AC contraindicated; route to cardio.dvt.core.v1 for diagnostic arc
    inputs: breakthrough_vte_documented
    advance: breakthrough VTE confirmed and root-cause workup initiated
  2. 2ENTRY
    Confirm DVT (US new thrombus vs chronic residual), document AC regimen and duration, screen for adherence and drug interactions
    inputs: age, current_ac_regimen
    advance: new DVT confirmed on AC ≥4 weeks
  3. 3CONTEXT
    AC regimen review: specific agent, dose appropriateness for weight/renal function, recent dose changes, missed doses, drug-drug interactions (rifampin, anticonvulsants, certain TKIs, P-gp inducers); adherence assessment via pharmacy refill history + patient self-report + family observation
    inputs: adherence_history, creatinine
    advance: adherence + interactions assessed
  4. 4RED_FLAGS
    Massive PE on AC (treatment failure with hemodynamic compromise — life-threatening); phlegmasia cerulea dolens; concurrent hemorrhage from over-AC; new occult malignancy with large burden
    actions: concurrent_pe_screen, phlegmasia_pathway
    advance: red flags screened
  5. 5INITIAL_WORKUP
    Compression US confirms new DVT; CBC + BMP + LFTs; drug-level testing — anti-Xa (calibrated for specific DOAC or LMWH) for DOAC/LMWH or INR for warfarin; if subtherapeutic, focus shifts to adherence/dose; if therapeutic, focus shifts to true treatment failure workup
    inputs: compression_us, cbc, creatinine, anti_xa_or_inr
    actions: panel.cardiac, panel.renal
    advance: DVT + drug-level documented
  6. 6BRANCHING_WORKUP
    If adherent + therapeutic level + true breakthrough: (1) occult cancer screen — low threshold for CT chest/abdomen/pelvis if not recently screened (SOME PMID 26095396 framing — recurrent breakthrough has higher pretest probability than first unprovoked); age-appropriate screening up-to-date; (2) antiphospholipid panel — lupus anticoagulant + anti-cardiolipin IgG/IgM + anti-β2GP1 IgG/IgM, repeated at 12 weeks if positive (defer thrombophilia workup until acute event resolves to avoid false positives); JAK2 V617F if MPN suspected; rare hereditary thrombophilia panel (factor V Leiden, prothrombin 20210, protein C/S/AT) only if young + strong family hx
    inputs: cancer_screening_status, antiphospholipid_history
    advance: occult cancer + APS workup decisions documented
  7. 7RISK_STRATIFICATION
    HAS-BLED for ongoing AC bleed risk; recurrence severity (extension, multi-segment, new PE) drives intensity decision; APS triple-positive status mandates warfarin INR 2-3
    actions: calc.has_bled
    advance: AC switch + duration plan documented
  8. 8TREATMENT
    Treatment ladder: (1) if subtherapeutic from adherence — re-educate, switch to LMWH for at least 1 month for guaranteed bioavailability, then re-trial DOAC; (2) if drug interaction — remove offender or switch AC; (3) if true treatment failure — switch AC class (DOAC → LMWH or LMWH → DOAC; warfarin → DOAC if no APS); (4) increase intensity — full-dose LMWH BID for 1 month then transition back, or escalate DOAC dose where evidence supports (limited); (5) APS triple-positive — warfarin INR 2-3 mandatory (TRAPS PMID 30196097, RAPS PMID 27932287); (6) IVC filter ONLY if absolute AC contraindication (PREPIC2 PMID 25919526)
    inputs: creatinine
    advance: AC switch + intensification + APS pathway documented
  9. 9DISPOSITION
    Inpatient if massive PE, phlegmasia, severe symptoms, or active bleed concern; outpatient if hemodynamically stable with switched AC; ICU for hemodynamically unstable PE on AC
    advance: unit assigned + AC plan documented
  10. 10MONITORING
    Anti-Xa or INR documented at switch and 1-2 weeks; CBC + BMP at week 1 then monthly; APS confirmatory testing at 12 weeks if initial positive; cancer surveillance per workup findings; recurrent VTE symptoms
    actions: panel.cardiac
    advance: monitoring plan documented
  11. 11FOLLOWUP
    Indefinite AC after second VTE event regardless of provoking factor (ACCP 2021); APS triple-positive lifelong warfarin; cancer-driven recurrence → switch to cancer-VTE pathway with cancer-active indefinite AC; share decision with patient on bleed-vs-recurrence tradeoff
    advance: extended/indefinite AC plan finalized