12-phase flow (12)

1. 1FRAME
   Establish the anticoagulation indication (VTE, AF, mechanical valve, APS, other) and clinical context (new initiation vs ongoing management vs perioperative vs reversal) — ASH 2020; ACCP AT10 Kearon Chest 2016
   inputs: indication_for_anticoagulation, current_anticoagulant
   advance: Indication confirmed; management context defined (initiation, maintenance, perioperative, or reversal) — ASH 2020
2. 2ENTRY
   Document anticoagulation history: agent, dose, duration on therapy, prior INR control (warfarin), compliance, prior bleeding/thrombotic events on therapy — ASH 2020
   inputs: current_anticoagulant, indication_for_anticoagulation
   advance: Anticoagulation history and current regimen documented — ASH 2020
3. 3CONTEXT
   Capture renal function (CrCl for DOAC dosing), hepatic function, body weight, age, medication interactions (P-gp/CYP3A4), bleeding risk factors (HAS-BLED), thrombotic risk factors (CHA2DS2-VASc for AF), planned procedures — ASH 2020; ACCP AT10 Kearon Chest 2016
   inputs: age, body_weight, bleeding_history, medication_list, planned_procedures
   advance: Patient-specific risk factors, renal function, and drug interactions documented — ASH 2020
4. 4RED_FLAGS
   Screen for active major bleeding (GI most common, intracranial, retroperitoneal) — agent-specific reversal: idarucizumab for dabigatran (near-complete reversal, RE-VERSE AD Pollack NEJM 2017 PMID 28693366), andexanet alfa for apixaban/rivaroxaban (good/excellent hemostasis ~80% at 12 h, ANNEXA-4 Connolly NEJM 2019 PMID 30730782), 4F-PCC + IV vitamin K for warfarin; HIT (platelet drop >50% days 5-10 + thrombosis on heparin — STOP all heparin, never warfarin acutely → argatroban/fondaparinux); supratherapeutic INR >9; DOAC-related critical bleeding; thrombotic recurrence on anticoagulation — ASH 2020; ASH 2018
   inputs: inr, platelet_count, cbc
   actions: protocol.massive_transfusion
   advance: Active bleeding addressed or excluded; HIT screened; critical INR managed — ASH 2020; ASH 2018
5. 5INITIAL_WORKUP
   CBC (platelets, Hgb), INR/PT, PTT, CrCl (Cockcroft-Gault), hepatic function (ALT, total bilirubin, albumin), type and screen if procedure planned — ASH 2020; ACCP AT10 Kearon Chest 2016
   inputs: cbc, inr, creatinine_and_crcl, hepatic_function, platelet_count, ptt
   actions: panel.coag, panel.renal, panel.lft
   advance: Baseline labs obtained; renal and hepatic function assessed for agent selection — ASH 2020
6. 6BRANCHING_WORKUP
   HIT sequential Bayesian testing: 4Ts pre-test — low (≤3) effectively rules out HIT (high NPV, stop); intermediate/high → PF4/heparin ELISA (sensitive, less specific) → confirmatory SRA (functional, high specificity); APS workup (lupus anticoagulant + anticardiolipin + anti-β2GPI — triple-positive → warfarin). If DOAC level needed → drug-specific anti-Xa (apixaban/rivaroxaban) or dTT/ecarin time (dabigatran); if bleeding on therapy → source identification; if VTE recurrence → anti-Xa, adherence, cancer screening — ASH 2020; ASH 2018
   inputs: hit_antibody_panel, anti_xa_level, thrombin_time
   advance: Branch identified: standard management vs HIT vs breakthrough VTE vs bleeding complication vs perioperative planning — ASH 2020; ASH 2018
7. 7DIFFERENTIAL
   Differentiate causes of INR elevation (drug interaction, dietary change, liver disease, occult bleeding, non-compliance with warfarin → variable INR); differentiate DOAC bleeding (mechanical vs drug interaction vs renal decline); exclude HIT mimics (sepsis-associated thrombocytopenia, DIC, drug-induced thrombocytopenia) — ASH 2020; ASH 2018
   advance: Root cause of anticoagulation complication identified; management pathway selected — ASH 2020
8. 8RISK_STRATIFICATION
   For AF: CHA2DS2-VASc (stroke risk) vs HAS-BLED (bleeding risk); for VTE: provoked vs unprovoked (duration decision), recurrence risk (male, D-dimer positive after stopping, residual DVT); for perioperative: procedure bleeding risk (high vs low) + thrombotic risk (high vs low) = bridging decision — ACCP AT10 Kearon Chest 2016; BRIDGE Douketis NEJM 2015; PAUSE Douketis NEJM 2019
   inputs: indication_for_anticoagulation, bleeding_history, planned_procedures
   advance: Risk-benefit assessment documented; agent selection, dose, and duration determined — ASH 2020; ACCP AT10 Kearon Chest 2016
9. 9TREATMENT
   DOAC selection (vs warfarin, NVAF effect sizes): apixaban 5 mg BID — stroke/SE HR ~0.79, major bleeding HR ~0.69, mortality HR ~0.89, lowest GI bleeding (Granger NEJM 2011 ARISTOTLE PMID 21870978); dabigatran 150 mg BID — stroke/SE HR ~0.65 but higher GI bleeding (Connolly NEJM 2009 RE-LY PMID 19717844); rivaroxaban 20 mg daily with food — non-inferior, less ICH/more GI bleed (ROCKET-AF PMID 21830957); edoxaban 60 mg daily, dose-reduce 30 mg if CrCl 15-50 / weight <=60 kg / potent P-gp inhibitor (ENGAGE AF-TIMI 48 PMID 24251359). Warfarin MANDATORY for mechanical valves (DOAC harmful — RE-ALIGN) and triple-positive APS (DOAC inferior — TRAPS Pengo 2018); preferred severe renal failure. Bridging is the EXCEPTION — no-bridging non-inferior with markedly lower major bleeding for most (BRIDGE Douketis NEJM 2015 PMID 26095867); periop DOAC interruption per PAUSE (30-day major bleeding ~1-2%, no heparin bridge, no preop testing — Douketis JAMA Intern Med 2019 PMID 31380891)
   inputs: creatinine_and_crcl, indication_for_anticoagulation, body_weight, bleeding_history, medication_list
   advance: Anticoagulant selected, dose adjusted for renal/weight/age, duration determined, patient education provided — ASH 2020; ACCP AT10 Kearon Chest 2016
10. 10DISPOSITION
    Outpatient management for stable anticoagulation; anticoagulation clinic referral for warfarin INR management; DOAC patients with renal function monitoring schedule; perioperative patients with interruption-restart timeline documented — ASH 2020; PAUSE Douketis NEJM 2019
    advance: Follow-up plan established: INR monitoring schedule (warfarin) or renal function monitoring (DOACs); patient education complete — ASH 2020
11. 11MONITORING
    Warfarin: INR q1-2 weeks during initiation, q4 weeks when stable, TTR target >65%; DOACs: CrCl at least annually (q6 months if CrCl 30-60; q3 months if CrCl 15-30); CBC annually; hepatic function annually; HAS-BLED reassessment annually; drug interaction review at each visit — ASH 2020; ACCP AT10 Kearon Chest 2016
    inputs: inr, creatinine_and_crcl, cbc
    advance: Monitoring plan active; TTR acceptable (warfarin) or renal function stable (DOACs); no breakthrough events — ASH 2020
12. 12FOLLOWUP
    Duration decision: provoked VTE 3-6 months; unprovoked VTE consider indefinite (D-dimer guided cessation — ACCP AT10 Kearon Chest 2016); AF indefinite if CHA2DS2-VASc >=2 males / >=3 females; mechanical valve lifelong; annual reassessment of indication, bleeding risk, renal function; patient self-management education for warfarin if appropriate — ASH 2020; ACCP AT10 Kearon Chest 2016
    advance: Duration plan documented; annual reassessment scheduled; patient education and shared decision-making for indefinite anticoagulation — ASH 2020; ACCP AT10 Kearon Chest 2016