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heme.anticoagulation-management.core.v1PRODUCTION
heme.anticoagulation-management.core.v1

Anticoagulation management

hematologychronicadult
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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 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
2
Actions
0
Advance rule
Set
Advance when

Indication confirmed; management context defined (initiation, maintenance, perioperative, or reversal) — ASH 2020

Patient inputs (16)

Indication drives agent selection, duration, and intensity: VTE (provoked vs unprovoked), AF (CHA2DS2-VASc), mechanical valve (warfarin only), antiphospholipid syndrome (warfarin preferred) — ASH 2020; ACCP AT10 Kearon Chest 2016

Current agent and dose dictate monitoring needs, drug interactions, perioperative management, and reversal strategy — ASH 2020

Prior major bleeding, GI bleeding, intracranial hemorrhage drive agent selection (GI: prefer apixaban over rivaroxaban/dabigatran) and contraindication assessment — ASH 2020

Drug interactions critical: warfarin (CYP2C9/3A4 interactions extensive); DOACs (P-gp and CYP3A4 dual inhibitors: ketoconazole, ritonavir); antiplatelet therapy increases bleeding — ASH 2020

Weight <60 kg: apixaban dose reduction criteria; extreme obesity (>120 kg or BMI >40): DOAC PK data limited, consider warfarin or drug-level monitoring — ISTH 2021 guidance

Age >=80: apixaban dose reduction criteria (if + Cr >=1.5 or weight <=60 kg); elderly at higher bleeding risk — ASH 2020

Baseline platelet count for HIT risk; hemoglobin for bleeding surveillance; MCV for compliance assessment — ASH 2020

INR is the primary monitoring parameter for warfarin; target 2.0-3.0 for most indications, 2.5-3.5 for mechanical mitral valve — ACCP AT10 Kearon Chest 2016

Renal function (CrCl by Cockcroft-Gault) determines DOAC selection and dosing: dabigatran CI if CrCl <30; apixaban dose-reduce if Cr >=1.5 + age >=80 or weight <=60 kg; rivaroxaban avoid if CrCl <15 — ASH 2020

Hepatic dysfunction affects warfarin metabolism (CYP2C9) and DOAC clearance; Child-Pugh B/C contraindication for rivaroxaban and apixaban — ASH 2020

Platelet count monitoring for HIT screening in heparin-exposed patients (4T score); thrombocytopenia may contraindicate anticoagulation — ASH 2018

Anti-Xa level for DOAC quantification when needed: perioperative assessment, renal failure, extremes of body weight, suspected non-compliance, bleeding on therapy — ASH 2020

Thrombin time is highly sensitive to dabigatran presence; normal TT excludes clinically significant dabigatran levels — ASH 2020

HIT antibody (PF4/heparin ELISA + serotonin release assay) if 4T score intermediate-high; HIT requires immediate heparin cessation and alternative anticoagulation — ASH 2018

Perioperative management requires assessment of procedure bleeding risk, DOAC/warfarin interruption timing, and bridging decision — PAUSE Douketis NEJM 2019

PTT elevated by dabigatran (qualitative screen); normal PTT does not exclude dabigatran effect; useful for heparin monitoring in bridging — ASH 2020

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (5)

5 need judgement
  • informationallife_threateninglife_threatening_bleeding
    Major bleeding on anticoagulation: intracranial hemorrhage, GI hemorrhage with hemodynamic instability, retroperitoneal bleed — ASH 2020
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateninghit_confirmed
    Heparin-induced thrombocytopenia confirmed (positive PF4/heparin ELISA + SRA or high clinical probability 4T >=6) — ASH 2018
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresupratherapeutic_inr_gt_9
    Warfarin INR >9 without bleeding — ACCP AT10 Kearon Chest 2016
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverevte_recurrence_on_therapeutic_anticoagulation
    New DVT/PE documented while on therapeutic anticoagulation with confirmed compliance — ASH 2020
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderaterenal_function_decline
    CrCl decline below safe threshold for current DOAC dose — ASH 2020
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

This dossier does not reference any calculators.

Recommended regimen

DOAC vs warfarin selection for anticoagulation — ASH 2020; ACCP AT10 Kearon Chest 2016
axis: doac_vs_warfarin_selectionstep 1 - Apixaban — first-line DOAC for most indications — ASH 2020
Selected step "Apixaban — first-line DOAC for most indications — ASH 2020" — VTE treatment/prevention, non-valvular AF; especially preferred if prior GI bleeding risk (lowest GI bleeding rate among DOACs) — Granger NEJM 2011 ARISTOTLE; ASH 2020
  • apixaban
    first line
    direct_factor_Xa_inhibitor
    5 mg BID • PO • BID (max: 5 mg BID; dose-reduce to 2.5 mg BID if >=2 of: age >=80, weight <=60 kg, Cr >=1.5 mg/dL — Granger NEJM 2011 ARISTOTLE)
    triggers: vte_treatment, afib_cha2ds2vasc_gte2, gi_bleeding_risk
    ARISTOTLE showed apixaban superior to warfarin for stroke prevention with significantly less major bleeding and lower GI bleeding than other DOACs — Granger NEJM 2011
    rxcui 1364430

outpatient playbook — drug actions (3)

  1. 1. apixaban
    rxcui 1364430
    5 mg BID (2.5 mg BID if dose-reduction criteria met) • PO • BID
    trigger: VTE or AF with preference for low GI bleeding — Granger NEJM 2011 ARISTOTLE
    First-line DOAC for most patients; lowest GI bleeding; predictable PK without monitoring — Granger NEJM 2011
  2. 2. rivaroxaban
    rxcui 1114195
    20 mg daily with food (15 mg if CrCl 15-50) • PO • daily
    trigger: VTE or AF when once-daily dosing preferred — Patel NEJM 2011 ROCKET AF
    Once-daily dosing may improve adherence; must take with food — Patel NEJM 2011
  3. 3. warfarin
    rxcui 11289
    5 mg daily adjusted by INR • PO • daily
    trigger: Mechanical valve, triple-positive APS, DOAC contraindication — ACCP AT10 Kearon Chest 2016
    Only option for mechanical valves and APS; requires frequent INR monitoring — ACCP AT10 Kearon Chest 2016

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: New VTE (DVT or PE) requiring anticoagulation initiation — ASH 2020; ACCP AT10 Kearon Chest 2016; Non-valvular atrial fibrillation with CHA2DS2-VASc indication for anticoagulation — ASH 2020; Mechanical heart valve requiring lifelong warfarin anticoagulation — ACCP AT10 Kearon Chest 2016.

Objective

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

Assessment

**Anticoagulation management** (heme.anticoagulation-management.core.v1).
Phenotype framing: 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
Scope: 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

No severity triggers fired against current inputs.

Plan

Regimen axis: **DOAC vs warfarin selection for anticoagulation — ASH 2020; ACCP AT10 Kearon Chest 2016** — step "Apixaban — first-line DOAC for most indications — ASH 2020".
1. apixaban 5 mg BID PO BID (direct_factor_Xa_inhibitor, first line) — ARISTOTLE showed apixaban superior to warfarin for stroke prevention with significantly less major bleeding and lower GI bleeding than other DOACs — Granger NEJM 2011

Setting playbook (outpatient) — Select optimal anticoagulant, monitor therapy, manage dose adjustments, plan for procedures, screen for HIT, and assess duration of anticoagulation — ASH 2020; ACCP AT10 Kearon Chest 2016
2. apixaban 5 mg BID (2.5 mg BID if dose-reduction criteria met) PO BID — VTE or AF with preference for low GI bleeding — Granger NEJM 2011 ARISTOTLE (First-line DOAC for most patients; lowest GI bleeding; predictable PK without monitoring — Granger NEJM 2011)
3. rivaroxaban 20 mg daily with food (15 mg if CrCl 15-50) PO daily — VTE or AF when once-daily dosing preferred — Patel NEJM 2011 ROCKET AF (Once-daily dosing may improve adherence; must take with food — Patel NEJM 2011)
4. warfarin 5 mg daily adjusted by INR PO daily — Mechanical valve, triple-positive APS, DOAC contraindication — ACCP AT10 Kearon Chest 2016 (Only option for mechanical valves and APS; requires frequent INR monitoring — ACCP AT10 Kearon Chest 2016)

Non-pharmacologic actions:
- Patient education: signs of bleeding, when to seek emergency care — ASH 2020
- Medical alert identification (bracelet/card) — ASH 2020
- Dietary counseling (consistent vitamin K intake for warfarin) — ACCP AT10 Kearon Chest 2016
- Anticoagulation clinic referral for warfarin management (improves TTR) — ASH 2020
- Pre-procedure planning at each visit (dental, surgical, endoscopic) — PAUSE Douketis NEJM 2019
- Annual reassessment of indication and duration — ACCP AT10 Kearon Chest 2016

AVOID / contraindication checks:
- DOACs_contraindicated_with_mechanical_heart_valves_RE_ALIGN_trial — Eikelboom NEJM 2013
- DOACs_inferior_to_warfarin_in_triple_positive_APS_TRAPS — Pengo Lancet Rheumatol 2018
- Dabigatran_CI_if_CrCl_lt_30_US_labeling — ASH 2020
- Rivaroxaban_avoid_if_CrCl_lt_15 — ASH 2020
- Edoxaban_CI_in_AF_if_CrCl_gt_95_paradoxical_reduced_efficacy — Giugliano NEJM 2013
- Dual_P_gp_CYP3A4_inhibitors_ketoconazole_ritonavir_CI_with_DOACs — ASH 2020
- Apixaban_dose_reduce_2_of_3_criteria_age_gte_80_weight_lte_60_Cr_gte_1_5 — Granger NEJM 2011
- Rivaroxaban_must_be_taken_with_food_bioavailability — Patel NEJM 2011

Monitoring

Regimen monitoring:
- warfarin INR q1 2weeks during initiation q4weeks stable TTR target gt 65pct — ACCP AT10 Kearon Chest 2016
- DOAC CrCl annually q6mo if CrCl 30 60 q3mo if CrCl 15 30 — ASH 2020
- CBC annually bleeding surveillance — ASH 2020
- hepatic function annually — ASH 2020
- HAS BLED reassessment annually — ASH 2020
- drug interaction review every visit — ASH 2020

Setting (outpatient) monitoring:
- Warfarin: INR q1-2 weeks during dose changes; q4 weeks when stable; TTR target >65% — ACCP AT10 Kearon Chest 2016
- DOAC: CrCl annually (q6mo if CrCl 30-60; q3mo if CrCl 15-30) — ASH 2020
- CBC annually for all; sooner if bleeding symptoms — ASH 2020
- Hepatic function annually — ASH 2020
- HAS-BLED score annually — ASH 2020

Follow-up plan: 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
- Close-out criterion: Duration plan documented; annual reassessment scheduled; patient education and shared decision-making for indefinite anticoagulation — ASH 2020; ACCP AT10 Kearon Chest 2016

Monitoring phase: 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

Disposition

Current setting: outpatient — Select optimal anticoagulant, monitor therapy, manage dose adjustments, plan for procedures, screen for HIT, and assess duration of anticoagulation — ASH 2020; ACCP AT10 Kearon Chest 2016

Disposition criteria:
- Continue outpatient management if stable on anticoagulation with no complications — ASH 2020
- Refer to hematology if recurrent VTE on anticoagulation, HIT confirmed, need for complex perioperative management, or antiphospholipid syndrome — ASH 2020; ASH 2018

Escalation triggers (move to higher acuity):
- Major bleeding (GI, intracranial, retroperitoneal) → ED for reversal assessment — ASH 2020
- Supratherapeutic INR >9 → hold warfarin + vitamin K 2.5-5 mg PO + close follow-up — ACCP AT10 Kearon Chest 2016
- Thrombotic event on therapeutic anticoagulation → assess compliance, drug levels, cancer screening — ASH 2020
- Platelet drop >50% on heparin → 4T score → HIT workup — ASH 2018
- CrCl decline below dosing threshold → dose adjust or switch agent — ASH 2020

Patient Action Plan

**Anticoagulation therapy self-management plan — ASH 2020**
Personalised values: anticoagulant_type, indication, target_INR, renal_function.

**Stable on anticoagulation — no bleeding, therapeutic range — ASH 2020** (green):
Triggers:
- INR 2.0-3.0 (warfarin) at last check — ACCP AT10 Kearon Chest 2016
- Taking DOAC as prescribed without missed doses — ASH 2020
- No bleeding symptoms — ASH 2020
Actions:
- Take medication at the same time(s) every day — ASH 2020
- Rivaroxaban: always take with food — Patel NEJM 2011
- Warfarin: maintain consistent vitamin K intake (do not eliminate green vegetables, keep intake steady) — ACCP AT10 Kearon Chest 2016
- Carry medical alert card/bracelet at all times — ASH 2020
- Inform all healthcare providers (including dentist) of anticoagulation — ASH 2020
- Avoid NSAIDs and aspirin unless prescribed — ASH 2020
- Keep follow-up appointments for INR checks (warfarin) or labs (DOACs) — ASH 2020

**Caution — minor bleeding or missed doses — ASH 2020** (yellow):
Triggers:
- Unusual bruising, prolonged bleeding from cuts — ASH 2020
- Nosebleeds lasting >10 min — ASH 2020
- Pink or dark urine — ASH 2020
- Missed one dose of DOAC or uncertain if took dose — ASH 2020
- INR 3.5-5.0 above target (warfarin) — ACCP AT10 Kearon Chest 2016
Actions:
- Contact anticoagulation clinic or provider within 24 h — ASH 2020
- Missed DOAC dose: take if <6 h late (BID) or <12 h late (daily); otherwise skip and resume normal schedule — ASH 2020
- Apply direct pressure for 15 min to bleeding sites — ASH 2020
- Do not double up doses — ASH 2020

**Emergency — major bleeding or thrombotic event — ASH 2020** (red):
Triggers:
- Vomiting blood or coffee-ground emesis — ASH 2020
- Black tarry stools or bright red blood per rectum — ASH 2020
- Sudden severe headache, vision change, or weakness (ICH or stroke) — ASH 2020
- Coughing up blood — ASH 2020
- Sudden leg swelling, chest pain, or shortness of breath (new clot despite anticoagulation) — ASH 2020
Actions:
- Call 911 immediately — ASH 2020
- Tell EMS which anticoagulant you take, dose, and last dose time — ASH 2020
- Bring medication bottles or list to the ED — ASH 2020
- Do NOT take additional anticoagulant doses until medically evaluated — ASH 2020

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Major bleeding on anticoagulation: intracranial hemorrhage, GI hemorrhage with hemodynamic instability, retroperitoneal bleed — ASH 2020
- [LIFE_THREATENING] Heparin-induced thrombocytopenia confirmed (positive PF4/heparin ELISA + SRA or high clinical probability 4T >=6) — ASH 2018
- [SEVERE] Warfarin INR >9 without bleeding — ACCP AT10 Kearon Chest 2016

Citations

- ASH 2020 VTE management guidelines + ACCP AT10 Kearon Chest 2016 antithrombotic therapy for VTE + BRIDGE trial Douketis NEJM 2015 + PAUSE trial Douketis NEJM 2019 + ANNEXA-4 trial Connolly NEJM 2019 [PMID:26867832](https://pubmed.ncbi.nlm.nih.gov/26867832/)
- Cited evidence (PMID 26095867) [PMID:26095867](https://pubmed.ncbi.nlm.nih.gov/26095867/)
- Cited evidence (PMID 31380891) [PMID:31380891](https://pubmed.ncbi.nlm.nih.gov/31380891/)
- Cited evidence (PMID 30730782) [PMID:30730782](https://pubmed.ncbi.nlm.nih.gov/30730782/)
- Cited evidence (PMID 19717844) [PMID:19717844](https://pubmed.ncbi.nlm.nih.gov/19717844/)

Last reconciled with current guidelines: 2026-05-22.
References
  • ASH 2020 VTE management guidelines + ACCP AT10 Kearon Chest 2016 antithrombotic therapy for VTE + BRIDGE trial Douketis NEJM 2015 + PAUSE trial Douketis NEJM 2019 + ANNEXA-4 trial Connolly NEJM 2019 — PMID:26867832
  • Cited evidence (PMID 26095867) — PMID:26095867
  • Cited evidence (PMID 31380891) — PMID:31380891
  • Cited evidence (PMID 30730782) — PMID:30730782
  • Cited evidence (PMID 19717844) — PMID:19717844