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cardio.dvt.jak2-mpn-related.v1PRODUCTION
cardio.dvt.jak2-mpn-related.v1

DVT in JAK2-V617F-positive myeloproliferative neoplasm (PV / ET / PMF)

cardiologyacuteadult
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Detailed

JAK2-V617F-positive MPN = clonal stem-cell disorder with thrombosis as leading cause of morbidity/mortality; venous (DVT / PE / splanchnic / CVST) + arterial (stroke / MI). Acute AC matches parent; AC duration + cytoreduction + hematocrit target + low-dose ASA define the MPN-specific arc

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JAK2-MPN phenotype framed

Patient inputs (11)

JAK2-V617F PCR (allele burden quantitation if available); first-line; if negative pursue JAK2 exon 12 in PV phenotype, CALR + MPL in ET / PMF phenotype

Suppressed EPO supports primary polycythemia (PV) over secondary causes (hypoxia, EPO-secreting tumor)

Younger patients (< 60) with JAK2-positive PV/ET have lower thrombosis risk per IPSET-thrombosis; age > 60 plus prior thrombosis defines high-risk ET requiring cytoreduction

Hematocrit target differs (men < 45%, women < 42%); JAK2-positive women on combined OCP have multiplicative VTE risk

PV vs ET vs PMF drives phlebotomy strategy, expected blast risk, and cytoreduction choice (hydroxyurea vs interferon vs ruxolitinib)

Cardinal symptom of proximal DVT

Initial confirmation of DVT location (proximal vs distal)

Polycythemia + thrombocytosis + leukocytosis pattern; smear shows giant platelets, immature granulocytes, dacrocytes (PMF); platelets > 1500 raise bleeding-paradox concern (acquired vWS)

Hepatic function for splanchnic vein thrombosis evaluation; PMF can drive extramedullary hematopoiesis with hepatosplenomegaly

HAS-BLED + GI bleed history + acquired vWS in extreme thrombocytosis drives AC + ASA combination decision

eGFR for DOAC dosing and contrast for any imaging

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

Severity triggers (4)

4 need judgement
  • informationallife_threateningleukocytosis_driven_thrombosis_storm_in_jak2_mpn
    JAK2-positive MPN with WBC > 25 × 10⁹/L and acute multi-site or extending VTE despite ongoing AC — leukocytosis-driven prothrombotic phenotype demands urgent cytoreduction and AC intensification
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningjak2_mpn_with_concurrent_aps_triple_positive_overlap
    Thrombophilia panel returns triple-positive antiphospholipid syndrome on top of JAK2-V617F-positive MPN — combined thrombophilia phenotype with very high recurrence risk
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresplanchnic_vein_thrombosis_as_index_event
    Splanchnic vein thrombosis (Budd-Chiari, portal, mesenteric, splenic) as the index venous event — JAK2-V617F-positive MPN diagnosis triggers indefinite AC and full cytoreduction even if peripheral CBC is normal
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereextreme_thrombocytosis_bleeding_paradox_in_et
    ET with platelets > 1500 × 10⁹/L plus mucocutaneous bleeding on AC and / or ASA — acquired von Willebrand syndrome from platelet binding of vWF multimers (bleeding paradox)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

JAK2-V617F-positive MPN VTE — acute AC + low-dose ASA + cytoreduction + phlebotomy (PV) — multi-axis regimen (ELN 2024; CYTO-PV; ECLAP; ASH 2020; Barbui 2021)
axis: jak2_mpn_vte_anticoagulation_plus_cytoreduction
Selected axis "JAK2-V617F-positive MPN VTE — acute AC + low-dose ASA + cytoreduction + phlebotomy (PV) — multi-axis regimen (ELN 2024; CYTO-PV; ECLAP; ASH 2020; Barbui 2021)" by default fallback (first axis)
  • apixaban
    first line
    doac_factor_xa_direct
    10 mg BID × 7 d → 5 mg BID full-dose; 2.5 mg BID extended-phase after first 6 mo if continuing indefinite • PO • BID × ≥3 months minimum, indefinite if splanchnic / recurrent / persistent high risk
    triggers: mpn_associated_vte, no_active_bleed, no_triple_positive_aps, platelets_below_1500_no_acquired_vws, egfr_above_25
    AMPLIFY (Agnelli NEJM 2013 PMID 23808982) — apixaban first-line; Barbui Blood Adv 2021 (PMID 33591542) — DOAC acceptable in MPN VTE; AMPLIFY-EXT supports 2.5 mg BID extended-phase
    rxcui 1364430
  • rivaroxaban
    first line
    doac_factor_xa_direct
    15 mg BID × 21 d → 20 mg daily; 10 mg daily extended-phase after first 6 mo if continuing indefinite • PO • BID then daily ≥3 months, indefinite per criteria
    triggers: mpn_associated_vte, no_active_bleed, no_triple_positive_aps, platelets_below_1500, egfr_above_30
    EINSTEIN-DVT (Bauersachs NEJM 2010 PMID 21128814); Barbui 2021 acceptable in MPN
    rxcui 1114195
  • edoxaban
    first line
    doac_factor_xa_direct
    60 mg PO daily (30 mg if CrCl 15-50, weight ≤60 kg, or with strong P-gp inhibitor) after 5-10 d LMWH bridge • PO • daily × ≥3 months, indefinite per criteria
    triggers: post_lmwh_bridge, doac_alternative
    Hokusai-VTE (Büller NEJM 2013 PMID 23991958)
    rxcui 1599538
  • warfarin
    first line
    vitamin_k_antagonist
    5 mg daily; INR target 2-3 (target 3 if triple-positive APS per ISTH) • PO • daily ≥3 months, indefinite per criteria
    triggers: concurrent_aps_triple_positive, splanchnic_vein_thrombosis_with_hepatic_instability, severe_renal_impairment_doac_unsafe, patient_preference
    TRAPS (Pengo Blood 2018 PMID 30002145) — warfarin > rivaroxaban in triple-positive APS; preferred in unstable hepatic dysfunction where DOAC clearance unpredictable
    rxcui 11289
  • enoxaparin
    first line
    lmwh
    1 mg/kg SC BID; reduce to 1 mg/kg daily if CrCl <30 • SC • BID
    triggers: pregnancy, aps_workup_pending, planned_invasive_procedure, doac_contraindicated, splanchnic_vein_thrombosis_acute
    ASH 2020 (PMID 33007077); ASH 2018 pregnancy (PMID 30482767) — LMWH first-line in pregnancy and as bridge during workup
    rxcui 67108
  • hydroxyurea
    first line
    cytoreductive_agent
    500 mg PO BID titrate to platelet target < 400 × 10⁹/L and Hct target • PO • BID
    triggers: high_risk_mpn_vte, pv_or_et_with_thrombosis, age_above_60_with_jak2
    ELN 2024 first-line cytoreduction in PV and high-risk ET; Carobbio 2007 (PMID 17566071) — leukocytosis-driven thrombosis suppressed by HU; long-track-record safety
    rxcui 5552
  • peginterferon-alfa-2a
    first line
    cytoreductive_agent
    45–90 µg SC weekly titrate • SC • weekly
    triggers: young_mpn_patient, pregnancy_planning_or_active, hu_intolerance
    PROUD-PV / CONTINUATION-PV — interferon non-inferior to HU with potential disease-modifying allele-burden reduction; preferred in pregnancy and young patients
    rxcui 120608
  • ruxolitinib
    second line
    jak_inhibitor
    10 mg PO BID titrate per platelets (RESPONSE protocol) • PO • BID
    triggers: hu_resistant_or_intolerant_pv, symptomatic_splenomegaly_pmf, severe_constitutional_symptoms
    RESPONSE (Vannucchi NEJM 2015 PMID 25629741) — ruxolitinib superior to best available therapy in HU-resistant/intolerant PV; ELN 2024 endorsed
    rxcui 1193325
  • aspirin
    first line
    antiplatelet_cox1
    81 mg daily • PO • daily indefinite
    triggers: pv_diagnosis, et_diagnosis, mpn_with_arterial_event_history
    ECLAP (Landolfi NEJM 2004 PMID 14702426) — low-dose ASA reduces thrombosis in PV; standard in PV and ET; HOLD if extreme thrombocytosis (> 1500) until cytoreduction lowers platelets and acquired vWS resolves
    rxcui 243670

outpatient playbook — drug actions (4)

  1. 1. maintenance apixaban
    rxcui 1364430
    apixaban 2.5 mg BID extended-reduced OR 5 mg BID full • PO • BID
    trigger: Per 3-mo decision
    AMPLIFY / AMPLIFY-EXT
  2. 2. continue cytoreduction
    rxcui 5470
    hydroxyurea per platelet / Hct target OR pegylated interferon 45–90 µg SC weekly OR ruxolitinib 10 mg BID titrate • PO / SC • BID / weekly
    trigger: MPN diagnosis
    ELN 2024
  3. 3. maintenance low-dose ASA
    rxcui 243670
    81 mg PO daily • PO • daily
    trigger: PV / ET on cytoreduction
    ECLAP
  4. 4. switch to LMWH if pregnancy planned or confirmed; switch HU to interferon
    rxcui 67108
    enoxaparin therapeutic 1 mg/kg BID antepartum + 6 weeks postpartum • SC • BID
    trigger: Pregnancy
    ASH 2018 pregnancy PMID 30482767

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Unilateral leg swelling in patient with aquagenic pruritus, erythromelalgia, splenomegaly, or unexplained polycythemia / thrombocytosis — suspect underlying MPN; Splanchnic vein thrombosis (Budd-Chiari, portal, mesenteric, splenic) or cerebral venous sinus thrombosis as index event — JAK2-V617F testing mandatory even with normal CBC; CBC at presentation with Hb > 16.5 (men) / > 16.0 (women), platelets > 450 × 10⁹/L, or WBC > 11 — order JAK2-V617F PCR.

Objective

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

Assessment

**DVT in JAK2-V617F-positive myeloproliferative neoplasm (PV / ET / PMF)** (cardio.dvt.jak2-mpn-related.v1).
Scope: JAK2-V617F-positive MPN = clonal stem-cell disorder with thrombosis as leading cause of morbidity/mortality; venous (DVT / PE / splanchnic / CVST) + arterial (stroke / MI). Acute AC matches parent; AC duration + cytoreduction + hematocrit target + low-dose ASA define the MPN-specific arc

No severity triggers fired against current inputs.

Plan

Regimen axis: **JAK2-V617F-positive MPN VTE — acute AC + low-dose ASA + cytoreduction + phlebotomy (PV) — multi-axis regimen (ELN 2024; CYTO-PV; ECLAP; ASH 2020; Barbui 2021)**.
1. apixaban 10 mg BID × 7 d → 5 mg BID full-dose; 2.5 mg BID extended-phase after first 6 mo if continuing indefinite PO BID × ≥3 months minimum, indefinite if splanchnic / recurrent / persistent high risk (doac_factor_xa_direct, first line) — AMPLIFY (Agnelli NEJM 2013 PMID 23808982) — apixaban first-line; Barbui Blood Adv 2021 (PMID 33591542) — DOAC acceptable in MPN VTE; AMPLIFY-EXT supports 2.5 mg BID extended-phase
2. rivaroxaban 15 mg BID × 21 d → 20 mg daily; 10 mg daily extended-phase after first 6 mo if continuing indefinite PO BID then daily ≥3 months, indefinite per criteria (doac_factor_xa_direct, first line) — EINSTEIN-DVT (Bauersachs NEJM 2010 PMID 21128814); Barbui 2021 acceptable in MPN
3. edoxaban 60 mg PO daily (30 mg if CrCl 15-50, weight ≤60 kg, or with strong P-gp inhibitor) after 5-10 d LMWH bridge PO daily × ≥3 months, indefinite per criteria (doac_factor_xa_direct, first line) — Hokusai-VTE (Büller NEJM 2013 PMID 23991958)
4. warfarin 5 mg daily; INR target 2-3 (target 3 if triple-positive APS per ISTH) PO daily ≥3 months, indefinite per criteria (vitamin_k_antagonist, first line) — TRAPS (Pengo Blood 2018 PMID 30002145) — warfarin > rivaroxaban in triple-positive APS; preferred in unstable hepatic dysfunction where DOAC clearance unpredictable
5. enoxaparin 1 mg/kg SC BID; reduce to 1 mg/kg daily if CrCl <30 SC BID (lmwh, first line) — ASH 2020 (PMID 33007077); ASH 2018 pregnancy (PMID 30482767) — LMWH first-line in pregnancy and as bridge during workup
6. hydroxyurea 500 mg PO BID titrate to platelet target < 400 × 10⁹/L and Hct target PO BID (cytoreductive_agent, first line) — ELN 2024 first-line cytoreduction in PV and high-risk ET; Carobbio 2007 (PMID 17566071) — leukocytosis-driven thrombosis suppressed by HU; long-track-record safety
7. peginterferon-alfa-2a 45–90 µg SC weekly titrate SC weekly (cytoreductive_agent, first line) — PROUD-PV / CONTINUATION-PV — interferon non-inferior to HU with potential disease-modifying allele-burden reduction; preferred in pregnancy and young patients
8. ruxolitinib 10 mg PO BID titrate per platelets (RESPONSE protocol) PO BID (jak_inhibitor, second line) — RESPONSE (Vannucchi NEJM 2015 PMID 25629741) — ruxolitinib superior to best available therapy in HU-resistant/intolerant PV; ELN 2024 endorsed
9. aspirin 81 mg daily PO daily indefinite (antiplatelet_cox1, first line) — ECLAP (Landolfi NEJM 2004 PMID 14702426) — low-dose ASA reduces thrombosis in PV; standard in PV and ET; HOLD if extreme thrombocytosis (> 1500) until cytoreduction lowers platelets and acquired vWS resolves

Setting playbook (outpatient) — Long-term MPN-thrombosis management: indefinite AC for indicated patients with annual reassessment; cytoreduction maintenance (HU, interferon, or ruxolitinib); phlebotomy for PV; JAK2 allele-burden surveillance; transformation surveillance (PV / ET → PMF / leukemia); pregnancy planning; cardiovascular risk optimization
10. maintenance apixaban apixaban 2.5 mg BID extended-reduced OR 5 mg BID full PO BID — Per 3-mo decision (AMPLIFY / AMPLIFY-EXT)
11. continue cytoreduction hydroxyurea per platelet / Hct target OR pegylated interferon 45–90 µg SC weekly OR ruxolitinib 10 mg BID titrate PO / SC BID / weekly — MPN diagnosis (ELN 2024)
12. maintenance low-dose ASA 81 mg PO daily PO daily — PV / ET on cytoreduction (ECLAP)
13. switch to LMWH if pregnancy planned or confirmed; switch HU to interferon enoxaparin therapeutic 1 mg/kg BID antepartum + 6 weeks postpartum SC BID — Pregnancy (ASH 2018 pregnancy PMID 30482767)

Non-pharmacologic actions:
- Compression stocking 30-40 mmHg if PTS symptoms
- OCP avoidance lifelong if MPN with VTE history
- Pre-procedure AC + ASA management plan documented
- Patient carries MPN-thrombosis card
- Phlebotomy maintenance for PV q4-12 weeks

AVOID / contraindication checks:
- Doac_avoid_active_bleeding (FDA labels)
- Apixaban_avoid_egfr_below_15 (FDA label)
- Rivaroxaban_avoid_egfr_below_30 (FDA label)
- Doac_avoid_triple_positive_aps_use_warfarin (TRAPS 2018; ISTH 2020)
- Hold_aspirin_if_platelets_above_1500_until_cytoreduction (acquired vWS — bleeding paradox)
- Hydroxyurea_avoid_pregnancy_use_interferon (teratogenic)
- Warfarin_avoid_pregnancy_use_lmwh (ASH 2018 pregnancy)
- Decision:phlebotomy_target_hct_below_45_men_below_42_women (CYTO PV PMID 23300175)
- Decision:cytoreduction_mandatory_after_mpn_vte_event (ELN 2024)
- Decision:splanchnic_vein_thrombosis_indefinite_AC (ASH 2018; ELN 2024)
- Decision:high_risk_et_age_above_60_or_prior_thrombosis_use_hu_or_anagrelide (ELN 2024)
- Decision:thrombophilia_panel_send_BEFORE_first_AC_dose_or_off_AC_2_weeks (Middeldorp 2012)

Monitoring

Regimen monitoring:
- cbc weekly during cytoreduction titration then monthly (ELN 2024)
- phlebotomy for pv to maintain hct target (CYTO-PV)
- jak2 allele burden q6 12mo for disease modification (interferon programs)
- cbc creatinine lfts at 4 weeks then quarterly during indefinite AC (FDA labels)
- pts villalta at 3 6 12mo (Kahn Lancet 2014)
- annual AC continuation decision with HASBLED reassessment (ACCP 2021)
- inr weekly during warfarin titration then q4 6 weeks (ACCP 2021)

Setting (outpatient) monitoring:
- Quarterly CBC + clinical reassessment
- Annual labs + organomegaly assessment
- Annual PTS Villalta
- Annual HAS-BLED

Follow-up plan: Long-term hematology + thrombosis clinic co-management; annual bone marrow if disease progression suspected (PV / ET → PMF / leukemia transformation); pregnancy planning (interferon + LMWH preferred over hydroxyurea + DOAC / warfarin); cardiovascular risk factor optimisation; education on splenic infarct + erythromelalgia + pruritus + transformation symptoms
- Close-out criterion: long-term plan and disease-progression surveillance documented

Monitoring phase: CBC weekly during cytoreduction titration then monthly; phlebotomy schedule for PV to maintain Hct target; JAK2 allele burden q6–12 mo to track disease modification; CBC + creatinine + LFTs at 4 weeks then quarterly during indefinite AC; bleed surveillance; PTS Villalta at 3 / 6 / 12 mo; annual reassessment of AC continuation + cytoreduction

Disposition

Current setting: outpatient — Long-term MPN-thrombosis management: indefinite AC for indicated patients with annual reassessment; cytoreduction maintenance (HU, interferon, or ruxolitinib); phlebotomy for PV; JAK2 allele-burden surveillance; transformation surveillance (PV / ET → PMF / leukemia); pregnancy planning; cardiovascular risk optimization

Disposition criteria:
- Indefinite annual hematology + AC clinic follow-up; cross-reference with MPN registry

Escalation triggers (move to higher acuity):
- New VTE despite AC → reassess adherence + AC adequacy + intensify cytoreduction
- Pregnancy → switch to interferon + LMWH
- Transformation suspicion → urgent bone marrow + transplant evaluation
- Major bleed → reverse, hold, reassess indefinite indication

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] JAK2-positive MPN with WBC > 25 × 10⁹/L and acute multi-site or extending VTE despite ongoing AC — leukocytosis-driven prothrombotic phenotype demands urgent cytoreduction and AC intensification
- [LIFE_THREATENING] Thrombophilia panel returns triple-positive antiphospholipid syndrome on top of JAK2-V617F-positive MPN — combined thrombophilia phenotype with very high recurrence risk
- [SEVERE] Splanchnic vein thrombosis (Budd-Chiari, portal, mesenteric, splenic) as the index venous event — JAK2-V617F-positive MPN diagnosis triggers indefinite AC and full cytoreduction even if peripheral CBC is normal

Citations

- ELN 2024 MPN management + ASH 2018 thrombophilia testing + ASH 2020 VTE Treatment + ACCP/CHEST 2021 [PMID:23300175](https://pubmed.ncbi.nlm.nih.gov/23300175/)
- Cited evidence (PMID 14702426) [PMID:14702426](https://pubmed.ncbi.nlm.nih.gov/14702426/)
- Cited evidence (PMID 17566071) [PMID:17566071](https://pubmed.ncbi.nlm.nih.gov/17566071/)
- Cited evidence (PMID 33591542) [PMID:33591542](https://pubmed.ncbi.nlm.nih.gov/33591542/)
- Cited evidence (PMID 25629741) [PMID:25629741](https://pubmed.ncbi.nlm.nih.gov/25629741/)

Last reconciled with current guidelines: 2026-05-15.
References