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cardio.dvt.nephrotic-syndrome.v1

Nephrotic-syndrome DVT (urinary AT-III/protein S loss; LMWH preferred over DOAC)

cardiologyacuteadultacuteinpatienttransitionoutpatient
Start encounter →Print handoutPRODUCTION

Phase E variant of cardio.dvt.core.v1 — narrowed to nephrotic syndrome (NS), the acquired hypercoagulable state produced by urinary loss of antithrombin III + free protein S + protein C + plasminogen plus hepatic up-regulation of fibrinogen / factor V/VIII / vWF. Sapporo-style criteria not applicable; NS itself defines the substrate. Membranous nephropathy carries highest VTE risk (~30% lifetime per Kerlin CJASN 2012). Inherits parent DVT diagnostic arc; SUBSTANTIALLY specializes long-term AC class and duration. KEY DIFFERENCES FROM PARENT: LMWH (enoxaparin 1 mg/kg SC BID) is first-line while heavy proteinuria persists. DOACs are AVOIDED — Sexton CJASN 2018 PK data + ISN 2021 + KDIGO 2021 cite urinary loss of free DOAC and unpredictable free-fraction shifts in hypoalbuminemia (apixaban 87% albumin-bound; rivaroxaban 92%). Warfarin acceptable after LMWH bridge if long-term oral AC needed. UFH only with anti-Xa monitoring + AT-III activity check (heparin requires AT-III cofactor; severe AT-III deficiency causes heparin resistance — AT-III concentrate replacement may be needed). Concurrent RENAL VEIN THROMBOSIS surveillance mandatory in membranous nephropathy with new flank pain / gross hematuria / AKI / asymmetric proteinuria — contrast CT or MR venography. Primary prophylactic AC recommended in membranous + albumin <2.5 g/dL + low bleed risk per Lee CJASN 2014 Markov + KDIGO 2021. AC duration tied to NS ACTIVITY — continue while proteinuria >3.5 g/day or albumin <2.5 g/dL; transition to DOAC only after sustained remission ≥3 mo. Manifest pointer reuses cardio.dvt.core.v1 manifest. Design-brief pointer reuses parent (NS-specific differences documented inline). EHR DOAC-avoidance flag during active NS is an operational safety requirement. Status INTEGRATED. Authored 2026-05-15 by shard-06-cardio-acute as nephrotic-syndrome DVT variant.

Entry points (6)

  • symptom
    Unilateral leg swelling/pain in a patient with known nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia) — VTE pretest probability sharply elevated
    unilateral_leg_swelling_with_proteinuria_or_known_ns
  • lab_abnormality
    Serum albumin <2.5 g/dL + UPCR >3.5 (or 24-h urinary protein >3.5 g) — high-risk VTE substrate; surveillance + prophylaxis decision triggered
    serum_albumin_below_2_5_with_heavy_proteinuria
  • history
    Biopsy-proven membranous nephropathy patient with new leg symptoms — highest-risk glomerular disease for DVT (~30% lifetime VTE per Kerlin CJASN 2012)
    membranous_nephropathy_with_new_le_symptoms
  • symptom
    New flank pain, gross hematuria, AKI, or asymmetric proteinuria in a known NS patient → concurrent renal vein thrombosis (RVT) screen with contrast CT or MR venography
    flank_pain_or_gross_hematuria_in_ns_patient
  • lab_abnormality
    Documented AT-III activity <70% in a heavy-proteinuria patient — acquired AT-III deficiency from urinary loss; predicts heparin resistance and elevates VTE risk
    antithrombin_iii_below_70_percent_in_proteinuric_patient
  • imaging
    Compression ultrasound confirming proximal DVT in a known NS patient — anchor diagnosis and route to NS-specific anticoagulation pathway
    us_proximal_dvt_with_known_ns

Required inputs (12)

  • agerequired
    demographic • used at CONTEXT
    Older NS patients (membranous nephropathy peaks 50-70 yr) have additive VTE risk; lifelong-AC tolerance considerations dominate
  • sexrequired
    demographic • used at CONTEXT
    Female patients with NS face OCP / pregnancy planning decisions; estrogen contraception must be discontinued; pregnancy in active NS is a high-risk overlap
  • underlying_glomerular_disease_histologyrequired
    history • used at CONTEXT
    Membranous nephropathy carries the highest VTE risk; FSGS, minimal-change, lupus nephritis, and amyloid each carry distinct VTE risk profiles and treatment implications
  • current_immunosuppressionrequired
    history • used at CONTEXT
    Steroids, rituximab, calcineurin inhibitors, cyclophosphamide — interactions with warfarin (cyclophosphamide), rituximab-related infusion reactions, and steroid-driven hyperglycaemia all influence AC plan
  • leg_swellingrequired
    symptom • used at ENTRY
    Cardinal symptom of proximal DVT; bilateral edema in NS may obscure unilateral DVT — measure calf circumferences and look for asymmetry
  • compression_usrequired
    imaging • used at INITIAL_WORKUP
    First-line imaging confirmation of DVT; assess proximal vs distal extent
  • serum_albuminrequired
    lab • used at CONTEXT
    Severity marker; <2.5 g/dL = highest VTE risk band; predicts free-DOAC fraction perturbation (apixaban + rivaroxaban are 87-92% albumin-bound)
  • urine_protein_creatinine_ratiorequired
    lab • used at CONTEXT
    Quantifies proteinuria; UPCR >3.5 (or 24-h urinary protein >3.5 g) defines nephrotic-range; >10 g/day is severe and shifts strongly toward LMWH over DOAC
  • creatininerequired
    lab • used at TREATMENT
    eGFR for LMWH dose adjustment (CrCl <30 → 1 mg/kg SC daily instead of BID); informs IV UFH alternative
  • antithrombin_iii_activityrequired
    lab • used at BRANCHING_WORKUP
    AT-III activity <70% indicates urinary loss; predicts heparin resistance (heparin requires AT-III cofactor); supports LMWH or DOAC over UFH; severe AT-III deficiency may justify AT-III concentrate replacement
  • cbcrequired
    lab • used at INITIAL_WORKUP
    Baseline platelet for AC; thrombocytosis is common in NS and adds to thrombotic risk
  • bleed_riskrequired
    history • used at RED_FLAGS
    HAS-BLED + biopsy timing (post-renal-biopsy AC needs ≥5-7 d delay) drives AC eligibility

12-phase flow (11)

  1. 1FRAME
    Nephrotic syndrome = acquired hypercoagulable state from urinary AT-III + protein S/C loss + hepatic up-regulation of fibrinogen / factor V/VIII / vWF; LMWH preferred over DOAC while heavy proteinuria persists; concurrent RVT surveillance in membranous nephropathy; primary prophylaxis if albumin <2.5 g/dL + MN per KDIGO 2021
    inputs: leg_swelling, underlying_glomerular_disease_histology
    advance: NS-DVT phenotype framed
  2. 2ENTRY
    Wells DVT score + compression US; document NS severity (albumin, UPCR, edema burden) and underlying histology; bilateral edema in NS may obscure unilateral DVT — measure asymmetry
    inputs: age, sex
    advance: pretest probability + NS severity documented
  3. 3CONTEXT
    Underlying glomerulonephritis (membranous, FSGS, minimal-change, lupus, amyloid); current immunosuppression (steroids, rituximab, CNI, cyclophosphamide); diuretic regimen (volume contraction adds VTE risk); recent renal biopsy; estrogen / OCP use (must hold); pregnancy plans
    inputs: current_immunosuppression, serum_albumin, urine_protein_creatinine_ratio
    advance: context complete
  4. 4RED_FLAGS
    Renal vein thrombosis (flank pain, gross hematuria, new AKI, asymmetric proteinuria) — contrast CT or MR venography; concurrent PE; phlegmasia; AKI on top of NS (cardiorenal vs RVT-related); severe AT-III deficiency causing heparin resistance; absolute AC contraindication after recent biopsy
    inputs: bleed_risk
    actions: pe_full, le_edema
    advance: critical features screened
  5. 5INITIAL_WORKUP
    Compression US + CBC + BMP + UA + UPCR + serum albumin; PT/INR/PTT; lipid panel (NS is hyperlipidemic); CXR if respiratory symptoms; ABG if hypoxia
    inputs: compression_us, cbc, creatinine
    actions: panel.cardiac, panel.renal, panel.coag, panel.abg
    advance: imaging confirms DVT + baseline labs available
  6. 6BRANCHING_WORKUP
    AT-III activity, free protein S, protein C activity, fibrinogen, vWF (NS-specific hypercoagulability profile); contrast CT or MR venography for RVT in membranous nephropathy or new flank/hematuria; renal biopsy if NS aetiology unknown (timing vs AC critical — biopsy first then AC ≥5-7 d later, or LMWH bridge with hold for procedure)
    inputs: antithrombin_iii_activity
    advance: NS hypercoagulability profile + RVT screen documented
  7. 7RISK_STRATIFICATION
    Wells DVT, HAS-BLED, eGFR; integrate NS severity (albumin <2.5 g/dL = highest band; >10 g/day proteinuria = severe); membranous histology = highest VTE risk; primary prophylaxis decision per Lee CJASN 2014 Markov in MN with albumin <2.5; recurrence risk on AC stopping is HIGH while NS active → AC continues until proteinuria <3.5 g/day or albumin >2.5 g/dL sustained
    inputs: bleed_risk
    actions: calc.ckd_epi_2021
    advance: AC duration plan documented (NS-activity-conditional)
  8. 8TREATMENT
    Acute: LMWH (enoxaparin 1 mg/kg SC BID; reduce to 1 mg/kg daily if CrCl <30) PREFERRED. DO NOT use DOAC while proteinuria >3.5 g/day or albumin <2.5 g/dL (PK unreliable — urinary loss + free-fraction shifts; ISN 2021 / KDIGO 2021 + Sexton CJASN 2018 PK data). Warfarin acceptable after LMWH bridge if long-term need (overlap until INR 2-3 × ≥2 d). UFH only with AT-III monitoring (heparin resistance possible if AT-III <50%; AT-III concentrate replacement may be needed). Primary prophylaxis with prophylactic-dose LMWH or warfarin if MN + albumin <2.5 g/dL + low bleed risk per KDIGO 2021
    inputs: creatinine, bleed_risk
    advance: LMWH initiated, DOAC explicitly avoided, RVT plan documented
  9. 9DISPOSITION
    Inpatient management commonly required for new NS-DVT diagnosis (LMWH initiation, RVT screen, biopsy timing, immunosuppression coordination); outpatient acceptable for known-NS patient with reliable LMWH self-administration + close nephrology follow-up
    advance: disposition documented
  10. 10MONITORING
    Albumin + UPCR every 2-4 weeks during NS treatment (drive AC continuation decision); CBC + creatinine quarterly; bleed surveillance; AT-III rechecked if heparin resistance suspected; PTS Villalta at 3/6/12 mo; reassess transition LMWH → DOAC if proteinuria <3.5 g/day or albumin >2.5 g/dL sustained ≥3 mo
    actions: panel.cardiac, panel.coag
    advance: monitoring schedule + transition criteria documented
  11. 11FOLLOWUP
    Co-management with nephrology for NS treatment (steroids ± rituximab ± CNI per histology); annual reassessment of AC continuation tied to NS activity; pre-conception planning for women (LMWH antepartum + 6-wk postpartum if active NS); estrogen avoidance lifelong while NS active; EHR flag against DOAC use during heavy proteinuria; PT/OT for deconditioning if prolonged inpatient
    advance: NS-specific AC continuation + reproductive plan + DOAC-avoidance EHR flag documented