This handout is for nephrotic-syndrome dvt (urinary at-iii/protein s loss; lmwh preferred over doac). Your care team identified this based on: unilateral leg swelling/pain in a patient with known nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia) — vte pretest probability sharply elevated.
Other reasons your team may use this plan: 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; biopsy-proven membranous nephropathy patient with new leg symptoms — highest-risk glomerular disease for dvt (~30% lifetime vte per kerlin cjasn 2012); 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.
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| enoxaparin | 1 mg/kg SC BID (reduce to 1 mg/kg SC daily if CrCl <30) | SC | BID; continue while proteinuria >3.5 g/day or albumin <2.5 g/dL | ASH 2020 (PMID 33007077); ISN 2021 + KDIGO 2021 — LMWH preferred over DOAC in heavy-proteinuria NS due to unreliable PK + free-fraction shifts; predictable subcutaneous absorption; AT-III independent of urinary loss when monitored by anti-Xa |
| warfarin | 5 mg PO daily; target INR 2-3 | PO | daily; AC duration tied to NS activity (continue while heavy proteinuria persists) | Acceptable long-term oral AC after LMWH bridge once NS activity moderating; not protein-bound so free-fraction concerns are less; INR-monitored (note vitamin-K losses in nephrotic urine may shift INR variability — narrow-band INR monitoring needed); ACCP 2021 framework |
| heparin | 80 U/kg IV bolus + 18 U/kg/h targeting aPTT 1.5-2.5× (use anti-Xa 0.3-0.7 IU/mL if AT-III deficiency causing aPTT-resistance) | IV | continuous | Reversibility for peri-procedural management (renal biopsy planning); UFH requires AT-III as cofactor — heparin resistance possible if AT-III <50%; consider AT-III concentrate replacement (50 IU/kg) if refractory aPTT despite escalating UFH per ASH 2020 |
| AVOID rivaroxaban during heavy proteinuria | AVOID | N/A | N/A | Sexton CJASN 2018 — variable apixaban PK in NS; rivaroxaban (87% albumin-bound) similarly affected; case-series reports of recurrent VTE on DOAC in active NS; ISN 2021 + KDIGO 2021 advise against DOAC during heavy proteinuria; revisit only when proteinuria <3.5 g/day or albumin >2.5 g/dL sustained ≥3 mo |
| AVOID apixaban during heavy proteinuria | AVOID | N/A | N/A | Sexton CJASN 2018 PK study — wide apixaban variability in NS patients; high albumin binding (87%) makes free-fraction unpredictable in hypoalbuminemia; ISN 2021 + KDIGO 2021 — DOAC avoided |
| apixaban (AFTER NS remission) | apixaban 5 mg PO BID once proteinuria <3.5 g/day AND albumin >2.5 g/dL sustained ≥3 mo | PO | BID after sustained NS remission | AMPLIFY (Agnelli NEJM 2013 PMID 23808982) — apixaban first-line outside NS; once NS proteinuria resolves, DOAC PK normalises and routine outpatient AC framework applies |
| aspirin | 81 mg PO daily | PO | daily | NS-driven dyslipidaemia + endothelial dysfunction accelerates atherosclerosis; low-dose ASA reasonable in NS patients with established ASCVD; antepartum low-dose ASA in NS-pregnancy reduces preeclampsia risk |
| antithrombin III concentrate | 50 IU/kg IV (target AT-III activity >80%) when refractory heparin resistance from severe NS-driven AT-III loss | IV | one-time, repeat as guided by AT-III activity | Heparin requires AT-III as cofactor; severe NS-driven AT-III deficiency blunts UFH response; AT-III concentrate replacement restores cofactor activity; case-series + ASH 2020 framework |
Plan: Nephrotic-syndrome DVT anticoagulation — LMWH preferred (urinary DOAC loss + albumin-binding shift); warfarin acceptable after LMWH bridge; DOAC avoided while proteinuria >3.5 g/day or albumin <2.5 g/dL (KDIGO 2021; ISN 2021)
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
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
Guideline: KDIGO 2021 Glomerular Diseases + ISN 2021 NS-VTE position + ASH 2020 VTE Treatment + ACCP/CHEST 2021