VTE prophylaxis in Nephrotic syndrome

• Variable incidence, depending on population being studied 3-36%(!)
• Can be any vascular bed, venous or arterial and include cerebral vein/arteries, coronaries.

Pathophysiology

• Loss of fibrinolytic factors such as antithrombin III, plasminogen, protein S, plasmin.
• Simultaneously, the liver upregulates thromboxane A1, VwF and Cholesterol, fibrinogen, Factor V, VIII
• Hypovolaemia may be a factor
• Heparin resistance due to urinary antithrombin loss?

VTE timeline

• Membranous Nephropathy (MN) has highest risk: HR of 10 vs non nephrotic control, about 8% overall incidence.
• MN has VTE sooner: Typically, about 150 days to first VTE vs 300 in other GN.
• MN: Median time to VTE 3.8 month (IQR 0-1 – 12.1)
• 4/56 clots discovered at time of first presentation with proteinuria
• Albumin: each 10g/L drop in alb increases HR by ~2
• Albumin of 28 is a reasonable cut off with a HR of 2.53 for VTE above and below
• Lionaki, CJASN,Toronto Data.
• Risk/benefit calculator: https://www.med.unc.edu/gntools/

Drug choice

• Warfarin first line
• LMWH second line, dosing slightly unclear, a level may be most appropriate.
• Multiple cautionary case reports of DOACs failing individual patients in NS, although they probably work for most people, highly variable kinetics. Avoid if possible.