Anticoagulants in "Irreversible" Acute Renal Failure

Intraglomerular fibrin, platelet aggregation, and subendothelial deposits in lipoid nephrosis

“…Under high magnification this material appeared very finely granular and did not resemble fibrin. It occasionally contained what appeared to be remnants of sub- [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. This was observed apparently unassociated with platelet aggregation in nine cases.…”

“…Nine cases of active lipoid nephrosis, five males (Nos. 4 Since this material has little structure it is more difficult to locate than the more dense and characteristically structured fibrin. Our immunofluorescence studies show poor correlation with our electron microscopic findings of fibrin.…”

“…Fibrin aggregates have been described in acute glomerulonephritis (3), and recently heparin has been successfully used in the therapy of acute renal failure in this and similar nephropathies (4). The association of spontaneous thrombosis in renal veins or pulmonary arteries with the nephrotic syndrome is also well known, and it has been suggested that steroid therapy may increase the incidence of thrombotic events (5).…”

Anti-heparin antibodies: part of the repertoire of anti-endothelial cell antibodies (AECA)

“…48 This is of interest as heparin has been used previously in immunosuppressive regimes to treat aggressive immune-mediated disorders such as rapidly progressive glomerulonephritis prior to the discovery of AECA. 49 In an animal model of scleroderma, the tight skin mouse, antibodies to heparan sulphate occur and may induce procoagulant phenomena by inhibiting thrombin-antithrombin III complexes. 50 Further evidence for the involvement of anti-heparan sulphate antibodies in disease is provided by a rat model where immunisation with heparan sulphate resulted in renal injury with circulating antibodies to heparan sulphate and a pro-coagulant state.…”

Editorial Review

“…Rix and colleagues suggest that through binding to GAGs, heparin may have a therapeutic role as a non-specific immunosuppressant. Indeed, although currently out of vogue, heparin has been previously used in immunosuppressive regimens to treat aggressive immune-mediated disorders such as ulcerative colitis and rapidly progressive glomerulonephritis [29,30]. However, before evaluating the role of anti-GAG therapies in human disease, a clearer understanding of the range and subtleties of the immunomodulating role of endothelial proteoglycans is required.…”