Plasma dermatan sulfate proteoglycan in a patient on chronic hemodialysis
MA Delorme, N Saeed, A Sevcik, L Mitchell, L Berry, M Johnston and M Andrew
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
A 68-year-old man on chronic hemodialysis for 6 years, presented with a
spontaneous psoas muscle hemorrhage. Investigations showed intermittently
elevated activated partial-thromboplastin time and thrombin time.
Preliminary investigations suggested a heparin-like inhibitor in the
patient's plasma, but no anti-Xa activity could be detected. Investigation
of the ability of patient plasma to inhibit exogenous thrombin showed that
most thrombin was inhibited by heparin cofactor II, in contrast to normal
plasma in which most thrombin was inhibited by antithrombin III. Treatment
of plasma with glycosaminoglycan-degrading enzymes suggested the presence
of dermatan sulfate (DS) in patient plasma. This was confirmed in a heparin
cofactor II-dependent antithrombin assay for DS that showed anticoagulant
equivalent to 2.2 +/- 0.3 micrograms/mL (mean +/- SD) of porcine mucosal
DS. Of this activity, approximately 90% was sensitive to enzymes that
degrade DS. The glycosaminoglycan containing fraction of plasma was
isolated and subjected to gel chromatography. Anticoagulant activity eluted
from Sephadex G-100 (Pharmacia, Montreal, Quebec, Canada) as two peaks with
Kav of 0.10 and 0.45. After treatment with base, the Kav of the higher
molecular weight species was increased to 0.55. This activity was
completely sensitive to enzymes that degrade DS. Thus, the active DS was
present as a proteoglycan. The lower molecular weight material was not
sensitive to enzymes that degrade DS or heparan sulfate and it was active
in the heparin cofactor II- dependent antithrombin assay but not in an
antithrombin III-dependent antithrombin assay. This activity was not
degraded by heating. Subsequently, measurement of DS activity was performed
in plasmas obtained from eight other patients on hemodialysis before
administration of heparin that showed that all patients had DS activity
present that varied from 0.05 to 0.4 microgram/mL. No enzyme-resistant
activity could be shown in these patients. In summary, a circulating
anticoagulant with properties of DS is present in patients requiring
hemodialysis.
Volume 82,
Issue 11,
pp. 3380-3385,
12/01/1993
Copyright © 1993 by The American Society of Hematology
