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Dermatan sulphate (MF 701) in haemodialysis for chronic renal failure
S116
ABSTRACTS OF 12TH INTNAT’L CONGRESS
Vol. 65, SuppI. 1
C227 COMPASSIONATE-USE OF THE HEPARINOID ORGARAN (ORG 10172) PARTICULARLY IN PATIENTS WITH HIT H.N. Magnani and J. Egberts Organon International BV, Oss, NL Sensitivity or insensitivity to anticoagulant treatment although uncommon can have dramatic clinical consequences. Patients may suffer arterial or venous thrombosis which can lead to death. Many others will have already suffered a thrombosis, hence the initial need for anticoagulation, or still have a high thrombotic risk. Another group of patients will have had such an episode in the past and now need anticoagulation to cover a procedure associated with a high thrombotic risk. Thus many of these patients often require urgent alternative anticoagulation. Orgaran (Org 10172) has been used for treatment of 334 requests in 320 such patients in a compassionate-use programme. 284 requests were for patients with a current (256) or past (28) history of heparin-induced thrombocytopenia (HIT). The remaining 50 were for other forms of anticoagulant hypersensitivity. Orgaran was necessary as thrombosis prophylaxis only in I I I patients, to treat thrombosis in 140 patients. Sixty-nine patients underwent haemo-dialysis-filtration for periods up to 6 months and 14 patients for DIG. Within the total number of patients 92 patients underwent various forms of surgery, including 20 cardiopulmonary by-passes. Orgaran treatment lasted for a median of 7 days (range I-I 370 days). The success rate for treatment of both HIT and non-HIT patients is over 92%. largely because of Orgaran’s low cross-reactivity rate with the antibody present in HIT. This rate is less than 10% compared with over 85% for the low molecular weight heparins. It is concluded that Orgaran can be a life-saving alternative to heparin in sensitive patients.
DERMATAN SULPHATE (MF 701) IN HAEMODIALYSIS FOR CHRONIC RENAL FAILURE K.E. Ryan, D.A. Lane, A. Flynn, H. Ireland, M. Boisclair, J. Shepperd, J.R. Curtis Departs of Haematol. Med., Charing Cross and Westminster Hospital and Medical School, London, UK We have performed dose ranging studies of dematan sulphate (DS) to determine its effectiveness as an antithrombotic agent in patients (n-23 total) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients d&sing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg@ DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efftcacy of a i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg/kg/hr and a DS bolus of 5 mg/kg plus an infusion of 1 mg/kg/hr over 5 hr, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. In Study I, 1304 dialyses required additional UFH to complete a normal - 6 hr session. In Study 2, increasing doses of DS allowed longer dialysis sessions (mean 4.57 hr c.f. 5.25 hr), approaching that obtained with UFH regime (5.86 hr). In Study 3,3/6 patients required additional UFH (mean dialysis duration with DS 4.33 hr c.f. 5.67 hr with U FH). Mean DS levels were maintained between 35-40 &n.l. In Study 4 mean DS levels were maintained constantly between 72-83 &ml throughout dialyses and all patients experienced a clinically effective dialysis. Overall, there was a dose-related reduction in FPA and TAT and plasma DS levels correlated inversely with the levels of these markers. In Study 4 these markers were suppressed to the normal range. This work has shown that DS functions as an effective anticoagulant/antithrombotic agent.
ABSTRACTS OF 12TH INTNAT’L CONGRESS
Vol. 65, SuppI. 1
C227 COMPASSIONATE-USE OF THE HEPARINOID ORGARAN (ORG 10172) PARTICULARLY IN PATIENTS WITH HIT H.N. Magnani and J. Egberts Organon International BV, Oss, NL Sensitivity or insensitivity to anticoagulant treatment although uncommon can have dramatic clinical consequences. Patients may suffer arterial or venous thrombosis which can lead to death. Many others will have already suffered a thrombosis, hence the initial need for anticoagulation, or still have a high thrombotic risk. Another group of patients will have had such an episode in the past and now need anticoagulation to cover a procedure associated with a high thrombotic risk. Thus many of these patients often require urgent alternative anticoagulation. Orgaran (Org 10172) has been used for treatment of 334 requests in 320 such patients in a compassionate-use programme. 284 requests were for patients with a current (256) or past (28) history of heparin-induced thrombocytopenia (HIT). The remaining 50 were for other forms of anticoagulant hypersensitivity. Orgaran was necessary as thrombosis prophylaxis only in I I I patients, to treat thrombosis in 140 patients. Sixty-nine patients underwent haemo-dialysis-filtration for periods up to 6 months and 14 patients for DIG. Within the total number of patients 92 patients underwent various forms of surgery, including 20 cardiopulmonary by-passes. Orgaran treatment lasted for a median of 7 days (range I-I 370 days). The success rate for treatment of both HIT and non-HIT patients is over 92%. largely because of Orgaran’s low cross-reactivity rate with the antibody present in HIT. This rate is less than 10% compared with over 85% for the low molecular weight heparins. It is concluded that Orgaran can be a life-saving alternative to heparin in sensitive patients.
DERMATAN SULPHATE (MF 701) IN HAEMODIALYSIS FOR CHRONIC RENAL FAILURE K.E. Ryan, D.A. Lane, A. Flynn, H. Ireland, M. Boisclair, J. Shepperd, J.R. Curtis Departs of Haematol. Med., Charing Cross and Westminster Hospital and Medical School, London, UK We have performed dose ranging studies of dematan sulphate (DS) to determine its effectiveness as an antithrombotic agent in patients (n-23 total) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients d&sing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg@ DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efftcacy of a i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg/kg/hr and a DS bolus of 5 mg/kg plus an infusion of 1 mg/kg/hr over 5 hr, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. In Study I, 1304 dialyses required additional UFH to complete a normal - 6 hr session. In Study 2, increasing doses of DS allowed longer dialysis sessions (mean 4.57 hr c.f. 5.25 hr), approaching that obtained with UFH regime (5.86 hr). In Study 3,3/6 patients required additional UFH (mean dialysis duration with DS 4.33 hr c.f. 5.67 hr with U FH). Mean DS levels were maintained between 35-40 &n.l. In Study 4 mean DS levels were maintained constantly between 72-83 &ml throughout dialyses and all patients experienced a clinically effective dialysis. Overall, there was a dose-related reduction in FPA and TAT and plasma DS levels correlated inversely with the levels of these markers. In Study 4 these markers were suppressed to the normal range. This work has shown that DS functions as an effective anticoagulant/antithrombotic agent.