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THURSDAY JUNE 28 1990 81 202 A new membrane for dialysis reportedly not requiring heparin: effects on blood clotting and platelet function PALARETI G, BUGI G, LEGNANI C, *COLI L, * STEFONIS, COCCHERIS Dept. AngiologV and Blood Coagulation and *Institute of Nephrology, University Hospital, Bologna, Italy A new synthetic dialytic membrane (Eval, ethilene-vinyl-al- cohol, 1.3 m2 surface area dialyzer), proposed for use also without heparin, has been evaluated in comparison with a customarily used membrane (Cuprophane, Cu) in 5 chroni- cally uremic pts (2 males, 53+7 y) on regular dialysis treat- ment for at least 6 months. Blood samples were obtained immediately before (but after heparinization when Cu was used, TO) and at the end (before heparin neutralization, TI) of dialysis sessions. Evd CO TO Tl To n aPTT set 3322 29k2 t66*34 5128 FbDP &ml .22*02 *52-e 18 .2S f 03 .28*02 t-PA @ml 9.8 f 1.9 1121 9.1 f 1.6 ?? 21*2 Plate 5 x 10 mm3 167228 ?? *146? 16 153k24 175 f 28 whole blood collagen 1121 16,2 11+1 1421 aggr.0 ADP 7*1 9kl 4&l 821 pTG-release ng/ml 19462417 37222380 1452~265*+4280~664 FbDP = fibrin-derived degradation products (Fibrinostika System, Organon Teknika) * = pcO.05, ** = pcO.01 (Wilcoxon test). Except for slight FbDP increase (within the normal values), no other signs of clotting activation were found with Eval, despite absence of heparin. The signs of platelet activation were more marked with Cu than with Eval. The marked increase in BTG release and t-PA antigen levels, recorded in Cu at Tl, may be ascribed to heparin administration. 203 In vitro effect on Heptest@ of low molecular weight heparin fractions and preparations with various anti-lla and anti-Xa activities BARA L, *MYRLXGUL4NJ, SAMXMA M Laboratoire Central d %It!matologie, H&e1 Dieu, Paris, France and Whone-Poulenc San&!, Gennevilliers, France The Heptest heparin assay has recently been introduced and evaluated for the laboratory monitoring of patients receiv- ing low molecular weight heparins (IMWI-I). The aim of the present study was to elucidate the relative role on the Heptest assay of the anti-factors Xa and IIa activities pre- sent in the three types of compounds that possess: 1. exclu- sively anti-Xa activity (LFl : LMWH fractions with MW ranging from 1,200 to 4,200 D); 2. both anti-Xa and anti-IIa activities (LF2 with MW from 4,800 to 12,000 D); 3. exclu- sive anti-IIa activity (Hirudin and Dermatan Sulfate). All compounds studied demonstrated dose-dependent activi- ties in both amidolytic and clotting assays. The LF2 in con- trast to the LFl, additionally enhanced the clotting times of Heptest. This enhancement was shown to be due to the anti-Factor IIa activity of the agents. Heptest does not ex- clusively reflect anti-Xa activity since it is influenced by agents containing exclusive anti-IIa activity like Hirudin and Dermatan Sulfate. At low concentrations of LF2, Heptest measures predominantly the anti-factor Xa activity while at higher concentrations it is influenced by the combined activ- ity of anti-factor Xa and anti-factor IIa. However, Heptest sensitivity to anti-factor IIa is significantly lower than anti- Xa activity. 204 Comparison of 5 assays for LMW heparin monitoring ABILDGAARD v, NORRHEIM L, URSENAE, NESVOLD A, ODEGAARD OR Hematological Research Laboratory, Aker Hospital, Oslo, NoMtay The APTT is insensitive to low molecular weight (LMW) heparin. Heptest, a new clotting assay is useful for monitor- ing standard heparin, and is also sensitive to LMW heparin. Heptest has been compared with two-stage and one-stage chromogenic substrate (CS) assays in monitoring treatment with LMW heparin Fragmin. The correlation between the methods was fairly high (r=0.70-0.97). In addition, LMW heparins (Fragmin, Enoxaparine, Logiparin) were added to plasma from patients with major disease, and the recoveries determined. The two-stage CS recovered (mean) 95% of added LMW heparin, with a CV of 7%. The one stage C’S assays (Rotachrom Stago, Coatest LMW heparin and Coacute Kabi) all recovered about 80% with a CV of 14- 20%. Heptest also recovered 80% but CV was about 40%. This means that with abnormal plasma protein patterns, Heptest is much less accurate than CS assays. Of the 5 assays, only the two-stage assay (Handeland G, Thromb Res 1986,42: 105-8) has linear standard curves nearly coinciding for LMW and standard heparin. An additional advantage with the two-stage assay, is that both LMW and standard heparin can be assayed with a single standard curve.

A new membrane for dialysis reportedly not requiring heparin: effects on blood clotting and platelet function

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THURSDAY JUNE 28 1990 81

202 A new membrane for dialysis reportedly not requiring heparin: effects on blood clotting and platelet function PALARETI G, BUGI G, LEGNANI C, *COLI L, * STEFONIS, COCCHERIS ’ Dept. AngiologV and Blood Coagulation and *Institute of Nephrology, University Hospital, Bologna, Italy

A new synthetic dialytic membrane (Eval, ethilene-vinyl-al- cohol, 1.3 m2 surface area dialyzer), proposed for use also without heparin, has been evaluated in comparison with a customarily used membrane (Cuprophane, Cu) in 5 chroni- cally uremic pts (2 males, 53+7 y) on regular dialysis treat- ment for at least 6 months. Blood samples were obtained immediately before (but after heparinization when Cu was used, TO) and at the end (before heparin neutralization, TI) of dialysis sessions.

Evd CO

TO Tl To n

aPTT set 3322 29k2 t66*34 5128 FbDP &ml .22*02 *52-e 18 .2S f 03 .28*02 t-PA @ml 9.8 f 1.9 1121 9.1 f 1.6 ??21*2 Plate

5 x 10 mm3 167228 ??*146? 16 153k24 175 f 28 whole blood collagen 1121 16,2 11+1 1421 aggr.0 ADP 7*1 9kl 4&l 821 pTG-release ng/ml 19462417 37222380 1452~265*+4280~664

FbDP = fibrin-derived degradation products (Fibrinostika System, Organon Teknika) * = pcO.05, ** = pcO.01 (Wilcoxon test).

Except for slight FbDP increase (within the normal values), no other signs of clotting activation were found with Eval, despite absence of heparin. The signs of platelet activation were more marked with Cu than with Eval. The marked increase in BTG release and t-PA antigen levels, recorded in Cu at Tl, may be ascribed to heparin administration.

203 In vitro effect on Heptest@ of low molecular weight heparin fractions and preparations with various anti-lla and anti-Xa activities BARA L, *MYRLXGUL4NJ, SAMXMA M Laboratoire Central d %It!matologie, H&e1 Dieu, Paris, France and Whone-Poulenc San&!, Gennevilliers, France

The Heptest heparin assay has recently been introduced and evaluated for the laboratory monitoring of patients receiv- ing low molecular weight heparins (IMWI-I). The aim of the present study was to elucidate the relative role on the Heptest assay of the anti-factors Xa and IIa activities pre- sent in the three types of compounds that possess: 1. exclu- sively anti-Xa activity (LFl : LMWH fractions with MW ranging from 1,200 to 4,200 D); 2. both anti-Xa and anti-IIa activities (LF2 with MW from 4,800 to 12,000 D); 3. exclu- sive anti-IIa activity (Hirudin and Dermatan Sulfate). All compounds studied demonstrated dose-dependent activi-

ties in both amidolytic and clotting assays. The LF2 in con- trast to the LFl, additionally enhanced the clotting times of Heptest. This enhancement was shown to be due to the anti-Factor IIa activity of the agents. Heptest does not ex- clusively reflect anti-Xa activity since it is influenced by agents containing exclusive anti-IIa activity like Hirudin and Dermatan Sulfate. At low concentrations of LF2, Heptest measures predominantly the anti-factor Xa activity while at higher concentrations it is influenced by the combined activ- ity of anti-factor Xa and anti-factor IIa. However, Heptest sensitivity to anti-factor IIa is significantly lower than anti- Xa activity.

204 Comparison of 5 assays for LMW heparin monitoring ABILDGAARD v, NORRHEIM L, URSENAE, NESVOLD A, ODEGAARD OR Hematological Research Laboratory, Aker Hospital, Oslo, NoMtay

The APTT is insensitive to low molecular weight (LMW) heparin. Heptest, a new clotting assay is useful for monitor- ing standard heparin, and is also sensitive to LMW heparin. Heptest has been compared with two-stage and one-stage chromogenic substrate (CS) assays in monitoring treatment with LMW heparin Fragmin. The correlation between the methods was fairly high (r=0.70-0.97). In addition, LMW heparins (Fragmin, Enoxaparine, Logiparin) were added to plasma from patients with major disease, and the recoveries determined. The two-stage CS recovered (mean) 95% of added LMW heparin, with a CV of 7%. The one stage C’S

assays (Rotachrom Stago, Coatest LMW heparin and Coacute Kabi) all recovered about 80% with a CV of 14- 20%. Heptest also recovered 80% but CV was about 40%. This means that with abnormal plasma protein patterns, Heptest is much less accurate than CS assays. Of the 5 assays, only the two-stage assay (Handeland G, Thromb Res 1986,42: 105-8) has linear standard curves nearly coinciding for LMW and standard heparin. An additional advantage with the two-stage assay, is that both LMW and standard heparin can be assayed with a single standard curve.