Heparin versus Low Molecular Weight Heparin K 2165 in Chronic Hemodialysis Patients: A Randomized Cross-Over Study

Abstract

Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight (LMW) heparin K 2165 in a single-blinded randomized cross-over study to assess: (1) effects on hemostasis and ex vivo platelet functions, and (2) effectiveness, i.e. prevention of fibrin formation in the extracorporeal circuit. The 20 dialysis treatments were without untoward side effects, for both drugs used. The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization. No differences between the drugs were observed regarding the Ivy bleeding time, platelet count and platelet aggregation (spontaneous, and induced by ADP and collagen). Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin. Both drugs did not influence the plasma levels of β-thromboglobulin, thromboxane B₂ and platelet serotonin content. K 2165 did not affect platelet adhesion to collagen, in contrast to heparin which substantially inhibited platelet adhesion. Under both treatments, 4 minor clots were observed in 4 artificial kidneys, despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml. K 2165 may therefore be considered as effective an anticoagulant as heparin, with less effects on ex vivo platelet functions.

Safety and Efficacy of Low Molecular Weight Heparins for Hemodialysis in Patients with End-Stage Renal Failure

“…Bleeding events were analyzed in six studies (28,29,31,36,39,40) (Tables 4 through 6). Most bleeding events were minor, occurring at vascular access sites.…”

“…Thrombosis that occurred within the dialysis circuit was analyzed in five of 11 possible studies (28,29,32,36,40) (Table 7). Two studies reported units that could not be converted to a proportion of hemodialysis sessions (11,30), and another two reported clotting per number of patients affected (31,33).…”

Efficacy and safety of low molecular weight heparin compared to unfractionated heparin for chronic outpatient hemodialysis in end stage renal disease: systematic review and meta-analysis

“…Among the 19 included RCTs (Aggarwal et al, 2004; Borm et al, 1986; Elisaf et al, 1997; Gritters et al, 2006; Harenberg et al, 1995; Hottelart et al, 1998; Lane et al, 1986; Lord et al, 2002; Mahmood et al, 2010; Naumnik, Borawski & Mysliwiec, 2003; Naumnik et al, 2007; Naumnik, Pawlak & Mysliwiec, 2007; Naumnik, Pawlak & Mysliwiec, 2009b; Naumnik, Pawlak & Mysliwiec, 2009a; Poyrazoglu et al, 2006; Ryan et al, 1990; Saltissi et al, 1999; Schrader et al, 1988; Verzan et al, 2004), 6 had a parallel group design and 13 had a cross-over design. Most regions of the world were represented, with 5 studies from Poland, 2 studies each from Netherland, Germany and United Kingdom and 1 study each from United States, Greece, France, Canada, Sweden, Turkey, Australia and Romania.…”

“…Harenberg et al (1995) reported that LMWH group (tinzaparin) did not differ with UH group as both groups had similar number of events (1/10 each). The remaining 4 studies Borm et al (1986), Schrader et al (1988), Saltissi et al (1999) and Lord et al (2002), had reported this outcome for the total number of dialysis sessions in each group. The number of extracorporeal circuit thrombosis/number of dialysis sessions encountered for the LMWH group in these 4 studies were respectively 4/10, 80/5045, 17/1111 and 32/378 compared to 4/10, 69/5197, 35/1141, 21/382 in the UH group.…”

Interactions of Heparins in the Vascular Environment

“…Heparin prolongs the bleeding time in healthy volunteers [5], decreases platelet ad hesion to collagen [6] and is inhibitory in some in vitro tests of platelet activation [5,7]. Paradoxically, it also exerts prothrombotic ef fects on platelets, and platelet aggregates are commonly found in blood collected directly into heparin.…”