The effect of low molecular weight dextran on platelet deposition onto prosthetic materials

Abstract

Low molecular weight dextran (LMD) has recently been shown in a randomized, multicenter trial to improve early patency in difficult lower extremity vascular bypass. The question remained as to whether this effect was due to plasma volume expansion by LMD or to its effects on platelets and coagulation. To analyze this we have studied the effects of LMD on platelet-graft interactions using an ex vivo baboon shunt. Indium 111-labeled autologous platelet deposition on expanded polytetrafluoroethylene and knitted Dacron grafts was monitored at a flow rate of 25 ml/min for 21/2 hours. LMD was given by intravenous bolus at a dose of 5 ml/kg and was followed by a continuous infusion of 10 ml/hr. Flow through the shunt was started after the initial dextran bolus. Control studies were performed in a similar manner without dextran. An additional series of experiments was performed with a 5 to 10 ml/kg bolus of 5% human serum albumin to analyze the contribution of plasma volume expansion to platelet deposition in this model. The results revealed a significant (p less than 0.05) reduction in platelet deposition on both graft materials with the LMD infusion. No difference was seen between the control group and the albumin group. These studies provide direct in vivo evidence of the antiplatelet effect of LMD.

Platelet activation in a circulating flow loop: combined effects of shear stress and exposure time

“…While low molecular weight (40-and 70-kDa) dextrans are known to interfere with platelet deposition on surfaces (such as vascular grafts), the effect is on adhesion and not activation. 17,18 In this regard it is pertinent that the buffer in which the platelets are suspended in the present study contains no von Willebrand factor (vWf), which is the major bridging molecule in platelet adhesion to surfaces. It is, however, possible that small amounts of vWf may be supplied by the platelets themselves on activation.…”

In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function.

“…Twenty-four hours after the infusion of autologous PKH2-labeled platelets, peripheral blood was routed through a 6 mm (diameter) x 6 cm (length) knitted double velour Dacron graft impregnated with purified collagen (Meadox Medicals, Oakland, CA) secured into an ex vivo femoral arteriovenous shunt, as described (21). The Dacron graft is known to be thrombogenic in this model (21).…”

“…Twenty-four hours after the infusion of autologous PKH2-labeled platelets, peripheral blood was routed through a 6 mm (diameter) x 6 cm (length) knitted double velour Dacron graft impregnated with purified collagen (Meadox Medicals, Oakland, CA) secured into an ex vivo femoral arteriovenous shunt, as described (21). The Dacron graft is known to be thrombogenic in this model (21). The arteriovenous shunt was clamped after 2 h of flow and an approximately 4 x 4 mm sample of the Dacron graft was immediately excised, placed in modified Hepes-Tyrode's buffer (pH 7.4), mixed gently for 30 min at 37°C with plasmin 1 CU/ml (Kabi-Pharmacia Hesper, Franklin, OH), and fixed in formaldehyde 1% (final concentration).…”

Inhibition of platelet retention on artificial microvascular grafts with monoclonal antibodies and a high-affinity peptide directed against platelet membrane glycoproteins.

“…For example, dextran has been shown to provide a striking improvement in the early patency of distal extremity bypass with larger PTFE grafts in humans and to reduce platelet retention by PTFE shunts in baboons. 23 - 24 In our AMG model, dextran had only a minimal inhibitory effect on the early stages of platelet retention, in which adhesion plays a larger role.…”