Alternatives to standard unfractionated heparin for pediatric hemodialysis treatments

Abstract

Despite advances in biomaterials and dialyzer design, thrombin generation occurs in the dialysis circuit because of platelet and leukocyte activation. As such, anticoagulation is required by the majority of children for successful dialysis to prevent clotting in the venous air detector and the capillary dialyzer, particularly for small children with slower blood flow rates. For many years unfractionated heparin has been the standard anticoagulant of choice, but is now being challenged by low-molecular-weight heparins (LMWHs) because they are simple to administer and reliable, particularly as the cost differential has been eroded. Alternative, nonheparin anticoagulants are more frequently available, but are often restricted to special circumstances: patients at high risk of hemorrhage; heparin allergy; or heparin-induced thrombocytopenia. These nonheparin alternatives are significantly more expensive than heparins, and may add a degree of complexity, such as citrate, which is a regional anticoagulant, although citrate-containing dialysate may permit short anticoagulant-free dialysis sessions. Systemic anticoagulants required for immune-mediated, heparin-induced thrombocytopenia are expensive and either have short half-lives, and therefore require continuous infusions, or prolonged half-lives, which, although allowing simple bolus administration, increases the risk of drug accumulation, over-dosage and hemorrhage.

Fig. 1

a Cartoon showing the action of unfractionated heparin (UFH) on the traditional coagulation cascades, the width of the black dotted arrow denotes the strength of action. The action of natural inhibitors AT and TFPI are indicated by gray dotted arrows. The width of the arrow denotes the strength of action. a activated factor, AT antithrombin III, F factor, HMWK high-molecular-weight kallikrein, KK kallikrein, LMWH low-molecular-weight heparin, PKK prekallikrein, TF tissue factor, TFPI tissue factor plasma inhibitor. b Cartoon showing the action of low molecular weight heparin (LMWH) on the traditional coagulation cascades, the width of the black arrow denotes the strength of action. The action of natural inhibitors AT and TFPI are indicated by gray dotted arrows. The width of the arrow denotes the strength of action. a activated factor, AT antithrombin III, F factor, HMWK high-molecular-weight kallikrein, KK kallikrein, LMWH low-molecular-weight heparin, PKK prekallikrein, TF tissue factor, TFPI tissue factor plasma inhibitor

Fig. 2

Cartoon depicting the five steps of regional citrate anticoagulation for hemodialysis. Ca²⁺ ionized calcium