Many patients suffer bleeding complications while on hemodialysis (HD). Although these events may be as clinically benign as prolonged bleeding after removal of the dialysis needles, they still have a significant impact on a patient who may miss their bus ride home as they sit that extra half hour waiting to clot. On the other hand, the bleeding can be life-threatening such as a cerebral hemorrhage. Heparin is regularly used during dialysis to prevent clotting and allow for efficient dialysis. A recent In Practice article in American Journal of Kidney Diseases discusses the use of heparin in the dialysis setting. Dr. Jenny Shen (JS) from Stanford University, corresponding author of this manuscript, discusses this important topic with eAJKD Blog Editor Kenar Jhaveri (eAJKD).
eAJKD: What prompted you to study this topic?
JS: Unfractionated heparin use during HD is virtually universal in the United States. Since most patients are exposed to this anticoagulant multiple times a week, we wondered if the drug was contributing to their bleeding risk. To our surprise, no national guidelines exist for the use of anticoagulation in HD to which the vast majority of our patients are exposed. Hence, this led to an interest in exploring this area.
eAJKD: In contrast to the United States, Europe has published European Best Practices as guidelines for heparin administration in chronic HD. Do you think United States dialysis units should have similar guidelines?
JS: National guidelines would be helpful. Many units are re-inventing the wheel when they develop their own protocols from scratch. Creating a reference dosing schedule would help standardize the procedure, leading to increased patient safety. For one thing, health care practitioners of all kinds—physicians, nurses, and technicians—are less likely to make dangerous errors in the prescription and administration of the drug if it is given similarly in all units. Also, having a standard protocol would simplify studying the safety of unfractionated heparin (UFH). However, further studies are needed as we currently do not have a high level of evidence on which to base our guidelines. In our review, for patients with a standard dialysis session of about 4 hours, we recommend an initial bolus of 25 IU/kg followed by a continuous infusion of 1000 IU/hr, to be stopped 30-60 minutes before the end of the session. If the patient routinely requires more than 15 minutes to clot at the needle puncture sites despite proper needle insertion technique, the maintenance infusion dose should be decreased to 500 IU/hr. UFH may need to be eliminated if the prolonged bleeding after removal of the needle does not improve with reduced maintenance dose. Conversely, if the extracorporeal circuit clots during the run and the practitioner has ruled out vascular access and dialyzer equipment as the causes, the rate of UFH infusion should be increased by 500 IU/hr. These recommendations are opinion based, as there are no data to support one particular dosing schedule over another.
eAJKD: Do you feel that there is increased risk of gastro intestinal (GI) bleed when you are on HD?
JS: For the average patient, the increase in risk is minimal and is outweighed by the benefit of providing reliable anticoagulation of the dialysis circuit. For patients who are prone to GI hemorrhages, for example those who are taking multiple anti-platelet and anticoagulant medications, the increased risk is mitigated by the prudent prescription habits of their physicians, who are likely prescribing lower doses of heparin to these patients.
eAJKD: “Not using heparin increases chances of fluid overload”. Is there evidence for that statement?
JS: It is well established that anticoagulant-free HD has a higher rate of clotting of the dialysis circuit than standard HD, which often precludes adequate volume removal. Few of these studies, however, monitored ultrafiltration rates and goals as an outcome. So, the statement is based on clinical practice and not evidence.
eAJKD: Can you elaborate on the mechanism of triglyceridemia from heparin? Has a comparison been done of the triglyceride levels of chronic HD patients receiving heparin with those receiving heparin-free treatment?
JS: Lipoprotein lipase (LPL) is an enzyme that degrades triglycerides, but is usually bound to the vascular endothelium. When unfractionated heparin is administered, it causes LPL to be dislodged and enter the circulation where it is eventually metabolized by the liver. This decreases the stores of LPL, allowing triglyceride levels to rise. No recent studies compare the TG levels of patients receiving heparin with those receiving heparin-free treatment, although numerous studies have compared UFH to low molecular weight heparin (LMWH).
eAJKD: Do you think if an ESRD patient is being anti coagulated per hour three times a week, they need standard DVT prophylaxis heparin as well when admitted to the hospital?
JS: As with all medical care, it is dependent on the patient. If the patient is at low risk for thrombosis (as defined in the ACCP 9th edition guidelines), DVT prophylaxis with heparin can likely be avoided. Unfortunately, most of our patients who end up in the hospital are critically ill and have multiple risk factors for thrombosis. The most important thing to remember is that if anticoagulants are used, UFH should be used over LMWH since it can be reliably reversed with protamine.