II. Use of anticoagulants during dialysis
When no anticoagulant is used, dialyzer clotting rate during a 3- to 4-hour dialysis session is substantial (5%–10%), and when this occurs, it results in loss of the dialyzer and blood tubings, plus loss of approximately 100–150 mL of blood (the combined fill volume of the dialyzer and blood line in the extracorporeal circuit). This is an acceptable risk in many patients judged to be at moderate to high risk of anticoagulant-induced bleeding, since bleeding in such patients may often result in catastrophic consequences, and for such patients anticoagulation-free dialysis (described below) can be appropriately used. However, for the great majority of patients, who are judged not to be at a markedly increased bleeding risk, some form of anticoagulation must be employed. In programs reusing dialyzers, proper levels of anticoagulation during dialysis are key to obtaining reasonable reuse numbers.
There is considerable variability among regions of the world, countries, and even dialysis units about what type of anticoagulation is used during intermittent hemodialysis. Despite a number of promising alternatives, heparin is the most common anticoagulant used. In the United States unfractionated heparin is mostly used, whereas in the European Union, low molecular weight heparin is the anticoagulant of choice
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recommended by the European Best Practice Guidelines (2002). A handful of dialysis units anticoagulate the blood circuit using trisodium citrate, and direct thrombin inhibitors such as argatroban are just beginning to be evaluated in clinical settings.
III. Measuring blood clotting during dialysis
While it is important to understand the principles of how clotting tests can be used to monitor heparin therapy, in the United States, because of economic constraints, the relatively low risk of bleeding complications from use of heparin during dialysis, and regulatory issues (the requirement for local laboratory certification), heparin therapy is ordinarily prescribed empirically, without monitoring of coagulation. In patients who are at an elevated risk of bleeding, the need to monitor anticoagulation is often circumvented by using heparin-free dialysis.
When clotting studies are done, blood for clotting studies should be drawn from the arterial blood line, proximal to any heparin infusion site, to reflect the clotting status of the patient rather than that of the extracorporeal circuit. It is very difficult to obtain baseline clotting studies from a venous catheter that has been locked with heparin, due to problems of residual heparin in the catheter, and this step is rarely attempted (Hemmelder, 2003).
A. Clotting tests used to monitor heparin therapy
Activated partial thromboplastin time (APTT). This is for unfractionated heparin monitoring only. This is the most commonly used test in a hospital setting. Heparin resistance states can be falsely suggested due to elevated levels of factor VIII. Baseline levels may be prolonged because of lupus anticoagulant (see Olson, 1998).
Whole-blood partial thromboplastin time (WBPTT). This is similar to above, but this is a bedside test. The WBPTT test accelerates the clotting process by addition of 0.2 mL of actin FS reagent (Thrombofax) to 0.4 mL of blood. The mixture is set in a heating block at 37В°C for 30 seconds and then tilted every 5 seconds until a clot forms. The prolongation of the WBPTT is linearly related to the blood heparin concentration (in the range applicable to dialysis). It should not be used to monitor low molecular weight heparin therapy.
Activated clotting time (ACT). The ACT test is similar to the WBPTT test but uses siliceous earth to accelerate the clotting process. ACT is less reproducible than WBPTT, especially at low blood heparin levels. Devices that automatically tilt the tube and detect clot formation facilitate standardization and reproducibility of both WBPTT and ACT. It is for unfractionated heparin monitoring only.
Lee-White clotting time (LWCT). The Lee-White test is performed by adding 0.4 mL of blood to a glass tube and inverting the tube every 30 seconds until the blood clots. Usually, the blood is kept at room temperature. Disadvantages of the LWCT test include the long period of time required before clotting occurs, extensive use of technician time required, and the relatively poor standardization and reproducibility of the test. LWCT is the least desirable
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method of monitoring clotting during hemodialysis. This test is now rarely used.
Factor Xa-activated ACT. This test has been proposed as a more sensitive test for monitoring anticoagulation during use of low molecular weight heparin (Frank, 2004).