What is anticoagulation?

Anticoagulation is the blocking, suppression, or delaying of clotting of the blood. Clot formation occurs when blood contacts “foreign” surfaces, such as it does when it enters the bloodlines and dialyzer. Normally blood does not clot within the vascular system. However, clots can form under certain conditions, most commonly after an injury, when the clot serves to seal the damaged vessel and prevent further blood loss.

What causes blood to clot?

Clotting is a part of a complex body process called hemostasis. This process involves (1) retraction and contraction of the injured vessel, (2) the ability of blood platelets to stick to the injured area, and (3) a complex interaction of coagulation factors, resulting in a formed clot. These coagulation factors are present in normal blood and are identified by roman numerals I through V and VII through XIII. Platelets are damaged by contact with a foreign surface. Platelet factor III is released, causing platelets to stick and start the clotting process. Plasma factors XI and XII are also activated by contact with a foreign surface and contribute to clotting.

Why doesn’t blood clot within the normal vascular system?

The lining of the blood vessels, the endothelium, is smooth, allowing the blood to flow freely through the vessels. The other surfaces of cells—vascular endothelial cells, platelets, and red blood cells—are gelatinous and hydrophilic, with a high water content. They have low interfacial tensions and have little tendency to adhere when intact.

Why is anticoagulation needed during dialysis?

Blood coagulates when it comes into contact with foreign surfaces, such as dialyzers and bloodlines. To avoid this, anticoagulants are used. The first anticoagulant was hirudin, obtained from the heads of medicinal leeches. In 1916 Jay McLean found an anticoagulant in the liver of animals. He called this extract heparin, but it was not purified for human use until 1936. Its potency was finally standardized in the U.S. in 1966.

What is the nature of heparin?

Heparin is an acid mucopolysaccharide and is neutralized by strong basic compounds such as protamine sulfate, toluidine blue, and quinidine, causing it to lose its anticoagulant properties. Heparin for clinical use includes a number of fractions, with molecular weights (MWs) ranging from 8000 to 14,000 Da. Heparin composed of only low MW (4000 to 6000 Da) is available in the U.S. and, although more expensive, has the benefit of single-dose administration, less bleeding risk, and less effect on circulating lipases, potentially resulting in lower triglyceride and cholesterol levels in long-term hemodialysis patients. This latter factor may be significant because high triglyceride and cholesterol levels are associated with cardiovascular disease.

How does heparin prevent coagulation?

Heparin combines with a blood protein fraction called heparin cofactor (antithrombin III). The complex of heparin–antithrombin III combines with and inactivates thrombin, activated factor X, and activated factor XI, thus preventing clotting at all three stages of coagulation (Fig. 11-1). The conversion of prothrombin to thrombin is inhibited, as is the conversion of fibrinogen to fibrin. Peak anticoagulant activity is reached 5 to 10 minutes after injection. The half-life is about 90 minutes for doses usually used in dialysis. The mechanism of heparin inactivation is not completely clear; it is metabolized by the liver and is taken up by the reticuloendothelial system.

Figure 11-1 Schematic diagram of heparin effect.

Are there different kinds of heparin?

Most heparin is derived from pork intestinal mucosa or from beef lung. Pork mucosal heparin is more abundant, less expensive, and most commonly used. The U.S. Pharmacopeia (USP) unitage (units of activity per milliliter) for both forms of heparin is the same, but there is a difference in their anticoagulant actions on a weight basis; that is, 1 mg of porcine heparin has more anticoagulant activity than 1 mg of beef lung heparin. Beef heparin is no longer commercially available. The reasons for this include the greater expense of beef heparin as well as concerns that beef heparin was associated with a higher incidence of thrombocytopenia.

What drugs interact with heparin?

Some medications, such as aspirin, nonsteroidal antiinflammatory agents, and dextran, may enhance the effectiveness of heparin and cause bleeding. Cardiac glycosides, nicotine, quinine, and tetracycline interfere with or decrease heparin’s effectiveness.

What is the unit measurement of heparin?

A unit is the measure of a drug’s activity in the body. For heparin, a unit dose is the measure of the drug’s ability to block the blood’s natural clotting ability (anticoagulation). Heparin’s potency is determined by the dose of the drug required to produce a specific level of anticoagulation (FDA, 2010).

The heparin concentration commonly used in dialysis is 1000 units/mL. The same number of units of either lung or mucosal heparin produces an equivalent degree of anticoagulation.

Heparin has recently gone through some new manufacturing controls and has a new reference standard for its unit dose as well as its potency. The Food and Drug Administration (FDA) suggests that dialysis practitioners expect a 10% reduction in the potency of the heparin marketed in the U.S. Heparin that is manufactured under the new USP unit will be labeled with an “N” next to the lot number (FDA, 2010). It is always prudent to use good clinical judgment and to monitor the patient’s response to heparin and to adjust the dose accordingly.

How is the heparin dosage determined?

The patient’s heparin dosage is prescribed by the physician and is generally based on the patient’s dry weight. Dosage adjustments need to be made if the patient has a change in weight, if the length of treatment changes, or if the dialyzer membrane changes. Erythropoietin may increase heparin requirements, necessitating an increase in the prescribed amount. The heparin dosage must be low enough to reduce the risk of bleeding yet high enough to prevent clotting of the extracorporeal circuit. With adequate heparinization, the patient will have better clearance of solutes through the dialyzer membrane. Adequate heparinization will also help the dialyzer to clear more thoroughly, allowing the patient to receive as many red blood cells as possible when the patient’s blood is returned to him or her at the end of the treatment. Because chronic outpatient dialysis units are not able to monitor clotting times due to Clinical Laboratory Improvement Act (CLIA) mandates, dialysis personnel must be attentive to indications that the patient may require more or less heparin. Clotting of the dialysis system, poor clearance of the dialyzer posttreatment, and inadequate urea clearance may indicate a need to increase heparin dosing. Excessive bleeding or bruising posttreatment may indicate a need to decrease heparin dosing.