Review of Hemodialysis for Nurses and Dialysis Personnel, 8th Edition

Chapter 11. Anticoagulation and heparin administration

Blood tends to clot when it encounters any surface that is not the lining of a normal blood vessel. This mechanism is vital to preserving the life of the individual. Thus blood will clot soon after entering the extracorporeal circuit of the hemodialysis system, rendering treatment impossible unless the ability to clot is interrupted. There are several methods to prevent coagulation of the extracorporeal circuit—each with advantages and drawbacks for patient or practitioner. It is essential that the dialysis practitioner be familiar with more than one method to safely and effectively meet the needs of each individual hemodialysis patient.

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.

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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.

What techniques are used in heparin administration?

Systemic heparinization is when an initial loading dose of heparin is given prior to dialysis treatment. It is typically a dose ordered by the physician and based on body weight. An initial bolus of heparin is administered intravenously after the needles are placed and no further heparin is administered. Dialysis personnel may administer additional heparin based on the patient’s orders if the system appears to be clotting during the dialysis treatment.

What is the intermittent intravenous heparin technique?

An activated clotting time (ACT) test is first performed. Normal is about 60 to 90 seconds. An intravenous priming dose of heparin is given at the beginning of dialysis, and smaller doses are repeated intermittently throughout the procedure. The usual objective is to maintain the ACT at about three times the baseline. In acute dialysis, when the patient could have a problem with bleeding, heparin dosage is set to give a clotting time between 150 and 180 seconds. Alternatively, given the CLIA limit on performing clotting times, the circuit can be rinsed at 30- to 60-minute intervals with about 100 mL of saline, the fibers and air-blood interface of both drip chambers can be inspected for signs of early clotting, and the heparin dose can be adjusted as needed. Naturally, the ultrafiltration (UF) goal must be increased to remove this extra fluid infusion.

The priming dose, most often around 25 to 50 units/kg of body weight, is given either through the venous side of the vascular catheter or via the last needle placed, if the patient has a graft or fistula. The latter method is intended to prevent any oozing of blood or hematoma formation if there is any difficulty with the initial needle insertion. In the few minutes before the patient is attached to the dialyzer, the entire blood volume will become anticoagulated. This is called systemic heparinization.

What is the continuous infusion technique of intravenous heparin?

A priming, or “loading,” dose of heparin is given as previously described. Heparin is then slowly injected into the extracorporeal system at a constant rate by an infusion pump. This is continued throughout the dialysis, usually at a rate of 1000 to 2000 units/h. Clotting is evaluated at intervals, usually by saline flushes and visual inspection of drip chambers and/or dialyzer fibers, and the heparin infusion rate is adjusted accordingly. The infusion is normally stopped 30 minutes to 1 hour before the end of the treatment to allow the clotting time to begin its return to normal, especially for those patients from whom needles must be removed postdialysis.

What is the danger of bleeding when heparin is used for hemodialysis?

There is always a danger of bleeding when heparin is used. Uremic patients tend to bleed easily. One must be particularly concerned about any patient who has had surgery within the preceding 24 to 48 hours or is scheduled for surgery immediately postdialysis, who has recently been injured, who has pericarditis, or who might have a hemorrhagic lesion of the gastrointestinal tract or uterus.

Are there special techniques for using heparin in hemodialysis when there is danger of bleeding?

Three approaches have been used for this situation: regional heparinization; low-dose, or “tight,” systemic heparinization; and no heparin–saline flush techniques.

What is regional heparinization?

In regional heparinization, an anticoagulant is infused continuously into the inlet (arterial) line of the dialyzer while simultaneously being neutralized by infusing an antidote into the outlet (venous) line before the blood returns to the patient.

In the past, heparin was used as the anticoagulant and protamine sulfate, a low molecular weight protein derived from salmon sperm, was infused into the venous line. Protamine, a strongly basic protein, bound the acidic heparin and thus neutralized its effect on the coagulation system. However, because of a number of difficulties—precise balancing of dosage of each infusion, a tendency toward rebound anticoagulation several hours postdialysis, and protamine-induced anaphylaxis—this method is rarely used today.

An alternative method of regional anticoagulation involves the use of sodium citrate. Regional citrate anticoagulation works by binding the ionized calcium present in the extracorporeal circuit; calcium ions are essential for clot formation. This technique involves infusing trisodium citrate into the arterial line. A calcium-free dialysate must be used. Because returning blood with decreased ionized calcium to the patient would be dangerous, the process is reversed by the infusion of calcium chloride into the venous line as close as possible to the vascular access connection.

The major disadvantages of this technique are that frequent laboratory tests must be done to check the patient’s total calcium level as well as clotting times. Metabolism of the citrate produces bicarbonate. Plasma level of bicarbonate increases, occasionally to significantly alkalotic levels. (An alternative version uses a large volume of dilute sodium citrate, normal dialysate, and no calcium infusion. The disadvantages are minimized, but UF goals must be adjusted to remove the extra fluid.)

Both types of regional anticoagulation require a high level of experience, skill, and attention to detail. With the low-dose, or “tight,” systemic and heparin-free techniques available today, regional methods are generally reserved for the most critically ill acute dialysis patients.

What is low-dose, or “tight,” heparinization?

Low-dose, or “tight,” heparinization consists of monitoring the patient with frequent clotting times and administering only enough heparin to keep the clotting time at 90 to 120 seconds by ACT. Low-dose, or “tight,” heparinization is usually the most practical technique for managing patients who are at risk for bleeding. These would include patients who have recently had surgery, those who are menstruating, or those who are having the central venous catheter removed posttreatment. A baseline clotting time is drawn through the first dialysis needle inserted, and this acts as a guide to the size of the priming dose and maintenance heparin requirements. After the administration of the minimal priming dose, usually 10 units/kg, heparin dosage is adjusted to provide an ACT of 110 ± 10 seconds.

In some centers, low-dose, or “tight,” heparinization is used for the patient’s first dialysis treatment. After several treatments a consistent dosage of heparin can be established. However, due to CLIA restrictions, anticoagulation methods that require the use of clotting time determinations present a problem.

Can patients be hemodialyzed without heparin?

Heparin-free dialysis has become the method of choice when treating actively bleeding patients and patients with an increased risk of bleeding, pericarditis, coagulopathy, or thrombocytopenia.

Several techniques can be used, but most commonly the following are used:

• The bloodlines and dialyzer are rinsed with saline containing 3000 units of heparin per liter. The saline priming dose with the heparin is then discarded. No heparin is used for the saline prime of dialyzers for patients who are at very high risk of bleeding (e.g., patients with liver disease).

• The blood flow rate is set as high as possible, 350 to 450 mL/min if it can be tolerated.

• The dialyzer is rinsed with 100 to 200 mL of saline as often as every 15 to 30 minutes but at least every hour. This is done by occluding the “arterial” line and infusing the saline rapidly. The dialyzer is visually inspected, if possible, for clotting during the rinse. The extra saline should be added to the UF goal unless the patient needs the extra fluid volume.

Most facilities do not prime the system with heparin when the patient is being dialyzed heparin free and will use only half-hourly or hourly saline rinses to monitor for clotting in the dialyzer or venous drip chamber.

Can blood be transfused into at-risk patients during heparin-free dialysis?

Blood transfusions can complicate heparin-free dialysis, especially because they commonly involve packed red blood cells. The transfused blood increases the viscosity of the blood in the dialyzer and may infuse clinically significant amounts of normal (i.e., nonuremic) clotting factors. Saline rinses help to keep the system patent and allow for observation of the fibers for any dark streaks that may indicate clotting. The other parameters—saline flushes, blood flow rate, etc.—remain the same as used in heparin-free dialysis.

How can vascular catheter patency be protected between treatments?

Although the anticoagulation methods need not be altered for use with vascular catheters, the method used for the “heparin lock” to preserve catheter patency between treatments has significant clinical implications. It is essential to keep sufficient heparin within the catheter lumen to prevent clotting, yet prevent any of the heparin from entering the circulation of an at-risk patient. The following method should be used. After dialysis, flush each lumen (side) of the catheter with 10 mL normal saline to clear it of blood cells, and then instill a prescribed volume of heparin sufficient to exactly displace the saline in the catheter lumen and clamp the lumen immediately. The key is to inject precisely the volume of heparin that the catheter can hold so that there is no excess to go into the patient and to inject it fast enough so that it does not mix with the saline and become diluted. This volume can be determined by noting the individual volume printed on each vascular catheter and injecting exactly that amount. Some facilities prefer to use 5000 units/mL heparin to close the patient’s catheters and some prefer to instill 1000 units/mL heparin. Always follow the facility guidelines and orders from the patient’s physician.

What are contributing factors that prevent hemorrhage during hemodialysis?

Success in preventing hemorrhage during the dialysis procedure rests on the general management of the patient and the care with which the dialysis is done. The bleeding tendency of uremic patients is correctable with adequate dialysis. The technique used for anticoagulation during dialysis is an important part of the process because any coagulation in the extracorporeal circuit will impair treatment outcome. Thus the timely institution of an adequate dialysis program is an important initial factor in the prevention of hemorrhage, but subsequent success depends on careful and continuous attention to all of the factors related to optimal treatment adequacy.

How is the effect of heparin measured clinically?

Heparin effect is estimated by the increase in the length of time necessary for a clot to form. There are several laboratory methods to determine this, including Lee-White clotting time, activated partial thromboplastin time (APTT or PTT), and ACT, all of which are discussed later. The clinician should be aware of the impact of CLIA. Although CLIA was intended to apply to noncertified employees doing lab tests in doctors’ offices, its broad wording encompasses all lab tests done by nonlaboratory-certified personnel in any setting. Thus CLIA effectively prohibits dialysis staff from performing clotting time determinations on acute and chronic hemodialysis patients unless provision is made for appropriate staff and equipment certification.

Which tests are best for clinical hemodialysis?

Normally one of three tests is used for monitoring clotting times during dialysis. The first of these is the Lee-White clotting time, which is performed by putting 0.4 mL of blood into a tube and inverting the tube every 30 seconds until the blood clots. Because of the long clotting times involved, poor standardization, and poor reproducibility, it is the least desirable method to use during dialysis. Normal clotting times with this test are 6 to 17 minutes. This test is rarely used today.

The second test is the PTT. This test must be performed in the laboratory and is reliable only at lower levels of anticoagulation.

The third test is the ACT. It is similar to the PTT but uses siliceous earth in the tube to hasten the clotting process. The test is done by an automated method that has excellent reproducibility. Evaluation of heparin effect can be done in 180 to 275 seconds. Because of this, the ACT test is easily used in dialysis units. Blood samples are drawn from the “arterial” line before the infusion of heparin, reflecting the status of the patient’s circulation rather than the extracorporeal circuit. This method is not used much today. Box 11-1 gives a protocol for clotting time using the ACT method.

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Box 11-1 Protocol for Activated Clotting Times

Regular control

150 to 180 seconds

Moderate control

105 to 150 seconds

Tight control

90 to 120 seconds

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