Anticoagulants ^*Drugs that interfere with specific clotting factors, thus prolonging the coagulation time. They are used for patients with potential or current heart, lung, and vessel disease. They do not dissolve established clots, nor do they “thin” blood, although they are commonly referred to as blood thinners.

Oral Anticoagulants: Warfarin Sodium (Coumadin) Frequently prescribed outpatient oral anticoagulant that inhibits vitamin K–dependent clotting factors. Tests to monitor coagulation with warfarin are the international normalized ratio (INR) test and prothrombin time (PT).

Parenteral Anticoagulants Heparin Sodium Heparin Calcium Heparin sodium or calcium acts on multiple coagulation factors. From bovine intestinal source, hep arin is given by IV or subcutaneous route. Activated partial thromboplastin time (PTT) test results must be monitored closely q4-6h until levels are stabilized, after dose adjustments, and then daily. Not suitable for home use. Interact with many drugs. Drug interactions can be fatal.

Low-Molecular-Weight Heparin (LMWH) Dalteparin (Fragmin) Enoxaparin (Lovenox) IV Ardeparin (Normaflo) Altered (fractionated) heparin with lower risk of thrombocytopenia than unfractionated heparins, thus lower risk of bleeding. Dose based on patient’s weight. It is given by subcutaneous or IV route. Does not need to be monitored frequently, as with unfractionated heparin, which requires frequent monitoring with the activated partial thromboplastin time test. Can be administered at home with selected patients. Used for prevention of thromboemboli for high-risk patients, including orthopedic surgical patients.

Fundaparinux sodium (Ariztra) A Factor Xa inhibitor given subcutaneously once daily for DVT prophylaxis or PE treatment. Not interchangeable with heparin.

Clotting Factors Proteins and enzymes in the blood that are essential for coagulation. Tests are performed to identify specific factor deficiencies as well as to monitor anticoagulant therapy.

Flush Solutions (Heplock Flush) Heplock Flush: Low-dose heparin (10 to 100 units per mL) used to maintain patency of indwelling IV devices. Up to 500 units per mL may be ordered for central lines. Saline Flush: Used to maintain patency of some indwelling IV devices. Trend has been to replace the heparin flush with the less dangerous saline flush when it will do the job.

Heparinoid (Danaparoid Sodium) Heparin-like drug that does not contain heparin (-oid means “like”) used for postoperative DVT prophylaxis.

Protamine Sulfate Antidote for heparin and heparinoid drugs.

Thrombolytic Agents Drugs that “lyse,” or dissolve, clots if given within a specified amount of time. Used for patients with acute stroke or pulmonary embolism.

Vitamin K Antidote for warfarin products.

^*Many new anticoagulants are in clinical trials pending FDA approval.

Q: Ask Yourself

1. What are some of the differences between heparin, warfarin, and LMWH products?

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A: My Answer

COAGULATION Tests

Control Values Laboratory derived “average normal values” for specific test results. May vary from laboratory to laboratory, depending on agents used for testing. Determined daily by laboratory tests for prothrombin time, partial thromboplastin time, and activated partial thromboplastin time tests to ensure efficacy of agents used for each batch of tests for accurate measurement.

International Normalized Ratio (INR) Standardized formula-derived laboratory value preferred for monitoring warfarin therapy. Normal blood has an INR of 1. Therapeutic target range for blood of anticoagulated patients is 2.0-3.0 INR value, derived from patient-specific prothrombin time value.

Prothrombin Time (PT, or Pro Time) Formerly used for monitoring warfarin therapy, it now may be used as adjunct to INR. It is not as reliable as INR. Normal control values in uncoagulated patients vary from laboratory to laboratory by from 11 to 15 seconds.

Activated Partial Thromboplastin Time (aPTT) Shortened form of the PT test with activators added, preferred for monitoring heparin therapy, not to be confused with PT test for warfarin or the longer partial thromboplastin time (PTT) test. “Normal” control aPTT time is about 30-40 seconds (about ½ minute), depending on test agents used.

Platelet Count Actual count of number of thrombocytes in blood (normal adult value, 150,000-400,000 per mcL). Less than 50,000 per mcL poses risk of bleeding from minor trauma and surgery. Less than 20,000 per mcL poses great risk of spontaneous hemorrhage.

Other Tests that May Be Bleeding time

Ordered for Patients Hematocrit (Hct)

Receiving Anticoagulant Hemoglobin (Hgb)

Therapy or Those with Stool test for occult blood

Coagulation Disorders Urine test for blood

Liver function tests (LFTs)

Renal function tests

Whole blood clotting time (WBCT)

Activated coagulation time (ACT)

Specific clotting factor assays

D-dimer test

Q: Ask Yourself

1. What is the preferred test for patients receiving heparin products, as opposed to the test for those receiving warfarin products?

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2. What is the main risk for patients who have thrombocytopenia?

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A: My Answer

FAQ

What is the difference between a normal (control) value for a PT or an aPTT and a therapeutic level?

ANSWER

The normal control value is the coagulation time in seconds for a specific test, such as the aPTT, for a person who is not receiving anticoagulants. It varies from test to test and laboratory to laboratory, depending on the agents used for the test.

When patients receive anticoagulants, they receive a “therapeutic amount” of drug that will extend their coagulation time to reduce their risk of having a thromboembolic event. Anticoagulant doses are individualized for each patient, or “patient-specific,” based on the patient’s test results.

The therapeutic level is based on the laboratory daily control value. It is the desired target coagulation range in seconds that prevents clot formation in patients who are at risk. It is longer than the normal control finding for an aPTT coagulation test, which is 30-40 seconds for a person who is not receiving heparin.

The therapeutic level for an aPTT test is within 1.5 to 2.5 times the control value in seconds (45-100 seconds), a narrow therapeutic range that will prolong clot formation but not be excessive enough to cause bleeding.

To evaluate a patient-specific coagulation test result:

• Obtain the therapeutic target range by multiplying the control value by the desired factors for the range.

• Compare the patient’s test result to see if it falls within the range.

CLINICAL RELEVANCE

Assess clients on anticoagulants for bleeding gums, bruises pinpoint and large, and prolonged bleeding after injections. Always check current coagulation test results.

Q: Ask Yourself

1. If a control value for a coagulation test is 12 seconds and the therapeutic range is 1.5 to 2.5 times the control value, would the patient’s test result be within therapeutic range if it was 24 seconds? (Use simple arithmetic with or without a calculator.)

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A: My Answer

RAPID PRACTICE 12-1 Vocabulary Review: Anticoagulants and Tests

Estimated completion time: 5-10 minutes Answers on page 561

Directions: Study the Introduction and Essential Vocabulary list. Select the correct response.

TEST TIP:

Quickly place a single line through the incorrect responses to narrow your choices.

1. Anticoagulants are used for the following purposes: _________

1. To dissolve well-established clots in high-risk patients

2. To decrease coagulation time

3. To treat hemorrhage

4. To prevent thrombi and emboli formation

2. An oral anticoagulant that is ordered for outpatient use is _________

1. Warfarin sodium (Coumadin, Sofarin, Warfilone)

2. Enoxaparin (Lovenox)

3. Streptokinase and alteplase

4. Danaparoid sodium

3. The standardized relevant laboratory test for monitoring therapeutic levels of warfarin is called _________

4. The most commonly used laboratory test to monitor therapeutic levels of heparin is _________

5. The main danger of excessive anticoagulant therapy is _________

1. DVT formation

2. PE

3. Hemorrhage

4. Increased platelet count

RAPID PRACTICE 12-2 Anticoagulant Agents and Antidotes

Estimated completion time: 5-10 minutes Answers on page 561

Directions: Identify the correct agent, term, purpose, or antidote for anticoagulant therapy.

1. The drug antidote for warfarin excess is _________

1. Blood transfusion

2. Iron

3. Vitamin K (phytonadione)

4. Protamine sulfate

2. The drug antidote for heparin excess is ___________

1. Blood transfusion

2. Iron

3. Vitamin K (phytonadione)

4. Protamine sulfate

3. Intravenous flush solutions are used for which purpose? _________

1. Occult blood in stool and hematuria

2. Epistaxis

3. Petechiae and ecchymoses

4. Patency of IV access devices

4. The difference between a control value and a therapeutic value for a specific anticoagulant test is _________

1. The control value is the extended blood coagulation time in seconds needed to prevent clots, whereas the therapeutic desired value is the normal coagulation time in seconds for a patient not receiving anticoagulants.

2. The control value is the level that the prescriber orders for the patient to control his or her blood coagulation. The therapeutic coagulation levels or range is less time in seconds than the control value.

3. The control value is the laboratory-derived normal coagulation time in seconds for a particular test for a patient who is not receiving anticoagulants. The therapeutic value is the desired extended time in seconds for the patient receiving a specific anticoagulant.

4. The control value and the therapeutic time in seconds for coagulation are the same for all patients receiving a specific anticoagulant.

5. Drugs that dissolve clots are classified as _________

1. Anticoagulants

2. Hormones

3. Thrombolytic enzyme agents

4. Salicylates

FAQ

What is the relationship between the PT value and the INR value?

ANSWER

A current INR standardized test value introduced by the World Health Organization in 1983 is required to adjust or titrate warfarin doses. The patient’s therapeutic INR range is determined daily by the individual laboratory based in part on the PT value. The INR is not a separate test. It is a formula-derived value:

The INR value is used to evaluate the patient’s response to treatment. Some prescribers also require the PT to be reported with the INR.

*ISI: International Sensitivity Index, a value assigned to the thromboplastin reagent by the manufacturer of the specific laboratory test material.

FAQ

How can I remember the differences between heparin therapy and warfarin therapy?

ANSWER

Write out a brief outline of the differences. Be able to reproduce this critical information. Following is one suggested format that emphasizes the differences.

All anticoagulant products are high-alert medications.

Comparison of Anticoagulant Products

	Warfarin	Heparin (Unfractionated)	Low Molecular Weight Heparin (LMWH)
Name	Coumadin	Heparin	dalteparin (Fragmin)
			enoxaparin (Lovenox)
			ardeparin (Normaflow)
Route	Oral	Subcutaneous or IV	Subcutaneous or IV
Tests	INR usual test; also PT	Frequently aPTT	aPTT infrequently needed
Action	Interferes with extrinsic (tissue injury site) vitamin K–dependent clotting mechanisms	Interferes with intrinsic (within vessel) clotting mechanisms	Interferes with intrinsic and extrinsic clotting mechanisms
Action			Less chance for bleeding than unfractionated heparin
Drug antidote	Vitamin K	Protamine sulfate	Protamine sulfate