Hematologic Products
Objectives
1. Describe the influence of anticoagulants on blood clotting.
2. Develop a teaching plan for patients taking anticoagulants on a long-term basis.
3. Identify at least three adverse reactions associated with hematologic products.
4. Identify drugs that act in the formation, repair, or function of red blood cells.
Key Terms
anticoagulants (ăn-tĭ-kō-ĂG-ū-lĕnts, p. 354)
fibrin (FĪ-brĭn, p. 354)
fibrinogen (fī-BRĬN-ō-jĕn, p. 354)
thrombi (THRŎM-bī, p. 354)
thromboplastin (thrŏm-bō-PLĂS-tĭn, p. 354)
Overview
http://evolve.elsevier.com/Edmunds/LPN/
Hematologic products act in the formation, repair, or function of red blood cells. There are four major groups of medications that have hematologic effects. They include the anticoagulants (heparin and warfarin [Coumadin]) and the heparin antagonist protamine sulfate. Thrombolytic agents and antiplatelet factors also have a major influence on blood clotting. Related vitamins and minerals needed for red blood cell development are iron, vitamin K, vitamin B12, and folic acid; these are presented in Chapter 24.
Anticoagulants
One of the body’s protective functions is to clot blood in response to tissue injury. Any damage to the cells starts a series of chemical reactions to protect the body (Figure 20-1). Cellular damage results in the formation of thromboplastin, which then acts on prothrombin to form thrombin. Calcium must be present for this reaction to occur. Thrombin then acts on fibrinogen (a protein found in the blood plasma) to produce fibrin, a netlike substance in the blood that traps red and white blood cells and platelets and forms the matrix, or skeleton, of the clot. Vitamin K must be present to produce prothrombin and other clotting factors that are made in the liver. All anticoagulants prevent the formation of blood clots, or thrombi, by interfering with this complex clotting mechanism of blood and increasing the time it takes for blood to clot. In cases of overdose, protamine sulfate is given to counteract the effect of heparin. In response to some bleeding disorders, vitamin K may be given either orally or parenterally to manufacture prothrombin and serve as an anticoagulant antagonist (see Chapter 24).
Action 
There are two major categories of anticoagulants. The first category, the coumarin and indanedione derivatives, limits formation of blood coagulation factors II, VII, IX, and X in the liver by interfering with vitamin K. These drugs do not destroy existing blood clots; however, they may limit the extension of existing blood clots or thrombi.
The second category, heparin sodium, acts at multiple sites in the normal coagulation system to stop reactions that lead to the clotting of blood and the formation of fibrin clots. It increases the action of antithrombin III (heparin cofactor) on several other coagulation factors, primarily activated factor X (Xa), to slow new clot development. Heparin does not dissolve existing clots either, although thrombolytic agents do. Low-molecular-weight heparin is a special formulation used in special circumstances, such as to prevent deep vein thrombosis (DVT) after surgery.
Uses
As part of the circulatory system, the arterial vessels carry oxygenated blood throughout the body. If these small arteries become plugged with thrombi (clots made of fibrin, platelets, and cholesterol), oxygen cannot get to the tissues, and death may result. Abnormal blood clotting may produce a thrombus in the coronary artery, which nourishes the heart muscle. Emboli (small pieces of a blood clot) may break off from a site of thrombophlebitis (inflammation and blood clot in a vein) in the lower extremities and travel through the bloodstream to block vessels in areas of the heart, brain, or lung. (See Chapter 15, Figure 15-7.) This blockage can cause stroke or death. Drugs that can slow or reduce clotting, then, are very helpful.
Anticoagulant therapy is used to prevent new clot formation or to stop existing clots from growing in size. Anticoagulant therapy is used prophylactically during and after many types of surgery, especially surgery involving the heart or circulation. It is also used in patients with heart valve disease, in patients with some dysrhythmias (irregular heartbeats), and in patients receiving hemodialysis. Any patient on bed rest for a long time is at risk for development of blood clots, especially patients with a history of clotting problems or recent orthopedic, thoracic, or abdominal surgery.
Heparin is the anticoagulant of choice when an immediate effect is needed. For long-term therapy, a coumarin or indanedione derivative is used. The U.S. Food and Drug Administration has classified coumarin preparations as “possibly” effective as part of the therapy for treatment of transient cerebral ischemic attacks. Indanedione derivatives (phenindione) are used to treat pulmonary emboli and as prophylaxis to treat DVT, myocardial infarction, rheumatic heart disease with valve damage, and atrial dysrhythmias. Low-intensity warfarin therapy (prothrombin time [PT] ratio between 1.2 and 1.5) greatly decreases the risk of stroke from nonrheumatic atrial fibrillation and has few side effects.
Adverse Reactions
By far, the most common adverse reactions from heparin and warfarin are excessive bleeding and thrombocytopenia. Early signs of overdose or internal bleeding include bleeding from gums while brushing teeth, excessive bleeding or oozing from cuts, unexplained bruising or nosebleeds, and unusually heavy or unexpected menses in women. These are the “must know” symptoms that suggest the patient needs prompt attention.
There are a number of other adverse reactions that may occasionally be seen. Warfarin may produce alopecia (hair loss), rash, urticaria (hives), cramping, diarrhea, intestinal obstruction, nausea, paralytic ileus, vomiting, excessive uterine bleeding, hemorrhage with excessive dosage, leukopenia, and fever. Heparin sodium may produce hypertension (high blood pressure); headache; hematoma, irritation, and pain at the injection site; conjunctivitis; tearing of eyes; rhinitis; frequent or persistent erection; hemorrhage; thrombocytopenia; shortness of breath; wheezing; chills; fever; alopecia; and hypersensitivity (allergic) reaction.
Drug Interactions
Other anticoagulants (coumarin or indanedione derivatives), methimazole, and propylthiouracil increase the anticoagulant effect of heparin.
Antihistamines, digitalis, nicotine, and tetracycline decrease the anticoagulant effect of heparin.
Acetylsalicylic acid (ASA), coumarin-derivative anticoagulants, dextran, nonsteroidal antiinflammatory drugs (NSAIDs), and other selected drugs increase the risk of bleeding and hemorrhage in a patient receiving heparin.
ASA, corticotropin, ethacrynic acid, glucocorticoids, and NSAIDs increase the risk of gastrointestinal (GI) bleeding and hemorrhage in a patient receiving heparin.
Allopurinol, ASA, anabolic steroids, antibiotics, androgens, many sedatives, some antacids, dextran, disulfiram, drugs affecting blood elements, glucagon, heparin, narcotics (with prolonged use), phenylbutazone, propylthiouracil, quinidine, quinine, salicylates, thyroid drugs, and vitamin E increase the PT response of patients receiving warfarin.
Adrenocorticosteroids, antacids, antihistamines, barbiturates, contraceptives (oral), estrogens, griseofulvin, haloperidol, meprobamate, primidone, rifam-pin, thiazide diuretics, and vitamin K decrease the PT/International Normalized Ratio (INR) response of a patient on warfarin.
Anticoagulant effects may be increased with acute alcohol intoxication and decreased with chronic alcohol abuse. Oral hypoglycemics taken with anticoagulants may increase the effect of either the hypoglycemic or anticoagulant.
Alkylating agents, antimetabolites, corticosteroids, ethacrynic acid, indomethacin, quinidine, and salicylates increase the risk of bleeding in a patient taking warfarin.
Nursing Implications and Patient Teaching
Patients requiring rapid anticoagulation are commonly hospitalized. Coagulation and PT/INR tests are ordered when the patient is started on anticoagulants. Heparin is usually started for an immediate effect and gradually replaced by oral anticoagulants. Thereafter, the physician or other health care provider orders coagulation and PT/INR tests at regular intervals. When the oral anticoagulant shows proper effect, and the prothrombin activity is in the therapeutic range, heparin therapy may be stopped and the oral anticoagulant therapy continued.
Standard heparin dosing protocols have been controversial for many years. Weight-based dosing is now the standard of care for determining the dosing of heparin. Weight-based dosing uses the patient’s body weight in kilograms, infusing 80 units/kg as an intravenous (IV) bolus. The maintenance infusion is 18 units/kg/hr through an infusion pump. There are indications that weight-based dosing is safer, achieves therapeutic levels in less time than with standard dosing, and results in fewer bleeding complications and a lower rate of thromboembolic recurrences.
The standard tests for determining the general effect of heparin on clotting are the Lee-White coagulation time, the whole-blood activated partial thromboplastin time, and the activated partial thromboplastin time (aPTT). The most commonly used test is the aPTT. The dosage of heparin is considered adequate when the whole blood clotting time is approximately 1.5 to 2.5 times the control value. The recommended method for establishing the unfractionated therapeutic range is by the anti-Xa method. This method is the most specific and is least affected by the variables inherent to the in vitro technique. Samples are collected from patients on unfractionated heparin. The samples are tested with aPTT and anti-Xa assays. The range of aPTT values correlate to anti-Xa levels in a range of 0.3-0.7 U/mL of heparin.
PTs are used to determine the dosage for coumarin preparations. These PT tests are done daily until the results stabilize in the therapeutic range (
to 
times the normal control value). After stabilization, tests are performed at 1-week to 4-week intervals, depending on patient status. Unfortunately, these test results vary from laboratory to laboratory and from day to day because of variations in the reagent chemical used to perform the test. However, this test is still used in many countries.
To avoid test variation, a system called the International Normalized Ratio (INR) is used to standardize PT reporting so that all laboratory reports are the same. The INR is based on the PT ratio supplied by the drugmaker that would be obtained if a standard reference testing chemical was used. PT numbers are changed to INR measurements by a standard math equation. Laboratories commonly report both numbers (PT/INR) when a PT is ordered.
The goal of prolonging the PT to 1.5 to 2.5 times the normal has largely been replaced in the United States and some other countries by specific INR goal recommendations for each clinical indication. The typical INR goal is 2 to 3, except in mechanical cardiac valve replacement, in which a higher INR is necessary to prevent clot formation.
n Assessment
Learn as much as possible about the patient’s health history, including the presence of hypersensitivity, underlying systemic disease, the current nature of the problem, and use of other medications. Inquire about conditions that contraindicate use of some anticoagulants, such as alcoholism; blood dyscrasias; bleeding tendencies of the GI, genitourinary, or respiratory tracts; or malignant hypertension. Patients with congestive heart failure may be more sensitive to coumarin anticoagulants and indanedione derivatives.
Heparin is derived from animal tissue and should be used with caution in any patient with a history of allergy. This drug should be used cautiously in patients with hepatic or renal disease or hypertension, during menses, after delivery, or in patients with indwelling catheters. A higher incidence of bleeding may be seen in women older than the age of 60. Make absolutely sure that female patients taking a coumarin or indanedione derivative are not pregnant or breastfeeding. These drugs are usually not given to children.
Lifespan Considerationsn Diagnosis
There are many medical and surgical contraindications to the use of anticoagulant drugs, particularly in patients who have recently had surgery, trauma, or obstetric complications. Review the patient’s problems and make certain that none of these contraindications exist.
