Before beginning heparin therapy with UFH, the patient's activated partial thromboplastin time (aPTT) should be obtained to help evaluate the functioning of the intrinsic pathway. The therapeutic range is 1.5 to 2.5 times the mean control value of 20 to 30 seconds. Additionally, knowing your patient's baseline hemoglobin, hematocrit, and platelet values is essential for the detection of adverse reactions. Within the first 2 to 3 days of heparin therapy, nearly 30% of patients develop a benign, reversible nonimmune thrombocytopenia, in which the platelet count falls 10% to 30% below baseline and resolves while heparin therapy continues.
A more serious disorder of platelet function, heparin-induced thrombocytopenia (HIT) is seen in 0.3% to 3% of patients. HIT is an immune-mediated process in which antibodies to heparin and platelet factor are produced. The process sets off platelet activation and triggers excess thrombin production, leading to multiple venous thrombi. Knowing your patient's baseline platelet count is essential because a fall to less than 100 × 109/L, or 50% below baseline, along with the development of deep vein thrombosis (DVT) may signal this serious disorder.
Bleeding is the primary adverse reaction of UFH and develops in about 10% of patients. You must monitor for petechiae and bruising at the site of injection, look for red or tarry black stools and discolored urine, and assess for headache or vital changes suggesting blood loss or hemorrhage. Intracranial, pericardial, and intraocular compartments are critical areas in which bleeding may be fatal; careful assessment is a must. If significant bleeding should occur, protamine sulfate is used for the reversal of heparinization. A dosage of 1 mg of protamine neutralizes 100 units of heparin; up to 50 mg may be given I.V. over at least 10 to 15 minutes. Slow administration may prevent a rapid drop in BP and bradycardia, but the risk of anaphylaxis exists.
Because heparin is extracted from animal tissue, hypersensitivity reactions may occur. Take note of fever, chills, or urticaria and immediately report any of these findings to the healthcare provider.
Low-molecular-weight heparin (LMWH) is a fragment of UFH; its smaller size molecule results in a more predicable anticoagulation response due to greater tissue bioavailability and decreased binding to proteins. It also has a lower incidence of thrombocytopenia. LMWH acts by interfering with factor X, which is the gatekeeper to the common pathway, preventing the growth and propagation of formed thrombi. Three preparations are available in the United States: enoxaparin, dalteparin, and tinzaparin.
Widely used for DVT prophylaxis, LMWH is generally administered subcutaneously in the abdomen or upper outer part of the thigh, but it may be given by continuous I.V. infusion. Although there's no need for routine lab monitoring, an anti-factor Xa assay may be drawn to evaluate patient response. Using this test, the therapeutic range for prevention of DVT is 0.2 to 0.4 units/mL (this value may vary according to the lab calibrations used). LMWH is absorbed slowly, and its longer half-life of 3 to 5 hours allows for daily or twice daily dosing. If an overdose of LMWH occurs, it may be reversed by administering protamine sulfate.
Before initiation of heparin therapy with LMWH, a baseline prothrombin time (PT), international normalized ratio (INR), aPTT, complete blood cell (CBC) count, and serum creatinine level should be obtained. Because LMWH achieves a predictable anticoagulant response in comparison with UFH, there's no need for routine lab monitoring. However, measurement of antifactor Xa activity is the method of choice when monitoring is indicated. The sample should be drawn after a steady state is reached and approximately 4 hours after subcutaneous injection, during the peak of antifactor Xa activity.
Factor Xa inhibitor
Fondaparinux sodium is a selective factor Xa inhibitor. By antagonizing the activity of factor Xa, this medication alters the common pathway at the point of its origin. Used primarily for the prevention of DVT in patients undergoing orthopedic surgical procedures, it's given subcutaneously once a day. Fondaparinux has no direct affect on thrombin, as does UFH and LMWH. Signs and symptoms of bleeding should be assessed, as with other anticoagulants, but routine coagulation testing isn't needed.
Direct thrombin inhibitors
These medications, including lepirudin, bivalirudin, and desirudin, are related to hirudin, the anticoagulant isolated from leech saliva. Interacting directly with thrombin, they inhibit both the circulating and clot-bound forms of thrombin. These agents are administered I.V. by bolus, followed by continuous I.V. infusion. Because immune-mediated thrombocytopenia doesn't occur with direct thrombin inhibitors, they're effective in patients who develop HIT and who need anticoagulation treatment. They're also prescribed for patients at risk for HIT, who require a percutaneous coronary intervention such as stent placement.
The patient's aPTT is monitored frequently, with a target range of 1.5 to 2.5 times the control. Baseline hemoglobin and hematocrit should be obtained and drawn periodically to detect potential bleeding. There's no antidote that reverses the activity of direct thrombin inhibitors, so monitor your patient closely for petechiae, bleeding, and allergic reactions.
Get to know the oral anticoagulants
Vitamin K antagonist
Prescribed for patients with acute ischemic stroke, persistent atrial fibrillation, acute myocardial infarction with left ventricular thrombus, mitral valve disease, mechanical prosthetic heart valves, DVT, or pulmonary embolism, warfarin interferes with vitamin K metabolism by inhibiting the liver enzyme epoxide reductase. Through this mechanism of action, factors II, VII, IX, and X and anticoagulant proteins C and S are altered (see Picturing warfarin's mechanism of action). By reducing the supply of vitamin K available to serve as a cofactor for these proteins, warfarin indirectly slows their rate of synthesis. It has no direct effect on clotting factors in the circulation or on already formed thrombi, but it prevents the extension of existing thrombi and the formation of new thrombi.
The time required to achieve the anticoagulant effect of warfarin depends on the half-life of the coagulation proteins. For example, factor VII has a half-life of 6 to 9 hours and is quickly inactivated, but factors II and X persist for 72 hours until their half-life is reached. These numbers help to explain why the full anticoagulant effect of warfarin isn't reached for 8 to 15 days after starting therapy.
A baseline PT and CBC count must be obtained before beginning warfarin and should be measured frequently during the first week of therapy. PT measures the biologic activity of factors II, VII, and X and correlates well with warfarin's anticoagulant effect. A normal PT value is 10 to 13 seconds. To achieve anticoagulation goals, the PT should be between 1.5 and 2.0 times the control. For example, if the control PT is 12 seconds and the patient's PT is 24 seconds, then 24 divided by 12 equals an INR of 2.0.
Patients are often prescribed heparin for immediate anticoagulation and then bridged with warfarin until the therapeutic INR is reached. INR is the ratio between the prothrombin control and the patient's prothrombin level, with a slight mathematical adjustment for the reagent used to perform the test. The target INR for DVT prophylaxis, pulmonary embolism, and atrial fibrillation is 2.0 to 3.0. For patients with a mechanical heart valve, the target is 2.5 to 3.5. Once stabilized, monthly monitoring of the INR may be obtained by a warfarin clinic or the patient may engage in self-management. Monitoring devices are available that enable patients to perform self-testing at home; results are reported to a clinician and the warfarin dosage is adjusted if needed.
Several drugs interact with warfarin, which will increase the risk of bleeding or decrease the anticoagulant effects and promote clot formation. Drug-to-drug interactions are due to a complex series of proteins in the liver (the cytochrome P450 system) that either speed up or slow down the metabolism of warfarin. It's important to know which medications, including over-the-counter drugs and herbal supplements, your patient is taking so that adjustments in warfarin dosage can be made. Elderly patients will metabolize warfarin more slowly due to declining liver function, so expect a smaller dosage of warfarin to achieve the target INR.
Warfarin is the number one cause of adverse drug reactions in the acute care setting. Bleeding is the main complication, with the gastrointestinal tract as the prime source. Be alert for back or stomach pain, black tarry stools, bruising, nosebleeds, pinpoint red spots on the skin, blood in the urine, or bleeding gums. Intracranial hemorrhage is a serious complication. Most experts regard major bleeding (a 2-g/dL drop in hemoglobin or the need for transfusion of two or more units of blood or plasma) as an event that necessitates hospitalization.
Vitamin K, given orally or I.V., rapidly reverses an elevated INR. It provides fuel for the liver hepatocytes to synthesize vitamin K-dependent clotting factors that cause the INR to decrease. Fresh frozen plasma, clotting factor concentrates, or recombinant factor VII may be indicated in cases where bleeding is difficult to manage.
Terrific teaching tips
Patient teaching for anticoagulants is vital because of the increased risk of bleeding.
- Advise your patient to wear a medical-alert bracelet or carry such identification in her wallet.
- Discuss ways to decrease the risk of falls in the home by using nonslip rugs, night lights, and handrails in bathrooms and hallways.
- Caution your patient to avoid sharp tools or knives and recommend the use of an electric razor.
- Stress the importance of regular lab monitoring of PT and INR to maintain therapeutic clotting levels.
- Instruct your patient to take her anticoagulant medication at the same time every day. If a dose is missed, she should take it as soon as possible; however, caution her not to double up on doses the following day.
- Teach her about the possibility of bleeding; stress that she should promptly report any unusual signs or symptoms to her healthcare provider.
- If your patient is taking warfarin and enjoys foods high in vitamin K, emphasize that vitamin K intake should be consistent to avoid wide fluctuations in INR values (see Diet and warfarin).
- Inform your patient that the effects of alcohol can be unpredictable and it may alter the INR in either direction.
- Advise her not to take over-the-counter medicines without first consulting with her healthcare provider. Nonsteroidal anti-inflammatory products, including aspirin, will increase the risk of bleeding and must be used with extreme caution. Daily use of acetaminophen, as few as four regular strength tablets, significantly increases the risk of elevating the INR.
- Tell your patient to contact her healthcare provider before having dental work or undergoing elective surgery. She should also make sure the dentist, surgeon, or other provider knows that she's taking an anticoagulant.
Managing individuals receiving anticoagulant therapy is challenging. You must obtain a detailed history and perform thorough assessments to identify factors that place patients at risk for complications. You need to know which tests are indicated for specific medications and be able to analyze trends in lab data. And remember that the information you provide to your patient may be lifesaving!
Contraindications to anticoagulation therapy
- Lack of patient cooperation
- Bleeding from the following systems:
- Hemorrhagic blood dyscrasias (abnormal conditions of the blood)
- Severe trauma
- Recent or impending surgery of the:
- Severe hepatic or renal disease
- Recent cerebrovascular hemorrhage
- Open ulcerative wounds
- Occupations that involve a significant hazard for injury
- Recent delivery of a baby
It's important to be aware of the black box warnings for select patients taking LMWH or fondaparinux. Epidural and spinal hematomas resulting in long-term or permanent paralysis have occurred in patients receiving these medications. Factors that increase the risk of this serious complication are the presence of an epidural catheter, traumatic or repeated epidural or spinal punctures, the presence of a spinal deformity, and a history of spinal surgery. Patients with these risk factors need to be assessed for signs and symptoms of neurologic impairment; if neurologic compromise is noted, urgent treatment is necessary.
Diet and warfarin
Because warfarin blocks the effects of vitamin K, the amount of dietary vitamin K consumed can dramatically change the drug's effects. Green leafy vegetables, such as broccoli, spinach, collard greens, cabbage, Swiss chard, and parsley, are rich in vitamin K as are certain oils, including mayonnaise and canola and soybean oil. It isn't necessary for your patient to eliminate these choices from her diet, but she needs to keep dietary intake of vitamin K consistent.
It's important for you to explain to your patient that she can enjoy these foods in moderation, but the warfarin dosage may need to be adjusted. For instance, if your patient increases her intake of vitamin K-rich foods, the dosage of warfarin may need to be increased to prevent clot formation. Likewise, if she eats fewer foods containing vitamin K, then the warfarin dosage may need to be lowered to prevent bleeding.
Dieting, particularly the high protein choices of the Atkin's and South Beach diets, may negate warfarin's anticoagulant effects. Warfarin is highly protein bound, which means that it has a strong attraction to albumin. Once connected to this protein, it has no effect on the body. Only unbound or free warfarin is able to exert its anticoagulant action. So if your patient substantially increases her protein intake, more warfarin will bind to albumin, making it less available to prevent clots. Advise your patient to check with her healthcare provider before starting any special diet, in addition to monitoring INR levels.
Learn more about it
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