Acquired Thrombophilia - Coagulation Disorders

ACQUIRED THROMBOPHILIA

Antibodies to phospholipids are common, acquired causes for thrombophilia (hypercoagulable states). The most common anti-bodies present against phospholipids are either lupus or anti-cardiolipin antibodies. Both of these antibodies can be transient, resulting from infection or certain medications. Most thrombotic events are venous, but arterial thrombosis can occur in up to one third of the cases. Patients who persistently test positive for either antibody and who have had a thrombotic event are at significant risk for recurrent thrombosis (greater than 50%). Recurrent throm-boses tend to be of the same type—that is, venous thrombosis after an initial venous thrombosis, arterial thrombosis after an initial arterial thrombosis.

Another common acquired cause for thrombophilia is cancer. Specific types of stomach, pancreatic, lung, and ovarian cancers are most commonly associated with thrombophilia. The type of thrombosis that results is unusual. Rather than deep vein throm-bosis or pulmonary embolism, the thrombosis occurs in unusual sites, such as the portal, hepatic, or renal vein or the inferior vena cava. Migratory superficial thrombophlebitis or nonbacterial thrombotic endocarditis can also occur. In these patients, anti-coagulation can be difficult to manage in that the thrombosis can progress despite standard amounts of anticoagulation.

Medical Management

The primary method of treating thrombotic disorders is antico-agulation. However, in thrombophilic conditions, when to treat (prophylaxis or not) and how long to treat (lifelong or not) can be controversial. Anticoagulation therapy is not without risks; the most significant risk is bleeding. The most common anticoagulant medications are identified in the following section.

PHARMACOLOGIC THERAPY

Along with administering anticoagulant therapy, concerns in-clude minimizing any risk factors that predispose a patient to thrombosis. When risk factors (eg, immobility after surgery, pregnancy) cannot be avoided, prophylactic anticoagulation may be necessary.

Unfractionated Heparin Therapy.

Heparin is a naturally occurringanticoagulant that enhances AT III and inhibits platelet function. To prevent thrombosis, heparin is typically given as a subcuta-neous injection, two or three times daily. To treat thrombosis, heparin is usually administered intravenously. The therapeutic effect of heparin is monitored by serial measurements of the acti-vated partial prothrombin time; the dose is adjusted to maintain the range at 1.5 to 2.5 times the laboratory control. Oral forms are being evaluated, but their absorption remains variable (Money & York, 2001).

A significant potential complication of heparin-based ther-apy is heparin-induced thrombocytopenia (HIT). Antibodies are formed within the body against the heparin complex. The actual incidence of HIT is unknown, but it is thought to occur in as many as 5% patients receiving heparin (Kelton, 1999). Whereas most patients remain asymptomatic, a significant pro-portion of those individuals with serologic HIT develop actual thrombocytopenia. A decline in platelet count typically devel-ops after 5 to 8 days of heparin therapy, and the platelets can drop significantly, although in most instances the level stays higher than 50,000/mm³. These patients are at increased risk for thrombosis, either venous or arterial, and the thrombosis can range from DVT to myocardial infarction, CVA (brain at-tack, stroke), and ischemic damage to an extremity necessitating amputation. The risk for development of HIT appears to be increased when heparin is used at higher concentrations (ie, ther-apeutic versus prophylactic dosage) and with preexisting comor-bidity, such as underlying cardiac disease.

Low-Molecular-Weight Heparin Therapy.

Low molecular-weightheparin (LMWH; eg, Dalteparin, Enoxaparin) is a special form of heparin that has a more selective effect on coagulation. Based on its biochemical properties, LMWH has a longer half-life and a less variable anticoagulant response than does standard heparin. These differences permit LMWH to be safely administered only once or twice daily, without the need for laboratory monitoring for dose adjustments. The incidence of HIT is much lower when LMWH is used. In certain conditions, the use of LMWH has allowed anti-coagulation therapy to be moved entirely to the outpatient setting. Many cases of uncomplicated DVT are being managed outside the hospital setting. LMWH is also being increasingly used as “bridge therapy” when patients receiving anticoagulation therapy (war-farin) require an invasive procedure (eg, biopsy, surgery). In this sit-uation, warfarin is stopped and LMWH is used in its place until the procedure is completed. After the procedure, warfarin therapy is resumed. LMWH is discontinued after a therapeutic level of war-farin is achieved.

Warfarin (Coumadin) Therapy.

Coumarin anticoagulants (war-farin; eg, Coumadin) are antagonists of vitamin K and therefore interfere with the synthesis of vitamin K–dependent clotting factors. Coumarin anticoagulants bind to albumin, are metabo-lized in the liver, and have an extremely long half-life. Typically, a patient is initially treated with both heparin (either the unfrac-tionated form or LMWH) and warfarin. When the international normalized ratio (INR) reaches the desired therapeutic range, the heparin is stopped. The dosage required to maintain the therapeutic range (typically using an INR of 2.0 to 3.0) varies widely among patients and even within the same patient. Frequent mon-itoring of the INR is extremely important so that the dosage of warfarin can be adjusted as needed. Warfarin is affected by many medications; consultation with a pharmacist is important to as-sess the extent to which concurrently administered medications, herbs, and nutritional supplements may interact with warfarin. It is also affected by many foods, so patients need dietary instruc-tion and may benefit from consultation with a dietitian when re-ceiving warfarin therapy. See Chart 33-15 for a listing of agents that interact with warfarin.

Nursing Management

Patients with thrombotic disorders should avoid activities that promote circulatory stasis (eg, immobility, crossing the legs). Ex-ercise, especially ambulation, should be performed frequently throughout the day, particularly during long trips by car or plane.

Medications that alter platelet aggregation, such as low-strength aspirin, may be prescribed. Some patients require life-long ther-apy with anticoagulants such as warfarin (eg, Coumadin).

Patients with thrombotic disorders, particularly those with thrombophilia, should be assessed for concurrent risk factors for thrombosis and should avoid concomitant risk factors if possible. For example, use of tobacco and nicotine products exacerbates the problem and should be avoided.

Just as for other conditions, patients with thrombotic disor-ders, particularly thrombophilia, should know the name of their specific condition and understand its significance. In many in-stances, younger patients with thrombophilia may not require prophylactic anticoagulation; however, with concomitant risk fac-tors (eg, pregnancy), increasing age, or subsequent thrombotic events, prophylactic or lifelong anticoagulation therapy may be re-quired. Being able to provide the health care provider with an ac-curate health history can be extremely useful and can help guide the selection of appropriate therapeutic interventions. Patients with hereditary disorders should be encouraged to have their sib-lings and children tested for the disorder.

When patients with thrombotic disorders are hospitalized, fre-quent assessments should be performed for signs and symptoms of beginning thrombus formation, particularly in the legs (DVT) and lungs (pulmonary embolism). Ambulation or range-of-motion ex-ercises as well as the use of elastic compression stockings should be initiated promptly to decrease stasis. Prophylactic anticoagulants are commonly prescribed.