Oral anticoagulants interfere with the hepatic synthesis of vitamin K–dependent clot- ting factors (factors II, prothrombin, VII, IX, and X), resulting in their eventual depletion and prolongation of clotting times; parenteral anticoagulants interfere with the conversion of prothrombin to thrombin, blocking the final step in clot formation but leaving the circulating levels of clotting factors unaffected.

Indications

Treatment and prevention of pulmonary embolism and venous thrombosis and its ex- tension

Treatment of atrial fibrillation with embolization

Prevention of DVT

Prophylaxis of systemic embolization after acute MI

Prevention of thrombi following specific sur- gical procedures and prolonged bedrest (low–molecular-weight heparins)

Unlabeled uses: Prevention of recurrent TIAs and MI

Contraindications and cautions

Contraindicated with allergy to the drug; SBE; hemorrhagic disorders; TB; hepatic diseases; GI ulcers; renal disease; indwelling catheters, spinal puncture; aneurysm; diabetes; visceral carcinoma; uncontrolled hypertension; severe trauma (including recent or contemplated CNS, eye surgery, recent placement of IUD); threatened abortion, menometror- rhagia; pregnancy (oral drugs cause fetal damage and death); or lactation (heparin if anticoagulation is required).

Use cautiously with heart failure, diarrhea, fever, thyrotoxicosis; patients with dementia, psychosis, depression.

Adverse effects

Bleeding:Hemorrhage;GI or urinary tract bleeding (hematuria, dark stools; paralytic ileus; intestinal obstruction from hemorrhage into GI tract); petechiae and purpura, bleed- ing from mucous membranes; hemorrhagic infarction, vasculitis, skin necrosis of female breast; adrenal hemorrhage and resultant adrenal insufficiency; compressive neuropathy secondary to hemorrhage near a nerve

Dermatologic: Alopecia, urticaria, dermatitis

GI: Nausea,vomiting, anorexia, abdominal cramping, diarrhea, retroperitoneal hematoma, hepatitis, jaundice, mouth ulcers

GU: Priapism, nephropathy, red-orange urine

Hematologic: Granulocytosis, leukopenia, eosinophilia

Other: Fever, “purple toes” syndrome

Interactions

Drug-drug

Increased bleeding tendencies with salicylates, chloral hydrate, phenylbutazone, disulfiram, chloramphenicol, metronidazole, cimetidine, ranitidine, cotrimoxazole, sulfinpyrazone, quinidine, thyroid drugs, glucagon, erythromycin, androgens, amiodarone, cefox- itin, ceftriaxone, mefenamic acid, famotidine, nizatidine, nalidixic acid, fluoroquinolones

Possible decreased anticoagulation effect with barbiturates, rifampin, phenytoin, carba- mazepine, vitamin K, vitamin E, cholestyramine

Adverse effects

in italics are most common; those in bold are life-threatening. U Do not crush.

Altered effects of warfarin with methimazole, propylthiouracil

Increased activity and toxicity of phenytoin with oral anticoagulants ?Drug-alternative therapy

Increased risk of bleeding with chamomile, garlic, ginger, ginkgo, ginseng therapy, turmeric, horse chestnut, green tea leaf, grape seed extract, fever few, dong quai ?Drug-lab test

Red-orange discoloration of alkaline urine may interfere with some lab tests

Nursing considerations

Assessment

History: Allergy to the drug; SBE; hemorrhagic disorders; tuberculosis; hepatic dis- eases; GI ulcers; renal diseases; indwelling catheters, spinal puncture; aneurysm; dia- betes; visceral carcinoma; uncontrolled hypertension; severe trauma; threatened abortion, menometrorrhagia; pregnancy; lactation; heart failure, diarrhea, fever; thyrotoxicosis; senile, psychotic, or depressed patients

Physical: Skin lesions, color, T, orientation, reflexes, affect; P, BP, peripheral perfusion, baseline ECG; R, adventitious sounds; liver evaluation, bowel sounds, normal output; CBC, urinalysis, guaiac stools, PT, INR, LFTs, renal function tests, WBCT, aPTT

Interventions

Monitor INR (warfarin) or aPTT (heparin) to adjust dosage.

Do not change brand names once stabilized; bioavailability problems can occur.

Evaluate patient for signs of blood loss (petechiae, bleeding gums, bruises, dark stools, dark urine).

Establish safety measures to protect patient from injury.

Black box

warning Do not give to patients receiving epidural/spinal anesthesia; risk of epidural/spinal hematoma with neurologic impairment.

Do not give patient IM injections. Monitor sites of invasive procedures; ensure prolonged compression of bleeding vessels.

Double-check other drugs that are ordered for potential interaction: Dosages of both drugs may need to be adjusted.

Use caution when discontinuing other medications; dosage of warfarin may need to be adjusted; carefully monitor PT and INR values.

Keep vitamin K available in case of overdose of oral drugs; keep protamine sulfate avail- able for parenteral drug.

Arrange for frequent follow-up, including blood tests to evaluate drug effects.

Evaluate for therapeutic effects: PT, 1.5– 2.5 times the control value; INR, 2–3 (2.5–3.5 with prosthetic valve in place); aPTT, 1.5–2 times the control.

Teaching points

Many factors may change your body’s response to these drugs—fever, change of diet, change of environment, other medications. The dosage of the drug may have to be changed. Be sure to write down all changes prescribed.

Do not change any medication that you are taking (adding or stopping another drug) without consulting your health care provider. Other drugs affect the way anticoagulants work; starting or stopping another drug can cause excessive bleeding or interfere with the desired effects of these drugs.

Carry or wear a medical alert tag stating that you are using one of these drugs. This will alert medical personnel in an emergency that you are taking an anticoagulant.

Avoid situations in which you could be easily injured—contact sports, shaving with a straight razor.

Arrange periodic blood tests to check on the action of the drug. It is very important that you have these tests.

Use contraceptive measures while taking these drugs; it is important that you do not become pregnant.

You may experience these side effects: Stomach bloating, cramps (passes with time; if it becomes too uncomfortable, contact your health care provider); loss of hair, skin rash (this is a frustrating and upsetting effect; if it becomes a problem, discuss it with your health care provider); orange-red discoloration to the urine (this may be mistaken for blood; add vinegar to urine, the color should disappear).

Report unusual bleeding (when brushing your teeth, excessive bleeding from injuries, excessive bruising), black or bloody stools, cloudy or dark urine, sore throat, fever, chills, severe headaches, dizziness, suspected preg nancy.

Representative drugs

Oral dabigatran rivaroxaban warfarin sodium Parenteral argatroban bivalirudin desirudin fondaparinux heparin lepirudin Low–molecular-weight heparins dalteparin enoxaparin tinzaparin