see >> Heparin
The indications are the prevention and treatment of phlebothrombosis, pulmonary embolism, atrial fibrillation, coronary occlusion, after cardiac valve replacements. Mechanism of action: interfere with hepatic synthesis of vitamin K dependent coagulation factors (II, VII, IX and X).
Distribution: they cross the placenta but do not enter the breast milk.
Metabolism: hepatic half-life: 0.5-3 days. Contraindications in: pregnancy, bleeding, open wounds, peptic ulcer, neoplasia, recent brain damage, bone marrow, ocular, surgical. Severe hypertension, severe liver disease.
Use with caution in: women who can remain pregnant. History of epigastralgia or gastric pyrosis (in doubt to make a gastroduodenoscopy first) Poor compliance of the patient with the drug or laboratory controls. Side effects: bleeding. Fever, nausea, cramps, necrosis of the dermis.
Interactions: drugs that, associated with oral anticoagulants, can
increase the risk of bleeding: non-steroidal anti-inflammatory drugs, thrombolytics, metronidazole, quinidine, valproate, androgens, chloramphenicol,
cefamandal, cefoperazone, cefotetan, disulfiram, sulfonamides. Drugs that reduce
the anticoagulant effect: oral contraceptives (containing estrogen), alcohol,
barbiturates.
Sodium warfarin dosing (Coumadin 5 mg cpr) 10 mg / day for 2-4 days then adjust the dose in relation to the prothrombin time (PT). The usual dose is between 2 and 10 mg. In elderly patients it is better to start with lower doses; or acenocoumarol (Sintrom cpr 1 and 4 mg) 4 mg / day for 1-2 days then adjust the dose in relation to PT (in practice the daily dose mostly ranges from 1 to 4 mg).
Laboratory tests: monitoring of oral anticoagulant therapy is carried out more with the prothrombin time (PT) dosage but with that of its variant called International Normalized Ratio (INR) which correlates the thromboplastin used in the single laboratory to thromboplastin used as standard international allowing to standardize the dosages carried out in the various laboratories. To maintain therapeutic anticoagulation, the PT must be maintained at values of M 2 times the norm (20-40%) and the INR at values between 2 and 3. In the first period, these parameters should be checked frequently, then the controls can be thinned out time. Fecal and urine tests for occult blood can be periodically carried out. Also check blood count and liver function.
In recent years some new oral anticoagulants have begun to replace the
dicumarolics (warfarin and acenocoumarol), albeit with limitations in the
indications in relation to the trials carried out.
1. Effectiveness in prophylaxis and treatment of thromboembolic episodes at
least as far as coumarins.
2. Significant reduction in the risk of major bleeding compared to coumarins.
3. Coagulation controls not required during treatment.
4. Contraindicated in severe renal impairment (Cr CI <30 ml / min).
5. In moderate renal impairment (Cr CI 30-49 mL / min) rivaroxaban and apixaban
should be administered at half doses while the dabigatran may be administered at
a dose of 110 mg x 2.
6. The dosage of creatinine is always indicated before starting treatment with
NAO
Dabigatran (Pradaxa cpr 110 and 150 mg). The drug is available in two effective and safe dosages: 150 mg twice a day (higher efficacy) and 110 mg twice a day (increased safety). This last dose is indicated in patients aged> 80 years or with concomitant use of verapamil or in other patients to be evaluated individually (age 75-80 years, moderate renal insufficiency, gastritis or esophagitis, increased risk of bleeding). and safe also in association with clopidogrel and / or ASA. And the only effective and safe NAO in cardioversion. Hemodialysis removes the dabigatran in case of overdose. Half-life: 12-15 hours.
Mechanism of action:
direct thrombin inhibition. Metabolism: 80% renal and 20% liver.
Indications: prevention of stroke and systemic embolism in adults with
non-valvular atrial fibrillation with one or more of the following risk factors:
- Previous transient ischemic attack or embolic event.
- Left ventricular ejection fraction <40%.
- Heart failure in NYHA class> 2.
- Age> 75 years.
- Age> 65 years with hypertension or diabetes mellitus.
Rivaroxaban (Xarelto cpr 10 mg). Pos: 10 mg per day in a single dose.
Half-life: 7-13 hours.
Mechanism of action: direct inhibition of factor Xa. Metabolism: 1/3 renal and 2/3 hepatic.
The drug is not dialysable. Indications:
prevention of stroke and systemic embolism in adults with non-valvular atrial
fibrillation with one or more of the following risk factors:
- Previous transient ischemic attack or embolic event.
- Left ventricular ejection fraction <40%
- Heart failure in NYHA class> 2.
- Age> 75 years.
- Age> 65 years with hypertension or diabetes mellitus
Treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and
pulmonary embolism after acute DVT in adults.
Apixaban (Eliquis cpr rev 2.5 mg). Pos: 2.5 mg 2 times a day.
The dose may be
halved in the presence of two of the following risk factors (age> 80 years,
weight <60 kg, creatinine> 1.5 mg / dL). Result superior to both aspirin and
warfarin. The drug is not dialysable.
Half-life: 7-13 hours.
Mechanism of action: direct inhibition of factor Xa.
Metabolism: 25% renal and 75% hepatic.
Indications: prevention of stroke and systemic embolism in adults with
non-valvular atrial fibrillation with one or more of the following risk factors:
- Previous transient ischemic attack or embolic event.
- Left ventricular ejection fraction <40%.
- Heart failure in NYHA class> 2.
- Age> 75 years.
- Age> 65 years with hypertension or diabetes mellitus or hypertension.
Fondaparinux (Arixtra fl syr 5-7.5-10 mg) is a specific factor Xa inhibitor. In the prophylaxis of thromboembolic events it was as effective as enoxaparin in patients with acute coronary syndrome but with a 50% reduction in major bleeding and consequent reduction in mortality (OASIS-5 trial).
The drug could be particularly useful in patients at high risk of bleeding even if current indications are still limited. Indications: prophylaxis of thromboembolic events in (1) patients undergoing hip replacement or (2) of knee, (3) with hip fractures or 4) subjected to venting of abdominal surgery.
When given together with oral anticoagulants. Treatment of pulmonary embolism together with oral anticoagulants (in a hospital setting).
Dosage: in the treatment of deep vein thrombosis 7.5 mg / day subcutaneously in patients weighing> 50 and <100 kg. In patients weighing <50 kg the dose is 5 mg / day and in those> 100 kg the dose is 10 mg / day. The treatment must be continued for at least 5 days and on average lasts 7-10 days.
Treatment with oral anticoagulants should be started immediately. In orthopedic prophylaxis 2.5 mg / day for the chin 10 days. Keep the INR around 2.5. Contraindications: severe renal insufficiency (creatinine clarance <30 mL / min), endocarditis, major bleeding in progress, autoimmune thrombocytopenia, side effects: minor or severe bleeding, anemia, fever, nausea, edema, constipation, rash.