Page 390 - Essential Haematology

376 / Chapter 27 Thrombosis and antithrombotic therapy

Table 27.7 Drugs and other factors that interfere with the control of coumarin (e.g. warfarin)

therapy.
Potentiation of coumarin anticoagulants Inhibition of coumarin anticoagulants
Drugs that increase the effect of coumarins Drugs that depress the action of coumarins
Reduced coumarin binding to serum albumin Acceleration of hepatic microsomal degradation
Sulphonamides of coumarin
Barbiturates
Inhibition of hepatic microsomal degradation of
Rifampicin
coumarin
Cimetidine Enhanced synthesis of clotting factors
Allopurinol Oral contraceptives
Tricyclic antidepressants
Hereditary resistance to oral anticoagulants
Metronidazole
Sulphonamides Pregnancy
Alteration of hepatic receptor site for drug
Thyroxine
Quinidine
Decreased synthesis of vitamin K factors
High doses of salicylates
Some cephalosporins, other antibiotics
Liver disease
Decreased synthesis of vitamin K factors
Decreased absorption of vitamin K
e.g. Malabsorption, antibiotic therapy, laxatives

NB. Patients are also more likely to bleed if taking antiplatelet agents (e.g. NSAIDs, dipyridamole or aspirin); alcohol in large
amounts enhances warfarin action.

factor Xa inhibitor. It is given subcutaneously, Direct thrombin (factor II) inhibitors Th ese
has a plasma half - life of 17 hours and like the include recombinant hirudins, bivalirudin, lepiru-
orally active factor Xa inhibitors does not require den, argatroban and dabigatran.
laboratory monitoring (by measuring factor Xa Bivalirudin and lepiruden have been used as
levels) except in especially obese patients, those an alternative to heparin in patients undergoing
with renal failure and children. percutaneous coronary interventions and are associ-
Rivaroxaban is an orally active irreversibile ated with less bleeding and a reduced need for
inhibitor of factor Xa. It has a rapid onset of adjunctive treatment with glycoprotein IIb/IIIa
action with a peak plasma level 2 hours after antagonists in patients undergoing stenting.

injection. It is given at a fixed dose and does not Dabigatran is given twice daily by mouth at

need monitoring. a fixed dose. It is as effective as conventional therapy
Extensive trials have demonstrated that the in preventing venous thrombous in orthopoedic
Xa inhibitors are effective antithrombotic agent and general surgery without an increased risk of

for prevention and treatment of both venous and major haemorrhage. It has had similar success in the
arterial thromboembolic disorders. They may also treatment of acute venous thrombosis and in the

reduce major bleeding and may improve long - prevention of stroke and systemic arterial embolism
term mortality and morbidity (e.g. in acute coro- in patients with atrial fi brillation. Like rivaroxaban,
nary syndromes). it has the potential to replace warfarin.