3.2.1. Dabigatran

2.3. Fondaparin

4 Anticoagulant Drugs

2.4. Hirudin

2.5. Argatroban

3. Oral anticoagulants

3.1. Vitamin K antagonists

Fondaparin (Arixtra®) is a synthetic pentasaccharide that closely resembles the pentasaccharide naturally occurring in the UFH and LMWH. It is an antithrombin-mediated factor Xa inhibitor that is devoid of any anti-factor IIa (thrombin) activity [15]. It is used for treating patients with acute coronary syndrome and heparin-induced thrombocytopenia. It is indicated also for certain patients with thrombophlebitis in a fixed dose of 2.5 mg daily s.c. Laboratory monitoring is not needed; however, if necessary fondaparin levels should only be determined using assays that use known fondaparin concentrations to generate their calibration curve. The use of fondaparin in patients with creatinine clearance below 30 mL/min is contraindicated [2].

Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches that irreversibly inhibits thrombin. Lepirudin, a recombinant hirudin derived from yeast cells, was used in clinical practice but is no longer available. Instead, the synthetic analog—bivalirudin (Angiox®)—with a short half-life is used at percutaneous coronary interventions and for treating patients with heparin-induced thrombocytopenia. The use of bivalirudin in patients

Argatroban (Argatra®) is a synthetic reversible direct thrombin inhibitor. It is metabolized solely in the liver and is, therefore, suitable for patients with renal failure. It is used in patients with heparin-induced thrombocytopenia. Treatment with argatroban requires laboratory monitoring with activated partial thromboplastin time (APTT) and the dose adjusted to reach 1.5–

The vitamin K-dependent coagulation factors II, VII, IX and X require γ-carboxylation for their procoagulant activity. Treatment with vitamin K antagonists results in the hepatic production of partially carboxylated and decarboxylated proteins with reduced coagulant activity. Among the most commonly used vitamin K antagonists are warfarin and acenocoumarol. Although vitamin K antagonists are absorbed quickly their full effect develops after about 5 days when

Warfarin therapy requires regular laboratory monitoring with prothrombin time (PT). Due to different sensitivities of thromboplastin reagents used for PT measurement the results are expressed as the International Normalized Ratio (INR). For the majority of indications the target INR range falls between 2.0 and 3.0. In certain patient populations, for example, in patients with mechanical heart valves, the target range is 2.5–3.5 INR. A rare non-hemorrhagic

with creatinine clearance below 30 mL/min is contraindicated [16].

3.0 times prolonged baseline APTT, but should not exceed 100 s [17].

the activity of all vitamin K-dependent coagulation factors is reduced [1].

Dabigatran etexilate (Pradaxa®) is a low-molecular weight prodrug that exhibits no pharmacological activity. After oral administration, dabigatran etexilate is converted to its active form, dabigatran, a potent, competitive and reversible direct thrombin inhibitor [18]. The binding of dabigatran to thrombin is specific and selective and includes both free and thrombus-bound thrombin. Maximal blood concentration of dabigatran is reached after 1–3 h after the intake [18]. About 35% of the drug is bound to plasma proteins. Eighty percent of dabigatran is excreted through the kidneys [18]. Dabigatran half-life is 14–17 h [18]. It is given in fixed doses of either 150 or 110 mg twice daily in patients with atrial fibrillation and 150 mg twice daily in patients with VTE [19, 20]. Prophylactic doses after total hip or knee replacement are 220 or 150 mg once daily with only half the dose given as the first dose after surgery [21].

The anticoagulant effect of dabigatran is predictive and, therefore, requires no regular laboratory monitoring. During dabigatran therapy, APTT and thrombin time (TT) are prolonged, but these two tests can only offer a rough approximation of dabigatran blood concentration. In certain situations when dabigatran concentration needs to be assessed, a specific test must be used, such as modified thrombin time or a chromogenic assay [22, 23].
