2.2. Low-molecular weight heparin

Low-molecular weight heparin (LMWH) is obtained by various methods of fractionation or depolymerization of polymeric UFH [8]. Because LMWHs differ in molecular mass, they also differ in pharmacological characteristics and anticoagulant effects [9]. All LMWHs inhibit coagulation factors II and X. Among the most commonly used LMWHs for treatment and the prevention of acute thromboembolic events are dalteparin (Fragmin®), enoxaparin (Clexane®) and nadroparin (Fraxiparine® and Fraxiparine forte®) in the form of subcutaneous injections. They can also be used as a bridging therapy in patients with high thromboembolic risk during a period when these patients cannot receive oral anticoagulants. Therapeutic dose is determined according to the patient's body weight [2] (Table 1).

For prevention of venous thromboembolism (VTE), lower (prophylactic) doses of LMWH are used [2] (Table 2). The adequate LMWH dose is selected according to the risk. Prophylactic doses are used in some patients during the interim cessation of oral anticoagulant therapy above all in the first days after large interventions.

The most important advantage of LMWH over UFH is the lower degree of binding to plasma proteins and endothelial cells making their pharmacokinetics and anticoagulant effects predictable [10, 11]. Regular laboratory monitoring with coagulation tests is therefore not needed, except in patients with kidney disease and patients with very low (under 45 kg) or very high (above 120 kg) body weight [2]. Although APTT may be mildly prolonged during LMWH therapy it cannot be used for monitoring. The chromogenic anti-Xa is the test of choice for the determination of plasma LMWH concentration [12]. The LMWH dose should be adjusted to

0.5–1.0 IU/mL 4 h after the last LMWH dose when administered twice daily or to 1.0–2.0 IU/mL 5–6 h after the last dose when administered once daily [13, 14]. The two main non-hemorrhagic side effects of LMWH therapy are osteopenia and thrombocytopenia; how-

LMWH Low prophylactic dose (moderate VTE risk) High prophylactic dose (high VTE risk)

0.6 ml/24 h sc at BW > 70 kg

Nadroparin (Fraxiparine®) 0.1 ml/10 kg BW /12 h sc (Fraxiparine FORTE®) 0.1 ml/10 kg BW/24 h sc

An Overview of the Anticoagulant Drugs Used in Routine Clinical Practice

http://dx.doi.org/10.5772/intechopen.76206

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ever, both these side effects are considerably rarer compared to UFH therapy [2].

Therapeutic dose

LMWH Twice daily Once daily

–59 kg 0.5 ml/12 h sc 0.5 ml/24 h sc –69 kg 0.6 ml/12 h sc 0.6 ml/24 h sc –79 kg 0.7 ml/12 h sc 0.7 ml/24 h sc –89 kg 0.8 ml/12 h sc 0.8 ml/24 h sc –120 kg 0.9 ml/12 h sc 0.9 ml/24 h sc

Dalteparin 2500 IU/24 h sc 5000 IU/24 h sc Enoxaparin 20 mg/24 h sc 40 mg/24 h sc

IU: International Units, BW: body weight, sc: subcutaneously, VTE: venous thromboembolism.

Nadroparin 0.3 ml/24 h sc 0.4 ml/24 h sc at BW ≤ 70 kg

IU: International Units, BW: body weight, sc: subcutaneously.

Table 1. LMWH therapeutic doses according to body weight.

Table 2. Prophylactic doses of LMWH.

Dalteparin (Fragmin®) 100 IU/kg BW/12 h sc 200 IU/kg BW/24 h sc –56 kg 5.000 IU/12 h sc 10.000 IU/24 h sc –68 kg 6.000 IU/12 h sc 12.500 IU/24 h sc –82 kg 7.500 IU/12 h sc 15.000 IU/24 h sc –120 kg 100 IU/kgBW/12 h sc 18.000 IU/24 h sc Enoksaparin (Clexane®) 1 mg/kg BW/12 h sc 1.5 mg/kg BW/24 h sc –54 kg 50 mg/12 h sc 80 mg/24 h sc –64 kg 60 mg/12 h sc 90 mg/24 h sc –74 kg 70 mg/12 h sc 100 mg/24 h sc –84 kg 80 mg/12 h sc 120 mg/24 h sc –94 kg 90 mg/12 h sc 135 mg/24 h sc –120 kg 100 mg/12 h sc 150 mg/24 h sc


Table 1. LMWH therapeutic doses according to body weight.


IU: International Units, BW: body weight, sc: subcutaneously, VTE: venous thromboembolism.

Table 2. Prophylactic doses of LMWH.

2. Parenteral anticoagulant drugs

Unfractionated heparin (UFH) binds antithrombin—a physiological inhibitor of coagulation and accelerates its inhibitory action against coagulation factors II and X and in minor degrees also factors IX, XI and XII [2, 3]. UFH is active in a parenteral form only and therefore administered by intravenous (i.v.) infusion [2]. It is used for the treatment of acute thromboembolic events. One of the major disadvantages of UFH is its binding to plasma proteins and endothelial cells making its anticoagulant effect unpredictable [2, 3]. Treatment with UFH must, therefore, be regularly monitored with activated partial thromboplastin time (APTT). Due to different sensitivities of APTT reagents the therapeutic APTT range must be determined by each laboratory and must correspond to heparin anti-factor Xa activity between 0.3 and 0.7 IU/mL [4–6]. Treatment is initiated with UFH bolus of 80 U/kg i.v. and continued with continuous infusion of 18 U/kg body mass/h [7]. Dosage must be adjusted according to the APTT result. At the beginning of treatment, laboratory monitoring is needed several times a day, the first one 6 h after UFH initiation. The two most important non-hemorrhagic side

Low-molecular weight heparin (LMWH) is obtained by various methods of fractionation or depolymerization of polymeric UFH [8]. Because LMWHs differ in molecular mass, they also differ in pharmacological characteristics and anticoagulant effects [9]. All LMWHs inhibit coagulation factors II and X. Among the most commonly used LMWHs for treatment and the prevention of acute thromboembolic events are dalteparin (Fragmin®), enoxaparin (Clexane®) and nadroparin (Fraxiparine® and Fraxiparine forte®) in the form of subcutaneous injections. They can also be used as a bridging therapy in patients with high thromboembolic risk during a period when these patients cannot receive oral anticoagulants. Therapeutic dose is deter-

For prevention of venous thromboembolism (VTE), lower (prophylactic) doses of LMWH are used [2] (Table 2). The adequate LMWH dose is selected according to the risk. Prophylactic doses are used in some patients during the interim cessation of oral anticoagulant therapy

The most important advantage of LMWH over UFH is the lower degree of binding to plasma proteins and endothelial cells making their pharmacokinetics and anticoagulant effects predictable [10, 11]. Regular laboratory monitoring with coagulation tests is therefore not needed, except in patients with kidney disease and patients with very low (under 45 kg) or very high (above 120 kg) body weight [2]. Although APTT may be mildly prolonged during LMWH therapy it cannot be used for monitoring. The chromogenic anti-Xa is the test of choice for the determination of plasma LMWH concentration [12]. The LMWH dose should be adjusted to

effects of UFH treatment are osteoporosis and thrombocytopenia [2].

mined according to the patient's body weight [2] (Table 1).

above all in the first days after large interventions.

2.1. Unfractionated heparin

2 Anticoagulant Drugs

2.2. Low-molecular weight heparin

0.5–1.0 IU/mL 4 h after the last LMWH dose when administered twice daily or to 1.0–2.0 IU/mL 5–6 h after the last dose when administered once daily [13, 14]. The two main non-hemorrhagic side effects of LMWH therapy are osteopenia and thrombocytopenia; however, both these side effects are considerably rarer compared to UFH therapy [2].
