**3.1. Heparins and low-molecular-weight heparins**

Heparan sulfate (HS) proteoglycans play vital functions in many biological processes in the animal kingdom, and the GAG moiety is essential for these functions. Heparin is synthesized from UDP-sugar precursors as a polymer of alternating D-glucuronic acid and N-acetyl-Dglucosamine residues [44]. Unfractionated heparin (UFH) is a glycosaminoglycan consisting of heterogeneous mixture of polysaccharide chains with alternating residues of D-glucosamin and uronic acid, glucoronic acid, or iduronic acid, with a molecular weight range of 3000– 30,000 Da. Low-molecular-weight heparins (LWMHs) are fragments of UFH produced by controlled enzymatic or chemical depolymerization processes with a mean molecular weight of about 5000 Da [45].

anticoagulant activity. Because of the unpredictable anticoagulant response, careful/close

Real-World Safety of Anticoagulants http://dx.doi.org/10.5772/intechopen.78023 93

LMWHs do not bind to endothelial cells, macrophages, or reticuloendothelial cells and have a 2–4 times longer half-life compared to UFH (3–6 hours). Furthermore, LMWHs have much lower affinity for heparin-binding plasma proteins and are mainly removed by nonsaturable renal filtration, and thus, their clearance is independent of dose and plasma concentration [50].

Heparin use should be avoided in case of concomitant treatment with antiplatelet drugs (NSAIDs, diclofenac, piroxicam, ketorolac, nimesulide, and acetylsalicylic acid), anticoagulant agents (warfarin), and glucocorticoids, due to increase in bleeding risk. Furthermore, LMWH should not be used in patients with previous heparin-induced thrombocytopenia/ thrombosis (HITT), known hypersensitivity or adverse reaction to LMWH (dalteparin or enoxaparin), severe renal impairment, active bleeding, severe or uncontrolled hypertension,

Heparin therapy for VTE treatment is typically administered by continuous intravenous infusion, but adjusted dose and fixed dose subcutaneous injections can also be utilized. Obese patients clear LMWHs faster than nonobese patients due to hyperfiltration, and their dose should be adjusted on total body weight or LMWHs should be substituted with UFHs [51]. Therapy monitoring comprehends regular CrCl, platelet count, and antifactor Xa assay

• dalteparin 5000 units subcutaneously once daily for 5–10 days or enoxaparin 40 mg subcutaneously once daily for 7–10 days in patients undergoing surgery interventions, who had

• dalteparin 2500 units subcutaneously once daily or enoxaparin 20 mg subcutaneously once

Dosing recommendations for treatment of NSTEMI with enoxaparin take into account renal

• enoxaparin 1 mg/kg subcutaneously every 12 hours if CrCl is between 30 and 50 mL/min

In case of thrombolysis, anticoagulation is generally given in addition to dual antiplatelet

In case of VTE prophylaxis, dosing and duration of LMWHs follow this pattern:

functions and concomitant therapies with antiplatelet agents. In particular:

• enoxaparin 1 mg/kg subcutaneously every 12 hours if CrCl is >50 mL/min;

with continue; monitoring of renal function and antifactor Xa levels;

• heparins use is not recommended if CrCl is <30 mL/min.

monitoring is essential, when UFH is given in therapeutic doses [48].

active peptic ulcerations, hemophilia, and severe liver disease.

*3.1.4. Interactions*

*3.1.5. Therapy management*

previously VTE or are bedridden;

daily in case of renal impairment.

therapy at doses adjusted on patient's age:

measurements.
