Bleeding Complications of Anticoagulation Therapy in Clinical Practice-Epidemiology and Management: Review of the Literature

Abstract

Due to their very wide range of indications, anticoagulants are one of the most commonly used drug groups. Although these drugs are characterized by different mechanisms of action, the most common complication of their use is still bleeding episodes, the frequency of which depends largely on the clinical condition of the patient using such therapy. For this reason, to this day, the best method of preventing bleeding complications remains the assessment of bleeding risk using scales such as HAS-BLED. There are many reports in the literature assessing the occurrence of this type of complication after the use of drugs affecting the coagulation process, as well as many reports comparing individual groups of drugs with different mechanisms of action. However, there are still no clear guidelines that would indicate which group of anticoagulants should be preferred in particular groups of patients. The aim of our article is to summarize the data collected so far regarding the safety of using specific groups of anticoagulants and the frequency of bleeding complications after their use.

Keywords: anticoagulation therapy; bleeding complications; direct oral anticoagulants; fondaparinux; heparins; vitamin K antagonists.

Figure 1

Visualization of a heparin polymer fragment. Visualization created based on the description of the crystal structure [13] using RSCB Protein DataBank 3D-viewer (RCSB.org, [14]).

Figure 2

Mechanism of action for heparins. LMWH—low molecular weight heparin; P—phospholipid surface; TF—tissue factor; UFH—unfractionated heparin. Unfractionated heparin inhibits both the contact activation and tissue factor pathways. In contrast, LMWH and fondaparinux inhibit the tissue factor pathway only. Tissue factor pathway: tissue factor/factor VIIa complex (TF/VIIa) triggers the coagulation and activates factor IX (IXa) and factor X (Xa). Contact activation pathway: activation of factor XII (XIIa) initiates the coagulation and activates factor XI (XIa). Factor XIa activates factor IX and the activated factor IX (IXa) further results in the activation of factor X in a reaction that uses activated factor VIII (VIIIa) as a cofactor. Activated factor X (Xa) converts prothrombin (II) to thrombin (IIa) using activated factor V (Va) as a cofactor. Finally, thrombin converts fibrinogen to fibrin.

Figure 3

Site of action of DOACs and VKAs.