Summary
Clot formation in the circulation is a physiological mechanism preventing bleeding
at sites of loss of vascular integrity. Clot formation may also occur intravascularly
under pathological conditions, e. g. leading to myocardial infarction, stroke, and
critical limb ischaemia. Clot formation involves activation of the coagulation cascade
and of platelets eventually leading to an occlusive clot. In the venous circulation,
clots are rich in erythrocytes and fibrin, while in the arterial circulation platelets
predominate. Accordingly, drugs have been developed to interfere with the activation
of the coagulation and/or platelets. As several coagulation factors such as factor
VII, VIIII, X and thrombin (factor II) are vitamin K-dependent, drugs interfering
with the effects of the vitamin (VKAs), i. e. warfarin, marcoumar or sintrom have
been used for decades to prevent thromboembolism and embolic stroke. With the advent
of selective inhibitors of factor X (apixaban, edoxaban and rivaroxaban) or factor
II (dabigratan) the therapeutic spectrum of anti-thrombotic therapy has been expanded.
On the other hand, platelet inhibitors such as aspirin and thienopyridines, i.e. clopidogrel,
prasugrel, and ticagrelor have extensively been used to treat arterial disease in
the coronary, cerebrovascular and peripheral circulation. Individualized antithrombotic
therapy considers (1) characteristics of the disease and (2) those of the patient.
Such a decision tree first separates “arterial” and “venous” thrombi. For the prevention
of arterial thrombi that occur in acute myocardial infarction and certain forms of
stroke and critical limb ischemia, platelet inhibitors are indicated. The first line
drug is aspirin which interferes with thromboxane A2 (TXA2) formation and partially inhibits platelet activation. In patients receiving a stent
or in acute coronary syndromes (ACS), the combination of aspirin with a thienopyri-dine
is indicated. On the other hand, patients with venous clots should be treated with
anticoagulants interfering with the activation of the coagulation cascade. While the
longest experiences exist with vitamin K antagonists, the novel oral anticoagulants
(NOACs) are at least as effective, but associated with less intracerebral and life-threatening
bleeding. VKAs remain the treatment of choice in patients receiving artificial heart
valves or with renal failure (in general a GFR of 30 ml/min/KG or less). In the remaining
patients, current evidence suggests that NOACs should be preferred. The NOACs are
well documented in patients with thromboembolism and atrial fibrillation. Whether
patients with an acute ACS should receive dual antiplatelet drugs plus a low dose
NOAC is a matter of debate, although conceptually it is an attractive concept. In
patients after stent implantation with atrial fibrillation, in which a triple therapy
with dual antiplatelet drugs and an anticoagulant is indicated, bleeding is an issue.
Recent data suggest that administering a thienopyridine plus warfarin (or possibly
a NOAC), while at the same time skipping aspirin may be an alternative to avoid severe
bleeding and to maintain antithrombotic efficacy. Conclusion: An extensive therapeutic
arsenal to interfere with clot formation requires an individualized approach considering
the disease condition and co-morbidities of the patient, the anticoagulants’ and patient
characteristics. This review builds on and extends previous publications of the authors
on this topic.
Zusammenfassung
Diese Übersicht bespricht die Rolle der Koagulations kaskade und der Thrombozytenaktivierung
für die Bildung arterieller und venöser Thromben. Weiter wird die Wirkweise und der
differenzielle Einsatz von Gerinnungshemmern und Thrombozytenhemmern bei verschiedenen
kardiovaskulären Erkrankungen besprochen.
Keywords
Antithrombotic therapy - platelet inhibitors - NOACs - differential therapy
Schlüsselwörter
Antithrombotische Therapie - Thromobozytenhemmer - NOACs - Differenzialtherapie
