ATC Group: B02BX Other systemic hemostatics

Avatrombopag is an orally active, small molecule thrombopoietin (TPO) receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in increased production of platelets. Avatrombopag does not compete with TPO for binding to the TPO receptor and has an additive effect with TPO on platelet production.

Concizumab is an anti-tissue factor pathway inhibitor (anti-TFPI) antibody. TFPI is an inhibitor of factor Xa (FXa). Concizumab binding to TFPI prevents TFPI inhibition of FXa. The increased FXa activity prolongs the initiation phase of coagulation and allows sufficient thrombin generation for effective haemostasis. Concizumab acts independently from FVIII and FIX.

Endogenous thrombopoietin (TPO) is the main cytokine involved in regulation of megakaryopoiesis and platelet production, and is the endogenous ligand for the TPO-R. Eltrombopag interacts with the transmembrane domain of the human TPO-R and initiates signalling cascades similar but not identical to that of endogenous thrombopoietin (TPO), inducing proliferation and differentiation from bone marrow progenitor cells.

Emicizumab is a humanized monoclonal modified immunoglobulin G4 (IgG4) antibody with a bispecific antibody structure. Emicizumab bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective haemostasis.

Etamsylate is a synthetic antihaemorrhagic and angioprotective drug acting on the first step of haemostasis (endothelium-platelet interaction). By improving platelet adhesiveness and restoring capillary resistance, it is able to reduce bleeding time and blood losses.

Fostamatinib mediates its activity effectively through its major metabolite, R406, which is a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK). R406 inhibits signal transduction of B-cell receptors and Fc-activating receptors, which play a key role in antibody-mediated cellular responses. The fostamatinib metabolite R406 reduces antibody-mediated destruction of platelets.

Lusutrombopag is an orally active TPO receptor agonist. Lusutrombopag acts on the haematopoietic stem cells and on the transmembrane domain of human TPO receptors expressed in megakaryocytes, to stimulate the megakaryocyte to proliferate and differentiate via the similar signal transduction pathway for up-regulating production used by endogenous TPO, thus leading to thrombocytopoiesis.

Marstacimab is a human monoclonal IgG1 antibody directed against the Kunitz domain 2 (K2) of tissue factor pathway inhibitor (TFPI), the primary inhibitor of the extrinsic coagulation cascade. TFPI initially binds to and inhibits the factor Xa active site via its second Kunitz inhibitor domain (K2). The action of marstacimab to neutralise the inhibitory activity of TFPI may serve to enhance the extrinsic pathway and bypass deficiencies in the intrinsic pathway of coagulation by increasing free factor Xa available to increase thrombin generation and promote haemostasis.

Romiplostim is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular transcriptional pathways via the TPO receptor (also known as cMpl) to increase platelet production.