ATC Group: B02B Vitamin K and other hemostatics

Adrenalone is a keton form of the natural substrate epinephrine. an adrenergic agonist that mainly acts on alpha-1 adrenergic receptors and has little affinity for beta receptors. Adrenalone inhibits the norepinephrine synthesis and dopamine beta oxidase. It is known to have very weak sympathomimetic activity when compared to adrenaline. Adrenalone has the high radioprotective effect. It is a topical nasal decongestant. Adrenalone has hemostatic, sympathomimetic and vasoconstrictor therapeutic functions.

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.

Factor IX is a single chain glycoprotein with a molecular mass of about 68,000 Dalton. It is a vitamin-K dependent coagulation factor and it is synthesised in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation pathway and by the factor VII/tissue factor complex in the extrinsic pathway. Activated factor IX, in combination with activated factor VIII, activates factor X.

Pharmacological doses of rFVIIa activate factor X directly on the surface of activated platelets, localized to the site of injury, independently of tissue factor. This results in the conversion of prothrombin into large amounts of thrombin independently of tissue factor.

Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X (factor Xa). Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C. By replacement therapy the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Coagulation factor X is derived from human plasma and used as a replacement for the naturally existing coagulation factor X in patients with hereditary factor X deficiency.

Factor XIII connects the amino group of lysine with glutamine via its enzymatic function (transamidase activity), thereby leading to the cross-linking of fibrin molecules. This is the final stage of blood coagulation. Fibrin cross-linking and stabilisation promote the penetration of fibroblasts and support wound healing.

Eftrenonacog alfa is a long-acting, fully recombinant, fusion protein comprising human coagulation factor IX covalently linked to the Fc domain of human immunoglobulin G1, and produced by recombinant DNA technology. Haemophilia B is an X-linked hereditary disorder of blood coagulation due to decreased levels of factor IX and results in bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. By replacement therapy the plasma level of factor IX is increased thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

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.

Epinephrine is a direct acting sympathomimetic agent, which exerts effects on both α and β adrenoceptors. It has more pronounced effects on β than on α adrenoceptors, although α effects prevail at high doses. The effects of adrenaline include increased rate and force of cardiac contraction, cutaneous vasoconstriction and broncho-dilatation.

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.

Etranacogene dezaparvovec is a gene therapy product designed to introduce a copy of the human Factor IX coding DNA sequence into hepatocytes to address the root cause of the Haemophilia B disease. Etranacogene dezaparvovec partially or completely ameliorates the deficiency of circulating Factor IX procoagulant activity in patients with Haemophilia B.

Fidanacogene elaparvovec is a gene therapy designed to introduce in the transduced cells a functional copy of the factor IX gene encoding a high-activity FIX variant (FIX-R338L, hFIX Padua). The AAVRh74var capsid is able to transduce hepatocytes, the natural site of factor IX synthesis. Single intravenous infusion of fidanacogene elaparvovec results in cell transduction and increase in circulating factor IX activity in patients with hemophilia B.

Fostamatinib is a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (SYK), through its major metabolite R406. R406 reduces antibody-mediated destruction of platelets. Fostamatinib is indicated for the treatment of chronic immune thrombocytopenia (ITP) in adult patients.

Human fibrinogen (coagulation factor I), in the presence of thrombin, activated coagulation factor XIII (F XIIIa) and calcium ions is converted into a stable and elastic three-dimensional fibrin haemostatic clot. The administration of human fibrinogen concentrate provides an increase in plasma fibrinogen level and can temporarily correct the coagulation defect of patients with fibrinogen deficiency.

Lonoctocog alfa is a recombinant human protein that replaces the missing coagulation factor VIII needed for effective hemostasis. Lonoctocog alfa is a single polypeptide chain with a truncated B-domain that allows for a covalent bridge to link the factor VIII heavy and light chains. Lonoctocog alfa has demonstrated a higher VWF affinity relative to full-length rFVIII. VWF stabilizes factor VIII and protects it from degradation. Activated lonoctocog alfa has an amino acid sequence identical to endogenous FVIIIa.

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.

Moroctocog alfa is a B-domain deleted recombinant coagulation factor VIII. Moroctocog alfa has functional characteristics comparable to those of endogenous factor VIII. Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C. By replacement therapy, the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Nonacog alfa is a recombinant coagulation factor IX. Recombinant coagulation factor IX is a recombinant DNA-based protein therapeutic which has structural and functional characteristics comparable to endogenous factor IX. Haemophilia B is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor IX. By replacement therapy the plasma levels of factor IX is increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Octocog alfa (Full length recombinant human coagulation factor VIII (rDNA)) is a purified protein that has 2,332 amino acids. It is produced by recombinant DNA technology in baby hamster kidney cells (BHK) into which the human factor VIII gene has been introduced.

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.

Rurioctocog alfa pegol, is a pegylated recombinant human factor VIII with an extended half-life. Rurioctocog alfa pegol is a covalent conjugate of octocog alfa consisting of 2,332 amino acids with polyethylene glycol (PEG) reagent (MW 20 kDa). The therapeutic activity of rurioctocog alfa pegol is derived from octocog alfa, which is produced by recombinant DNA technology from a Chinese hamster ovary cell line. Octocog alfa is then covalently conjugated with the PEG reagent. The PEG moiety is conjugated to octocog alfa to increase the plasma half-life.

Susoctocog alfa is a recombinant, B-domain deleted, porcine sequence Factor VIII. It is a glycoprotein. Acquired haemophilia is a rare bleeding disorder in which patients with normal Factor VIII genes develop inhibitory autoantibodies directed against Factor VIII. These autoantibodies neutralize circulating human Factor VIII thus creating a deficiency of available Factor VIII. Susoctocog alfa temporarily replaces the inhibited endogenous Factor VIII that is needed for effective haemostasis.

Valoctocogene roxaparvovec is an adeno-associated virus serotype 5 (AAV5) based gene therapy vector causing the expression of the B-domain deleted SQ form of a recombinant human factor VIII (hFVIII-SQ) under the control of a liver-specific promoter. The expressed hFVIII-SQ replaces the missing coagulation factor VIII needed for effective haemostasis.

The presence of vitamin K (i.e. vitamin K or substances with vitamin K activity) is essential for the formation within the body of prothrombin, factor VII, factor IX and factor X. Lack of vitamin K leads to an increased tendency to haemorrhage. When an antidote to an anticoagulant is necessary it is essential to use vitamin K₁ itself, as vitamin K analogues are much less effective.

Administration of von Willebrand factor allows correction of the haemostatic abnormalities exhibited by patients who suffer from von Willebrand factor deficiency.