Last update 01 Nov 2024

Antithrombin Deficiency Type 2

Last update 01 Nov 2024

Basic Info

Synonyms

Antithrombin deficiency type 2, 抗凝血酶缺乏症2型

Introduction-

Drugs associated with Antithrombin Deficiency Type 2

Antithrombin alfa

Target

thrombin

Mechanism

thrombin inhibitors

Active Org.-

Originator Org.

rEVO Biologics, Inc.

Active Indication-

Inactive Indication

Acute Lung Injury [+8]

Drug Highest PhaseWithdrawn

First Approval Ctry. / Loc.

EU [+3]

First Approval Date28 Jul 2006

HMB-AT3

Target

thrombin

Mechanism

thrombin inhibitors

Active Org.-

Originator Org.

Hemab Therapeutics ApS

Active Indication-

Inactive Indication

Antithrombin Deficiency Type 2

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Antithrombin Deficiency Type 2

NCT03090893 / WithdrawnEarly Phase 1IIT

A Pilot Study, Prospective, Non-Randomized, Non-Blinded, Single-Center Study Evaluating the Response of Continuous Recombinant Antithrombin (ATryn) Infusion in Postcardiotomy ECMO Patients

The objective of this study will be to prospectively evaluate the response of a continuous infusion of recombinant human antithrombin concentrate (rhAT) (ATRYN®) to achieve and maintain the AT activity within a specified range in adult patients that require extracorporeal membrane oxygenation (ECMO) following cardiopulmonary bypass (CPB) and cardiac surgery.

Start Date01 Jun 2018

Sponsor / Collaborator

Mayo Clinic

[+1]

100 Clinical Results associated with Antithrombin Deficiency Type 2

100 Translational Medicine associated with Antithrombin Deficiency Type 2

0 Patents (Medical) associated with Antithrombin Deficiency Type 2

Literatures (Medical) associated with Antithrombin Deficiency Type 2

13 Sep 2024·Archives of Pathology & Laboratory Medicine

Reduced Plasma Selenoprotein P Is Associated With Type I Antithrombin Deficiency and a Prothrombotic State

Article

Author: Kopytek, Magdalena ; Corral, Javier ; Jankowska, Urszula ; Treliński, Jacek ; Natorska, Joanna ; Klajmon, Adrianna ; Hanarz, Maksymilian ; Skupien-Rabian, Bozena ; Ząbczyk, Michał ; Bravo-Pérez, Carlos ; de la Morena-Barrio, Maria Eugenia

Context.—A positive association between antithrombin activity and selenium level was reported. Selenoprotein P, the most important selenium carrier, was identified within human plasma fibrin clots.Objective.—To investigate the relationship between selenoprotein P and antithrombin and its role in modulation of fibrin clot properties in antithrombin-deficient patients.Design.—Proteomic analysis of plasma fibrin clots was performed with mass spectrometry. In 108 patients with genetically confirmed type I (57%) or type II (43%) antithrombin deficiency and in healthy controls (n = 50), we assessed plasma selenoprotein P levels and thiobarbituric acid–reactive substances by enzyme-linked immunosorbent assay, along with fibrin clot permeability, clot lysis time, and thrombin generation.Results.—Clot-bound antithrombin concentration was 0.46 ± 0.32 mg/g protein, while selenoprotein P level was 30-fold lower (0.015 ± 0.012 mg/g). Type I compared to type II antithrombin-deficient patients had higher clot-bound antithrombin and selenoprotein P levels (both P < .001), associated together (ρ = 0.93, P < .001). Individuals with type I compared to type II antithrombin deficiency or controls had about 40% lower plasma selenoprotein P levels (P < .001). In antithrombin-deficient patients, plasma selenoprotein P was associated with antithrombin antigen (ρ = 0.35, P < .001) and thiobarbituric acid–reactive substances (ρ = 0.42, P < .001). Plasma selenoprotein P correlated also with endogenous thrombin potential (r = −0.33, P < .001), fibrin clot permeability (r = 0.43, P < .001), and clot lysis time (r = −0.40, P < .001) in antithrombin-deficient patients but not in controls.Conclusions.—Patients with type I antithrombin deficiency had higher clot-bound selenoprotein P and reduced plasma selenoprotein P levels. Plasma selenoprotein P was associated with prothrombotic fibrin clot phenotype and enhanced thrombin generation.

01 Mar 2024·Blood Coagulation & Fibrinolysis

Exploring antithrombin: insights into its physiological features, clinical implications and analytical techniques

Review

Author: Saboor, Muhammad ; Hamali, Hassan A. ; Mobarki, Abdullah A. ; Madkhali, Aymen M. ; Dboie, Gasim

Antithrombin is an essential protein that acts as a natural anticoagulant in the human body. It is synthesized by the liver and belongs to the serine protease inhibitors, which are commonly referred to as the SERPINS superfamily. The antithrombin molecule comprises 432 amino acids and has a molecular weight of approximately 58 200 D. It consists of three domains, including an amino-terminal domain, a carbohydrate-rich domain, and a carboxyl-terminal domain. The amino-terminal domain binds with heparin, whereas the carboxyl-terminal domain binds with serine protease. Antithrombin is a crucial natural anticoagulant that contributes approximately 60–80% of plasma anticoagulant activities in the human body. Moreover, antithrombin has anti-inflammatory effects that can be divided into coagulation-dependent and coagulation-independent effects. Furthermore, it exhibits antitumor activity and possesses a broad range of antiviral properties. Inherited type I antithrombin deficiency is a quantitative disorder that is characterized by low antithrombin activity due to low plasma levels. On the other hand, inherited type II antithrombin deficiency is a qualitative disorder that is characterized by defects in the antithrombin molecule. Acquired antithrombin deficiencies are more common than hereditary deficiencies and are associated with various clinical conditions due to reduced synthesis, increased loss, or enhanced consumption. The purpose of this review was to provide an update on the structure, functions, clinical implications, and methods of detection of antithrombin.

01 Sep 2023·Thrombosis and haemostasis

Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.

Article

Author: Natorska, Joanna ; Corral, Javier ; Bagoly, Zsuzsa ; de la Morena-Barrio, Maria Eugenia ; Klajmon, Adrianna ; Ząbczyk, Michał ; Witkowski, Michał ; Undas, Anetta ; Treliński, Jacek ; Bereczky, Zsuzsanna ; Bravo-Pérez, Carlos

BACKGROUNDDeficiency of antithrombin increases risk of venous thromboembolism. We hypothesized that antithrombin deficiency affects fibrin clot structure and function.METHODSWe evaluated 148 patients (age: 38 [32-50] years; 70% women) with genetically confirmed antithrombin deficiency and 50 healthy controls. Fibrin clot permeability (K_s) and clot lysis time (CLT) along with thrombin generation capacity were assessed before and after antithrombin activity normalization in vitro.RESULTSAntithrombin-deficient patients had lower antithrombin activity (-39%) and antigen levels (-23%) compared with controls (both p < 0.01). Prothrombin fragment 1 + 2 levels were 26.5% higher in patients with antithrombin deficiency than in controls along with 94% increased endogenous thrombin potential (ETP) and 108% higher peak thrombin (all p < 0.01). Antithrombin deficiency was associated with 18% reduced K_s and 35% prolonged CLT (both p < 0.001). Patients with type I (n = 65; 43.9%) compared with type II antithrombin deficiency (n = 83; 56.1%) had 22.5% lower antithrombin activity (p < 0.001) and despite similar fibrinogen levels, 8.4% reduced K_s, 18% prolonged CLT, and 30% higher ETP (all p < 0.01). Reduced K_s was associated with lower antithrombin antigen level (β = - 6.1, 95% confidence interval [CI]: -1.7 to -10.5), while prolonged CLT was associated with lower antithrombin antigen (β = - 69.6, 95% CI: -9.6 to -129.7), activity (β = - 2.4, 95% CI: -0.3 to -4.5), higher PAI-1 (β = 12.1, 95% CI: 7.7-16.5), and thrombin-activatable fibrinolysis inhibitor levels (β = 3.8, 95% CI: 1.9-5.7). Addition of exogenous antithrombin reduced ETP (-42%) and peak thrombin (-21%), and improved K_s (+8%) and CLT (-12%; all p < 0.01).CONCLUSIONOur study suggests that enhanced thrombin generation and prothrombotic plasma fibrin clot phenotype can contribute to increased risk of thrombosis in patients with antithrombin deficiency.

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Antithrombin Deficiency Type 2

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