Clinical and laboratory characteristics of antithrombin deficiencies: A large cohort study from a single diagnostic center

Gindele, Réka; Selmeczi, Anna; Oláh, Zsolt; Ilonczai, Péter; Paragh, György; Marján, E; Nemes, L.; Nagy, Ágnes; Losonczy, Hajna; Mitić, Gorana; Kovač, Mirjana; Balogh, Gábor; Komáromi, István; Schlammadinger, Ágota; Rázsó, Katalin; Boda, Zoltán; Muszbek, László; Bereczky, Zsuzsanna

doi:10.1016/j.thromres.2017.10.023

Cited by 19 publications

(24 citation statements)

References 42 publications

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“…60 In a Hungarian cohort of 246 AT-deficient individuals, ATE was associated more often with AT Basel (43%) and ATBp3 (10.5%) than with type I AT deficiency; the median age at first presentation was only 29 years in AT Basel and 33 years in AT Bp3 heterozygotes. 89 In this cohort, ATE was reported in 3 children; 2 of them had IS and in one of them both MI and IS were found in the case history. In 2 smaller cohort studies involving 26 patients from southern Italy, only 4 patients were registered with type IIHBS AT deficiency and one of them had IS.…”

Section: Resultsmentioning

confidence: 66%

“…In this field, large cohort studies of 5 study groups are available. 60,63,[88][89][90] In the study by Alhenc-Gelas et al, 88 330 probands in France with AT deficiency and their relatives were recruited, and the prevalence of ATE was 4.8% in the whole population at a mean age of 38 years at the first presentation. The frequency of ATE was somewhat higher in type IIHBS (ATBp3, AT Basel, and AT Toyama), as compared with other types.…”

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confidence: 99%

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Inherited thrombophilia and the risk of myocardial infarction: current evidence and uncertainties

2019

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thrombophilia and the risk of myocardial infarction 419 large arteries, sometimes with coexistent VTE, and linked the events to hypercoagulability of the patients' plasma. 2,3 Some decades later, research on thrombophilia expanded by investigating families with frequent or unusual events of VTE. Today, due to this field of extensive research, the term thrombophilia is used to describe a hemostasis disorder leading to an elevated risk of developing VTE that can be inherited, acquired, or both. The well-established factors of inherited thrombophilia are as follows: different loss-of-function mutations of the inhibitors of plasma coagulation that cause deficiencies of antithrombin (AT), protein C (PC), and protein

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Section: Resultsmentioning

confidence: 66%

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confidence: 99%

Inherited thrombophilia and the risk of myocardial infarction: current evidence and uncertainties

2019

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“…The AT Budapest 3 (ATBp3) mutation leads to changes in the type II heparin-binding site (IIHBS) and, subsequently, to a functional AT deficiency due to decreased heparin-AT interactions. This was shown to be associated with an increased risk for thrombosis [11,12].…”

Section: Overviewmentioning

confidence: 99%

Antithrombin and Its Role in Host Defense and Inflammation

Schlömmer

Brandtner

Bachler

2021

IJMS

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Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects: depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.

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“…Thrombosis was diagnosed and categorized into spontaneous and provoked according to guidance of the International Society of Thrombosis and Haemostasis (48). Clinical and laboratory data were collected as previously described (13). Patient clinical, laboratory, and genetic data were recorded in a database for further evaluation.…”

Section: Patients' Groups Recruited For the Investigation Of The Association Between Type Iihbs At Deficiency And Thrombotic Diseasesmentioning

confidence: 99%

“…The different AT deficiency subtypes, however, do not have the same clinical phenotype, and based on the results of some clinical studies, type IIHBS deficiency seems to exert a lower thrombotic risk (10)(11)(12). Additionally, the situation is even more complicated, since type IIHBS homozygotes present the most severe thrombotic symptoms among all AT-deficient patients (13). The first-line laboratory assay in the diagnosis of AT deficiency is a functional amidolytic test in which the inhibitory effect of AT on active FXa or thrombin is investigated in the presence of heparin (14,15).…”

Section: Introductionmentioning

confidence: 99%

Age and Origin of the Founder Antithrombin Budapest 3 (p.Leu131Phe) Mutation; Its High Prevalence in the Roma Population and Its Association With Cardiovascular Diseases

Bereczky

Gindele

Fiatal

et al. 2021

Front. Cardiovasc. Med.

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Background: Antithrombin (AT) is one of the most important regulator of hemostasis. AT Budapest 3 (ATBp3) is a prevalent type II heparin-binding site (IIHBS) deficiency due to founder effect. Thrombosis is a complex disease including arterial (ATE) and venous thrombotic events (VTE) and the Roma population, the largest ethnic minority in Europe has increased susceptibility to these diseases partly due to their unfavorable genetic load. We aimed to calculate the age and origin of ATBp3 and to explore whether the frequency of it is higher in the Roma population as compared with the general population from the corresponding geographical area. We investigated the association of ATBp3 with thrombotic events in well-defined patients' populations in order to refine the recommendation when testing for ATBp3 is useful.Methods and Results: Prevalence of ATBp3, investigated in large samples (n = 1,000 and 1,185 for general Hungarian and Roma populations, respectively) was considerably high, almost 3%, among Roma and the founder effect was confirmed in their samples, while it was absent in the Hungarian general population. Age of ATBp3—as calculated by analysis of 8 short tandem repeat sequences surrounding SERPINC1—was dated back to XVII Century, when Roma migration in Central and Eastern Europe occurred. In our IIHBS cohort (n = 230), VTE was registered in almost all ATBp3 homozygotes (93%) and in 44% of heterozygotes. ATE occurred with lower frequency in ATBp3 (around 6%); it was rather associated with AT Basel (44%). All patients with ATE were young at the time of diagnosis. Upon investigating consecutive young (<40 years) patients with ATE (n = 92) and VTE (n = 110), the presence of ATBp3 was remarkable.Conclusions: ATBp3, a 400-year-old founder mutation is prevalent in Roma population and its Roma origin can reasonably be assumed. By the demonstration of the presence of ATBp3 in ATE patients, we draw the attention to consider type IIHBS AT deficiency in the background of not only VTE but also ATE, especially in selected populations as young patients without advanced atherosclerosis. We recommend including the investigation of ATBp3 as part of thrombosis risk assessment and stratification in Roma individuals.

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Clinical and laboratory characteristics of antithrombin deficiencies: A large cohort study from a single diagnostic center

Cited by 19 publications

References 42 publications

Inherited thrombophilia and the risk of myocardial infarction: current evidence and uncertainties

Inherited thrombophilia and the risk of myocardial infarction: current evidence and uncertainties

Antithrombin and Its Role in Host Defense and Inflammation

Age and Origin of the Founder Antithrombin Budapest 3 (p.Leu131Phe) Mutation; Its High Prevalence in the Roma Population and Its Association With Cardiovascular Diseases

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