Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment

Pitkänen, Hanna; Kärki, Mari; Niinikoski, Harri; Tanner, Laura M.; Näntö‐Salonen, Kirsti; Pikta, Marika; Kopatz, Wil F.; Zuurveld, Marleen; Meijers, Joost C. M.; Brinkman, Herm Jan M.; Lassila, Riitta

doi:10.1111/hae.13543

Cited by 13 publications

(9 citation statements)

References 48 publications

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“…Indeed, it could be that patients with the most decreased Fg activity have significantly higher ETP and peak height, and shortened lag time when challenged to low concentration of TF. Furthermore, in vivo TG was enhanced in patients with lower Fg levels, as occurs in a rare metabolic genetic disorder of lysinuric protein intolerance, LPI [21]. However, the clinical phenotype failed to be associated with TG variables.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, abnormal structure of fibrin paradoxically increases thrombotic risk by impairing fibrin degradation by plasmin or facilitating clot fragmentation [18,19] and even enhancing TG due to poorly polymerizing fibrin [20]. Therefore, TG and other coagulation activation markers, such as prothrombin activation fragments, fibrin structure and consequences of the fibrinolytic system are of particular interest in CFD [21].…”

Section: Discussionmentioning

confidence: 99%

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Whole Blood Thromboelastometry by ROTEM and Thrombin Generation by Genesia According to the Genotype and Clinical Phenotype in Congenital Fibrinogen Disorders

Szántó

Lassila

Lemponen

et al. 2021

IJMS

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The outcome of congenital fibrinogen defects (CFD) is often unpredictable. Standard coagulation assays fail to predict the clinical phenotype. We aimed to assess the pheno- and genotypic associations of thrombin generation (TG) and ROTEM in CFD. We measured fibrinogen (Fg) activity and antigen, prothrombin fragments F1+2, and TG by ST Genesia® with both Bleed- and ThromboScreen in 22 patients. ROTEM was available for 11 patients. All patients were genotyped for fibrinogen mutations. Ten patients were diagnosed with hypofibrinogenemia, nine with dysfibrinogenemia, and three with hypodysfibrinogenemia. Among the 17 mutations, eight were affecting the Fg γ chain, four the Fg Bβ chain, and five the Fg Aα chain. No statistical difference according to the clinical phenotypes was observed among FGG and FGA mutations. Median F1+2 and TG levels were normal among the different groups. Fg levels correlated negatively with F1+2 and peak height, and positively with lag time and time to peak. The pheno- and genotypes of the patients did not associate with TG. FIBTEM by ROTEM detected hypofibrinogenemia. Our study suggests an inverse link between low fibrinogen activity levels and enhanced TG, which could modify the structure–function relationship of fibrin to support hemostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Whole Blood Thromboelastometry by ROTEM and Thrombin Generation by Genesia According to the Genotype and Clinical Phenotype in Congenital Fibrinogen Disorders

Szántó

Lassila

Lemponen

et al. 2021

IJMS

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“…Once this inhibition is lifted, cytokines are produced and released in large amounts. Besides, bleeding events were reported in some cases (7). Patients do not have spontaneous bleeding tendency but mucocutaneous bleeds can be triggered by invasive and surgical interventions or postpartum.…”

Section: Slc7a7 Deficiencymentioning

confidence: 99%

Novel Discoveries in Immune Dysregulation in Inborn Errors of Immunity

et al. 2021

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With the expansion of our knowledge on inborn errors of immunity (IEI), it gradually becomes clear that immune dysregulation plays an important part. In some cases, autoimmunity, hyperinflammation and lymphoproliferation are far more serious than infections. Thus, immune dysregulation has become significant in disease monitoring and treatment. In recent years, the wide application of whole-exome sequencing/whole-genome sequencing has tremendously promoted the discovery and further studies of new IEI. The number of discovered IEI is growing rapidly, followed by numerous studies of their pathogenesis and therapy. In this review, we focus on novel discovered primary immune dysregulation diseases, including deficiency of SLC7A7, CD122, DEF6, FERMT1, TGFB1, RIPK1, CD137, TET2 and SOCS1. We discuss their genetic mutation, symptoms and current therapeutic methods, and point out the gaps in this field.

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“…To assess clot lysis, optical density of clotting plasma, triggered with tissue factor, was measured in the presence of tissue plasminogen activator to induce fibrinolysis. This technique has previously been described 11 . Clot lysis time is defined as the time between the maximal rate of fibrin generation and the maximal rate of clot lysis.…”

Section: Study Design and Outcomesmentioning

confidence: 99%

Transient ST-elevation myocardial infarction versus persistent ST-elevation myocardial infarction. An appraisal of patient characteristics and functional outcome

Janssens

Lemkes

Hoeven

et al. 2021

International Journal of Cardiology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment

Cited by 13 publications

References 48 publications

Whole Blood Thromboelastometry by ROTEM and Thrombin Generation by Genesia According to the Genotype and Clinical Phenotype in Congenital Fibrinogen Disorders

Whole Blood Thromboelastometry by ROTEM and Thrombin Generation by Genesia According to the Genotype and Clinical Phenotype in Congenital Fibrinogen Disorders

Novel Discoveries in Immune Dysregulation in Inborn Errors of Immunity

Transient ST-elevation myocardial infarction versus persistent ST-elevation myocardial infarction. An appraisal of patient characteristics and functional outcome

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