Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

Ambroziak, Michał; Kuryłowicz, Alina; Budaj, Andrzej

doi:10.1007/s11239-019-01856-3

Cited by 12 publications

(12 citation statements)

References 31 publications

(33 reference statements)

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“…In the current study the allele frequency of FXIII Val34Leu polymorphism was not significantly different between patients and controls. This is consistent with some European studies on premature MI [ 34 , 35 ], but is contrary to others, including a meta-analysis suggesting that it had an unexplained protective role in young MI patients as compared to healthy controls [ 36 – 38 ].…”

Section: Resultssupporting

confidence: 91%

Genetic polymorphisms in early-onset myocardial infarction in a sample of Iraqi patients: a pilot study

et al. 2020

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Objectives Early-onset myocardial infarction constitutes nearly one third of cases of myocardial infarction among Iraqis, which is rather higher than the proportions reported in many Western countries. Thus this study was initiated to investigate the role of some genetic polymorphisms, as well as acquired risk factors in this condition. Results A total of 102 Iraqi patients with first myocardial infarction aged 50 years, and 77 matched controls were enrolled. The DNAs of participants were screened for nine polymorphisms, namely: β-Fibrinogen (− 455G > A), Factor XIII (V34L), Plasminogen Activator inhibitor-1 (PAI-1, 4G/5G), Human Platelet Antigen-1 (HPA1a/b), 5,10-Methylenetetrahydrofolate Reductase MTHFR (C677T) and MTHFR (A1298C), Angiotensin-Converting Enzyme (ACE) 287 bp insertion/deletion (I/D), Apolipoprotein-B (ApoB: R3500Q), and Apolipoprotein-E (Apo E: E2/E3/E4), using PCR and reverse hybridization technique. Among traditional risk factors, univariate analysis revealed that smoking (OR 2.86 [95%CI 1.53–5.34]), hyperlipidemia (OR 5.23 [95%CI 2.66–10.29]), and diabetes mellitus (OR 4.05 [95% CI 1.57–10.41]) were significantly higher among patients compared to controls (P<0.001, <0.001 and 0.002 respectively), while none of the nine genetic polymorphisms reached significance. Multivariate Logistic regression, however, revealed that only smoking and hyperlipidemia retained significance (P of < 0.001 each). The need to initiate further studies on larger cohorts is paramount to understand the higher than expected frequency of early-onset myocardial infarction in our population.

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Section: Resultssupporting

confidence: 91%

Genetic polymorphisms in early-onset myocardial infarction in a sample of Iraqi patients: a pilot study

et al. 2020

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“…Abnormal FXIIIa appears to cause thrombotic states such as cardiovascular diseases. 18,49,50 The same abnormal activity has been reported in cancer patients. 17,20 A study in non-small cell lung cancer found that FXIIIa levels in advanced-stage patients are higher than those in healthy controls.…”

Section: Discussionsupporting

confidence: 77%

<p>Clinical Significance of Factor XIII Activity and Monocyte-Derived Microparticles in Cancer Patients</p>

Sawai¹,

Yamanaka²,

Nomura³

2020

VHRM

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Background: The aim was to evaluate factor XIII activity (FXIIIa) and monocyte-derived microparticles (MDMPs) in cancer patients. Methods: In total, 138 cancer patients (31 malignant lymphomas, 39 multiple myelomas, and 68 lung cancers) were analyzed. We measured various biomarkers including FXIIIa and MDMPs. Results: The values of endothelial activation markers, monocyte chemoattractant peptide (MCP)-1, soluble (s)CD14, and MDMPs were higher in cancer patients than in noncancerous controls. MCP-1, sCD14, and MDMPs were significantly correlated with FXIIIa in multivariate analysis in cancer patients. In addition, MCP-1, sCD14, and MDMP levels were significantly increased in the high FXIIIa group of patients. Finally, the survival rate of the high FXIIIa group was significantly poor in the Kaplan-Meier analysis. Conclusion: These results suggest that abnormal levels of FXIIIa and MDMPs may offer promise as poor prognostic factors in cancer patients.

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“…This might represent a missing biochemical link related to clinical observations on the role of FXIII in acute thrombotic events. It has been published that elevated FXIII levels increase the risk of myocardial infarction in young adults and particularly in women [37][38][39]. Reduced fibrinolytic capacity has been defined as a risk factor for myocardial infarction and stroke in young patients, but the exact mechanisms have not been identified as yet [40,41].…”

Section: Discussionmentioning

confidence: 99%

Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

et al. 2021

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Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

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Increased coagulation factor XIII activity but not genetic variants of coagulation factors is associated with myocardial infarction in young patients

Cited by 12 publications

References 31 publications

Genetic polymorphisms in early-onset myocardial infarction in a sample of Iraqi patients: a pilot study

Genetic polymorphisms in early-onset myocardial infarction in a sample of Iraqi patients: a pilot study

<p>Clinical Significance of Factor XIII Activity and Monocyte-Derived Microparticles in Cancer Patients</p>

Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

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