Thrombin generation in pediatric patients with Crohnʼs disease

Bernhard, Heike; Deutschmann, Andrea; Leschnik, B.; Schweintzger, Sabrina; Novak, M. John; Hauer, A.; Muntean, W.

doi:10.1002/ibd.21631

Cited by 30 publications

(30 citation statements)

References 20 publications

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“…PLT plays a vital role in the physiology of primary hemostasis and in the pathophysiological activity of arterial thrombosis. Over the past decades it has been demonstrated that PLT also plays a crucial role in the pathophysiology of inflammation, especially invascular inflammation . PLT interacts with leukocytes, small muscle cells (SMCs) and endothelial cells, and secretes a large amount of cytokines and chemokines, thereby, initiates and propagates the inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…The sensitivity and specificity of these parameters are not quite satisfactory, especially in patients with relatively low high‐sensitivity CRP (hs‐CRP) levels, while the disease may be remarkably active as verified by the Crohn's disease activity index (CDAI) and endoscopy. There is emerging evidence that platelet (PLT) may play a role in the pathogenesis of CD . PLT value can be obtained from the routine complete blood count, which is less invasive with a lower cost compared with the abovementioned methods.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plateletcrit: A sensitive biomarker for evaluating disease activity in Crohn's disease with low hs‐CRP

Tang

Gao

Mao

et al. 2015

J of Digest Diseases

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plateletcrit: A sensitive biomarker for evaluating disease activity in Crohn's disease with low hs‐CRP

Tang

Gao

Mao

et al. 2015

J of Digest Diseases

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“…10 In addition, the role of thrombin generation extends far beyond the sole coagulation system. Several recent findings have emphasized its key impact in atherosclerosis, 11 diabetic nephropathy, 12,13 and inflammatory diseases such as sepsis, 14 Crohn disease, 15 and sickle cell disease. 16 Altogether these observations clearly emphasize the importance of identifying factors controlling the interindividual variability of thrombin generation.…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

Rocañín-Arjó

Cohen

Carcaillon

et al. 2014

Blood

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Key Points• Genetic variations at the ORM1 locus and concentrations of the encoded protein associate with thrombin generation.• These findings may guide the development of novel antithrombotic treatments.Thrombin, the major enzyme of the hemostatic system, is involved in biological processes associated with several human diseases. The capacity of a given individual to generate thrombin, called the thrombin generation potential (TGP), can be robustly measured in plasma and was shown to associate with thrombotic disorders. To investigate the genetic architecture underlying the interindividual TGP variability, we conducted a genome-wide association study in 2 discovery samples (N 5 1967) phenotyped for 3 TGP biomarkers, the endogenous thrombin potential, the peak height, and the lag time, and replicated the main findings in 2 independent studies (N 5 1254). We identified the ORM1 gene, coding for orosomucoid, as a novel locus associated with lag time variability, reflecting the initiation process of thrombin generation with a combined P value of P 5 7.1 3 10 215 for the lead single nucleotide polymorphism (SNP) (rs150611042). This SNP was also observed to associate with ORM1 expression in monocytes (P 5 8.7 3 10 210 ) and macrophages (P 5 3.2 3 10 23 ). In vitro functional experiments further demonstrated that supplementing normal plasma with increasing orosomucoid concentrations was associated with impaired thrombin generation. These results pave the way for novel mechanistic pathways and therapeutic perspectives in the etiology of thrombin-related disorders. (Blood. 2014;123(5):777-785)

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“…Çocukluk çağı ülseratif kolit hastalığına bağlı beyin ven trombozu / Cerebral venous thrombosis associated with childhood ulcerative colitis artış ve azalmış antitrombin III düzeyi bildirilmektedir (12). Yine aktif hastalık döneminde belirgin olarak artan endojen trombin potansiyeli trombin oluşumunu hızlandırarak doğal antikoagülan yollarda işlev bozukluğuna neden olur ve tromboza eğilimi arttırır (13,14). Tüm bunlara ek olarak tümör nekrozis faktör α üretiminde artış (15), bağırsaktaki glikozaminoglikan üretiminde azalma da prokoagülan etki yapabilir (16).…”

Section: Discussionunclassified

Çocukluk çağı ülseratif kolit hastalığına bağlı beyin ven trombozu

Kutluk¹,

Hacıfazlıoğlu²,

Horozoğlu³

et al. 2013

Tpa

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ÖzetBeyin ven trombozu çocuklarda enflamatuar bağırsak hastalığının; özellikle ülseratif kolitin seyri sırasında gelişebilen nadir ancak önemli bir komplikasyondur. Dokuz yaşında kanlı, mukuslu dışkılama ve beraberinde gelişen şiddetli başağrısı yakınması ile gelen ülseratif kolit ile aynı anda beyin ven trombozu tanısı alan bir olgu sunuldu. Dokuz yaşında erkek hasta üç haftadır süren kanlı ve mukuslu dışkılama nedeni ile başvurdu. Tetkiklerinde anemi, lökositoz, trombositoz ve yüksek eritrosit çökme hızı saptanan hastanın kolonoskopik incelemesinde yaygın ülserler ile seyreden pankolit görüldü ve tanı histopatolojik inceleme ile ülseratif kolit olarak kesinleştirildi. Kolonoskopiden bir gün sonra sürekli, zonklar tarzda, frontal ve sol oksipital bölgeye yerleşik başağrısı yakınması gelişen hastanın nörolojik değerlendirilmesinde sol göz kapağında pupil seviyesinde pitoz, her iki göz dibinde birinci derece papil ödem saptandı. Kraniyal manyetik rezonans görüntüleme ve manyetik rezonans venografi incelemesinde sol transvers ve sigmoid sinüsde tromboz saptanan hastaya antikoagülan tedavi ile ülseratif kolit için mesalamin ve steroid başlandı. Trombofili açısından da değerlendirilen hastanın protein C, protein S, antitrombin III, faktör VIII, homosistein, protrombin II and fibrinojen düzeyleri normal sınırlarda; metilen tetrahidrofolat redüktaz gen mutasyonu ise heterozigot pozitif saptandı. Tedavinin ikinci haftasında kanlı dışkılaması kontrol altına alınan hastanın başağrısı azaldı, papilödem ve pitozu kayboldu. Mesalamin, prednisolon, azatiyopürin ve düşük molekül ağırlıklı heparin ile tedavisi devam ettirilen olgumuzda tedavinin birinci yılında manyetik rezonans venografi incelemesinde trombozda radyolojik açıdan artma yada düzelme izlenmedi. (Türk Ped Arfl 2013; 48: 160-4) Anahtar sözcükler: Beyin ven trombozu, komplikasyon, ülseratif kolit Summary Ulcerative colitis (UC) can be complicated by various extra-intestinal manifestations such as thromboembolic disease. Most thrombotic events occure in lower extremities, whereas the incidence of cerebral venous involvement is very rare and serious in children. We present a case of a nine years old boy with UC and cerebral venous thrombosis diagnosed at the same time. A nine years old boy with a 3week history of bloody diarrhea and abdominal pain was admitted to our hospital. On admission his laboratory data showed anemia, leukocytosis , thrombocytosis and elevated erythrocyte sedimentation rate. Colonoscopic evaluation revealed severe active pancolitis with diffuse ulceration. The day after colonoscopy he had complained of severe headache. Neurolological examination revealed pitosis of the left palpebra and bilateral papilledema. Magnetic resonance (MR) imaging and MR venography revealed thrombosis in the left transvers sinus and sigmoid sinus. The patient was treated immediatly with heparin. At the same time he was diagnosed with severe active UC based upon histopathological findings and managed initially with mesalamin and prednisolon. He also had been screened...

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Thrombin generation in pediatric patients with Crohnʼs disease

Abstract: Our study clearly shows that the active state of CD in children is associated with the potential for high thrombin generation, but this seems to be caused mainly by the inflammatory process and not by a preexisting propensity for high thrombin generation.

Cited by 30 publications

References 20 publications

Plateletcrit: A sensitive biomarker for evaluating disease activity in Crohn's disease with low hs‐CRP

Plateletcrit: A sensitive biomarker for evaluating disease activity in Crohn's disease with low hs‐CRP

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

Çocukluk çağı ülseratif kolit hastalığına bağlı beyin ven trombozu

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