Background To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands).
Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2). This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting loadbearing defects in trauma and orthopaedic surgery.
To cite this article: Emonts M, de Bruijne ELE, Guimarã es AHC, Declerck PJ, Leebeek FWG, de Maat MPM, Rijken DC, Hazelzet JA, Gils A.Thrombin activatable fibrinolysis inhibitor is associated with severity and outcome of severe meningococcal infection in children. J Thromb Haemost 2008; 6: 268-76.Summary. Background and objectives: In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis. Patients and methods: Children with severe meningococcal sepsis (n = 112) previously included in Rotterdam-based trials participated in this study. Clinical and laboratory parameters and severity scores were assessed. TAFI and TAFI activation markers were determined: TAFI activation peptide (TAFI-AP) and (in)activated TAFI [TAFIa(i)]. The -438G/A, Ala147Thr, and Thr325Ile polymorphisms were genotyped. Results: TAFI levels were significantly decreased in patients with meningococcal disease at admission compared to the convalescence state. TAFI was decreased in patients with septic shock vs. those with no shock. TAFI-AP levels were increased in patients with disseminated intravascular coagulation (DIC) vs. patients without DIC. TAFI-AP and TAFIa(i) were significantly increased in non-survivors vs. survivors. TAFI-AP levels and the TAFI-AP/TAFI ratio were also strongly correlated to severity scores and laboratory parameters. The TAFI 325Ile/Ile genotype was overrepresented in patients with DIC. Conclusions: Activation markers of TAFI were associated with the occurrence of DIC and mortality in meningococcal sepsis patients. A determination of TAFI, TAFI-AP, and TAFIa(i) is required to enable coherent interpretation of the role of TAFI in disease.
To cite this article: de Maat MPM, Jansen MWJC, Hille ETM, Vos HL, Bloemenkamp KWM, Buitendijk S, Helmerhorst FM, Wladimiroff JW, Bertina RM, de Groot CJM. Preeclampsia and its interaction with common variants in thrombophilia genes. J Thromb Haemost 2004; 2: 1588-93.Summary. Recently, it has been proposed that abnormalities in coagulation and fibrinolysis contribute to the development of preeclampsia by increasing the thrombotic tendency. This hypothesis was tested in women who have had preeclampsia (cases) compared with matched controls. Polymorphisms in the thrombophilia genes {plasminogen activator inhibitor type 1 [PAI-1 )675(4G/5G)], thrombin activatable fibrinolysis inhibitor (TAFI )438G/A and 1040C/T), methylenetetrahydrofolate reductase (MTHFR 677C/T), factor V (FV Leiden R/Q506), prothrombin (FII 20210G/A) and factor XIIIA (FXIIIA V/ L34)} were determined in 157 women with preeclampsia and 157 women with uncomplicated pregnancy. The associated risk of preeclampsia was analyzed using logistic regression methods. The frequency distributions of the genotypes of these six polymorphisms in thrombophilia genes were similar in the case and control groups. We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with controls, which makes it unlikely that these polymorphisms are risk factors for preeclampsia.
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