Emonts M, de Bruijne E L E, Guimarães A H C, Declerck P J, Leebeek F W G, de Maat M P M, Rijken D C, Hazelzet J A, Gils A
Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands.
J Thromb Haemost. 2008 Feb;6(2):268-76. doi: 10.1111/j.1538-7836.2008.02841.x. Epub 2007 Nov 15.
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.
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.
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.
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.
在儿童脑膜炎球菌败血症中，凝血与纤溶失衡以及促炎作用发挥着主要作用。我们推测凝血酶激活的纤溶抑制物（TAFI）和/或TAFI激活标志物参与了脑膜炎球菌败血症的发病机制。
先前纳入鹿特丹相关试验的112例重症脑膜炎球菌败血症患儿参与了本研究。评估了临床和实验室参数以及严重程度评分。测定了TAFI和TAFI激活标志物：TAFI激活肽（TAFI-AP）和（未）激活的TAFI [TAFIa(i)]。对-438G/A、Ala147Thr和Thr325Ile多态性进行了基因分型。
与恢复期相比，脑膜炎球菌病患者入院时TAFI水平显著降低。感染性休克患者的TAFI水平低于无休克患者。与无弥散性血管内凝血（DIC）的患者相比，DIC患者的TAFI-AP水平升高。非幸存者的TAFI-AP和TAFIa(i)显著高于幸存者。TAFI-AP水平以及TAFI-AP/TAFI比值也与严重程度评分和实验室参数密切相关。TAFI 325Ile/Ile基因型在DIC患者中占比过高。
TAFI激活标志物与脑膜炎球菌败血症患者DIC的发生及死亡率相关。需要测定TAFI、TAFI-AP和TAFIa(i)，以便连贯解读TAFI在疾病中的作用。
