Streptococcus pneumoniae infection is a leading cause of morbidity and mortality worldwide. One of the most severe complications of invasive pneumococcal disease (IPD) is haemolytic uraemic syndrome (HUS). This study was undertaken to determine the risk factors and role of pneumococcal neuraminidases in HUS in children with IPD. Eighteen cases of HUS and 54 patients with IPD without HUS were identified. The controls were patients with culture-confirmed IPD without HUS. Clinical and laboratory characteristics of the two groups of patients were compared. Bacterial isolates from both groups were serotyped, sequence typed and examined for their carriage of three neuraminidase genes. Necrotizing pneumonia and serotype 3 infection were significantly associated with HUS in children with IPD, suggesting that a severe pulmonary suppurating disease increase the risk of HUS. Serotype 14 was associated with necrotizing pneumonia but not HUS. Children with HUS were more likely to require surgery and had a longer duration of hospitalization. The study identified a significantly higher carriage of a neuraminidase gene, nanC, in the causative pneumococcal isolates from patients with HUS (89% versus 41%, p 0.001). The sensitivity and specificity of nanC to predict HUS were 89% and 59%, respectively. In conclusion, necrotizing pneumonia, serotype 3 infection and neuraminidase gene nanC were associated with HUS in children with IPD. The result suggests that NanC could provide an additive effect to NanA and NanB in the overall activity of pneumococcal neuraminidases to expose Thomsen-Friedenreich antigen on various cells in patients with HUS.

Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis. J Thromb Haemost 2014; 12: 2054-64.Summary. Background: Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated. Objectives: The hemostatic activity of Reelin is investigated and defined in this study. Methods: The interplay of Reelin with coagulation components was elucidated by far-Western and liposome/platelet binding assays. In vivo and ex vivo hemostasis-related analyses of Reelin-deficient mice and plasma were also performed. Results: Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin b1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated with the Kd of 11.7 and 21.2 nM, respectively. Reelin-deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency.Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern. Conclusions: By interacting with platelet phospholipids and the coagulation factors, thrombin and FXa, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.

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