[How does the time of diagnosis affect the course of disease in children with kawasaki syndrome? A retrospective analysis at one center]. / Welchen Einfluss haben unterschiedliche Diagnosezeiten auf den Krankheitsverlauf von Kindern mit Kawasaki-Syndrom? Eine retrospektive monoinstitutionelle Analyse.

BACKGROUND: Kawasaki syndrome was described for the first time by Tomisaku Kawasaki in 1967. This disease is characterized by panvasculitis of the small blood vessels of the skin, the mucous membranes, the internal organs and the coronary vessels and has an unclear etiology. Inflammatory changes in the coronary vessels or late diagnosis are prognostically unfavorable for the early and late mortality. AIM OF THE STUDY: Since two of our patients with Kawasaki syndrome with a short, severe course died despite receiving state-of-the-art treatment, we retrospectively evaluated the medical records of all the children we have treated since October 1978 with regard to the symptoms at the time of diagnosis, intervals between the onset of the disease, diagnosis, beginning of treatment and the result of treatment. PATIENTS: Kawasaki syndrome was diagnosed in 80 patients in the period from October 1978 to October 2007. The patients were grouped according to the phase of the disease and the number of organs affected at the time of diagnosis (Asai-Score) as well as the treatment carried out. The time of the first presentation for diagnosis by the pediatrician was also considered. METHOD: This is a single-institution retrospective analysis of the medical records, echocardiography and angiography findings of all patients. In view of the change of therapy in that year, patients who had been diagnosed before 1987 were compared with those diagnosed after 1987. RESULTS: Before 1987, the patients were treated solely with high doses of acetylsalicylic acid (50-100 mg/kg/day p.o. over two to four weeks). Out of a total of 36 patients, 13 showed involvement of the coronary arteries that persisted in seven patients despite treatment. After 1987, all patients received intravenous immunoglobulins (4 x 0.5 g/kg/day resp. 1 x 2 g/kg i.v. over 12 hours). In 18 out of 44 patients, the coronary arteries were affected at the time of diagnosis, but this did not persist in any of the patients. One child died in each group. Comparing the two treatment groups also revealed that a physician was consulted for the first time after a very much shorter duration of the disease in the second treatment period (3+/-1.8 vs. 6+/-2.4 days after onset of the illness) and that a pediatrician was consulted much more frequently as the first port of call. This was reflected in a significantly earlier beginning of treatment and a simultaneous significantly lower Asai score. CONCLUSION: The retrospective evaluation of all medical records did not reveal any plausible explanation for the fatal course of the disease in one child in each of the two treatment periods. Besides the combination therapy with intravenous immunoglobulin and oral administration of acetylsalicylic acid, the greater age and the earlier commencement of treatment appeared to be salient factors resulting in complete cure of the disease in the surviving patients in the second period of treatment.

Thrombin generation in paediatric patients with congenital heart disease. Determination by calibrated automated thrombography.

UNLABELLED: Thrombin generation was studied in paediatric patients with congenital heart disease (CHD) undergoing cardiac surgery using the calibrated automated thrombography (CAT) in terms of the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. The suitability to determine the coagulation status of these patients was investigated. PATIENTS, MATERIAL, METHODS: CAT data of 40 patients with CHD (age range from newborn to 18 years) were compared to data using standard coagulation parameters such as prothrombin (FII), antithrombin (AT), tissue factor pathway inhibitor (TFPI), prothrombin fragment 1.2 (F 1.2), thrombin-antithrombin (TAT), activated partial thromboplastin time (aPTT), and prothrombin time (PT). RESULTS: A significant positive correlation was seen between ETP and FII (p < 0.01; r = 0.369), as well as between peak height and FII (p < 0.01; r = 0.483). A significant negative correlation was seen between ETP and TFPI values (p < 0.05; r = -0.225) while no significant correlation was seen between peak height and TFPI. A significant negative correlation was seen between F 1.2 generation and ETP (p < 0.05; r = -0.254) and between F 1.2 generation and peak height (p < 0.05; r = -0.236). No correlation was seen between AT and ETP or peak. CONCLUSIONS: CAT is a good global test reflecting procoagulatory and inhibitory factors of the haemostatic system in paediatric patients with CHD.

Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor.

BACKGROUND: Bleeding in hemophilic neonates has a low incidence. A possible explanation for this could be the peculiarities of the neonatal hemostatic system, especially low levels of the inhibitors tissue factor pathway inhibitor (TFPI) and antithrombin (AT). OBJECTIVE: We investigated the influence of an elevation of these inhibitors to adult levels on the thrombin generation (TG) in normal neonatal plasma and factor (F) VIII-depleted neonatal plasma by means of incubation with anti-FVIII-antibodies. PATIENTS/METHODS: TG was measured after activation with low amounts of tissue factor (TF) by using Calibrated Automated Thrombography. RESULTS: TG in FVIII-depleted neonatal plasma was nearly as high as in normal neonatal plasma. TG decreased after elevation of AT in both neonatal plasmas. After elevation of TFPI TG decreased much more in FVIII-depleted neonatal plasma than in normal neonatal plasma. After elevation of both inhibitors their synergistic effect led to a stronger decrease of TG in FVIII-depleted neonatal plasma. TG measured in plasma of one hemophilic newborn showed the same pattern as in FVIII-depleted neonatal plasma. CONCLUSION: Our observation provides a biochemical basis for the rare bleeding in hemophilic neonates and shows the important role of the natural inhibitors in the hemostatic system of hemophilic patients.

Effects of the glycoprotein IIb/IIIa receptor antagonist c7E3 Fab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge in vitro.

The present study was performed to investigate the combined effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab (abciximab) and the anticoagulants unfractionated heparin (UH), low molecular weight heparin (LMWH), and recombinant hirudin (rH) on platelet aggregation and thrombin generation under high coagulant challenge by extrinsic activation of platelet-rich plasma. Platelet aggregation and thrombin generation were assessed simultaneously in the presence of different concentrations of abciximab and anticoagulants. Increasing concentrations of abciximab resulted in a dose-dependent anti-aggregating effect with a maximum at 20 microg/ml. Doses of 5, 10, and 20 microg/ml abciximab prolonged the lag phase until the onset of platelet aggregation, but this effect was independent of the dosage used. Abciximab had no influence on the thrombin potential under our high coagulant challenge. UH, LMWH, and rH showed a dose-dependent prolongation of the lag phase until the onset of platelet aggregation and decreased the thrombin potential. Addition of anticoagulants did not contribute to further inhibition of platelet aggregation in the presence of abciximab, but the combination of abciximab and anticoagulants exhibited an additive effect on prolongation of the lag phase until the onset of platelet aggregation. Addition of abciximab to anticoagulants did not result in further decrease of the thrombin potential. Our study demonstrates the respective specific effects of abciximab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge, and also an additive effect of abciximab and the anticoagulants UH, LMWH, and rH on the lag phase until the onset of platelet aggregation.