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We found no association between RAP and H pylori infection in children and conflicting evidence for an association between epigastric pain and H pylori infection. We found evidence for an association between UAP but could not confirm this finding in children seen in primary care.

To cite this article: van Leeuwen Y, Rosendaal FR, Cannegieter SC. Prediction of hemorrhagic and thrombotic events in patients with mechanical heart valve prostheses treated with oral anticoagulants. J Thromb Haemost 2008; 6: 451-6. Summary. Background: Variability in the intensity of antico-agulant therapy is considered a risk factor for complications, but it is unclear how best to quantify variability. Objective: We evaluated the association of three methods to measure variability with complications of oral anticoagulant therapy. Methods: We conducted a nested case-control study within a cohort of patients with prosthetic heart valves. 210 patients with a first hemorrhagic or thrombotic event during follow-up were selected with two controls per case, matched on age and sex. We calculated the time spent at an International Normalized Ratio below, above, and between 2.5 and 4.0, and the variance growth rate according to three different methods (A, B1, B2); method A combines variability and time in range, and methods B1 and B2 purely look at variability. Results: Odds ratios of the variance growth rates for thrombotic events for patients in the second and third tertiles varied between 2 and 3, with the highest odds ratio for complications for the method that purely looked at variability. For hemorrhagic complications, the highest odds ratios were found for method A, which also incorporated time in range, with odds ratios of 2.6 (95% CI: 1.3-5.1) and 3.1 (95% CI: 1.6-6.0) for the second and third tertiles as compared to the first. The combination of time spent out of range with the highest tertile of variability increased the risk 2.6-fold (95% CI: 1.6-4.2) as compared to subjects with stable anticoagulation within the target range. Conclusion: Unstable anticoagulation was associated with hemorrhagic and thrombotic complications. Method A was best associated with complications, but methods B1 and B2, in combination with time spent in range, were equally well associated. As we prefer to disentangle variability and intensity of anticoagulation, we propose to use methods B1 or B2 to reflect pure variability of oral anti-coagulant therapy.

Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF-dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF-cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF-dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow-mediated VWF-dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications.

In all 15 samples, a substantial and clinically relevant variation in the calculated MELD score was observed between laboratories. The mean difference in the MELD score between the highest- and the lowest-scoring laboratory was 4.8. The variation in creatinine measurements resulted in differences of up to three MELD points in a single patient when comparing the highest and the lowest scoring lab. The variation in bilirubin measurements only accounted for a difference of one point between the highest- and the lowest-scoring laboratory, but the variation in INRs resulted in differences of 2 to 12 MELD points. MELD scores or INR values were not substantially different in laboratories that used the Owren instead of the more widely used Quick methodology for INR measurements. The variability in the INR in patients on oral anticoagulants was substantially less as compared with the variability in patients with liver disease. In conclusion, we observed a large interlaboratory variation in the MELD score. This variation in the MELD score is primarily caused by the INR.