Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration.

BACKGROUND: The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. RESULTS: 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. CONCLUSION: The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.

Deficiencies of antithrombin, protein C and protein S - practical experience in genetic analysis of a large patient cohort.

Deficiencies of natural anticoagulant proteins including antithrombin (AT), protein C (PC) and protein S (PS) are important causes of inherited thrombophilia. This study aimed to report on the practical experience gained in performing genetic analyses of a large cohort of patients with AT, PC and PS deficiencies and to relate this knowledge to clinical application. We genotyped a large cohort of 709 unrelated patients with AT (231), PC (234) and PS (244) deficiencies referred to us by physicians throughout Germany. Mutations were detected by direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The highest mutation detection rate (MDR) was found for the SERPINC1 gene (83.5%), followed by the PROC (69%) and PROS1 (43%) genes. Even at AT activities close to the normal range (75%), the MDR was 70%. Contrastingly, for PC and PS deficiencies, the MDR dropped significantly and mildly lowered to subnormal values. At PS activities >55% for PS no mutations were detected. Mutation profiles of all three genes were similar with the highest prevalence for missense mutations (63-78%), followed by nonsense (7-11%), splice-site mutations (7-13%), small deletions (1-8%), small insertions/duplications (1-4%) and large deletions (3-6%). In conclusion, genetic testing is a useful diagnostic tool for diagnosing thrombophilia. Based on our data, genetic analysis for patients with AT deficiency is indicated for all subnormal activities. In contrast, genotyping is not advisable for PC activities >70% and for PS activities >55%.

ProTime self-management yielding improvement of fluency and quality of life.

Patient self-management (PSM), as the standard of care for vitamin K-antagonist therapy management in Germany requires a detailed, point-of-care (POC) device-specific training program to ensure quality patient care. In a multi-center trial using the ProTime System (Training program plus POC device), 105 patients were enrolled to evaluate efficacy of training, knowledge retention, patient satisfaction and quality of life (QoL). Patients returned to the centers 1, 3 and 6 months after training to complete questionnaires and demonstrate INR test proficiency. Training assessment employed self-evaluation and comparison of POC results between PSM and professional operators. Patient satisfaction and QoL were assessed using a modification of the questionnaire described by Sawicki and the SF12v2 QoL Survey, respectively. Patients demonstrated statistically significant improvements in knowledge post training (p < 0.001) and retained the acquired information (p = NS vs. post-training; N = 45) after 6 months. Trained patients yielded equivalent INR results to professional operators (r = 0.92) with little or no bias across all clinic visits. Compliance with weekly testing improved from 1 to 3 months (p = 0.03), remaining at the required weekly frequency through 6 months. Average patient satisfaction improved significantly during the first month and remained constant thereafter. There was a statistically significant improvement in the Physical Component Summary of SF12 between baseline and 3/6 month assessments in all centers. In conclusion, PSM requires a comprehensive system including appropriate disease and POC device training. Such a system fosters compliance, improved knowledge about underlying disease, patient satisfaction and QoL.

Adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology and pathogenesis. AOSD is a rare condition, usually presenting with high fever accompanied by systemic manifestations. The disease is a heterogeneous pathological entity with a range of etiologies, manifestations and prognosis. There is no single diagnostic test for AOSD; rather, the diagnosis is based upon clinical criteria such as arthralgia, fever, skin rash, lymphadenopathy, and hepatosplenomegaly. Determination of the procalcitonin level and the biological response to empirical corticosteroid therapy generally helps the diagnosis, while immune-serology, as a 'screening' test, will not add meaningful information in most cases. Treatment consists of anti-inflammatory medications. Non-steroid anti-inflammatory drugs have limited efficacy, corticosteroid therapy and disease-modifying antirheumatic drugs are usually required. Novel therapeutic approaches, such as anti-tumor necrosis factor blockade and stem cell transplantation, are promising. In this chapter we present clinical and laboratory parameters of 18 patients diagnosed with AOSD at our institution between 1997 and 2003, and review the literature.

[Adult-onset Still-disease: survey of 18 cases]. / Felnóttkorban megjelenó Still-betegség--18 eset kapcsán.

INTRODUCTION: Adult onset Still's disease (juvenile rheumatoid arthritis with septic appearance) is rare, leading to clinical signs similar to those seen in bacterial sepsis, lymphomas, rheumatological, or systemic autoimmune diseases. The disease can present with a fever of unknown origin, and can cause difficulties in the diagnosis. It is based upon, partly, the exclusion of other diseases and on diagnostic criteria. Its characteristic feature is the rise of acute phase proteins. Exanthemata are temporary. The basis of treatment is immunosuppression, however relapses can occur. AIM: The aim of the authors was to evaluate on the most characteristic clinical signs and laboratorical data of their patients, and to examine the revealing parameters of the course of the disease. METHOD: Retrospective epidemiological survey of the data obtained from 18 patients. RESULTS: The characteristic signs of the disease were, fever, sore throat, arthritis, joint pain, exanthemata, hepato-splenomegaly, lymphadenomegaly, pleurisy. The typical laboratorical data were: elevated CRP, low PCT, negative Waaler-Rose and ANA test, low serum iron level, leukocytosis, thrombocytosis, elevated alkalic phosphatase activity, high LDH, positive bone scintigraphy. The fever was steroid dependent. Generally, the illness was recognised after 2-3 months, and relapses were frequent. CONCLUSIONS: Still's disease has an important role in the differential diagnosis of fever of unknown origin. The diagnosis is based upon the evaluation of clinical signs and laboratorical data together. Prolonged immunosuppressive therapy is required.