Canakinumab as monotherapy for treatment of familial Mediterranean fever - first report in Central and Eastern Europe region.

Autoinflammatory disorders (AID) are characterized by spontaneous attacks of acute inflammation with a broad spectrum of clinical symptoms. Ongoing inflammation and reoccurrence of acute flares can lead to the development of amyloidosis. One group of AID is represented by monogenic periodic fever syndromes while familial Mediterranean fever (FMF) is the most common form of AID from this group. Its prevalence in Central and Eastern Europe was reported to be very low. We report a case of FMF patient with a very severe clinical course of FMF and intolerance to colchicine, which is a gold standard for FMF treatment. The clinical effect of the application of anakinra was insufficient and accompanied with side effects and low tolerability. Switching to canakinumab (human monoclonal antibody against IL-1ß) at dose of 150 mg every 4 weeks induced a rapid remission of the disease activity and inflammatory markers. However, due to relapse of acute flares after three weeks from application, the escalation of dose to 300 mg every 4 weeks induced a complete remission of symptoms and significantly improved the quality of life. This is the first report of successful canakinumab administration in FMF patient in Central and Eastern Europe, a region with very low incidence of FMF (Tab. 1, Ref. 16).

[Autoimmune polyendocrine syndrome type 2 associated with autoimmune hypophysitis and coeliac disease]. / Autoimunitný polyglandulárny syndróm typ 2 asociovaný s autoimunitnou hypofyzitídou a coeliakiou.

Autoimmune polyendocrine syndromes (APS) are organ-specific autoimmune disorders affecting multiple endocrine glands; these are gradually destroyed by action of autoantibodies. Similarly to other autoimmune diseases, the presence of certain genetic predisposition is an essential prerequisite to the disease development; polymorphism of the main histocompatible system (HLA in humans) appears to play the most important role. APS are categorized into four types, based on what combination of endocrine glands is affected. APS type 1, characterised by hypoparathyreosis, mucocutaneous candidiasis and Addison's disease, is frequently seen in childhood. For a more common APS type 2 to be diagnosed, Addison's disease together with autoimmune thyroiditis (Schmidt's syndrome) and/or together with diabetes mellitus type I (Carpenter's syndrome) must be present. The third type of autoimmune polyendocrine syndromes (APS type 3) involves the same disorder of endocrine glands as type 2 but usually without any defect of adrenal cortex. If the autoimmune endocrine gland disorder does not fulfil the criteria of APS 1-3, the disease may be categorized as autoimmune polyendocrine syndrome type 4. The authors present a case of 33 years old APS type 2 patient who, over 20 years, developed a wide range of autoimmune endocrinopathies, including endocrinopathies that are less common, such as adenohypophysitis, and are associated with other organ-specific diseases (coeliac disease). The case is presented to demonstrate the fact that APS represent a dynamic process and that it is always important to keep in mind that, over time, a patient may develop other autoimmune diseases. To conclude, the authors emphasise the recommendation to test patients with monoglandular endocrinopathy for the presence of any secondary endocrine disorders.

Fibrinolytic activity disturbances in malignant blood diseases.

Repeated investigation of 105 patients suffering from different blood disorders demonstrated a more frequent occurrence of disturbances in fibrinolysis (66% as in blood clotting tests (40%) indicating a compensated or decompensated intravascular blood clotting. In the group of patients with thrombocythaemia the disturbance of fibrinolysis as much as in 83% was present, and always in sense of insufficiency. In myeloproliferative diseases without proliferation of megakaryocytes the antithrombotic treatment improved both the fibrinolysis as well as the clotting disturbances. In thrombocythaemia the long-termed treatment with anti-platelet drugs, eventually with other antithrombotics favourably influenced the blood clotting parameters as well as the symptomatology from vascular occlusion, however the euglobulin lysis remained unchanged. In sense of the idea on the ineffective megakaryocytopoiesis in primary and other myeloproliferative diseases accompanying thrombocythaemia attention is called to the specificity of the fibrinolytic insufficiency in thrombocythaemia in comparison with other myeloproliferative diseases without thrombocythaemia.

Care for patients with hereditary coagulopathies in Slovakia.

Contemporary situation with the care for hereditary coagulopathies in Slovakia is discussed. The mode of obtaining the data for central registration of patients suffering from hereditary coagulopathies in Slovakia is elucidated. Importance of such a registration for prospective planning guaranteeing needs of patients and of concentration of medical care in hands of specialists in haematology and blood transfusion is pointed out. The specialists in Slovakia are responsible for both diagnosis and registration as well as for effective therapy of haemorrhagic incidents in the patients. The care is mostly realized in 3 of 4 regional departments of haematology and blood transfusion, occasionally also in some chosen district departments. Preparation of antihaemolytic blood fractions in Slovakia is connected exclusively to the national transfusion fractionation programme in departments of haematology and blood transfusion. With regard to the principle of free of charge blood donation and medical care, this mode of preparation is the most effective economically, because of the relatively high yield of active coagulation factors. Concrete data on the prevalence of hereditary coagulopathies in Slovakia are presented. Comparison of the number of registered haemophiliacs in Slovakia with that given in other countries indicates a very high registration of the hereditary haemorrhagic diseases in our country, which also follows from the centralized active medical care. To secure further rise of the haemophiliacs demands, however, it will be necessary to increase efforts in blood donor campaigns and to improve equipment of regional departments of haematology and blood transfusion which are responsible for medical care.

[Importance of PPSB fraction in the treatment of hemophilia A with antibodies against factor VIII]. / Die Bedeutung der PPSB-Fraktion in der Behandlung der Hämophilie A mit Antikörpern gegen Faktor VIII.

On the basis of the indirectly established statement that activated forms of the coagulation factor are also present in PPSB fractions of own production, the activated concentrate of factor IX and of the prothrombin complex were applied in haemophilia-A patients with antibodies against factor VIII. The fraction was administered to 4 patients during 14 bleeding times, mostly during bleedings of joints an soft tissues, twice during haematuria in a dose of 40-200 E-factor IX per kg of body weight and per day. The total dose was mainly administered in a fractionized way at an interval of 8 or 12 hours. This treatment lasted for 2 to 7 days. With regard to haemostasis no fundamental improvement of global blood coagulation tests (which have pathological results in haemophilia-A patients) could be identified in the course of the treatment. However, the increase of factor II, VII, and X in the patient's plasma was striking. Contrary to exceptations, there was a less distinct increase of factor IX activity. Concluding from these findings it may be assumed that the "strengthening" of the "extrinsic system" is decisive for the haemostatic effect in the treatment mentioned.