A comparative analysis of different automated von Willebrand factor glycoprotein Ib-binding activity assays in well typed von Willebrand disease patients.

Essentials Von Willebrand ristocetin cofactor activity (VWF:RCo) is not a completely reliable assay. Three automated VWF activity assays were compared within a von Willebrand disease (VWD) cohort. Raw values for all three assays were virtually the same. An overall problem within type 2A/IIE VWD using VWF:GPIb-binding activity/VWF:Ag was observed. SUMMARY: Background von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative (type 1 and 3) or qualitative (type 2) von Willebrand factor (VWF) defect. VWD diagnosis and classification require numerous laboratory tests. VWF: glycoprotein Ib (GPIb)-binding activity assays are used to distinguish type 1 from type 2 VWD. Objectives Three different automated VWF:GPIb-binding activity assays were compared. Patients and methods BC-VWF:RCo (Siemens Healthcare Diagnostics), HemosIL® VWF:RCo (Instrumentation Laboratory) and INNOVANCE® VWF:Ac (Siemens Healthcare Diagnostics) were performed in a well typed VWD cohort (n = 142). Results Based on the three most used VWD parameters (FVIII:C, VWF:Ag and VWF:GPIb-binding activity) and using a cut-off of <0.70 for type 2 VWD revealed sensitivity and specificity of, respectively, 92% and 72.4% for VWF:RCo/VWF:Ag, 84% and 89.7% for VWF:GPIbR/VWF:Ag, and 92% and 85.1% for VWF:GPIbM/VWF:Ag, whereas a lowered cut-off of < 0.60 resulted in reduced sensitivity with increased specificity for all assays. Conclusion VWD classification based on FVIII:C, VWF:Ag and VWF:GPIb-binding activity revealed an overall problem with normal VWF:GPIb-binding activity/VWF:Ag within type 2, especially type 2A/IIE. Although all assays were practically identical, BC-VWF:RCo had higher %CV compared with both new assays but comparable lower limit of quantification (LLOQ) ~4 IU dL-1 . No clear improved distinction between type 1 and 2 VWD with new assays was seen. BC-VWF: RCo and HemosIL® are ristocetin dependent, whereas INNOVANCE® does not rely upon ristocetin and is not influenced by VWF polymorphisms increasing VWF:GPIb-binding activity levels. INNOVANCE® seems to be the best choice as a first-line VWF:GPIb-binding activity assay, providing the best balance between sensitivity and specificity for type 2 VWD.

Interdisciplinary Global Health Forum: conference report.

In spring of 2012, students and staff at the First Faculty of Medicine at Charles University in Prague invited distinguished public health stakeholders and experts to engage in a Global Health Forum. The forum lasted an afternoon, was academically and clinically engaging and offered students and medical faculty a venue to discuss the most pressing global public health concerns. Main outcomes from the forum included describing outstanding public issues in public health policy and prevention, infectious disease and public health systems raised by the speakers, stakeholders and attendees. One major result of this forum is the establishment of the Prague Center for Global Health - an interdepartmental and interdisciplinary research collaborative to further the discussion and much needed field and academic research in global public health. The Prague Center for Global Health will include multiple international research centers and main function and results will include new courses at the university, publications based on best practices and research and a venue to learn, share and create in the academic space.

[Acquired haemophilia A]. / Získaná hemofilie A.

Acquired haemophilia A is a rare auto-immune disease caused by an inhibitory antibody to factor VIII. Patients with this disorder are at high risk of severe bleeding until the inhibitor has been eradicated. Management of this disorder consists in rapid accurate diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. The cessation of bleeding is based mainly on recombinant factor VIIa and activated prothrombin complex concentrate which are approximately equally efficacious. Immunosuppression is still based on steroids alone or with combination with cyclopfosphamide which may result in a higher rate of remission. New drugs as rituximab or cyclosporine A are the second line option. In case of life-threatening bleeding immunoadsorption and high dose of fac-tor VIII could be advantageous.

FEIBA in treatment of acute bleeding episodes in patients with haemophilia A and factor VIII inhibitors: a retrospective survey in regional haemophilia centre.

FEIBA (factor eight inhibitor by-passing activity) is used to achieve haemostasis in haemophiliacs with inhibitor. The aim of this study was to evaluate efficacy and consumption of the product in treatment of haemorrhages in haemophiliacs with factor VIII inhibitor, and determine factors that can influence the results of treatment. We used data from our haemophilia centre from years 2000-2008. Six haemophiliacs with factor VIII inhibitor were treated on demand with FEIBA for 61 bleeding episodes (45 haemarthroses, six muscle bleeds, six other sites bleeds and four multiple sites bleeds). The median cumulative dose of FEIBA per bleeding episode was 205 U kg(-1). Bleeding was stopped in 96.7% (59 of 61) of events but re-bleeding occurred in 3 events (4.9%) within 48 h after cessation of bleeding. In home treatment (20 of 61) bleeding stopped in 90% (18 of 20) without recurrence and the median consumption per event was reduced to 153 U kg(-1). Without the use of home treatment the median consumption was 250 U kg(-1) per event and bleeding ceased definitely in 92.7% (38 of 41) of cases. The cumulative dose of FEIBA was lower for three episodes with re-bleeding: median 96 U kg(-1) but not in the two cases of ineffective treatment: 361 U kg(-1). FEIBA in management of bleeding episodes completely resolved the haemorrhage in 91.8% of events and in a further 4.9% if treatment was restarted. Using home treatment saved expenditure due to the lower cumulative dose needed for treatment of haemorrhage.

Effect of rFVIIa dose and time to treatment on patients with haemophilia and inhibitors: analysis of HemoRec registry data from the Czech Republic.

Identifying haemophilia patients with inhibitors for clinical trials is difficult due to the limited number of patients available. Registries are therefore being established as an additional means of data collection. The aim of this study was to investigate the effect of different recombinant activated factor VII (rFVIIa; NovoSeven dose ranges and dosing schedules on the incidence of re-bleeding in haemophilia patients with inhibitors. In this retrospective, uncontrolled study, data on the bleeding patterns of adult haemophilia patients with high responding inhibitors were analysed. Only data from the Czech Republic, obtained by the HemoRec registry, were used. This study analysed 'real-life' clinical data and focused on the collection of the same parameters in different patients: time from bleeding onset to first injection, effect of first injection, number of re-bleedings, total number of injections and total amount of haemostatic drug used. Fifteen patients met the inclusion criteria and were included into the study (128 bleeding episodes). Patients treated within 2 h of bleeding onset experienced less re-bleeding than patients treated after 2 h of bleeding onset (5.2% vs. 13.7%, respectively). In addition, patients who were treated after 2 h of bleeding onset experienced fewer re-bleedings when high-dose rFVIIa was used (15.8% and 0%; <120 microg kg(-1) and >250 microg kg(-1), respectively). Initial high-dose rFVIIa was also associated with a decline in total rFVIIa consumption. This registry has provided a unique insight into the bleeding patterns of inhibitor patients, highlighting the importance of early treatment initiation and appropriate starting dose.

[Hemophilia]. / Hemofilie.

Hemophilia is the most spread hereditary bleeding disorder with severe bleeding symptoms. Although the number of hemophiliacs is below 0.1 per thousand in population, the care of these patients consumes a lot of financial expenditures, especially for treatment in appearance of inhibitor. Management of hemophilia is best provided by specialist in a hemophilia treatment centre. However, all physicians can meet the patients with hemophilia in urgent situation or with their chronic problems. The aim of this article is to give an overview of this disease from pathophysiology, clinical manifestation and diagnosis (including prenatal) to treatment. We describe most frequent complications of hemophilia treatment, particularly management of inhibitor.

[Preparation of patients with haemostatic disorder for invasive medical interventions]. / Príprava pacientu s poruchou hemostázy k invazivním lékarským zákrokum.

The current trend in medicine is to sustain the possibility for necessary procedures to be performed in patients who suffer from haemostatic disorders which complicate eventual surgery. Among such disorders are congenital blood coagulation disorders, haemostatic disorders concomitant with other diseases and also therapies which affect haemostasis either on purpose or as part of adverse effects. Among coagulation disorders are congenital haemorrhagic or thrombotic conditions, acquired blood coagulation disorders--combined in the vast majority of cases-- and associated with pregnancy, severe internal diseases and surgery related diseases, severe injuries, wounds, burns, malignancies, systemic connective tissue diseases, inflammatory bowel disease, and a number of other diseases. A separate issue is that ofanticoagulation therapy--both antiplatelet, used in the treatment or prevention of venous thrombosis, and anticoagulation, predominantly used to manage venous thromboembolism. Also considered should be any therapy which may have a negative impact on coagulation due to its adverse effects.

[Preparation of patients with haemostasis disorder for dental surgery]. / Príprava nemocných s poruchou hemostázy ke stomatochirurgickým výkonum.

The most of patients need dental care during their time of life. It can be situation to detect bleeding disorder in patients who have been suggested apparently healthy to this time. In patients with known bleeding tendency it can be situation in which good interdisciplinary coordination is necessary. In the most cases patients with anticoagulation treatment are involved between those with haemostasis problems. Nevertheless, they do not need therapy interruption in the most of cases, only the knowing actual therapeutic level of INR and appropriate stomatologist's erudition. Another situation is in patients with severe haemostatic bleeding disorder. They don't need only special procedure in dental extractions but also lifelong dental care. One can establish patients, in whom it is not possible only outpatient treatment but in whom a few days hospitalization is necessary. Above all they are patients with haemophilia and inhibitor, those with multiple or surgery extractions and persons with multiple haemostasis impairment.

[Von Willebrand disease]. / Von Willebrandova choroba.

Von Willebrand disease is the most spread hereditary bleeding disorder with prevalence up to the 1% in the population. Haemorrhagic symptoms are various intensity, mostly not severe. A large part of affected patients do not come to see a doctor. However these patients are potentially endangered by a serious haemorrhage after a trauma, surgery or during another illness. The estimated number of patients with von Willebrand disease is 1,500-3,500 per 1,000,000 of population; the number of persons with symptomatic von Willebrand disease was estimated to be at least 100 per million. This disease deserves attention not only by haematologists but other physicians too. In our communication we present short overview about von Willebrand disease: there are briefly described pathophysiology, classification, diagnosis and treatment of this illness.

[Our experience with diverticulectomy in symptomatic Zenker's diverticulum]. / Unsere Erfahrungen mit der Zenkerdivertikelresektion.

INTRODUCTION: The frequency of endoscopic procedures for management of Zenker's diverticulum has increased rapidly in the last years. Endoscopic methods are highly effective. We tried to answer the question whether the development of endoscopic methods means the end of open surgery. PATIENTS AND METHODS: In this retrospective study 30 patients (11 men, 19 women) with an average age of 70.9 (49-88) years with Zenker's diverticulum (ZD) were included. All patients were treated with an open transcervical approach between October 2000 and July 2005. In all cases the region of ablation of the diverticulum was closed with a primary handmade suture. In two cases an additional myotomy was performed. For evaluation of the long-term results the patients were sent a questionnaire. To objectify the findings, all patients underwent postoperatively an X-ray examination of the esophagus. The literature was searched by PubMed. RESULTS: 30 patients underwent 32 operations. 91 % of the inquired patients evaluated the operation as successful. An anastomotic leakage was observed in 3 patients, a lesion of the recurrent laryngeal nerve occurred in 2 patients. CONCLUSION: Despite the rapid development of endoscopic methods the open surgical approach remains a reliable and minimal invasive solution of ZD with excellent results and low complication rate. In patients that cannot undergo endoscopic procedures the surgical approach represents the only therapeutic option. Therefore surgical training for repairing ZD is also necessary for the future.

[Simultaneous cardiac and thoracic operations]. / Simultane Herz- und Lungenoperationen.

BACKGROUND: Optimal surgical strategy in patients with combined disease of heart (mainly ischemic heart disease or critical valve disease) and other thoracic organs (mainly pulmonary carcinoma) is still controversial. METHODS: From 1997 to 2004, 13 simultaneous cardiac and thoracic operations were performed in 13 patients. Most of them were necessary for combinations of symptomatic coronary artery disease (CAD) and bronchogenic carcinoma (BCA). PATIENT CHARACTERISTICS: 11 patients showed CAD, mean preoperative LVEF was 44 %. SURGICAL PROCEDURE: Surgical exposure was performed via sternotomy in 10 patients, the rest of the patients underwent thoracotomy. Seven patients were operated on cardiopulmonary bypass, the others underwent an off-pump procedure. Eleven patients underwent CABG, mean number of anastomoses were 2.1 (range 1-4), two patients underwent aortic valve replacement. One patient underwent radical removal of pulmonary adenocarcinoma with local expansion into the left atrium. For the lung cancer lobectomy was necessary in 8, pneumectomy in 1, extirpation of multiple metastases in 1, resection of the trachea in 1 patient. Histological diagnosis was epidermoid carcinoma in 6, adenocarcinoma in 3, undifferentiated carcinoma in 1, metastasis of Grawitz tumor in 1, pneumoconiosis in 1 patient. RESULTS: No patient died in hospital. One patient had to be re-explored for bleeding. Mean blood loss, duration of intubation and length of hospital stay were not different from other patients who underwent cardiac operation only. CONCLUSION: In accordance with the majority of the data published in the literature, combined procedures did not negatively influence hospital morbidity and mortality. Simultaneous operations eliminate the necessity of a second operation and do not delay the postoperative oncological therapy. Long-term results are primarily determined by histological diagnosis and by the extent of the tumor.

[Paliative managment of oesophageal carcinomas--our experience]. / Paliativmní osetriení karcinomu jícnu--nase zkusenosti.

The authors of this presentation explain their experience with methods of paliative care of oesophagus carcinoma. The indication criteria are described and compared advantages and disadvantages of those methods. There is an accent in most frequent method--oesophagus stent implementation. The results in the group of patients after the stent implementation are described, also complications and other solutions.

[The preparation of a patient with long-term anticoagulant cumarin treatment for invasive surgery]. / Príprava nemocných na dlouhodobé antikoagulacní lécbe kumariny k invazivním zákrokum.

Coumarins belong to drugs widely used and the spectrum of their use is going to grow. From this point of view and/or because the coumarins are adminstrated in patients who are treated for the other diseases--medical or surgical--at the same time, it is necessary to modify, interrupt or replace peroral anticoagulant treatment in the dependence on various aspects. It requires to compound different algorithms for given situations solution. It is always to decide, if the situation is imperative from the view of solution planed, what risk brings proposed treatment and what is the risk of anticoagulant treatment modification.

Efficacy and safety of chronic hepatitis C treatment in hemophilic patients.

BACKGROUND/AIMS: Chronic hepatitis C infection is very common among hemophiliacs in the developed World. METHODOLOGY: Retrospective evaluation of the treatment results in hemophiliacs with chronic hepatitis C, all infected with genotype 1b. Twelve patients were treated with interferon-alpha monotherapy, 21 patients with interferon-alpha and ribavirin, and 3 patients with pegylated interferon and ribavirin, all for 48 weeks. RESULTS: Sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was not achieved in any of 12 patients treated with interferon-alpha alone. Combination therapy with interferon-alpha and ribavirin was associated with better results: 4/10 (40%) patients still untreated with interferon-alpha, 2/4 (50%) relapsers, and 2/7 (29%) non-responders to previous interferon-alpha monotherapy achieved sustained virologic responses. Combination therapy with pegylated interferon and ribavirin has been used in 3 patients. Sustained response was achieved in one patient who had relapsed after treatment with interferon-alpha and ribavirin and in 1 of 2 non-responders to this combination therapy. There were no serious adverse events and it was not necessary to reduce dosages or even cease therapy prematurely. CONCLUSIONS: The efficacy and tolerability of antiviral treatment in hemophiliacs did not differ from other patients with chronic hepatitis C.

[The cystadenocarcinoma of the appendix]. / Kystadenokarcinom apendixu.

The authors present a case-review of a patient with a large retroperitoneal tumor. A right-sided hemicolectomy with a removal of a large retroperitoneal cyst extending behind the liver up to the diaphragm on the right side, was conducted. Histology confirmed a mucous cystadenocarcinoma of the appendix. Furthermore, the authors discuss this fairly rare type of the GIT carcinoma. This tumor is low-invasive, mucus producing and rarely metastazing. During the tumor progression, the tumorous cells enter the peritoneal cavity and cause, so called, pseudomyxoma peritonei. The treatment principle is to complete a radical surgical removal of the tumor and, furthermore, in case of the pseudomyxoma periotenei, also application of the local peroperative chemotherapy.

Treatment of chronic hepatitis C in hemophilic patients.

Chronic hepatitis C infection is common among hemophiliacs in all the developed countries. Since 1996, only alpha-interferon (alpha-IFN) in monotherapy has been used for the treatment of chronic hepatitis C in hemophiliacs (6 patients). In Czech Republic a combination therapy with alpha-IFN and ribavirin has been used since 1999 (13 patients). Finally, a combination therapy with pegylated alpha-IFN (PEG-alpha-IFN) and ribavirin is being used since 2001 (still 3 patients). In all cases, the treatment lasted 48 weeks. A sustained virological response (SVR, defined as an undetectable serum HCV RNA level 24 weeks after the treatment was completed) was not achieved in any of 6 patients treated with alpha-IFN alone. A combination therapy with alpha-IFN and ribavirin yielded better results: four of eight patients still untreated with alpha-IFN (naive patients), one of two relapsers, and one of three non-responders to previous alpha-IFN monotherapy achieved SVR. So far the combination therapy with PEG-alpha-IFN and ribavirin has been used only in 3 patients. SVR was achieved in one patient who had relapsed after the combination therapy with IFN-alpha and ribavirin, and in 1 of 2 non-responders to this therapy. We conclude that the efficacy and tolerability of the treatment of chronic hepatitis C in hemophiliacs did not differ from that of chronic hepatitis C in other patients.

[Successful treatment of chronic hepatitis C in hemophiliacs based on historical development of therapeutic protocols]. / Uspesnost lécby chronické hepatitidy C u hemofiliku v závislosti na historickém vývoji doporucených lécebných schémat.

Chronic infection with hepatitis C virus is very frequent among hemophilic patients in all developed counties, including the Czech Republic. Because of a possibility of developing serious terminal stages of infection, liver cirrhosis and hepatocellular carcinoma, the tendency in treatment of patients with chronic hepatitis C is to start it as soon as possible and thus reduce the probability of developing these advanced stages of disease which are difficult to treat. Treatment of hemophilic patients with chronic hepatitis C started in the Department of Infectious Diseases, University Hospital Brno Bohunice, in 1996. Used treatment schemes have reflected historical evolution of treatments used to treat chronic hepatitis C. Initially, alpha-interferon (IFN) was administered in monotheraphy (6 patients), later, since 1999, a combination of alpha-IFN and ribavirin was administered (13 patients), and since 2001 a combination of pegylated interferon (PEG-IFN) and ribavirin (3 patients) was administered. In all the patients the individual treatments took 12 month. Sustained negativization of HCV RNA in serum has not been achieved in any patient treated only with alpha-IFN. In patients who were administered the combination of alpha-IFN and ribavirin this effect appeared in 4 from 7 cases without history of treatment with alpha-IFN (57%), one from 2 relapses and one from 3 non-responders. The combination PEG-IFN and ribavirin was effective in the only one patient who relapsed after alpha-IFN and ribavirin and in one from the two non-responders to this combination. The tolerance and safety of treatment was good in haemophilia patients and could be fully compared to those in other patients with chronic hepatitis C.

[Hereditary thrombocytopenia. Differential diagnosis of a case]. / Dedicné trombocytopenie. Diferenciální diagnostika jednoho prípadu.

Hereditary thrombocytopenias are a heterogeneous group of extremely rare diseases characterized by a reduced number of blood platelets and by bleeding tendency of variable severity. Some of these diseases are exclusive to platelets, while in others the pathology extends to other cell types. Although rare, hereditary thrombocytopenias should be considered in the diagnosis. Hereditary thrombocytopenias have been classified into three groups depending on platelet volume. Hereditary thrombocytopenias with giant platelets form one of these groups. About fourteen clinical entities of inherited giant platelet disorders have been described. Bernard-Soulier syndrome, grey platelet syndrome and May-Hegglin anomaly are the most common giant platelet thrombocytopenias. May-Hegglin anomaly is condition characterized by the triad of thrombocytopenia, giant platelets, and pale-blue inclusions in leukocytes. May-Hegglin anomaly has an autosomal-dominant mode of inheritance. We described clinical and laboratory features of three adult women from one family with recently diagnosed May-Hegglin anomaly. Described cases are probably the first observed cases of May-Hegglin anomaly in the Czech lands.