[Thrombophilic mutation by women with serious pregnancy complications]. / Výskyt trombofilních mutací zen se závaznými tehotenskými komplikacemi.

OBJECTIVE: The purpose of this study was to determine whether maternal or fetal genotype frequencies of the inherited thrombophilic gene mutation (F V Leiden, F II) are altered in adverse pregnancy outcomes - severe preeclampsia, IUGR, abruption of placenta and stillbirth. DESIGN OF THE STUDY: Retrospective study. SETTING: Department of Gynecology and Obstetrics of the Teaching Hospital and the 2nd Medical Faculty of the Charles University in Prague. METHODS: We studied 232 women who had pregnancy complications. All women were tested postpartum for mutation of factor V Leiden and G20210A prothrombine gene. At the same time were tested the newborns of those women. RESULTS: In the group of women with preeklampsia (n=141) we have demonstrated 5 women with mutation encoding for F V, 5 women with mutation encoding for F II and 1 combination of both. In the group of IUGR 2 women with mutation F V, 1 with mutation F II a 1 combination of both were found. In women after stillbirth occure two mutation of F V, one mutation of F II and one combination of both. In the group with abruptio of placenta was 1 case of mutation F V and 3 cases of mutation F II. When we tested a newborn we found 4 cases of mutation F V and 3 cases of F II in the group with preeclampsia, 4 cases of mutation F V 3 cases od mutation of F II in the group with IUGR, no case in the group with abruptio of placenta and 1 case in a death fetus. There was no assotiation between any severe pregnancy complications and any of the maternal or fetal inherited thrombophilia. CONCLUSION: Factor V Leiden and prothrombin gene mutations did not seem play a significant role in adverse pregnancy outcome in our population.

[Does the asymptomatic carriage of FV Leiden and FII prothrombin in heterozygous configuration represent the increased risk of thrombembolic complications during pregnancy, childbirth and postpartum?]. / Predstavuje asymptomatické nosicství mutace FV Leiden a FII protrombin v heterozygotní. Konfiguraci zvýsené riziko trombembolických komplikací v prubehu tehotenství, porodu a sestinedelí?

OBJECTIVE: To evaluate the course of pregnancy and puerperium in asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration in terms of risk of thrombembolic disease and late pregnancy complications. To evaluate whether global prophylactic LMWH administration already during pregnancy has brought some benefit to these women. TYPE OF STUDY: Prospective study. METHODS: From June 2007 to June 2011, we monitored the incidence of thrombembolic events (TED) and severe late pregnancy complications in 473 asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration. We also compared the ongoing changes of commonly clinically available hemocoagulation tests. In selected women, we added to coagulation tests a thrombin generation test (TGA) and thrombin-antithrombin test (TAT). In 253 women (Group A), preventive LMWH application was introduced already during pregnancy. In 220 women (Group B), the application of LMWH was commenced as late as on the delivery day. In both groups application of LMWH continued during the puerperium. RESULTS: The incidence of TED in the whole group of carriers of thrombophylic mutations accounted for 0.19%. The incidence of severe late pregnancy complications was very low - 3%. Medians of the monitored parameters of the hemocoagulation in compared groups and 'healthy' controls did not show statistically significant differences at any stage of pregnancy, labor or end of puerperium, with the exception of the results of TAT test at the end of puerperium. CONCLUSIONS: No direct causal relationship has been established between asymptomatic carriage of Leiden and prothrombin mutation in heterozygous configuration and the occurrence of severe late pregnancy complications. These types of mutation represent only a slightly increased risk in terms of development of thrombophylic events. General LMWH prophylaxis during pregnancy is not indicated. However, individual careful monitoring of hemocoagulation changes and early detection of associated transient situations potentiating risk of thrombembolic events is desirable. Statistically significant differences in the TAT results between group A and B at the end of puerperium revealed that the recommended extended LMWH prophylaxis until the end of puerperium was not followed by a number of women who started the prophylaxis on the date of labor.

[Thrombotic thrombocytopenic purpura in pregnancy. Case report]. / Trombotická trombocytopenická purpura v tehotenství. Kazuistika.

OBJECTIVE: Description of case of patient with rare thrombotic thrombocytopenic purpura in pregnancy. SUBJECT: Case report. SETTING: Department of Gynecology and Obstetrics, Charles University and University Hospital Motol, Prague. CONCLUSION: Thrombotic thrombocytopenic purpura (TTP) is a rare and substantial disorder characterized with combination of microangiopathic haemolytic anemia, consumption trombocytopenia and symptoms of organs dysfunction--especially kidneys and neurological deficiency. It's caused by production of microthrombi affecting small blood vessels. These palatelets-rich microtrombi are formed due to deficiency of the enzyme ADAMTS13--metalloprotease which is responsible for cleaving of ultralarge multimers of von Willebrand factor into smaller units. In our case report we describe patient with TTP in pregnancy. Therapy with corticosteroids and immunoglobulines was not effective, improvement of thrombocytopenia appeared after plasmapheresis (total count 14). The delivery was induced at term without complications. Target examination confirmed diagnosis of secondary TTP.

[The results of patients with essentials thrombocythemia and other myeloproliferation-related thrombocythemia--a report of patients treated with Thromboreductin]. / Výsledky lécby nemocných s esentiální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductin (anagrelide) in the Czech Republic contains data concerning patients that have been treated using this drug since 2004. As of June 2009, the total number of patients was 549. The current analysis focused mainly on evaluation of anagrelide dosage needed to achieve a complete response in high-risk patients: reduction in platelet count to below 400 x 10(9)/l, which was also considered as reaching the therapeutic goal. The outcomes of the registry confirm that although anagrelide (Thromboreductin) is a very effective platelet-reducing agent, the administration of which is related to a low incidence of adverse effects and complications, the therapeutic goal is not achieved in all cases and or despite a quick treatment response, the therapeutic goal is achieved more slowly.

[What is the current treatment of patients with essential thrombocytopenia and other myeloproliferations accompanied with thrombocythemia [corrected] and what can be the predictive sign of the risk of thrombosis in such patients--a report from the registry of patients treated by Thromboreductine]. / Jak lécíme nemocné s esenciální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií a co muze být prediktivní známkou rizika trombózy u techto nemocných--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductine (anagrelid) in the contributing centres in the Czech Republic has been updated with data on the patients receiving this medication since 2004. The original purpose of the registry was to record responses to Thromboreductine therapy and adverse drug reactions in patients with essential thrombocytopenia. However, data on additional Ph negative myeloproliferations, as well as data on cytoreductive therapies other than exclusively that using Thromboreductine has also been recorded in the course of its compilation, including data on combined regimes. At present, the database contains data on 421 patients, and valid conclusions can be drawn if the level of data filling is enhanced. Evaluation has been currently focused on the analysis of the risk of development of clinical symptoms of thrombosis and on the standards of treatment from the viewpoint of the achieved treatment response. Analyses of data from the registry corroborate the special importance of the proof of JAK2 mutation, and of the test for factor V Leiden mutation, and of protein of S for the assessment of the risk of thromboembolic complications. The output of the analysis confirms that anagrelid is a very efficient thromboreductive agent the administration of which is associated with a low incidence of non-serious adverse effects (10.9%). However, in spite of a fast response to therapy, the therapeutic goal consisting in the reduction of the platelet count below 400 (or below 600) x 10(9)/l, i.e. the complete (or partial) treatment response, is relatively slow to achieve. This is likely to be due to lack of radical corrections in the dosage of the drug for different reasons.

[Essential thrombocytemia and other myeloproliferations with thrombocytemia in the data of the register of patients treated with Thromboreductin till the end of 2006]. / Esenciálni trombocytemie a dalsí myeloproliferace s trombocytemií v údajích registru pacientu lécených Thromboreductinem do konce roku 2006.

Since 2005, registers of patients treated with Thromboreductin (anagrelid) kept by some centres in the Czech Republic have been supplied with data concerning patients whose treatment with this preparation started in 2004. The purpose of the register is to record responses to therapy by Thromboreductin and adverse events in patients with essential thrombocytemia and other myeloproliferations, and to subsequently analyse the data. Another objective is to detect predisposition to clinical symptomatology and disease complications. Apart from thrombocyte count, additional risk factors are monitored. The database currently contains data for 336 patients. Initial analyses of data from the register point to the fact that anagrelid is a highly effective thromboreductive agent the administration of which is associated with relatively low incidence of adverse events (11.8 %) of mild and usually transitory nature. The therapeutic objective is attained at a relatively slow rate (according to overall stratification under 400 or under 600 x 10(9)/l thrombocytes), which is probably due to insufficient dose adjustment.

[Anagrelide in the treatment of essential thrombocythemia (ET) and other myeloproliferative disorders with thrombocythemia based on data from patient register in the CR]. / Anagrelid v lécbe esenciální trombocytemie a dalsích myeloproliferací s trombocytemií sledovaných v registru pacientu v CR.

Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.

[Reimplantation of heart valve prosthesis at the 25th week of gestation]. / Reimplantace umelé srdecní chlopne ve 25. týdnu tehotenství.

OBJECTIVE: Pregnancy in a woman with thrombosis of heart valve prosthesis at the 25th week of gestation and fetal death during reimplantation of prosthesis with the use of extracorporeal circulation. SUBJECT: Case report. SETTING: Department of Gynecology and Obstetrics, 2nd Medical Faculty of Charles University, Motol Hospital, Prague. SUBJECT AND METHOD: Patient L. S., 24 years old, first pregnancy, admitted to coronary heart unit at the 25th week of gestation with a blocked heart valve prosthesis, NYHA IV, left heart failure, and pulmonary edema. There was an insufficient anticoagulation therapy during pregnancy and a thrombosis of the prosthetic heart valve was suspected from that reason. Reimplantation of a prosthetic heart valve with the use of extracorporeal circulation was indicated in spite of a possible risk for the fetus. The thrombosis was confirmed during cardio surgical operation and a change of the prosthesis was successfully performed. After the patient was converted to extracorporeal circulation, bradycardia and intrauterine fetal death occurred. With regard to the patient's coagulation and circulatory instability, further management was necessary because of fetal death--termination of pregnancy by minor caesarean section was the only alternative. Six hours later an 850 g weight dead fetus was delivered. There were no serious complications during the postoperative period. CONCLUSION: Reimplantation of a prosthetic heart valve from vital indication was performed at the 25th week of gestation. After conversion of mother to extracorporeal circulation, fetal death occurred. The patients was released with satisfactory cardiopulmonal compensation.

Coagulation profile and liver function in 102 patients after total cavopulmonary connection at mid term follow up.

OBJECTIVE: To examine coagulation factors and liver function test abnormalities in patients after total cavopulmonary connection (TCPC). DESIGN: Cross sectional study comprising clinical and echocardiographic evaluation, and biochemical and coagulation profile screening. SETTING: Tertiary referral centre. METHODS: 102 patients aged 4-24 years (median 10 years) at one to eight years (median five years) after TCPC were examined. All patients were maintained on a low dose of aspirin. 96% of patients were in a good clinical condition (New York Heart Association class I or II). No intracardiac thrombi were detected on echocardiography and ventricular function was good in 91% of patients. RESULTS: Total bilirubin was increased in 27% and gamma glutamyltransferase in 54% of patients. Serum total protein, albumin, and prealbumin were normal in almost in all patients. Compared with the control group, patients after TCPC had significantly lower fibrinogen, factor V, factor VII, and protein C concentrations, prolonged international normalised ratio, and increased antithrombin III concentration. Factor V concentration was abnormally decreased in 35%, factor VII in 16%, and protein C in 28% of patients. Antithrombin III was increased in 23% of patients. Factor VII, factor V, protein C, and antithrombin III correlated significantly with serum prealbumin. There was also a significant correlation between procoagulant factor VII and both anticoagulant protein C and antithrombin III. CONCLUSIONS: Almost half of patients after TCPC had laboratory signs of mild cholestasis. Decreased liver synthesis of procoagulant and anticoagulant factors was observed but overall coagulation homeostasis appeared to be in balance in this selected group of patients with a good clinical outcome.

[Assessment of speed of an anti-platelet effect after two different doses of acetylsalicylic acid by flocculation]. / Stanovení rychlosti nástupu úcinku protidestickového vlivu dvou ruzných dávek kyseliny acetylsalicylové agregometrickou metodou.

UNLABELLED: Acetylsalicylic acid inhibits aggregation of blood platelets through affecting arachidon acid metabolism--a precursor of thromboxan which is a strong platelet aggregation inhibitor. A standard method for measurement of aggregation activity blockade (in percents) of platelet rich plasma is turbidimetric aggregomethry based on spectrophotometric principle. According to results of recent studies administration of acetylsalicylic acid is one of the basic pillars of prevention of thrombotic complications in atherosclerotic arterial disease. Acetylsalicylic acid doses differ from study to study. An aim of our work was to measure speed of two different doses of acetylsalicylic acid. RESULTS: Level of aggregation activity blockade in samples of platelet rich plasma was measured by aggregometry in 26 healthy volunteers after administration of four inductors of thrombocyte aggregation (arachidon acid, adenosindiphosphate, collagen, and ristocetin). The samples were taken before administration and 120, 240, and 360 minutes after single peroral administration of 100 or 400 mg of acetylsalicylic acid. Samples of plasma were analysed immediately after sampling. Before drug administration there was no aggregation activity in 27.7% of the sample after arachidon acid administration, 28.3% after ADP administration, 21.5% after collagen administration and 25.3% after ristocetin administration. After administration of 400 mg of acetylsalicylic acid and administration of arachidon acid as an inductor 89.9% of the aggregation activity of the sample was blocked after 120 minutes, 89.6% after 240 minutes, and 90.6% after 360 minutes. After administration of adenosindiphosphate as an inductor 71.7% of the aggregation activity of the sample was blocked after 120 minutes, 68.3% after 240 minutes, and 69.9% after 360 minutes. And, after administration of ristocetin as an inductor 64% of the aggregation activity of the sample was blocked after 120 minutes, 66.4% after 240 minutes, and 54% after 360 minutes. Blockade of aggregation activity after collagen administration was not statistically significant. After administration of 100 mg of acetylsalicylic acid and administration of arachidon acid 83.8% of the aggregation activity of the sample was blocked after 120 minutes, 89.2% after 240 minutes, and 89.6% after 360 minutes. After adenosindiphosphate administration statistically significant blockade of aggregation activity was achieved after 360 minutes in the 56.7% of the sample. Also after collagen administration 42.5% of aggregation activity of the sample was blocked significantly after 360 minutes while ristocetin has not proved to influence aggregation in a statistically significant manner. CONCLUSION: Both doses of acetylsalicylic acid influenced aggregation activity of platelets in a statistically significant manner as soon as after 120 minutes following their peroral administration. However, they had different ability to influence platelets response to alternative ways of activation--by adenosindiphosphate, collagen, and ristocetin. 400 mg dose blocked these ways while 100 mg dose was efficient in blocking these ways after 360 minutes and in case of ristocetin--an inductor used to monitor platelet adhesion ability--100 mg dose has not led to statistically significant blockade at all.

[Serious surgical complications associated with chronic anticoagulant therapy]. / Závazné chirurgické komplikace chronické antikoagulacní lécby.

Chronic anticoagulant treatment is administered mostly for cardiological reasons. Cumarin derivatires are used in the majority of cases (Warfarin, Pelentan). It is necessary to monitor this treatment regularly and to control the dose according to the INR value. Different complications can occur; the haemorrhage represents a serious one. The authors discuss several aspects of anticoagulant therapy and possible prevention of the complications. The importance of the problems is demonstrated on the authors' clinical experience--two cases of haemorrhage after Warfarin administration simulating an acute surgical event.

[Perioperative hypothermia and its sequelae]. / Perioperacní hypotermie a její dusledky.

UNLABELLED: Perioperative hypothermia is associated with the development of haemocoagulation, cardiovascular and metabolic disorders leading to an increased morbidity and mortality. The objective of the investigation was to assess the extent of hypothermia and its clinical and laboratory consequences. A group of 30 patients subjected to elective radical laparotomy on account of colorectal carcinoma was divided into to equivalent groups. To the first group heated infusions were administered, to the second group not heated ones. In all patients the central and peripheral temperature, rate of postoperative normalization of the temperature, postoperative thermal comfort, consumption of analgesics and biochemical and haematological parameters were monitored. RESULTS: In patients with non-heated infusions more marked and longer perioperative hypothermia was recorded with a significant alteration of the number of leucocytes and thrombocytes. In the other investigated indicators there was no significant difference between the two groups. Hypothermia did not cause serious complications in any of the patients. CONCLUSION: Although no serious clinical complications induced by hypothermia were recorded, the authors recommend an active approach and provisions for the perioperative maintenance of body temperature as a standard of contemporary perioperative care.

[Occult fibrin production during surgery in cyanotic congenital heart defects and extracorporeal circulation]. / Skrytá produkce fibrinu pri operacích cyanotických vrozených srdecních vad v mimotelním obehu.

In 10 patients with complex cyanotic congenital defects detailed coagulation examinations were made at the beginning and end of the extracorporeal circulation after neutralization of heparin by protamine and the results were compared with a control examination, made before general heparinization, after introduction into general anaesthesia. The authors examined the activated period of blood (ACT) by means of testing tubes with a celite activator (Hemochron) as well as the HR-ACT test with a kaolin activator (Medtronic) for comparison of the results. The authors assessed quantitatively plasma levels of heparin, antithrombin III and fibrinopeptide A which is a sensitive indicator of intravascular coagulation. They assessed also the fibrinogen level and total number of thrombocytes in the blood stream. The degree of haemodilution was recorded as well as the temperature at the periods of assessment. The values of both ACT test were within the range of values above 420 secs., evaluated according to the authors protocol as adequate for total heparinization during operations under conditions of extracorporeal circulation. Despite of this heparin levels lower than those recommended in the literature were found, as well as reduced antithrombin III levels during extracorporeal circulation and a rise of fibronopeptide A levels at the end of extracorporeal circulation which suggest latent fibrin production in the patients. Laboratory results were compared with clinical symptoms of post-operation bleeding. In 50% patients after surgery signs of increased haemorrhage in the surgical field and from thoracic drains were observed, in two patients the surgical wound had to be revised. Laboratory tests revealed in two patients thrombocytopenia after surgery, one patient had a prothrombin test reduced below 45% and in one patient there was a significantly reduced fibrinogen level calling for supplementation of this factor. After improvement of the laboratory results and surgical treatment haemostasis returned to normal. All patients survived the operation and were discharged from hospital to domestic treatment.

[Advances in the treatment of acute lymphoblastic leukemia in childhood: experience with intensive protocol treatments]. / Pokrok v lécbe detské akutní lymfoblastické leukémie: zkusenosti s lécbou pomocí intenzívních protokolu.

The authors analyzed a group of 64 children with acute lymphoblastic leukaemia (ALL) treated according to three protocols of different intensity. The best therapeutic results were obtained in children treated according to the most intensive protocol of the West German Multicentre Investigation BFM 83 which is graded as to its intensity with regard to the degree of risk of an adverse course. Successful remission in the entire group of patients was 93%, one third of the children developed during the investigation period a relapse of the basic disease. 12% of the children died during remission from complications of treatment. The surprising agreement of therapeutic results of different protocols after three years' complete remission is apparent from the fact that early relapses during the first two years of treatment, implying resistance to administered therapy, are at present the greatest problem of effective treatment which is not resolved even by the ever increasing intensity of treatment. In the conclusion the authors define the group of patients with a high risk of early relapse for whom new therapeutic procedures must be sought.