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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 57 (1979), S. 81-86 
    ISSN: 1432-1440
    Keywords: Blutgerinnung bei Neugeborenen ; Vitamin K-Mangel ; Disseminierte intravasale Gerinnung ; Blood coagulation in newborns ; Vitamin K deficiency ; Disseminated intravascular coagulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In the newborn period low vitamin K dependent coagulation factors are frequently found in connection with normal global tests. To investigate this peculiar coagulation status studies were performed in 54 newborns who were divided into three groups according to their clinical course and the existence of bleeding. The results are compared to coagulation tests used for the diagnosis of disseminated intravascular coagulation (DIC). An early sign of an increased turnover of coagulation factors is a difference in the fibrinogen concentration determined by an immunological technique and a coagulation test which is sensible to fibrin(ogen)-degradation-products (FDP's). At this stage factor II, V and VII levels are still within the normal range suggesting an increased production. In a more severe disturbance of the clotting system the increased turnover is no longer compensated by an increased production, and platelets and later on factor II and VII levels are lowered. At this early stage of DIC the vitamin K dependent factors are correlated to the factors I and V. Finally factors I and V drop as well. This stage in most infants is accompanied by the clinical symptom of bleeding. The clotting tests results are well correlated to the severity of the disease.
    Notes: Zusammenfassung Bei Neugeborenen sind trotz normaler Globaltests die Vitamin K abhängigen Gerinnungsfaktoren häufig vermindert. Um diesen Befund näher zu untersuchen, wurden Gerinnungstests bei 54 Neugeborenen durchgeführt, die je nach ihrem klinischen Zustand und dem Auftreten von Blutungen in 3 Gruppen aufgeteilt wurden. Die Ergebnisse wurden mit Tests verglichen, die eine Verbrauchskoagulopathie anzeigen. Ein frühes Anzeichen eines Verbrauchs von Gerinnungsfaktoren ist die Diskrepanz zwischen dem immunologisch bestimmten und dem gerinnungsaktiven Fibrinogen. Bekanntlich können die Spaltprodukte die Fibrinogenbestimmung mit Thrombin erschweren, während sie immunologisch wie Fibrinogen bestimmt werden können. In diesem Stadium sind die Faktoren II, V and VII noch im Normbereich, was auf eine erhöhte Neubildung schließen läßt. Mit zunehmendem Verbrauch kommt es zuerst zu einer Abnahme der Plättchenzahl sowie der Faktoren II und VII. In diesem Stadium der Verbrauchskoagulopathie korrelieren die Vitamin K abhängigen Faktoren mit den Faktoren I und V. Klinisch kommt es in diesem Stadium häufig zu Blutungen. Die Ergebnisse der Gerinnungsuntersuchungen korrelieren gut mit dem Schweregrad der Erkrankung.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 137 (1981), S. 189-194 
    ISSN: 1432-1076
    Keywords: Factor VIII: C ; Factor VIII R: Ag ; Newborns ; DIC ; Diagnosis of hereditary bleeding disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Higher levels of factor VIII: C and factor VIII R: Ag were found in healthy newborns (n=60) as compared to adults. This could be explained as a stress reaction due to birth and the adaptation to extrauterine life. A further stress factor is disease. The highest values for factor VIII R: Ag were found in ill (n=32) and in severely ill newborns (n=21). The large ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in healthy newborns can be explained by an increased turnover of coagulation factors. Diseases in the newborn period lead to an increase of this process, resulting in even larger ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in ill and extremely ill newborns. Consumption of factor VIII: C with a low ratio of factor VIII: C/VIII R: Ag predominates in extremely ill newborns. The ratio of factor VIII: C/VIII R: Ag is more valuable than factor VIII: C for diagnosis of DIC in newborns. A diagnosis of hemophilia and von Willebrand's disease cannot be established with certainty in severely ill newborns. Stress and DIC may influence the characteristic changes of laboratory parameters.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1076
    Keywords: Acute lymphoblastic leukaemia ; Childhood ; Combination chemotherapy ; Rotation of drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (cach combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year eventfree survival (EFS) rate for the whole group is 69%±3%, and the survival rate 75%±3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12%±7% vs. 75%±3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged 〈1 year (6/6 relapses) or aged 〉=10 years had a worse prognosis (EFS 64%±5% vs. 77%±4% in patients 1–10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC〉=100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72%±5% vs. RR 67±5%).
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: Key words Acute lymphoblastic ; leukaemia ; Childhood ; Combination chemotherapy ; Rotation of drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (each combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year event-free survival (EFS) rate for the whole group is 69% ± 3%, and the survival rate 75% ± 3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12% ± 7% vs. 75% ± 3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged 〈 1 year (6/6 relapses) or aged ^ 10 years had a worse prognosis (EFS 64% ± 5% vs. 77% ± 4% in patients 1–10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC ^ 100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72% ± 5% vs. RR 67 ± 5%). Conclusion The COALL 85/89 treatment protocol with early intensive therapy and rotation of different drug combinations offers long-term disease-free survival for children with high-risk ALL. A continuous 4-week exposure to one drug combination may be necessary to achieve optimal results, especially in children with a high leukaemic cell burden.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1076
    Keywords: Key words Chronic relapsing ; Thrombotic thrombocytopenic purpura ; Von Willebrand factor-cleaving protease ; Prophylactic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults but also children have been described with this condition. The disorder may take a relapsing course, termed chronic relapsing TTP (CRTTP), which although very rare, may also begin in childhood. Deficiency of a recently identified enzyme, the von Willebrand factor (vWF)-cleaving protease, seems to play a major role in the development of TTP. We report on a 3-year-old boy with a dramatic but typical clinical course of CRTTP. At the time of diagnosis, neurological deficits and multiple cerebral infarctions had already occurred. In plasma, vWF-cleaving protease was completely absent, both during acute TTP and in remission. There was no protease inhibitor detected. Regular infusions of fresh frozen plasma were successfully given for replacement on a prophylactic basis. Conclusion Assay of von Willebrand factor-cleaving protease helps to diagnose a form of thrombotic thrombocytopenic purpura which may be managed by prophylactic treatment with fresh frozen plasma.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1076
    Keywords: Juvenile laryngeal papillomatosis ; Leukocyte interferon ; Fibroblast interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The efficiency of human fibroblast interferon (IFN-β) and human leukocyte interferon (IFN-α) was evaluated in two children with recurrent laryngeal papillomatosis. Both children failed to respond to fibroblast interferon, however the laryngeal papillomatosis disappeared when leukocyte interferon was applied. Possible explanations for these findings are discussed.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1076
    Keywords: Key words Haemophilia ; Bleeding ; Diagnosis ; On-demand therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this single-centre study was to obtain data prospectively on when children are diagnosed as having severe haemophilia and when they start to bleed. Results of this 10-year PUP study suggest that severe haemophilia is nowadays diagnosed much earlier than in the Sixties. Patients with severe haemophilia (n = 37; FV III 〈0.01 U/ml) start to bleed at very different ages. While 44% of patients have their first bleeding episode within the first year of life, others do not bleed before the age of four. The onset of joint bleedings generally occurs about half a year later than other types of bleeding. While half our patients developed their first bleeding by the age of 1.22 years, the mean age for the first joint bleeding was 1.91 years. Conclusion Early-onset prophylactic therapy can prevent damage to the joints, but for rational therapy the age at onset of bleeding must also be taken into account. A non-bleeding child does not benefit from prophylactic treatment.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1076
    Keywords: Acute lymphocytic leukaemia ; Chemotherpy ; Methotrexate ; Vincristine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One hundred and fifty-one children with acute lymphocytic leukaemia (ALL) received multiple agent induction chemotherapy followed by intensive phase treatment. One hundred and thirty-seven patients were randomised for the first year of maintenance treatment to receive reinforcement therapy (pulses) with either intermediate-dose methotrexate (ID-MTX) and prednisone (PRED) or vincristine (VCR) and PRED. The probablity of continuous complete remission (CCR) at 5.5 years is 0.80 for the ID-MTX group and 0.84 for the VCR group. Extramedullary relapses were not prevented either in the ID-MTX group nor in the VCR group. Since in previous studies VCR/PRED pulses did not increase CCR rates when given after intensive combination chemotherapy, it can be concluded from this study that neither did ID-MTX reinforcement therapy further improve treatment results in our patients with ALL when given after aggressive chemotherapy.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1076
    Keywords: Key wordsE. coli asparaginase ; Erwinia asparaginase ; Childhood ALL ; Coagulation ; Fibrinolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently we reported the influence of two different Escherichia coli asparaginase (ASP) preparations on fibrinolytic proteins in childhood acute lymphoblastic leukaemia (ALL) demonstrating a significant association between ASP activity and haemostatic alterations. The present study was designed for prospective evaluation of coagulation and fibrinolytic parameters in leukaemic children receiving different ASP preparations during the course of re-induction. Forty leukaemic children receiving ASP (Medac: n = 13; Bayer: n = 10; Erwinia: n = 17) at 3-day intervals during re-induction were enrolled in this study. Blood samples for coagulation studies were obtained before each ASP administration together with serum samples for pharmacokinetic monitoring. Compared with Medac ASP 10,000 IU/m2, patients receiving Bayer ASP or Erwinia ASP showed significantly higher fibrinogen values. Antithrombin and plasminogen showed normal values in children after Erwinia ASP. α2-antiplasmin and D-Dimer were no different in the groups studied. Neither side-effects, nor sustained asparagine depletion was observed in the majority of children treated with Erwinia ASP. Conclusion Data of this study show a down-regulation of coagulation proteins in children treated with Medac ASP, less pronounced in patients after Bayer or Erwinia ASP. Since children treated with Erwinia ASP showed no adequate asparagine depletion during the course of ASP therapy, a dose adjustment should be discussed to guarantee asparagine depletion, the specific metabolic therapy for ALL.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1076
    Keywords: Respiratory distress syndrome ; Disseminated intravascular coagulation ; Heparin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Forty newborns with severe shock and disseminated intravascular coagulation were randomized for treatment with heparin or placebo. Mortality was equal in both groups. The heparin group required significantly shorter periods of artificial ventilation. The coagulation system improved faster, and the coagulation pattern showed normal values in the treatment group. Due to the low number of cases, these differences could not be statistically confirmed.
    Type of Medium: Electronic Resource
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