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Das hereditare Angioodem (HAE) aufgrund eines Mangels an funktionellem C1-Inhibitor (HAE-C1-INH) ist eine seltene Erkrankung, die oft bereits im Kindesalter zu unregelmasig auftretenden Episoden potenziell lebensbedrohlicher Odeme fuhrt. Eine fruhe Diagnose ist wichtig, um unwirksame Therapiemasnahmen zu vermeiden und Odeme richtig zu behandeln. Auf einem Konsenstreffen im Juni 2011 diskutierten Kinderarzte und Dermatologen aus Deutschland, Osterreich und der Schweiz die Literatur einschlieslich der internationalen Konsensempfehlungen zur HAE-Therapie fur alle Altersgruppen. Aufgrund des derzeitigen Zulassungsstatus konnen diese Empfehlungen nicht ohne Vorbehalt fur die Padiatrie in deutschsprachigen Landern ubernommen werden. Dieser Artikel gibt einen Uberblick und diskutiert die zur HAE-Therapie erhaltlichen Medikamente, den Zulassungsstatus und Studien mit Erwachsenen und padiatrischen Patienten. Empfehlungen fur adaquate Behandlungsstrategien fur Kinder und Jugendliche im deutschsprachigen Raum werden gegeben. Die derzeit beste zugelassene Option fur die Behandlung akuter HAE-C1-INH-Attacken und fur die Kurz- und Langzeitprophylaxe bei padiatrischen Patienten im deutschsprachigen Raum ist aus Plasma gewonnenes C1-Inhibitor-Konzentrat.

Hintergrund. In einer prospektiven Studie wurden Viruslastsenkung, CD4-Zellanstieg, Compliance und Resistenzentwicklung bei 16 therapienaiven padiatrischen Patienten uber einen Zeitraum von 24 Monaten unter einer initialen 3fach-Therapie untersucht. Die Auswertung erfolgte als Intention-totreat-Analyse.

Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0-16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0-17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1, combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92-17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6-65.6; P0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients.Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.

To evaluate the role of multiple established and potential causes of childhood thrombophilia, 285 children with a history of thrombosis aged neonate to 18 years (first thrombotic onset) were investigated and compared with 185 healthy peers. APC- resistance (FV:Q506), protein C, protein S, antithrombin, heparin cofactor II (HCII), histidine-rich glycoprotein (HRGP), and prothrombin (F.II), factor XII (F.XII), plasminogen, homocysteine and lipoprotein (a) (Lp(a)) were investigated. In 59% of patients investigated one thrombotic defect was diagnosed, 19.6% showed two thrombotic risk factors, while in 21.4% of children investigated no risk factor could be identified. Single defects comprised established causes of inherited thrombophilia: FV:Q506 (homozygous n = 10, heterozygous n = 69), protein C (homozygous n = 1; heterozygous n = 31), heterozygous type I deficiency states of protein S (n = 7), antithrombin (n = 7) and homocystinuria (n = 6); potentially inherited clotting abnormalities which may be associated with thrombophilia: F.XII (n = 3), plasminogen (n = 2), HCII (n = 1), increased HRGP (n = 4); new candidate risk factors for thrombophilia: elevated plasma levels of Lp(a) (n = 26), F.II (n = 1). Heterozygous FV:Q506 was found in combination with heterozygous type I deficiency states of protein C (n = 2), protein S (n = 13), antithrombin (n = 8) and HCII (n = 1), increased Lp(a) (n = 13), and once each with elevated levels of F.II, moderate hyperhomocysteinemia, fibrinogen concentrations >700 mg/dl and increased HRGP. In addition to the association with FV:Q506, heterozygous protein C type I deficiency was combined with deficiencies of protein S (n = 2), antithrombin (n = 1), and increased Lp(a) (n = 3). One patient showed protein C deficiency along with familially increased von Willebrand factor >250%. Besides coexistence with FV:Q506 and protein C deficiency, protein S deficiency was combined with decreased F.XII and increased Lp(a) in one subject each. Furthermore, we found combinations of antithrombin deficiency/elevated Lp(a), hyperhomocysteinemia/Lp(a), deficiency of HCII/plasminogen, and plasminogen deficiency along with increased Lp(a) each in one. Increased prothrombin levels were associated with fibrinogen concentrations >700 mg/dl and with HCII deficiency in one child each. Carrier frequencies of single and combined defects were significantly higher in patients compared with the controls. Conclusion In conclusion, data of this multicentre evaluation indicate that paediatric thromboembolism should be viewed as a multifactorial disorder.

A survey among centres of the paediatric group of the GTH was performed to evaluate the prevalence and outcome of haemophiliacs with intracerebral haemorrhage. A questionnaire sent to the centres covered the following points: number of patients with severe, moderate and mild haemophilia A and B; for each patient with ICH: birth date, age at bleeding, aetiology and neurological sequelae. Overall, 30 ICH in 744 haemophiliacs (4.0%) were reported by 17/40 centres (42.5%). There was no significant difference between the prevalence of patients with haemophilia A and B (3.5% vs. 6.3%) and among the age groups. Bleeding was diagnosed within 1 week of birth in 11/27 patients (41%). For 3 patients, no age-related information was given. The most important factor was trauma (17/30 = 57%), either during birth (9/30 = 30%) or later in life (8/30 = 27%). Seizures were common, occurring in 19/30 patients (63%). As 1 patient died after posttraumatic ICH, the neurological outcome of 29 patients could be evaluated. Psychomotor and statomotor retardation and cerebral palsy were reported in 17/29 (59%), 15/29 (51%) and 13/29 (45%) patients respectively. Only 7/29 (24%) showed no neurological sequelae. Severity of deficits was not correlated with birth date but to age at bleeding. Older children showed a better neurological outcome than neonates.The frequency and outcome of ICH in haemophiliacs have not changed in our cohort over the past 20 years. Trauma at birth is an important risk factor for ICH in patients with haemophilia A or B. Intracranial haemorrhages in older children are rare, and a better outcome may be expected.

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of >400, cells/μl per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of

Background Manifestation of acute edema in hereditary angioedema (HAE) is characterized by interindividual and intraindividual variability in symptom expression over time. Flexible therapy options are needed. Methods We describe and report on the outcomes of the highly individualized approach to HAE therapy practiced at our HAE center in Frankfurt (Germany). Results The HAE center at the Frankfurt University Hospital currently treats 450 adults with HAE or AAE and 107 pediatric HAE patients with highly individualized therapeutic approaches. 73.9% of the adult patients treat HAE attacks by on-demand therapy with pasteurized pd C1-INH concentrate, 9.8% use additional prophylaxis with attenuated androgens, 1% of the total patient population in Frankfurt has been treated with Icatibant up to now. In addition adult and selected pediatric patients with a high frequency of severe attacks are instructed to apply individual replacement therapy (IRT) with pasteurized pd C1-INH concentrate. Improvement on Quality of Life items was shown for these patients compared to previous long-term danazol prophylaxis. Home treatment of HAE patients was developed in the Frankfurt HAE center in line with experiences in hemophilia therapy and has so far been implemented over a period of 28 years. At present 248 (55%) of the adult patients and 26 (24%) of the pediatric patients are practicing home treatment either as on demand or IRT treatment. Conclusions In conclusion, the individualized home therapies provided by our HAE center, aim to limit the disruption to normal daily activities that occurs for many HAE patients. Furthermore, we seek to optimize the economic burden of the disease while offering a maximum quality of life to our patients.

We report on a 14-year-old boy with severe haemophilia A who developed a portal vein thrombosis during continuous infusion of F VIII. For treatment of a posttraumatic intramural jejunal haematoma with extension into the mesenterium the patient received continuous infusion (CI) of a high purity F VIII concentrate, starting with an initial bolus injection of 100 IU F VIII/kg bw and followed by 4-5 IU F VIII/kg bw/h i.v. F VIII plasma activity ranged between 47 and 88%. Resorption of the haematoma was proven by abdominal ultrasonic follow-ups. After 3 weeks of CI a thrombus formation in the portal vein was detected by ultrasound and confirmed by duplex ultrasound. Subsequent to diagnosis the patient was heparinised with unfractionated heparin (UFH 300-450 IU/kg/d i.v.). In order to induce further resorption of the haematoma. F VIII concentrate was given concomitantly (50 IU/kg bw twice daily) during the initial phase of treatment. After 14 days of anticoagulant therapy with UFH, the regimen was changed to low molecular weight heparin (LMWH; Fraxiparin 0.3; 2850 IU anti-X activity/d s.c.; bw 60 kg). F VIII dosage was gradually reduced with advanced resorption of the haematoma and thereafter switched to prophylaxis (40 IU/kg bw 3 times weekly). Complete lysis of the thrombus was observed after 6 months of treatment with UFH and LMWH respectively without any further complications. Thereafter LMWH was discontinued. Thrombophilic screening revealed no abnormalities except heterozygous F V G1691A.The coexistence of a common prothrombotic risk factor and haemophilia may cause severe complications, in particular if the bleeding disorder has to be corrected temporarily by administration of the concerning deficient agent.

Introduction: Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods: In Germany, patients receiving protein C concentrate (Ceprotin(R), Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this National, retrospective, multi-centered study. Results: Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions: This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.