I. Scharrer

Immune tolerance therapy in paediatric haemophiliacs with factor VIII inhibitors: 14 years follow-up.

We report our clinical experience in the immune tolerance (IT) therapy of 21 paediatric haemophiliacs with FVIII inhibitor: high responders (16HR) received initially FVIII twice daily at a dosage of 50–300 U/kg/day, 11/16 received a concomitant treatment with activated prothrombin complex concentrate (100–200 U/kg/day). Low responders (five LR) received 20–100 FVIII U/kg every second or third day. Inhibitor elimination was achieved in 19/21 patients in a median time of 4 months in HR and 1.5 months in LR. The outcome and length of time needed to induce IT was significantly correlated with FVIII exposure between the first inhibitor detection and onset of IT therapy and to interruption of IT therapy. For a rapid elimination of FVIII inhibitors it is important to start continuous administration of high‐dose FVIII (≥ 100 FVIII U/kg/day) before repeated exposure to FVIII, in order to prevent rebooster effects, prolongation of elimination time, and to reduce expense.

Treatment patterns and cost-of-illness of severe haemophilia in patients with inhibitors in Germany.

Summary.u2002 To evaluate current treatment patterns and resource utilization as well as related cost in the management of severe haemophilia patients with inhibitors in Germany, a cost‐of‐illness study was conducted. Generally, data were generated by structured literature search. Missing data were collected by expert interviews. All data were validated by a panel of German experts in haemophilia care. In Germany, immune tolerance therapy (ITT) is first‐line therapy in inhibitor management for children in the initial year after inhibitor development, particularly for high responders (HR). In adult HR patients ITT is applied but to a remarkably lower extent than in children. To treat bleeding episodes, factor VIII (FVIII) is first‐line therapy in low responders (LR). For paediatric HR patients, bleeds are mainly treated with recombinant FVIIa (rFVIIa). In adult HR patients, activated prothrombin complex concentrate (aPCC) and rFVIIa are more equally distributed as treatment options. Treatment costs were calculated for paediatric patients (15u2003kg) and adult patients (75u2003kg) from third party payers’ perspective. Cost for ITT ranges from €70u2003290 (2u2003months; LR) to €3u2003812u2003400 (24u2003months; with aPCC; HR) in a paediatric patient. For an adult patient ITT cost ranges from €287u2003500 (6u2003months; LR) to €17u2003253u2003000 (36u2003months; HR). For on average 12.5 acute bleeds, average annual treatment costs amount to €77u2003000 for a child and €354u2003000 for an adult. Assessing the results it has been taken into consideration that ITT can last longer and annual number of bleeds can be extremely higher than on average 12.5 episodes. This indicates more health care resource consumption in some patients.

Efficacy of a sucrose-formulated recombinant factor VIII used for 22 surgical procedures in patients with severe haemophilia A.

A sucrose‐formulated recombinant FVIII (rFVIII‐SF) was investigated under clinical trial conditions during surgical procedures in previously treated patients (PTPs). Fifteen PTPs with severe haemophilia A (FVIIIu2003≤u20031%) underwent 22 surgical procedures. The procedures performed cover a spectrum from minor to major surgery. Haemostatic outcome was assessed by the investigators to be excellent in 16 procedures and good in the remaining six procedures. It is concluded that rFVIII‐SF is efficacious and safe in severe haemophilia A patients undergoing minor or major surgery.

Experience with KOGENATE Bayer in surgical procedures.

Summary.u2002u2002 The study objectives were to assess the efficacy of KOGENATE® Bayer (Kogenate® FS) in achieving haemostasis during surgical procedures in patients with severe haemophilia A and to evaluate its safety when given in the doses needed for this purpose. Dosing for surgical procedures was in accordance with clinical practice in the management of haemophilia A patients during and after surgery. Efficacy was evaluated by estimated blood loss and assessment of haemostasis as determined by the attending physician. Safety was assessed by the incidence of adverse events related to study drug and the incidence of viral seroconversions. In total, 15 previously treated patients (PTPs) and seven previously untreated patients (PUPs)/minimally treated patients (MTPs) underwent 30 surgical procedures ranging from minor (port placement/tooth extraction) to major (orthopaedic endoprosthesis/brain tumour excision) surgery. The efficacy profile was good to excellent as assessed by the attending physician, and recorded blood loss was minimal to none. No adverse events were recorded that were related to study drug. No viral seroconversions were observed. In conclusion, KOGENATE® Bayer was shown to be safe and efficacious in patients with severe haemophilia A during surgical procedures.

A high‐purity double virus inactivated FVIII/vWF concentrate (Immunate) in the successful treatment of patients with von Willebrand disease

Patients with severe forms of von Willebrand disease (vWD) most frequently require substitution of both factor VIII and von Willebrand factor (vWF). Immunate is a high‐purity, double‐virus inactivated FVIII/vWF concentrate derived from human plasma. The clinical efficacy of Immunate concerning the management of acute bleeding episodes and surgical prophylaxis in patients with von Willebrand disease (vWD) is being investigated and documented in a prospective, phase III, open‐label, single‐armed multicenter trial. Data on its pharmacokinetics are collected, and the products safety with respect to adverse experiences is monitored.

Chronische Hepatitis bei HBV-, HCV-, HIV-infizierten und koinfizierten Patienten mit angeborener Hämophilie A oder B

Mit Verfugbarkeit des Anti-HCV-Tests [1–3] stellte sich heraus, das von einer hohen Pravalenz von HCV-Antikorpern, insbesondere bei Vorliegen einer chronisch viralen Hepatitis, unter Blut- und Blutprodukt-Empfangern auszugehen ist [4–14]. Ein erheblicher Anteil HCV-Infizierter mus mit der Entwicklung einer chronisch aktiven Hepatitis bzw. einer Leberzirrhose rechnen [14–18]. Auch das hepatozellulare Karzinom scheint bei HCV-seropositiven Patienten haufiger vorzukommen [19–24]. Viele parenteral HCV-infizierte Hamophile sind zugleich HIV-infiziert [16, 25–27]. Indes ist unklar, welchen Einflus eine HIV-Infektion auf den Verlauf einer durch HCV verursachten Hepatitis ausubt. Die Befurchtung, HIV konne bei HCV-Infizierten zu einer uberdurchschnittlich haufigen bzw. raschen Entwicklung eines Leberversagens fuhren [28–32], veranlaste diese retrospektive Untersuchung, die Klinik und Laborparameter HCV-infizierter und HIV-seropositiver Patienten einerseits und HIV-seronegativer Hamophiler andererseits vergleicht.

Prävalenz und klinische Relevanz von Helicobacter pylori-Infektionen bei Patienten mit Gerinnungsstörungen

Die Isolierung von Helicobacter pylori (HP) aus der Magenschleimhaut gelang Marshall und Warren Anfang der achtziger Jahre [1]. Helicobacter pylori ist ein gramnegatives, mikroaerophil wachsendes, kommaformiges Stabchen mit 2 bis 4 Windungen. Im Gegensatz zur Spezies Campylobacter ist es lophotrich, begeiselt, Urease bildend, Nalidixinsaure resistent und hat ein eigenes Protein-, Fettsaure-und Enzymprofil [2].

In-vitro-Untersuchungen zur Sicherheit und Stabilität von Faktor-Konzentraten während kontinuierlicher Infusion

Die Substitutionstherapie fur Patienten mit Hamophilie A oder B bzw. schwerem v.-Willebrand-Syndrom erfolgt ublicherweise durch intravenose Applikation von Bolusinjektionen und ergibt typischerweise starke Schwankungen der minimalen und maximalen Plasmalevel des verabreichten Faktorkonzentrates im Laufe eines Behandlungstages und in Abhangigkeit von der Halbwertszeit des jeweiligen Konzentrats [1].

Verlaufsbeobachtung von Sexualhormonen bei HlV-infizierten Patienten mitTestosteronsubstitution bei Hypotestosteronämie

Die HIV-Infektion ist durch Defekte des Immunsystems gekennzeichnet, die insbesondere in den fortgeschrittenen Stadien der Erkrankung zu multisystemischen Storungen fuhrt, in deren Folge endokrine Dysfunktionen beobachtet warden

PAI-1 und t-PA bei Patienten mit Thrombozytosen im Rahmen von chronischen myeloproliferativen Erkrankungen

Bei Patienten mit Thrombozytosen infolge von chronischen myeloproliferativen Erkrankung (CMPE), insbesondere bei Patienten mit essentieller Thrombozythamie (ETZ), Osteomyelofibrose (OMF) und Polycythaemia rubra vera (PRV), stellen hamorrhagische und thromboembolische Episoden typische Manifestationen dar, ohne das gesagt werden kann, ob und welche Komplikationen sich im Einzelfall einstellen [8,9,15,22,23,27,28].