Variability of thromboelastographic responses following the administration of rFVIIa to haemophilia A dogs supports the individualization of therapy with a global test of haemostasis

SummarySince 1978 an annual multicentric survey regarding the epidemiology of patients suffering of haemophilia is performed with support of haemophilia treating centres of any size. Again the actual compilation is resting upon a broad database returning to over 30 years of inquiry well representing both the actual and retrospective status of mortality. Prompted was exclusively information about patients with haemophilia A, B and von Willebrand disease. In particular anonymous data concerning the last 12 months about number of treated patients, type and severity of illness, HIV-status and detailed information about causes of death was inquired. This data was merged with existing data and analyzed statistically. In the 2007/2008 survey, a total

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Thrombin generation in paediatric patients with congenital heart disease

Hämostaseologie ◽

10.1055/s-0037-1617119 ◽

2008 ◽

Vol 28 (S 01) ◽

pp. S61-S66 ◽

Cited By ~ 1

Author(s):

G. Cvirn ◽

A. Rosenkranz ◽

B. Leschnik ◽

W. Raith ◽

W. Muntean ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Negative Correlation ◽

Congenital Heart ◽

Thrombin Generation ◽

Significant Negative Correlation ◽

Peak Height ◽

Global Test ◽

Paediatric Patients ◽

Age Range

SummaryThrombin generation was studied in paediatric patients with congenital heart disease (CHD) undergoing cardiac surgery using the calibrated automated thrombography (CAT) in terms of the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. The suitability to determine the coagulation status of these patients was investigated. Patients, material, methods: CAT data of 40 patients with CHD (age range from newborn to 18 years) were compared to data using standard coagulation parameters such as prothrombin (FII), antithrombin (AT), tissue factor pathway inhibitor (TFPI), prothrombin fragment 1.2 (F 1.2), thrombin-antithrombin (TAT), activated partial thromboplastin time (aPTT), and prothrombin time (PT). Results: A significant positive correlation was seen between ETP and FII (p < 0.01; r = 0.369), as well as between peak height and F II (p < 0.01; r = 0.483). A significant negative correlation was seen between ETP and TFPI values (p < 0.05; r = –0.225) while no significant correlation was seen between peak height and TFPI. A significant negative correlation was seen between F 1.2 generation and ETP (p < 0.05; r = –0.254) and between F 1.2 generation and peak height (p < 0.05; r = –0.236). No correlation was seen between AT and ETP or peak. Conclusions: CAT is a good global test reflecting procoagulatory and inhibitory factors of the haemostatic system in paediatric patients with CHD.

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Inhibitor treatment by rituximabin congenital haemophilia A

Hämostaseologie ◽

10.1055/s-0037-1617028 ◽

2009 ◽

Vol 29 (02) ◽

pp. 151-154 ◽

Cited By ~ 13

Author(s):

Escuriola Ettingshausen ◽

R. Linde ◽

G. Kropshofer ◽

L.-B. Zimmerhackl ◽

W. Kreuz ◽

...

Keyword(s):

B Cell ◽

Immune Tolerance ◽

High Titre ◽

Clotting Factor ◽

Severe Bleeding ◽

High Morbidity ◽

Haemophilia A ◽

Concomitant Treatment ◽

Bleeding Tendency ◽

Severe Haemophilia

SummaryThe development of neutralizing alloanti-bodies (inhibitors) to factor VIII (FVIII) is one of the most serious complications in the treatment of haemophiliacs. Inhibitors occur in approximately 20 to 30% of previously untreated patients (PUPs), predominantly children, with severe haemophilia A within the first 50 exposure days (ED). Immune tolerance induction (ITI) leads to complete elimination of the inhibitor in up to 80% of the patients and offers the possibility to restore regular FVIII prophylaxis. However, patients with high titre inhibitors, in whom standard ITI fails, usually impose with high morbidity and mortality and therefore prompting physicians to alternate therapy regimens. Rituximab, an anti-CD 20 monoclonal antibody has been successfully used in children and adults for the management of B-cell mediated disorders. We report on the use of a new protocol including rituximab in two adolescents with severe haemophilia A and high titre inhibitors, severe bleeding tendency and high clotting factor consumption after failing standard ITI. Both patients received a concomitant treatment with FVIII according to the Bonn protocol, cyclosporine A and immunoglobulin. Treatment with rituximab resulted in a temporary B-cell depletion leading to the disappearance of the inhibitor. FVIII recovery and half-life turned towards normal ranges. In patient 1 the inhibitor reappeared 14 months after the last rituximab administration. In patient 2 complete immune tolerance could be achieved for 60 months. Bleeding frequency diminished significantly and clinical joint status improved in both patients. In patient 1 the treatment course was complicated by aspergillosis and hepatitis B infection. Conclusion: Rituximab may be favourable for patients with congenital haemophilia, high-titre inhibitors and a severe clinical course in whom standard ITI has failed. Prospective studies are required to determine safety, efficacy and predictors of success.

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Molecular genetic background of haemophilia A patients with discrepancy between one-stage and two-stage factor VIII assays

Hämostaseologie ◽

10.1055/s-0037-1619100 ◽

2010 ◽

Vol 30 (S 01) ◽

pp. S153-S155

Author(s):

D. Delev ◽

S. Pahl ◽

J. Driesen ◽

H. Brondke ◽

J. Oldenburg ◽

...

Keyword(s):

Factor Viii ◽

Genetic Background ◽

Molecular Genetic ◽

Haemophilia A ◽

Two Stage ◽

One Stage

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Inhibitorentwicklung nach früher hoher Exposition und Hirnblutung

Hämostaseologie ◽

10.1055/s-0037-1619091 ◽

2010 ◽

Vol 30 (S 01) ◽

pp. S115-S118

Author(s):

C. Moorthi ◽

A. Bade ◽

C. Niekrens ◽

G. Auerswald ◽

K. Haubold

Keyword(s):

High Titer ◽

Cerebral Haemorrhage ◽

High Dose ◽

Haemophilia A ◽

Severe Haemophilia ◽

Intron 22 Inversion ◽

Neurosurgical Intervention

SummarySevere haemophilia A was diagnosed postpartum in a newborn. The mother was known as a conductor (intron 22 inversion) and an uncle had a persistently high titer inhibitor after failed ITI.Due to a cephalhaematoma, a high-dose pdFVIII substitution was given within the first days after birth. At the age of six month a severe cerebral haemorrhage occurred, making a high-dose pdFVIII substitution and neurosurgical intervention necessary. Several days later a porth-a-cath-system was implanted. The development of a high titer inhibitor occured six days later, an ITI was started according to the Bonn Protocol. Initially rFVIIa was given in addition to the pdFVIII substitution. Seven days after the beginning of treatment the inhibitor was no longer detectable. At monthly intervals the FVIII dosage was reduced until the dosage complied with a prophylaxis in severe haemophilia A.The duration of the ITI was nine months. A total of 30 mg rFVIIa and 276 000 IU pdFVIII were used; costs in total: 280 173.60 Euro.

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Management of acute haemarthrosis in haemophilia A

Hämostaseologie ◽

10.1055/s-0037-1619070 ◽

2010 ◽

Vol 30 (S 01) ◽

pp. S44-S45

Author(s):

R. Klamroth ◽

M. von Depka ◽

M. Richards ◽

P. de Moerloose ◽

K. Fischer ◽

...

Keyword(s):

Haemophilia A

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