[Incidence of thromboembolic events after major operations in patients with haemophilia]. / Untersuchung zum postoperativen Verlauf bei Patienten mit Hämophilie.

UNLABELLED: Thromboembolic complications may occur in patients with major operations even after routine thromboprophylaxis with low-molecular-weight-heparin. In this retrospective, single center survey the post-operative course of patients with haemophilia was investigated. PATIENTS, METHODS: Overall, the postoperative course in 85 patients with haemophilia A and B (median age: 43 years, 18-73 years) and 139 surgical procedures was analyzed. The surgical procedures mainly consist of major orthopedic surgery (58 total knee replacement, 15 hip replacement, 17 other major orthopedic surgery, 15 minor orthopedic procedures). Additional surgical procedures were abdominal-surgical (18), urological (8), neurosurgical (5). RESULTS: During the post-operative observation period a small number of wound healing complications occurred (4%). None of the patients developed symptomatic deep vein thrombosis or lung embolism. CONCLUSION: There seems to a decreased risk of postoperative thromboembolism in patients with haemophilia.

[Inhibitor development after changing FVIII/IX products in patients with haemophilia]. / Hemmkörperentwicklung bei Hämophilie-Patienten nach Präparatewechsel. Steigt das Risiko beim Präparatewechsel an?

UNLABELLED: The retrospective observational study surveys the relationship between development of inhibitors in the treatment of haemophilia patients and risk factors such as changing FVIII products. A total of 119 patients were included in this study, 198 changes of FVIII products were evaluated. RESULTS: During the observation period of 12 months none of the patients developed an inhibitor, which was temporally associated with a change of FVIII products. A frequent change of FVIII products didn't lead to an increase in inhibitor risk. The change between plasmatic and recombinant preparations could not be confirmed as a risk factor. Furthermore, no correlation between treatment regimens, severity, patient age and comorbidities of the patients could be found.

[Does FVIII-activity increase with age in patients with haemophilia A and carriers of haemophilia A?]. / Hämophilie-A-Patienten und Konduktorinnen für Hämophilie A. Steigt die FVIII-Aktivität mit dem Lebensalter?

UNLABELLED: The retrospective cohort study surveys the influence of age, co-morbidity and laboratory values on FVIII-activity (FVIII:C) in patients with haemophilia A with (mild n = 48, moderate n = 10, severe n = 7 and carriers n = 23). Median observation was 19 years for patients with haemophilia A and 9,5 years for carriers. RESULTS: FVIII:C levels collected from patients with mild haemophilia A displayed a significant median increase of 6.5% with proceeding age (p = 0.0013). Patients with moderate haemophilia A (and carriers of haemophilia A) showed a non significant median increase of 1.05% (carriers 8%). Eight patients showed FVIII:C levels at last blood withdrawal that indicated a change of severity from moderate to mild haemophilia A. A significant correlation was found between FVIII:C and VWF:RCo (p = 0.0203) and AFP (p < 0.0005). The correlation between FVIII:C and triglycerides and LDH was significant negative (p < 0.0005). No significant correlation could be found for FVIII:C and co-morbidity, fibrinogen, cholesterol and VWF:Ag.

Clinical assessment of efficacy and safety of DDAVP.

UNLABELLED: The efficacy of DDAVP (1-deamino-8-D-arginine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29±0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP. RESULTS, CONCLUSION: Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.

Treatment of haemophilia in the elderly.

UNLABELLED: Treatment of elderly patients with haemophilia is an upcoming challenge in haemophilia care. We included patients with haemophilia A older than 60 years of age, who visited our haemophilia centre between 2006 and 2008. We conducted a retrospective study focussing on the patients' co-morbidities as well as changes in their bleeding patterns between 2003 and 2008. RESULTS: There is a tendency of increasing bleeding symptoms with increasing age of the patients due to more frequent spontaneous joint bleedings, malignancies or treatment with phenprocoumon or ASS. In consequence, FVIII dosage had to be increased for 8 patients (28%). Chronic hepatitis C, coronary heart disease and malignancies are the most frequent co-morbidities.

Age-dependent increase of FVIII:C in mild haemophilia A.

Variability of FVIII:C levels in healthy individuals and age-dependent increase are a known phenomenon. In haemophilia, increasing FVIII:C levels with age have not been described yet. In our study, we evaluated this issue retrospectively in a cohort older than 45 years of 29 patients with mild haemophilia and 14 patients with moderate or severe haemophilia at last visit at the haemophilia centre Frankfurt. The median duration of observation evaluated in this study was 17 years (range 5-28). Results show a significant correlation of increasing FVIII:C levels with age in mild haemophilia (P = 0.000041) and a non-significant tendency to a higher increase in higher age (P = 0.085652). The median difference of FVIII:C level between the first and last measurement was 8% of normal plasma concentration (range -3% to +35%). Median FVIII:C level increase of patients younger than 62 years was 7.5% (range -3 to 22), median increase in older patients was 12% (range 0-35). This tendency could not be correlated to decreased number of bleedings, but FVIII substitution dosage should be adapted to changing plasma levels at higher age to prevent overdosing or thrombotic risks. Possible causes and contributing factors for increasing FVIII:C levels are discussed. Statistical significance remains to be confirmed in larger prospective studies also including younger patients.

Comorbidities and bleeding pattern in elderly haemophilia A patients.

The increasing numbers of comorbidities related to higher age and their treatment constitute a challenge in the treatment of haemophiliacs. Comparing prevalences of morbidities in the elderly haemophilia A population (n = 29) and the general elderly population of Germany reveals some differences. HCV infections are more frequent in the elderly haemophilia population (69% vs. 0.6%). Prevalence of cancer was five times higher than in the age matched general population (28% vs. 5.2%). Cardiac diseases seem to be less frequent although the prevalences of cardiovascular risk factors like hypertension, diabetes, and body mass index (BMI) >25 do not differ in comparison to the general population. A reduction of bleeding symptoms or dosage of FVIII could not be observed. There is a tendency of increasing bleeding symptoms with increasing age of the patients due to more frequent spontaneous joint bleedings, malignancies or treatment with phenprocoumon or ASA. In consequence, FVIII dosage had to be increased in eight patients (28%). Our patient population at the age >60 years is very small and no statistical evidence can be shown, therefore appropriate treatment of elderly haemophiliacs needs further evaluation in multicentre studies with sufficient patient numbers.

Non-steroidal and steroidal anti-inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis.

The role of dendritic cells (DCs) in allergic contact dermatitis has been clearly demonstrated for the induction phase. However, the situation during the elicitation phase is very complex within a distinct inflammatory response. This study was performed to exploit DC migration in the elicitation phase in a mouse model of allergic contact dermatitis and to evaluate the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) on DC migration through skin in the elicitation phase of allergic contact dermatitis. Topically and systemically administered acetylsalicylic acid (ASA) did not reduce the inflammatory response. However, systemically administered ASA significantly reduced the DC migration to the draining lymph node. In contrast, topically administered indomethacin reduced the inflammatory response, but had only minor effects on DC migration, whereas diflorasone diacetate reduced both inflammatory reaction and DC migration. Thus, NSAIDs may differ in their inhibitory action in immunological inflammation.