Congenital combined deficiency of coagulation factors VII and X--different genetic mechanisms.

Combined coagulation factor VII (FVII) and factor X (FX) deficiency (combined FVII/FX deficiency) belongs to the group of bleeding disorders in which both factors show reduced plasma activity. It may arise from coincidental inheritance of separate coagulation factor deficiencies or a common cause as large deletions comprising both gene loci. The F7 and F10 genes are located on the long arm of chromosome 13. Here, we describe 10 cases with combined FVII/FX deficiency representing both genetic mechanisms of occurrence. Genetic analyses included direct sequencing of the F7 and F10 genes and MLPA (multiplex ligation-dependent probe amplification) for detection of heterozygous large deletions. In four patients, the combined deficiency was due to a large deletion within the terminal end of chromosome 13. In the remaining six cases the deficiency resulted from coincidental inheritance of different genetic alterations affecting both genes independently. In most cases, the genetic defects were heterozygous, presenting with prolonged PT, normal aPTT and mild or no bleeding symptoms. Only in one case compound heterozygous mutations were detected in the F10, resulting in prolonged aPTT and a more severe bleeding phenotype. To avoid a misdiagnosis of combined FVII/FX deficiency, analyses of single factor activities have to be performed in all cases with prolonged PT even if aPTT is normal. Genetic analyses are substantial for correct prediction of an inheritance pattern and a proper genetic counselling.

In vitro characterization of recombinant factor VIII concentrates reveals significant differences in protein content, activity and thrombin activation profile.

Recombinant factor VIII (rFVIII) concentrates differ due to cell lines, culture conditions, presence of the B domain and authorized potency assays. This study characterizes three commercially available rFVIII concentrates: a second-generation full length (A), a third-generation full length (B) and a third-generation B domain-deleted (BDD) product (C). rFVIII concentrates were characterized for FVIII activity (FVIII:C) by one-stage clotting and chromogenic assays, FVIII antigen (FVIII:Ag), thrombin activation profile and FXa-generation assay. The rFVIII concentrates exhibited significant differences with regard to FVIII:C, FVIII:Ag and thrombin activation profile. Product A had significantly greater FVIII:C and FVIII:Ag relative to the measured values of products B and C. In addition, product A demonstrated faster and more complete activation by thrombin than the two others. BDD product C had the slowest measured thrombin activation rate. Product A exhibited a greater in vitro FXa generation than products B and C. We found no differences in FXa generation among all three products when FXa generation was normalized for FVIII:Ag. The greater FVIII:C and FVIII:Ag values for product A compared with that for products B and C are due to application of different authorized potency assays (one-stage assay for A vs. chromogenic assay for B and C). The variation in thrombin activation profiles may arise from differences in cell line-dependent posttranslational modifications of the various recombinant proteins.

[Prevalence and prognostic importance of riskfactors for long hospital stay within elderly patients admitted to a hospital; a clinical-empirical study]. / Prevalentie en prognostisch belang van risicofactoren voor lange opnameduur onder ouderen bij ziekenhuisopname; een klinisch-empirische studie.

BACKGROUND: Of elderly patients (> 70 years) admitted to a general hospital 35% suffer from loss of self-care abilities compared to the level before admission. Risk of loss of self-care ability increases with age up to 65% after tthe age of 90. In addition, for many of these patients the duration of hospitalisation is relatively long. OBJECTIVE It is important to identify in an early stage frail-elderly patients who are at risk of a relatively long hospital stay. We conducted a study of the prevalence at intake (1st of 2nd admission day) of ten clinically relevant, patient-bound risk factors for a long hospital stay among 158 patients (> 60 years), acute and planned admitted to Vlietland Hospital. In addition, the prognostic value of the dichotomous risk factors for length of hospital stay was estimated as indicator of treatment complications. The ten clinically relevant risk factors were home care, history of falling, medication (> 4), weight loss, cognitive level and functioning, self-care, psychiatric symptoms, health status and quality of life. RESULTS: There was a high prevalence of risk factors; 47.5% of the elderly patients had four or more risk factors at intake. Home care and global cognitive deterioration were significant predictors of longer length of hospital stay. Furthermore, acute admission, weight loss, psychiatric symptoms and health status seemed important. The explained variance of the prognostic model was relatively small. CONCLUSION: The findings in this explorative-observational study showed a high prevalence of clinically relevant, patient-bound risk factors in elderly people in a general hospital. Some risk-factors were of prognostic interest for long hospital stay, although the explained variance was relatively small. This indicates that a more comprehensive study should be designed and conducted to include other patient-bound risk factors like co-morbidity, caregiver issues and social environment. Moreover, non-patient-bound factors should be addressed like intrinsic and logistic factors within the hospital, and the quality of recuperation programmes. Understanding of these factors contributes to timely identification of elderly patients, who are at high risk of a long hospital stay. Future policy is to perform specific treatment programmes for elderly patients identified as being patients at risk. Multidisciplinary person-oriented interventions and case management focussed on risk factors and functional recovery will be provided parallel and after hospital treatment period. Comprehensive scientific research on the cost-effectiveness of such a programme has started at the end of 200oo9 in Vlietland Hospital, Schiedam.

Oral contraceptive induced paraballism.

We report a case of paraballism in a young female, which became apparent 4 months after initiating oral contraception. When the oral contraceptive was discontinued, the paraballism decreased and was replaced by choreic movements for a period of approximately 2 weeks. The abnormal movements disappeared gradually. Only 13 cases of paraballism have been reported in medical literature, and none has been attributed to the use of oral contraceptives.

PIP: Paraballism in a 28-year old woman, associated with her 4 month intake of oral contraceptives, is described here. This constitutes only the 14th such case in the literature, and the only one in a pill user. The woman had pain in the head and neck when she first took the pill, Ovostat (1 mg lynestrenol, and 50 mcg ethinyl estradiol. Later she developed abnormal movements in the arms, neck and face. She was hospitalized in a psychiatric ward for depression, in response to the movements, and treated briefly with propanolol for palpitations. Her neurological findings were ballet-like movements of both arms, torsion movements of the neck, grimacing of the face, choreiform movements of both hands, and involuntary kicking while walking. The only other findings were an ejection murmur, and hypertrophied interventricular septum on the echocardiogram. When the pill was discontinued, the ballistic movements disappeared within days and the chorea within 2 weeks. The woman was discharged in a month with no complaints. A year later she bore her first child, with no return of abnormal movements.