Franz Keller

Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women.

Women with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregnant women at increased risk of VTE. In a prospective trial (Efficacy of Thromboprophylaxis as an Intervention during. Gravidity [EThIG]), 810 pregnant women were assigned to one of three management strategies according to pre-defined risk factors related to history of VTE and thrombophilic profile. Low-risk women (group I), received 50-100 IU dalteparin/kg body weight/day for 14 days postpartum, or earlier when additional risk factors occurred. Women at high (group II) or very high risk (group III) received dalteparin from enrollment until six weeks postpartum (50-100 IU and 100-200 IU/kg/day, respectively). Objectively confirmed, symptomatic VTE occurred in 5/810 women (0.6%; 95% confidence interval [CI], 0.2 to 1.5%) (group I, 0 of 225; II, 3/469; III, 2/116). The rate of serious bleeding was 3.0% (95 % CI, 1.9 to 4.4%); 1.1% (95 % CI, 0.5 to 2.2%) was possibly dalteparin-related. There was no evidence of heparin-induced thrombocytopenia, one case of osteoporosis, and rates of miscarriage and stillbirth were similar to previous, retrospective studies. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomaticVTE and few clinically important adverse events. Antepartum heparin prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis or symptomatic thrombophilia.

Familial Clustering of High Factor VIII Levels in Patients With Venous Thromboembolism

Abstract —High levels of factor VIII (FVIII) but not von Willebrand factor (vWF) are known to increase the risk for venous thromboembolism. Whether high FVIII levels originate from hereditary defects or from acquired conditions remains unanswered. The objective of our study was to investigate whether there is evidence for familial clustering of elevated FVIII levels in families in which ≥1 member has been affected by a thromboembolic event and had reproducibly high FVIII levels. We investigated FVIII levels in 361 patients with previous venous thromboembolism. FVIII levels were measured by a chromogenic assay; the cutoff value was defined as the 98th percentile of FVIII plasma levels of 266 blood donors. vWF levels were determined by an enzyme immunoassay. After exclusion of known causes of FVIII elevation, such as the acute thrombotic event itself; inflammation; malignancy; liver, renal, or vascular disease; surgery; or pregnancy, we included 17 patients with unexplained, reproducibly high FVIII levels. The investigation was also extended to these patients’ relatives. Multiple regressive analysis of blood donors and asymptomatic family members showed that the affiliation with a family in which 1 member suffered from venous thromboembolism and had reproducibly high FVIII levels is the second most important predictor for FVIII levels. Familial clustering was analyzed by the Houwing-Duistermaat familial aggregation test. After adjustment for the influence of age, sex, blood group, and vWF, FVIII levels were significantly (P =0.038) clustered within families. In conclusion, FVIII levels seem to be familially determined in families in which a member showed high FVIII levels after previous venous thromboembolism.

MODULAR ANALYTICS: A New Approach to Automation in the Clinical Laboratory

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.

Therapy of coagulation factor VIII autoantibodies with long-term extracorporeal protein A adsorption and immunosuppression.

UNLABELLED Acquired factor VIII (FVIII) inhibitors in non-haemophiliacs may pose serious treatment problems. MATERIALS AND METHODS For IgG-adsorptions we utilized an automated plasma separation device and a plasma flow monitor. CASE REPORTS A 63-year old woman showed life-threatening bleeding because of an inhibitor. After stabilization by porcine FVIII three cycles of a modified Malmoe treatment protocol were applied, followed by long-term cyclophosphamide p.o. and weekly IgG-adsorptions. Within twelve months the patient exhibited a complete remission. A 54-year old man presented a comparable history. Because of a good response after the first cycle he was subsequently switched to the long-term therapy. Up to now (> 7 months) FVIII activities and inhibitor titers remained stable (10-20% rsp. < 3 BU/ml). In both cases no FVIII substitution therapy was necessary. CONCLUSIONS A modified Malmoe protocol combined with long-term cyclophosphamide p.o. and weekly IgG-adsorptions seems to be an efficient, safe and cost-effective regimen for non-haemophiliacs with FVIII inhibitors.

Transient Alkaline Hyperphosphatasaemia in an Adult: Biochemical Peculiarities

We report on a 27-year-old healthy female with transient hyperphosphatasaemia of adulthood (it is the eighth case ever recorded). A maximum alkaline phosphatase activity of 1950 U/l, 11-fold the upper reference limit, was measured. The activity normalized within 11 weeks. Electrophoresis revealed the typical pattern for alkaline phosphatase isoenzymes observed in transient hyperphosphatasaemia of infancy: a fast-migrating liver isoenzyme and a bone isoenzyme. Contrary to the findings in transient hyperphosphatasaemia of infancy the liver isoenzyme did not precipitate with wheat-germ lectin whereas the bone isoenzyme partially bound to lectin. Biochemical features of transient hyperphosphatasaemia in an adult may be different from those in infancy. Recognition of an atypical pattern could help avoid unnecessary extensive investigations.

Is there any influence of the protein C system on perioperative blood loss in total knee or hip arthroplasty

ORIGINAL ARTICLE Is There Any Influence of the Protein C System on Perioperative Blood Loss in Total Knee or Hip Arthroplasty? Ralf Grossmann1, Behrouz Mansouri Taleghani2, Christoph Rader3, Christian Kramer3, Jochen Eulert3, and Franz Keller1 1Central Laboratory of the University Medical Centre, 2Department of Transfusion Medicine and Immunohaematology, University Clinics, Wuerzburg, 3Clinic f. Orthopaedic Surgery, Konig-Ludwig-Haus, Wuerzburg, Germany.