Summary Background. No data exist regarding the inter-laboratory reproducibility of the heparin-induced-platelet-activation (HIPA) test, the most widely used functional assay in Germany for the detection of heparin-induced thrombocytopenia (HIT) antibodies. Methods. Nine laboratories used an identical protocol to test eight different sera with the HIPA test. Five laboratories also tested the sera with a platelet factor 4 (PF4)/heparin-complex ELISA. Cross-reactivity with danaparoid-sodium was assessed using 0.2 aFXa units instead of heparin in the HIPA test. Results. Two of nine laboratories had no discrepant HIPA test results. Four laboratories differed in one sample, one reported two discrepant results, and two laboratories reported more than two discrepant results. Cross-reactivity with danaparoid-sodium test results differed among laboratories. PF4/heparin ELISA results were identical in all five laboratories. Conclusion. The HIPA test requires strict quality control measures. Using both a sensitive functional assay (HIPA test) and a PF4/heparin ELISA will allow detection of antibodies directed to antigens other than PF4/heparin complexes as well as detection of IgM and IgA antibodies with PF4/heparin specificity.

The advantages of microstructured reactors were utilized in a twostep process for the preparation of intermediates of vitamin D analogues, which are known to be important compounds in bone and mineral metabolism. The reaction sequence consisting of an ozonolysis step of a double bond and a subsequent reduction was successfully performed in a microplant. Concerning the feasibility and optimization of the two reaction steps in different microreactors, ozonolysis and reduction have initially been investigated separately. A miniaturized ATR sensor was employed for online monitoring of the ozonolysis step. The overall process was then performed in a continuous manner. The utilization of microstructured devices allows for the realization of a safe and highly controlled multistep process with online analysis via FTIR.

Abecarnil, a partial agonist of the benzodiazepine receptor, crystallizes in three modifications, A, B, and C. Depending on the solvent, the form crystallized in an unseeded process is one of the two metastable forms A or B. Isopropyl acetate was chosen as solvent for the crystallization of the drug substance Abecarnil, yielding the B form for an unseeded crystallization. However, the crystals undergo a slow solution-mediated phase transformation into the stable C form. More readily observed is a partial phase transformation into the A modification. The rate of transformation depends sensitively on the purity of the material. To access this second metastable form quantitatively, reproducibly and irrespective of the purity of the material, a seeding strategy for a batch cooling crystallization from isopropyl acetate is developed. The technique is optimized under laboratory conditions and transferred to pilot plant scale. The physicochemical data necessary for the effective development are given and their relevance is discussed.

BACKGROUND AND PURPOSE:Clopidogrel resistance is blamed for thromboembolic complications in neurovascular stent placement. Platelet-function assays are weakly standardized. The aim of this study was to correlate the results of 3 different platelet-inhibition measurements (from light transmission aggregometry, the VerifyNow P2Y12 test, and the Multiplate analyzer) and their relation to periprocedural thromboembolic complications in elective neurovascular stent placement.