A proposal for managing bleeding in patients on therapeutic factor XI(a) inhibitors

Several drugs that reduce functional levels of the plasma protease zymogen factor XI (FXI), or that inhibit its activated form (FXIa), are being evaluated as treatments to prevent thrombosis. Based on the observation that individuals with inherited FXI deficiency have a relatively mild bleeding disorder, it is anticipated that therapeutic FXI(a) inhibitors will have a smaller impact on hemostasis than anticoagulants targeting thrombin or factor Xa. However, even if FXI(a) inhibitors are determined to be safer than currently used anticoagulants, some patients on these drugs will experience abnormal bleeding or require emergent surgery. Strategies for dealing with such situations are required. Treatment with antifibrinolytic agents and low doses of recombinant factor VIIa effectively prevent abnormal bleeding in FXI-deficient patients with alloantibody inhibitors to FXI who undergo surgery. We propose that a similar strategy can be used for patients on therapeutic FXI(a) inhibitors who are bleeding or require invasive procedures.     

Controlled environment culture of bone marrow explants from human myeloma.

Bone marrow biopsy specimens from patients with myeloma were cultured in either 1 of 2 thin-film culture systems, a controlled environment steady state system or a rocker tube configuration of the system, for periods up to 42 days. Both functional and morphological characteristics of the myeloma cells were well-maintained in these systems. Cytocentrifuge preparations of the culture media disclosed hematopoietic cells that included from 5% to almost 100% plasma cells. Histological examination of the cultured specimens disclosed infiltration of the marrow with myeloma cells. Myeloma proteins were released at a steady rate throughout the period of culture after the 1st 4 days. Bone-resorbing activity was demonstrated in the culture media in 7 of 9 myeloma culture media and was well maintained, particularly during the 1st week of culture. This activity was associated with severe osteolytic lesions in the donor patient and marked infiltration of the cultured specimen by myeloma cells. The potential use of these organ culture systems for the further definitive identification of the factor responsible for bone destruction in myeloma is discussed.     

Factor XI/ADAMTS13 complexes are quantitatively insignificant in human plasma

Reportedly, complexes between factor XI and ADAMTS13 are detected with a commercial ADAMTS13/FXI ELISA kit in plasma and are decreased in thrombotic thrombocytopenic purpura (TTP). Using this kit, control and TTP patient plasma contained varying amounts of signal (25-670% of a reference plasma) but no signal was observed for mixtures of recombinant enzymes, suggesting little interaction. ADAMTS13/FXI complexes were undetectable by immunoprecipitation or gel filtration chromatography in control plasma or mixtures of recombinant proteins. These results suggest that ADAMTS13/FXI complexes are insignificant in plasma and unlikely to affect the function of either protein during normal hemostasis or in TTP.     

Effect of Two Immediate Dentin Sealing Approaches on Bond Strength of Lava™ CAD/CAM Indirect Restoration

The objective of this work was to compare the micro-tensile bond strength (µTBS) of CAD/CAM (Computer-Aided Design/ Computer-Aided Manufacturing) specimens cemented with different pairing of adhesives and resin-cements using two Immediate Dentin Dealing (IDS) approaches in comparison with Delay Dentin Sealing (DDS). Coronal dentin from 108 molars were divided into nine groups (n = 12) depending on the adhesive/resin-cement (A-C) assigned. Lava™ Ultimate (4 × 10 × 10 mm) was cemented according to different strategies: IDS1(cementation after dentin sealing), DDS (dentin sealing and cementation at 2-weeks), IDS2 (immediate dentin sealing and cementation at 2-weeks). Samples were sectioned and tested until failure to determine the µTBS. Failure mode was categorized as dentin/cement (DC), at Lava™ Ultimate/cement (LC) and hybrid (H). Kruskal–Wallis and Mann–Whitney U tests and influence of the type of failure on the µTBS by survival analysis with competing risk was explored. Mostly, µTBS values were equal or higher in IDS2 than DDS. In general, A-Cs that showed higher µTBS, have high percentages of LC failure. Survival analysis with competing risk between DC + H and LC values showed that some A-Cs would significantly increase the µTBS values for IDS2. A-Cs with the highest adhesion values showed a high percentage of fractures at the LC interface, suggesting that the adhesion at the adhesive/dentin interface would be higher.