Acquired Hemophilia A After Multiple Transfusions Following Trauma.

Acquired hemophilia A (AHA) is a coagulative disorder that is caused by the presence of inhibitors of factor VIII (FVIII). The presence of coagulation factor inhibitors can lead to severe episodes of bleeding in patients with no previous history of bleeding conditions. We present the clinical case of a man with severe bleeding two weeks after falling from a bicycle. The patient denied any previous history of bleeding disorders. The case clinically presented with a large retroperitoneal hematoma and continued to show signs of active bleeding even after multiple transfusions were administered. Coagulation studies showed an elevated inhibitor titer of 24.4 BU/mL (normal range is below 5 BU/mL) and a reduced FVIII activity level of 2% (normal range is between 50% to 150%), providing evidence of AHA. Hemostatic and immunosuppressive agents were then administered to the patient, whose condition improved in response to the treatments.

Distinctive cellular response to aluminum based adjuvants.

Aluminum-based adjuvants (ABAs) are used in human vaccines to enhance the magnitude of protective immune responses elicited against specific pathogens. One hypothesis is that stress signals released by aluminum-exposed necrotic cells play a role in modulating an immune response that contributes to the adjuvant's effectiveness. We hypothesized that aluminum adjuvant-induced necrosis would be similar irrespective of cellular origin or composition of the adjuvant. To test this hypothesis, human macrophages derived from peripheral monocytic cell line (THP-1) and cells derived from the human brain (primary astrocytes) were evaluated. Three commercially available formulations of ABAs (Alhydrogel, Imject alum, and Adju-Phos) were examined. Alum was also used as a reference. Cell viability, reactive oxygen species formation, and production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were quantified. Cells were exposed to different concentrations (10-100 µg/mL) of the adjuvants for 24 h or 72 h. The two FDA approved adjuvants (Alhydrogel and Adju-Phos) decreased cell viability in both cell types. At the 72 h time point, the decrease in viability was accompanied with increased ROS formation. The size of the aluminum agglomerates was not relatable to the changes observed. After exposure to ABAs, astrocytes and macrophages presented a distinct profile of cytokine secretion which may relate to the function and unique characteristics of each cell type. These variations indicate that aluminum adjuvants may have differing capability of activating cells of different origin and thus their utility in specific vaccine design should be carefully assessed for optimum efficacy.