Fatal cerebral hemorrhage in a patient with thrombotic thrombocytopenic purpura with a normal platelet count during treatment with caplacizumab.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy with a severe mortality and morbidity. Caplacizumab has recently been approved in the Netherlands as a new therapeutic option in patients with life-threatening organ failure due to aTTP. We describe the case of a 50 year old patient with aTTP who was referred to our hospital for treatment with caplacizumab. After undergoing treatment with plasmapheresis, prednisolone, rituximab and caplacizumab, her platelet count recovered and she was ready to be discharged. Unfortunately, before discharge she developed a fatal intra-cerebral hemorrhage. Fatal hemorrhage as an adverse event of caplacizumab has not been described before. Up to now there is no evidence-based treatment for caplacizumab induced heavy bleeding.

Effects of different training modalities on phosphate homeostasis and local vitamin D metabolism in rat bone.

OBJECTIVES: Mechanical loading may be an important factor in the regulation of bone derived hormones involved in phosphate homeostasis. This study investigated the effects of peak power and endurance training on expression levels of fibroblast growth factor 23 (FGF23) and 1α-hydroxylase (CYP27b1) in bone. METHODS: Thirty-eight rats were assigned to six weeks of training in four groups: peak power (PT), endurance (ET), PT followed by ET (PET) or no training (control). In cortical bone, FGF23 was quantified using immunohistochemistry. mRNA expression levels of proteins involved in phosphate and vitamin D homeostasis were quantified in cortical bone and kidney. C-terminal FGF23, 25-hydroxyvitamin D3, parathyroid hormone (PTH), calcium and phosphate concentrations were measured in plasma or serum. RESULTS: Neither FGF23 mRNA and protein expression levels in cortical bone nor FGF23 plasma concentrations differed between the groups. In cortical bone, mRNA expression levels of sclerostin (SOST), dental matrix protein 1 (DMP1), phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and matrix extracellular phosphoglycoprotein (MEPE) were lower after PT compared to ET and PET. Expression levels of CYP27b1 and vitamin D receptor (VDR) in tibial bone were decreased after PT compared to ET. In kidney, no differences between groups were observed for mRNA expression levels of CYP27b1, 24-hydroxylase (CYP24), VDR, NaPi-IIa cotransporter (NPT2a) and NaPi-IIc cotransporter (NPT2c). Serum PTH concentrations were higher after PT compared to controls. CONCLUSION: After six weeks, none of the training modalities induced changes in FGF23 expression levels. However, PT might have caused changes in local phosphate regulation within bone compared to ET and PET. CYP27b1 and VDR expression in bone was reduced after PT compared to ET, suggesting high intensity peak power training in this rat model is associated with decreased vitamin D signalling in bone.