Anticoagulation Therapy in a Patient With Heterozygous Factor V Leiden and Coexisting Homozygous Prothrombin Gene Mutations.

Coexistent heterozygous factor V Leiden and homozygous prothrombin G20210A gene mutations is a rare and potentially life-threatening occurrence. This inherited thrombophilia often presents as non-specific venous thromboemboli and can mimic a variety of emergent medical conditions. The pathophysiology of the disease has been well documented; however, long-term treatment efficacy remains poorly understood. We report the case of a 25-year-old male presenting with acute chest pain. A comprehensive workup revealed bilateral pulmonary emboli arising in part from concomitant heterozygous factor V Leiden and homozygous prothrombin G20210A gene mutations. Immediate and continuous treatment with anticoagulants enoxaparin and apixaban significantly reduced the patient's symptoms and D-dimer within one week. This case provides insight into an effective treatment regimen for this rare and inherited thrombophilia.

The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis.

Copper is required for the activity of cytochrome c oxidase (COX), the terminal electron-accepting complex of the mitochondrial respiratory chain. The likely source of copper used for COX biogenesis is a labile pool found in the mitochondrial matrix. In mammals, the proteins that transport copper across the inner mitochondrial membrane remain unknown. We previously reported that the mitochondrial carrier family protein Pic2 in budding yeast is a copper importer. The closest Pic2 ortholog in mammalian cells is the mitochondrial phosphate carrier SLC25A3. Here, to investigate whether SLC25A3 also transports copper, we manipulated its expression in several murine and human cell lines. SLC25A3 knockdown or deletion consistently resulted in an isolated COX deficiency in these cells, and copper addition to the culture medium suppressed these biochemical defects. Consistent with a conserved role for SLC25A3 in copper transport, its heterologous expression in yeast complemented copper-specific defects observed upon deletion of PIC2 Additionally, assays in Lactococcus lactis and in reconstituted liposomes directly demonstrated that SLC25A3 functions as a copper transporter. Taken together, these data indicate that SLC25A3 can transport copper both in vitro and in vivo.