Hemostasis is a complex process for the cessation of bleeding from an injured blood vessel, involving the interplay of 12 coagulation factors in the coagulation cascade with activated blood platelets and the vessel wall. Hence, the coagulation factors are important to control hemorrhage. However, the low abundance of many coagulation factors in human plasma proteins limited their production in therapeutic drugs and their clinical applications. With the development of modern biotechnology, commercially manufactured recombinant coagulation factors became available as hemostatic therapeutics, emerging a huge potential in pharmaceutical manufacturing market. Unlike antibodies, whose standard operation unit or platform purification processes in the industrial-scale downstream processing has been well-established, the complexity in post-translational modification and differences in structures of the coagulation factors posed specific challenges with respect to the downstream processing, which have long been limiting their industrial-scale production. This review presents a comprehensive overview of the technological development of commercially manufactured recombinant coagulation factors, with emphasis on their advances and challenges in the separation and purification processes. Firstly, the licensed products of the plasma derived and recombinant coagulation factors are summarized. Then, typical recombinant coagulation factors, i.e. factors VII, VIII and IX, are introduced with detailed discussion on their preparative separation procedures for both the licensed products of industrial-scale and the experimental cases of laboratory-scale. Finally, perspectives and challenges in the future development of the purification technology of recombinant coagulation factors are highlighted to provide new insight into the design of cost-effective purification processes of recombinant coagulation factors.
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http://dx.doi.org/10.1016/j.chroma.2024.464662 | DOI Listing |
Mol Pharm
January 2025
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland.
Dendrimers are a wide range of nanoparticles with desirable properties that can be used in many areas of medicine. However, little is known about their potential use in wound healing. This study examined the properties of phosphorus dendrimers that were built on a cyclotriphosphazene core and pyrrolidinium (DPP) or piperidinium (DPH) terminated groups, to be used as potential factors that support wound healing ().
View Article and Find Full Text PDFJ Clin Med
December 2024
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria.
: Acute stent thrombosis (ST) is a rare yet severe complication following percutaneous coronary intervention (PCI). Herein, we investigated the possible association between routinely available coagulation and fibrinolysis markers with early ST. : Within a single-center registry, we investigated the association between the preprocedural platelet count, plasma levels of fibrinogen and D-Dimer, and the incidence of early ST in the first 30 days after PCI.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, Russia.
Inflammation is a physiological response of the immune system to infectious agents or tissue injury, which involves a cascade of vascular and cellular events and the activation of biochemical pathways depending on the type of harmful agent and the stimulus generated. The Kunitz peptide HCIQ2c1 of sea anemone is a strong protease inhibitor and exhibits neuroprotective and analgesic activities. In this study, we investigated the anti-inflammatory potential of HCIQ2c1 in histamine- and lipopolysaccharide (LPS)-activated RAW 264.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Clinical Biochemistry, University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.
From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca transfers. In addition, from around the eighth week of gestation, increasing amounts of calcium must be routed directly from maternal blood to the foetus for bone mineralisation through a flow-through system, which does not impact the intracellular Ca concentration.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, Germany.
Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN-, and 30 healthy controls.
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