Use Of Plasma-derived Products Research Articles

Chronic Wound Management: From Gauze to Homologous Cellular Matrix.

Chronic wounds are a significant health problem with devastating consequences for patients' physical, social, and mental health, increasing healthcare systems' costs. Their prolonged healing times, economic burden, diminished quality of life, increased infection risk, and impact on patients' mobility and functionality make them a major concern for healthcare professionals. This review offers a multi-perspective analysis of the medical literature focusing on chronic wound management. We evaluated 48 articles from the last 21 years registered in the MEDLINE and Global Health databases. The articles included in our study had a minimum of 20 citations, patients > 18 years old, and focused on chronic, complex, and hard-to-heal wounds. Extracted data were summarized into a narrative synthesis using the same health-related quality of life instrument. We evaluated the efficacy of existing wound care therapies from classical methods to modern concepts, and wound care products to regenerative medicine that uses a patient's pluripotent stem cells and growth factors. Regenerative medicine and stem cell therapies, biologic dressings and scaffolds, negative pressure wound therapy (NPWT), electrical stimulation, topical growth factors and cytokines, hyperbaric oxygen therapy (HBOT), advanced wound dressings, artificial intelligence (AI), and digital wound management are all part of the new arsenal of wound healing. Periodic medical evaluation and proper use of modern wound care therapies, including the use of plasma-derived products [such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF)] combined with proper systemic support (adequate protein levels, blood sugar, vitamins involved in tissue regeneration, etc.) are the key to a faster wound healing, and, with the help of AI, can reach the fastest healing rate possible.

Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO

A United Kingdom Haemophilia Centre Doctors’ Organization (UKHCDO) guideline approved by the British Committee for Standards in Haematology Peter W Collins, Elizabeth Chalmers, Daniel Hart, Ian Jennings, Ri Liesner, Savita Rangarajan, Kate Talks, Michael Williams and Charles R. M. Hay School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, Royal Hospital for Sick Children, Glasgow, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK NEQAS Blood Coagulation, Sheffield, Great Ormond Street NHS Trust, London, Hampshire Hospital NHS Foundation Trust, Basingstoke & North Hampshire Hospital, Basingstoke, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, and Manchester University Dept of Haematology, Manchester Royal Infirmary, Manchester, UK

Manufacture of plasma-derived products in France and measures to prevent the risk of vCJD transmission: Precautionary measures and efficacy of manufacturing processes in prion removal

The emergence of the variant Creutzfeldt-Jakob disease in the mid 1990s soon raised concerns about its possible transmission through the use of blood and plasma-derived medicinal products. A risk analysis approach was initiated by health authorities, based on updated scientific knowledge and precautionary measures were implemented in France and other countries for the management of this new possible risk. Assessment of the vCJD risk is based on epidemiology and estimates of the number of potential cases in the future, on blood infectivity data from models of transmissible spongiform encephalopathies and on data from studies of the capacity of manufacturing processes to remove the agent, should it be present in the plasma of infected donors. The transmission of vCJD by non leukocyte-depleted labile blood components has recently been confirmed. There have been no reports of cases associated with the use of plasma-derived products and the scientific data, and risk analyses for those plasma products, which are of the greatest therapeutic interest, support their safety with respect to this transmission risk. The precautionary measures applied in France and the data contributing to the risk assessment of plasma products are reviewed and updated in the present paper. The uncertainties, which remain, are also addressed and discussed, as well as the ongoing research and developments in this area.

Safety and efficacy of a sucrose‐formulated recombinant factor VIII product for the treatment of previously treated patients with haemophilia A in China

The use of plasma-derived products has contributed to a high rate of blood-borne infections among haemophilia patients in China. Recombinant factor VIII (rFVIII) products that are manufactured without human or bovine albumin and include dedicated viral inactivation steps, hold a significant safety advantage over plasma products. However, there is little information published on the use of rFVIII products in non-caucasian populations. This is the first reported evaluation of the efficacy and safety of a rFVIII product in Chinese haemophiliacs. An open-label, non-randomized, prospective, multicentre trial enroled previously treated Chinese patients with haemophilia A. All treatments were administered using a sucrose-formulated rFVIII-FS (Kogenate((R))). Forty-nine patients received totals of 291 infusions (mean, 5.94/patient) and 742 140 IU rFVIII-FS (mean, 2550.3 IU/infusion). Of the 60 acute bleeding episodes that were treated, 90% were successfully managed with only one (81.7%) infusion or two (8.3%) infusions. Physicians reported haemostasis control for acute bleeds to be 'Excellent' or 'Improved' with rFVIII-FS therapy. No FVIII inhibitors were detected in any patient. Only one treatment-related adverse event was reported, which was mild dizziness that resolved spontaneously. rFVIII-FS was efficacious, safe and well tolerated in the treatment of previously treated patients with haemophilia A in China.

Development of recombinant human polyclonal antibodies for the treatment of complex human diseases

Antibodies are a central factor in the immunity against invading pathogens, such as bacteria and viruses, as well as against malignantly transformed cells. Natural antibody responses are polyclonal, comprising antibodies against several epitopes, thus increasing the probability of eliminating the invading pathogen or malignant cell. The pharmacological advantage of polyclonality is exploited in the plasma-derived immunoglobulin products used at present to treat a number of infectious diseases. However, the use of plasma-derived products is limited by their cost, inconvenience of use and potential for transferring diseases from the donor to the patient. Symphogen has developed technologies to capture the advantages of antibody polyclonality while eliminating the potential safety risk associated with the sourcing of human material. Hence, the Symplex™ technology has been developed to identify diverse repertoires of target-specific, fully human antibodies. For the controlled manufacture of recombinant polyclonal antibody drugs, Symphogen has developed the Sympress™ technology. Combined, these two technologies allow the identification and industrial manufacturing of recombinant human polyclonal antibodies for medical use in humans. The authors believe that this new class of therapeutic antibodies will be advantageous in the treatment of complex human diseases, such as cancer and infection, as it allows the combination of several treatment modalities in one drug.

A comparison of antifibrinolytic agents used in hemostatic fibrin sealants.

Fibrin sealants used as hemostatic and adhesive surgical adjuncts invariably combine fibrinogen and thrombin. The use of plasma-derived products to facilitate hemostasis was first described in 1909. Because the approach relied on in vivo concentrations of fibrinogen and thrombin the quality of the resulting fibrin clot was poor. During the 1940s human fibrinogen and thrombin became available in large quantities as byproducts of plasma fractionation. Fibrinogen and thrombin, derived from plasma supplied by the American Red Cross, were used to enhance adhesion of skin grafts in soldiers who had sustained severe burn injuries. In the years after World War II bovine thrombin came to replace human thrombin because of concerns about the potential of human thrombin to transmit hepatitis. During the 1960s a method for the cryoprecipitation of fibrinogen led to the availability of a sealant with a high concentration of fibrinogen. This improved product was used in skin grafting to promote wound healing and dural sealing, to obtain hemostasis in microvascular surgery and parenchymal injury, and to serve as a matrix in the repair of bone defects; but fibrinogen concentrates were found to transmit hepatitis and all US licenses for commercially prepared fibrinogen (human) concentrates were revoked in 1977. Commercial concentrates containing clottable human fibrinogen and factor XIII (fibrin stabilizing factor) plus bovine thrombin became available in Europe in the late 1970s and have been used extensively since then for hemostasis and other indications. These products all contained an antifibrinolytic agent. The risk of viral transmission was reduced through careful donor selection followed by heat treatment of the human fibrinogen component. Virally inactivated human thrombin has now replaced bovine thrombin in most European products. During the 1980s and 1990s, before the availability of fibrin sealants approved by the US Food and Drug Administration (FDA), US surgeons used so-called homemade sealants, a practice that may still continue to some extent. These homemade formulations combined bovine thrombin and human fibrinogen from pooled cryoprecipitate or autologous fibrinogen. The cryoprecipitate was not subjected to viral inactivation and had a variable fibrinogen concentration. Bovine thrombin was obtained as a commercial preparation but was not regulated with respect to factor V content or other impurities. A number of investigators described the development of antibodies to bovine thrombin in postoperative patients. For these reasons regulators and manufacturers considered homemade fibrin sealants to be suboptimal. The first so-called new generation of virus-inactivated or virus-removed fibrin sealant marketed in the United States (US) was Tisseel (Baxter Healthcare), approved by the FDA in 1998. A second-generation product, Crosseal (American Red Cross), received FDA approval in March 2003. Crosseal is marketed as Quixil (Omrix Biopharmaceuticals) outside of the US. Both Tisseel and Crosseal consist of human fibrinogen and human thrombin, which are combined at the time of use to form a crosslinked fibrin matrix at the site of bleeding. The respective formulations differ in an important way: Tisseel contains bovine aprotinin (BA), while Crosseal contains tranexamic acid (TA). BA and TA are antifibrinolytic agents added to the respective formulations of these products to slow the natural dissolution of the clot that is produced at the site of application. The differences between these antifibrinolytics warrant a detailed discussion. No competing interests declared. Supported by an unrestricted educational grant from the American Red Cross.

The future of plasma-derived clotting factor concentrates.

In developed countries, preferred treatments for both haemophilia A and B have moved toward recombinant clotting factor concentrates, while plasma-derived replacement therapies are still required by many patients. Great improvements have been made in producing relatively pathogen-free clotting factor replacements from pooled plasma. The fluidity and complexity of the worldwide plasma product market are discussed in the context of the 'yin and yang' of plasma therapeutics, showing how multiple issues can influence the safety and availability of clotting factor concentrates. Use of plasma-derived products will likely continue for the next decade for patients with inhibitors, patients with von Willebrand disease, those requiring bypassing agents, in immune tolerance induction, and for treatment of rare inherited deficiencies of procoagulant or anticoagulant proteins. Furthermore, in developing countries many of the most advanced therapies are not available for the majority of haemophilia patients, and thus plasma-derived replacement concentrates will continue to be used even for noninhibitor patients.