ARTICLE


haemostasis long before human study did the same. Workers in diagnostic haemostasis laboratories tend to be more familiar with snake venom fractions that directly activate specific coagulation factors, such as the FX activator in Russell’s viper venom, the thrombin-like enzyme of the common lancehead and the prothrombin activators in coastal Taipan and saw-scaled viper venoms. Perhaps less-well known are venoms that interact with blood vessels, von Willebrand factor (VWF) or platelets, many of which have diagnostic and even therapeutic applications. Snake venom proteins affecting primary haemostasis belong to various classes, including metalloproteinases, disintegrins, C-type lectins, proteinases, phospholipase A2


,


5’-nucleotidases and L-amino acid oxidases. The metalloproteinase BaP-1 from the Fer-de- Lance (Bothrops asper) induces haemorrhage by proteolytic degradation of blood vessel basement membrane components, which affects interactions with endothelial cells. The cells undergo morphological and functional alterations and gaps form between endothelial cells, leading to extravasation. Botrocetin from the Jararaca (Bothrops jararaca) is a C-type lectin that enhances the affinity of the VWF A1 domain for the platelet receptor GpIb·α leading to platelet activation that contributes to bleeding and host death. Biticetin from the puff adder (Bitis arietans) works in a similar way. Crotavirin is a disintegrin from the western rattlesnake (Crotalus viridis) that inhibits GpIIbIIIa, thereby preventing platelet aggregation. Mambin from Jameson’s mamba (Dendroapsis jamesoni) is another GpIIbIIIa inhibitory disintegrin. Botrocetin can be used in the diagnostic laboratory to distinguish between Bernard-Soulier syndrome and severe von Willebrand disease in platelet aggregometry. A botrocetin-based assay has been described for detection of VWF inhibitors. Convulxin is a C-type lectin from the Cascabel (Crotalus durissus terrificus) that activates mammalian platelets via binding and clustering of GPVI receptors and can be used in platelet aggregometry and flow cytometry to define platelet receptor collagen-binding defects. Echicetin is a C-type lectin from the saw- scaled viper (Echis carinatus) that binds GpIb to block VWF binding and then agglutinates platelets via IgM. It can be used to facilitate VWF-independent, GpIb-dependent platelet aggregometry, and FITC-labelled echicetin can be employed in a flow cytometric assay for GpIb expression. The drug captopril, which is used for the treatment of hypertension and some types of congestive heart failure, was developed from a peptide found in Jararaca venom. Contortrostatin is a disintegrin from southern copperhead (Agkistrodon contortrix contortrix) venom that has been shown to inhibit cancer cell migration and invasion. Tirofiban (Aggrastat) is a synthetic version of a GpIIbIIIa inhibitory disintegrin from Echis carinatus used as an anticoagulant.


DECEMBER 2013


Nutristasis: the effect of diet and vitamins on haemostasis Vitamins are life-essential organic substances that are not produced by the human body. They are a structurally diverse group of compounds required to support a wide array of functions. Thirteen vitamins have been identified. Seven of these (E, K, B2


, B6 , B12 ,


folate and C) have an impact on haemostasis. Vitamin K is required for the synthesis of four procoagulation factors (II, VII, IX and X) and the anticoagulant proteins C and S; vitamin C is essential for the production of collagen, a structural protein required for cellular integrity; and vitamin B12


and folate are


required for erythropoiesis. Vitamins C and E are involved in the antioxidant preservation of vascular integrity. An extreme in the status of any one of three vitamins increases the risk of bleeding; for example, vitamin K deficiency and insufficient of clotting factor synthesis, vitamin C deficiency and poor capillary and erythrocyte structural integrity, and high-dose vitamin E supplementation and impedance of vitamin K activity. Conversely, chronic deficiencies of folate, vitamins B2


, B6 and B12


are associated with the increased risk of thrombotic events. Vitamin deficiency can develop as a consequence of malnutrition; however, there may be complicating factors leading to an increased requirement, such as impaired absorption or limited bioavailability caused by in inherited defect, co-morbidity or the presence of an antagonist. Today, in Western society, the classical manifestations of vitamin deficiencies such as scurvy in vitamin C deficiency are very rare. It is now recognised that although suboptimal vitamin status may not produce any discernable symptoms in the short term, it could be associated with chronic degeneration and diseases associated with old age. The application of appropriate laboratory assays that indicate physiological states to establish vitamin status enables the physician to make evidence-based interventions. It also facilitates the monitoring of replacement regimens that may be limited by physiological barriers (eg by a maximal rate of absorption from a pharmacological vitamin dose). Effective monitoring can also guard against over-exposure to vitamins that are associated with toxicity (eg sensory neuropathy in response to prolonged high- dose pyridoxine supplementation). The Nutristasis Unit at St Thomas' Hospital develops and applies laboratory tools to enable the evidenced-based monitoring of optimal vitamin status to support metabolic and developmental processes.


Whole blood aggregometry Whole blood aggregometry (WBA) is a technique that enables platelet functional responses to activating agonists to be determined in whole anticoagulated blood. This circumvents the need to prepare platelet-rich plasma, which may be an important source of pre-analytical variation in


KEY TO SPEAKERS Haematology


•Paediatric complications in sickle cell disease and thalassaemias


Dr Baba Pd Inusa, Evelina Children’s Hospital, St Thomas’ Hospital, London


•The role of artemisinin and its derivatives in haemato-oncology


Charlotte Humphreys, University of Portsmouth


•Integration of haematology malignancy diagnostics: the North Central London experience Dr Christopher McNamara, Royal Free Hospital, London


•Introduction to lysosomal storage disorders Professor Atul Mehta, Royal Free Hospital, London


•Immune thrombocytopenia Dr Drew Provan, The Royal London Hospital


•Genetic forms of iron deficiency anaemia Dr Sukhjinder Marwah, City Hospital NHS Trust, Birmingham


•Iron overload in haemoglobinopathies Dr Farrukh Shah, The Whittington Hospital NHS Trust


•Measuring new anticoagulants Dr Ian Jennings, UK NEQAS


•The influence of haemophilia on 20th-century politics


Jackie Cutler, Guy’s and St Thomas’ NHS Foundation Trust, London


•Current guidelines for testing inherited platelet disorders


Dr Andrew Mumford, Bristol Haematology and Oncology Centre


•Snake venoms and primary haemostasis Dr Gary Moore, Guy’s and St Thomas’ NHS Foundation Trust, London


•Nutristasis: the effects of diet and vitamins on haemostasis David Card, Guy’s and St Thomas’ NHS Foundation Trust, London


•Whole blood aggregometry Kurtis Lee, Bristol Royal Infirmary


Transfusion science


•Transfusion management of haemoglobinopathies Sonal Bhura, North Middlesex University Hospital NHS Trust, London


•Introducing the new IT guidelines for transfusion laboratories Debbie Asher, Norfolk and Norwich University Hospital


•In vitro production of platelets from human induced pluripotent cells by GMP-compatible methods Dr Cedric Ghevaert, University of Cambridge


•Good blood in bad places Dr Heidi Doughty, NHS Blood and Transplant, Birmingham


•Update on the MNS blood group system Dr Jill Storry, Lund University Hospital, Sweden


•Use of microarrays in transfusion and transplantation Dr Juraj Petrik, SNBTS RDI


•Root cause analysis Richard Haggas, Leeds Teaching Hospitals


•Roles and responsibilities in transfusion Chris Elliott, South Tees Hospitals


THE BIOMEDICAL SCIENTIST 713


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