Entity

Time filter

Source Type


Makris M.,University of Sheffield | Makris M.,Sheffield Haemophilia and Thrombosis Center | Van Veen J.J.,University of Sheffield | MacLean R.,University of Sheffield
Journal of Thrombosis and Thrombolysis | Year: 2010

The management of patients with supra-therapeutic INR in a common clinical problem. The risk of bleeding is influenced by the intensity, variability and duration of anticoagulation, patient age, presence of co-morbidities and concomitant drug therapy. For the asymptomatic patient, warfarin discontinuation is all that is usually required but for individuals at high risk of bleeding and those with INR > 10, oral vitamin K administration is recommended. In the presence of major bleeding, treatment with intravenous vitamin K and prothrombin complex concentrate is the most effective therapy. © 2009 Springer Science+Business Media, LLC. Source


Norja P.,University of Helsinki | Lassila R.,University of Helsinki | Makris M.,University of Sheffield | Makris M.,Sheffield Haemophilia and Thrombosis Center
British Journal of Haematology | Year: 2012

The introduction of dual viral inactivation of clotting factor concentrates has practically eliminated infections by viruses associated with significant pathogenicity over the last 20 years. Despite this, theoretical concerns about transmission of infection have remained, as it is known that currently available viral inactivation methods are unable to eliminate parvovirus B19 or prions from these products. Recently, concern has been raised following the identification of the new parvoviruses, human parvovirus 4 (PARV4) and new genotypes of parvovirus B19, in blood products. Parvoviruses do not cause chronic pathogenicity similar to human immunodeficiency virus or hepatitis C virus, but nevertheless may cause clinical manifestations, especially in immunosuppressed patients. Manufacturers should institute measures, such as minipool polymerase chain reaction testing, to ensure that their products contain no known viruses. So far, human bocavirus, another new genus of parvovirus, has not been detected in fractionated blood products, and unless their presence can be demonstrated, routine testing during manufacture is not essential. Continued surveillance of the patients and of the safety of blood products remains an important ongoing issue. © 2012 Blackwell Publishing Ltd. Source


Cooper P.C.,Sheffield Haemophilia and Thrombosis Center | Goodeve A.C.,University of Sheffield | Beauchamp N.J.,Sheffield Diagnostic Genetics Service
Seminars in Thrombosis and Hemostasis | Year: 2012

As the understanding of the genetic basis of the inherited thrombophilias has increased over recent years, their routine diagnostic genetic analysis has also matured. This review considers methods used to test for the factor V (F5) Leiden mutation and prothrombin 20210A (F2 c. *97G>A) allele, and analysis of the SERPINC1, PROC, and PROS1 genes in cases of antithrombin, protein C (PC), and protein S (PS) deficiency, respectively. Issues relating to quality are explored, highlighting where analytical and sample handling errors may occur. Detection of the factor V Leiden mutation and the prothrombin c.*97G>A allele are best performed using real-time polymerase chain reaction analysis as this relatively simple technique allows their discrimination from rare variants of neighboring nucleotides; not possible using the more time-consuming restriction digestion assays. With the advent of low-cost and high-throughput sequence analysis, direct sequencing has become the first-line method to provide a definitive diagnosis of inherited, rather than acquired, deficiencies. Large cohort studies have shown that antithrombin and PC mutations are identified in between 61 and 87% of patients, whereas the detection rate in PS deficiency is substantially lower in around 40% of patients. Large gene deletions make up between 7 and 10% of PS and antithrombin mutations and only 1% of PC mutations, but it is suggested that dosage analysis techniques such as multiplex ligation-dependent probe amplification should be used for all three genes as part of routine analysis to ensure mutations are not missed. Best practice guidelines are available from EuroGentest covering a wide variety of the issues raised in this review and all laboratories should participate in appropriate external quality assurance schemes to ensure they continue to offer high quality service. © 2012 by Thieme Medical Publishers, Inc. Source


Millar C.M.,Imperial College London | Makris M.,Sheffield Haemophilia and Thrombosis Center
British Journal of Haematology | Year: 2012

The identification of variant Creutzfeldt-Jakob disease (vCJD) in the UK in 1996 led to significant concerns about the possibility of secondary transmission, however the prevalence of subclinical vCJD and risks of vCJD transmission by plasma are not known. In the UK, public health precautions have been implemented in all recipients of coagulation factor concentrates manufactured from UK plasma pools between 1980 and 2001. The recent demonstration of abnormal prion protein in a spleen sample at autopsy of a UK haemophilic patient who received coagulation factor concentrates to which a donor incubating vCJD had contributed most likely represents the first case of vCJD transmission by coagulation factor concentrates. We review the uncertainties that surround risk of vCJD transmission by coagulation factor concentrates, the challenges in dealing with undefined risks, the rationale behind current policies and the implementation of vCJD surveillance and risk management measures in bleeding disorder patients in the UK. © 2012 Blackwell Publishing Ltd. Source


Kitchen S.,Sheffield Haemophilia and Thrombosis Center | Gray E.,UK National Institute for Biological Standards and Control | Mertens K.,Sanquin Blood Supply Foundation
Haemophilia | Year: 2014

The dawning era of novel recombinant factor VIII and factor IX concentrates, many of which have been bioengineered to achieve prolonged activity, brings with it the need to consider the most appropriate clinical laboratory approaches for potency assignment, as well as the measurement of postinfusion levels. This session will highlight the known limitations and inconsistencies between existing assay methodologies with respect to currently available products, and discuss some of the early data with respect to the novel agents. © 2014 John Wiley & Sons Ltd. Source

Discover hidden collaborations