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Journal of Thrombosis and Haemostasis: JTH

Petur I Jonsson, Loic Letertre, Sigurdur J Juliusson, Brynja R Gudmundsdottir, Charles W Francis, Pall T Onundarson
BACKGROUND: The prothrombin time (PT) is equally prolonged by reduction in each of vitamin K dependent (VKD) factors (F) II, VII and X. The Fiix-PT is only affected by FII and FX, the main contributors to thrombin generation (TG). OBJECTIVE: To test the hypothesis that warfarin anticoagulation variability is reduced early during monitoring with normalized PT-ratio calculated from Fiix-PT (Fiix-INR) compared to traditional PT-INR monitoring. Also, that due to its insensitivity to FVII, Fiix-PT more accurately reflects TG when Fiix-INR and PT-INR are discrepant...
October 23, 2016: Journal of Thrombosis and Haemostasis: JTH
I Mancini, I Ricaño-Ponce, E Pappalardo, A Cairo, M M Gorski, G Casoli, B Ferrari, M Alberti, D Mikovic, M Noris, C Wijmenga, F Peyvandi
BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor cleaving protease, ADAMTS13. Similarly to other autoimmune disorders, evidences of a genetic contribution have been reported, including the association of the human leukocyte antigen (HLA) class II complex with disease risk OBJECTIVE: To identify novel genetic risk factors in acquired TTP...
October 20, 2016: Journal of Thrombosis and Haemostasis: JTH
H Zöllner, R Jouni, S Panzer, A Khadour, L Janzen, J Wesche, M Ten Berg, S Schellong, A Heinken, A Greinacher, T Bakchoul
BACKGROUND: Protamine (PRT) is used to stabilize insulin in Neutral Protamine Hagedorn (NPH) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT/heparin-complexes is common in diabetic patients. OBJECTIVES: To investigate the impact of NPH-insulin on the interaction between anti-PRT/heparin antibodies and platelets. METHODS: The interaction between NPH-insulin and anti-PRT/heparin antibodies was tested using in-house enzyme immunoassays...
October 19, 2016: Journal of Thrombosis and Haemostasis: JTH
Edward Tuddenham
The declarative title is a fair summary of research described in this paper (Targeting Factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice)(10) , is a fair summary of research described in this paper, which is itself the 14th in a series from the group of researchers led by Montgomery who, since 2003 have progressively advanced the idea of storing factor VIII in platelets to treat hemophilia A. Why, one might ask, would one do such a thing when evolution has selected endothelial cells as both the site for synthesis and release of factor VIII complexed with Von Willebrand factor to provide the cofactor when and where needed?(1,2) The answer lies in the unfortunate fact that a high proportion of patients with hemophilia develop resistance to factor VIII due to alloimmunity to the protein, which is foreign to their immune system, leading to production of inhibitory antibodies to the cofactor...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
V Gurewich
The interesting article on the antifibrinolytic effect of Factor XIII by Rijken et al [1] was predicated on the assumption that fibrinolysis is mediated only by tPA, since that is what was studied. However, there is evidence that this common assumption should be put into question. In a study published almost thirty years ago, we showed that whereas spontaneous lysis of platelet poor plasma clots was mediated by tPA, that of platelet-rich plasma clots, with which this article was concerned, could not be abolished by tPA antibody, but instead was abolished by the addition of uPA antibody...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
G N Nguyen, L A George, J I Siner, R J Davidson, C B Zander, X L Zheng, V R Arruda, R M Camire, D E Sabatino
BACKGROUND: The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a Paired basic Amino acid Cleaving Enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
D C Rijken, S Abdul, J J M C Malfliet, F W G Leebeek, S Uitte de Willige
We thank Dr. Gurewich [1] for his critical evaluation of the impact of our recently published article on factor XIII [2]. This article describes that mechanical compaction or platelet-mediated retraction of plasma clots is essential to fully reveal the antifibrinolytic effect of factor XIII on tPA-induced plasma clot lysis. Dr. Gurewich argues that we cannot assume that these results are applicable to endogenous fibrinolysis in vivo, because endogenous fibrinolysis does depend not only on tPA, but also on uPA...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
Matthew J Flick, Thomas H Bugge
The cell surface orchestrates plasminogen activation through the concomitant binding of plasminogen and plasminogen activators to specific receptors. In this issue, Miles and colleagues describe their detailed phenotypic characterization of mice deficient in Plg-RKT , a key plasminogen receptor expressed in numerous tissues, but highly expressed by proinflammatory macrophages. The analysis provides critical and surprising new insights into the biology of this receptor. This article is protected by copyright...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
Zhiying Luo, Xi Li, Mingfeng Zhu, Jie Tang, Zhi Li, Xinming Zhou, Guobao Song, Zhaoqian Liu, Honghao Zhou, Wei Zhang
BACKGROUND: The variation among patients in warfarin response complicated the management of warfarin therapy, improper therapeutic dose usually result in serious adverse events. OBJECTIVE: A two-stage extreme phenotype strategy was conducted to discover novel warfarin dose associated mutations in heart valve replacement (HVR) patients. PATIENTS/METHOD: A total of 1617 warfarin stable dose (WSD) patients were enrolled and divided randomly into two cohorts...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
Andreas Hanslik, Erwin Kitzmüller, Ulrich S Tran, Katharina Thom, Hratsch Karapetian, Nicole Prutsch, Jasmin Voitl, Ina Michel-Behnke, Fiona Newall, Christoph Male
BACKGROUND: Unfractionated heparin (UFH) is used for prophylaxis and treatment of thrombosis in children. Laboratory monitoring of UFH is needed to prevent over- or under-anticoagulation. OBJECTIVES: Study objectives were to investigate i) the association between UFH dose and UFH effect as monitored by anti-IIa, ii) the relationship of anti-IIa and anti-Xa effects, and iii) the influence of patients' age and other factors on UFH effect. PATIENTS AND METHODS: Randomized controlled trial in children during cardiac catheterization, comparing high-dose UFH (100 units/kg bolus) versus low-dose UFH (50 units/kg bolus)...
October 13, 2016: Journal of Thrombosis and Haemostasis: JTH
Luuk J J Scheres, Willem M Lijfering, Saskia Middeldorp, Suzanne C Cannegieter
BACKGROUND: World Thrombosis Day (WTD) was launched in 2014 and is to be held every year to increase global awareness of venous thrombosis. Measuring impact of health awareness days is challenging, however, use of internet based data seems promising. METHODS: Google trends data were used to quantify digital searches for "venous thrombosis" worldwide and "trombose" in the Netherlands. The relative search volume (RSV), which is the proportion of the term of interest amongst all google searches for a specific region and timeframe was used...
October 13, 2016: Journal of Thrombosis and Haemostasis: JTH
Jamie M O'Sullivan, Sonia Aguila, Emily McRae, Soracha E Ward, Orla Rawley, Padraic G Fallon, Teresa M Brophy, Roger J S Preston, Lauren Brady, Orla Sheils, Alain Chion, James S O'Donnell
BACKGROUND: Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. OBJECTIVE: To define the molecular mechanisms through which VWF N-glycan structures influence in vivo clearance. METHODS: Using a series of exoglycosidases, different pd-VWF glycoforms were generated...
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
H Cohen, D R Arachchillage, S Middeldorp, J Beyer-Westendorf, R Abdul-Kadir
We thank Dr Desborough and colleagues for their response to the recently published guidance from the SSC of the ISTH on the management of direct oral anticoagulants (DOACs) in women of childbearing potential [1,2]. We have carefully examined their view and seriously considered their proposal regarding the recommendation of this guidance as detailed below. We hereby, provide a detailed response to their letter. This article is protected by copyright. All rights reserved.
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
Nick van Es, Suzanne Bleker, Marcello Di Nisio, Ankie Kleinjan, Jan Beyer-Westendorf, Giuseppe Camporese, Anita Aggarwal, Peter Verhamme, Marc Righini, Harry R Büller, Patrick M Bossuyt
BACKGROUND: Among patients with clinically suspected upper extremity deep vein thrombosis (UEDVT), a clinical decision rule based on the Constans score combined with D-dimer testing can safely rule out the diagnosis without imaging in approximately one-fifth of patients. OBJECTIVES: To evaluate the performance of the original Constans score, an extended Constans score, and an age-adjusted D-dimer positivity threshold. METHODS: Data of 406 patients with suspected UEDVT previously enrolled in a multinational diagnostic management study were used...
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
(no author information available yet)
No abstract text is available yet for this article.
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
F R Rosendaal, P H Reitsma
No abstract text is available yet for this article.
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
Da-Xiong Zeng
We read the article by Chung and colleagues with great interest [1]. The authors showed that elevated mean platelets volume (MPV) at admission was associated with poor neurological outcomes and mortality at 30 days. MPV levels might be a critical prognostic marker among resuscitated patients. It is an attractive result, but we have some minor criticisms about the study. This article is protected by copyright. All rights reserved.
October 11, 2016: Journal of Thrombosis and Haemostasis: JTH
L A Miles, N Baik, S Lighvani, S Khaldoyanidi, N M Varki, H Bai, B M Mueller, R J Parmer
BACKGROUND: Plg-RKT is a novel integral membrane plasminogen receptor that binds plasminogen via a C-terminal lysine exposed on the cell surface and promotes plasminogen activation on the cell surface by both tissue plasminogen activator and urokinase plasminogen activator. OBJECTIVES: To evaluate the role of Plg-RKT in vivo we generated Plg-RKT(-/-) mice using a homologous recombination technique. METHODS: We characterized the effect of Plg-RKT deletion on reproduction, viability, health, and spontaneous thrombosis and inflammation...
October 7, 2016: Journal of Thrombosis and Haemostasis: JTH
I J Welsby, E F Krakow, J A Heit, E C Williams, G M Arepally, S Bar-Yosef, D F Kong, S Martinelli, I Dhakal, W W Liu, J Krischer, T L Ortel
BACKGROUND: Heparin induced thrombocytopenia (HIT) is a prothrombotic response to heparin therapy with platelet activating, anti-PF4/heparin antibodies leading to thrombocytopenia associated with thromboembolism. OBJECTIVE: We tested the hypothesis that anti-PF4/heparin antibodies are associated with thromboembolism after cardiac surgery. METHODS: This multi-center, prospective cohort study collected laboratory and clinical data up to 30 days after surgery and longer-term clinical follow up...
October 7, 2016: Journal of Thrombosis and Haemostasis: JTH
Bob Siegerink
As an early career investigator, starting one's own research group is often the next important step towards a tenured academic position. As a clinical epidemiologist who has recently moved from Leiden in The Netherlands, where I obtained my PhD, to become a group leader in Berlin, Germany, I have been through this transition. In the first few months as a group leader, I encountered several new situations, as might be expect for any other novice group leader. This paper, which describes my own experiences of dealing with these new situations, may help other early career researchers in their preparations and efforts to find their own approach to handling the new situations typically encountered as a group leader This article is protected by copyright...
October 7, 2016: Journal of Thrombosis and Haemostasis: JTH
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