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Journal of Thrombosis and Haemostasis: JTH

Elan Mohanty, Salik Nazir, Jo-Ann I Sheppard, Daniel A Forman, Theodore E Warkentin
Spontaneous HIT syndrome is an autoimmune HIT (aHIT) disorder characterized by thrombocytopenia, thrombosis, and HIT antibodies despite no proximate heparin exposure. For unknown reasons, many cases occur after total knee arthroplasty. A 52-year-old woman presented 12 days post-total knee replacement (aspirin thromboprophylaxis) with gastrointestinal bleeding (superior mesenteric vein thrombosis); the platelet count was 63 × 109 L-1 . After bowel resection and a brief course of heparin, treatment was changed to argatroban followed by fondaparinux...
February 18, 2019: Journal of Thrombosis and Haemostasis: JTH
Ludvig B Rinde, Vania M Morelli, Birgit Småbrekke, Ellisiv B Mathiesen, Maja-Lisa Løchen, Inger Njølstad, Tom Wilsgaard, Erin Smith, Frits R Rosendaal, Kelly A Frazer, Sigrid K Braekkan, John-Bjarne Hansen
BACKGROUND: Patients with ischemic stroke have a transient increased risk of subsequent venous thromboembolism (VTE). Prothrombotic genotypes may augment VTE risk under conditions of high thrombosis risk related to stroke. AIMS: To investigate the effect of prothrombotic genotypes in patients with ischemic stroke on the risk of VTE in a population-based case-cohort study. METHODS: Cases with incident VTE (n=664) and a randomly selected age-weighted sub-cohort (n=1817) were sampled from three surveys of the Tromsø Study (1994-2008)...
February 18, 2019: Journal of Thrombosis and Haemostasis: JTH
A D Protopopova, A Ramirez, D V Klinov, R I Litvinov, J W Weisel
BACKGROUND: Factor XIII (FXIII) is a precursor of the blood plasma transglutaminase (FXIIIa) that is generated by thrombin and Ca2+ and covalently cross-links fibrin to strengthen blood clots. Inactive plasma FXIII is a heterotetramer with two catalytic A subunits and two non-catalytic B subunits. Inactive A subunits have been characterized crystallographically, while the atomic structure of the entire FXIII and B subunits is unknown and the oligomerization state of activated A subunits remains controversial...
February 17, 2019: Journal of Thrombosis and Haemostasis: JTH
Sukhi Singh, Tor Damén, Mikael Dellborg, Anders Jeppsson, Andreas Nygren
BACKGROUND: New approaches to prevent bleeding complications during cardiac surgery are needed. OBJECTIVE: To investigate if noradrenaline (NA) enhances platelet aggregation in CABG patients. PATIENTS/METHODS: Twenty-four CABG patients were included in a prospective parallel-group randomized study. All patients but one, were treated with acetylsalicylic acid (ASA). In the treatment group (n=12), mean arterial blood pressure (MAP) was maintained at pre-induction levels by NA infusion...
February 14, 2019: Journal of Thrombosis and Haemostasis: JTH
Barbara Ferrari, Andrea Cairo, Maria Teresa Pagliari, Ilaria Mancini, Sara Arcudi, Flora Peyvandi
Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disorder characterized by multiple organ ischemia due to disseminated thrombi formation in the microvasculature. The congenital form of the disease (Upshaw-Schulman syndrome) is related to ADAMTS13 mutations. Adulthood-onset of TTP does not exclude the congenital form of the disease and a diagnostic delay may account for a great morbidity burden in these patients. We describe the case of a middle-aged woman who presented to our attention with a clinical diagnosis of a chronic relapsing form of TTP...
February 14, 2019: Journal of Thrombosis and Haemostasis: JTH
Jenny K McDaniel, Mohammad S Abdelgawwad, Audra Hargett, Matthew B Renfrow, Khalil Bdeir, Wenjing Cao, Douglas B Cines, X Long Zheng
BACKGROUND: Human neutrophil peptides (HNPs), also known as α-defensins, are released from degranulated neutrophils and play an important role in innate immunity. However, their biological roles in hemostasis under flow are not fully explored. OBJECTIVE: This study aims to determine the role of HNP-1 on platelet adhesion and aggregation on a collagen surface or ultra large von Willebrand factor (ULVWF) on endothelium under flow and elucidate the structural elements required for its activity...
February 11, 2019: Journal of Thrombosis and Haemostasis: JTH
Andrea S Rothmeier, Henri H Versteeg, Wolfram Ruf
BACKGROUND: Cell injury signal-induced activation and release of tissue factor (TF) on extracellular vesicles (EV) from immune and vessel wall cells propagate local and systemic coagulation initiation. TF trafficking and release on EV occurs in concert with the release of cell adhesion receptors, including integrin β1 heterodimers which control trafficking of the TF-FVIIa complex. Activation of the TF signaling partner, protease activated receptor (PAR) 2, also triggers TF release on integrin β1+ EV from endothelial cells, but the physiological signals for PAR2-dependent EV generation at the vascular interface remain unknown...
February 11, 2019: Journal of Thrombosis and Haemostasis: JTH
B Dahlbäck, L J Guo, B Zöller, S Tran
BACKGROUND: Protein S is an anticoagulant cofactor to both activated protein C and tissue factor pathway inhibitor (TFPIα). The TFPIα-cofactor activity of protein S is stimulated by a short isoform of factor V (FV-Short), the two proteins functioning in synergy. OBJECTIVE: Using the synergistic TFPIα-cofactor activity between protein S and FV-Short to develop a functional test for plasma protein S. PATIENTS/METHODS: TFPIα-mediated inhibition of FXa in the presence of FV-Short, protein S and negatively charged phospholipid vesicles was monitored in time by synthetic substrate S2765...
February 11, 2019: Journal of Thrombosis and Haemostasis: JTH
L L Swystun, C Notley, I Georgescu, J D Lai, K Nesbitt, P D James, D Lillicrap
BACKGROUND: von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely cleared by VWF-dependent pathways. Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies. The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized. The human liver expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown OBJECTIVES: The interaction between FVIII and CLEC4M was characterized in the presence or absence of VWF...
February 11, 2019: Journal of Thrombosis and Haemostasis: JTH
A R Hubbard, C Thelwell, P Rigsby
The WHO International Standard (WHO IS) for Factor V in plasma defines the International Unit (IU) for factor V clotting activity and thereby supports the quantification, harmonisation and long-term continuity of measurements internationally. Measurement of factor V in plasma is pertinent to the diagnosis of rare bleeding disorders as well as being a quality control marker for solvent-detergent treated fresh, frozen human plasma [1,2]. Declining stocks of the WHO 1st IS (NIBSC code: 03/116) has made it necessary to prepare a replacement standard and this report describes the value assignment of the WHO 2nd IS Factor V plasma (16/374) for clotting activity and a new analyte, factor V antigen...
February 7, 2019: Journal of Thrombosis and Haemostasis: JTH
Kanagasabai Vadivel, Herman A Schreuder, Alexander Liesum, Amy E Schmidt, Gunaseelan Goldsmith, S Paul Bajaj
BACKGROUND: Activated coagulation factor IX (FIXa) consists of a γ-carboxyglutamic acid domain, two epidermal growth factor-like (EGF) domains and C-terminal protease domain. Consensus sequence and biochemical data support the existence of Na+ -site in FIXa protease domain. However, soaking experiments or crystals grown in high concentration of ammonium sulfate did not reveal Na+ -site in wild-type or mutant FIXa EGF2/protease domain structure. OBJECTIVE: Determine structure of FIXa EGF2/protease domain in presence of Na+ ; perform molecular dynamics (MD) simulations to explore the role of Na+ in stabilizing FIXa structure...
February 6, 2019: Journal of Thrombosis and Haemostasis: JTH
S R Baker, M Zabczyk, F L Macrae, C Duval, A Undas, R A S Ariëns
BACKGROUND: Venous thromboembolism (VTE) is associated with a high risk of recurrent events after withdrawal of anticoagulation. OBJECTIVES: The aim of this study was to determine the difference in plasma clot mechanical properties from patients having recurrent (r) versus non-recurrent (nr) VTE. METHODS: We previously developed a system for determining clot mechanical properties using an in-house magnetic tweezers system. This system was used to determine the mechanical properties of clots made from plasma of 11 patients with rVTE and 33 with nrVTE...
February 6, 2019: Journal of Thrombosis and Haemostasis: JTH
Alexis R Peedin, Julie Katz Karp
As apheresis providers, we are very interested in actively collaborating with multidisciplinary care teams that refer patients for our procedures. We read with interest the recently published McMaster RARE-Bestpractices clinical practice guideline on the diagnosis and management of catastrophic antiphospholipid syndrome (CAPS) [1]. However, the clinical practice guideline had several shortcomings that call into question the authors' conclusion that therapeutic plasma exchange (TPE) should be used as first-line therapy...
February 5, 2019: Journal of Thrombosis and Haemostasis: JTH
Keiji Nogami
Emicizumab is a humanized, recombinant bispecific monoclonal antibody to factor IX/IXa and factor X/Xa that mimics the cofactor function of factor VIIIa by positioning factor IXa and factor X suitably to promote the enzymatic activity of factor IXa in the tenase complex. Emicizumab recognizes the epidermal growth factor (EGF)-like domain 1 of factor IX/IXa with one arm, and the EGF-like domain 2 of factor X/Xa with the other arm. This bispecific antibody does not induce antibody-dependent accumulation of factor IX/IXa and/or factor X/Xa in circulation due to much weaker binding than those of other therapeutic monoclonal antibodies...
February 1, 2019: Journal of Thrombosis and Haemostasis: JTH
Laura J Sommerville, Kristen L Gorman, Stacey A Snyder, Dougald M Monroe, Maureane Hoffman
BACKGROUND: Embryonic- and tumor-associated angiogenesis are linked to elevated expression of the pro-coagulant transmembrane receptor, tissue factor (TF). By contrast, we have reported that high baseline TF expression by perivascular cells (pericytes) is dramatically reduced during angiogenesis at sites of wound healing. This is the only setting in which active TF downregulation has been reported, thus revealing a novel mechanism of TF regulation. OBJECTIVES: This study aimed to define mechanisms underlying the unique pattern of TF expression in pericytes...
January 30, 2019: Journal of Thrombosis and Haemostasis: JTH
Umer Daraz, Soodeh Shahsavari
We read with interest the article recently published in Journal of Thrombosis and Haemostasis entitled "The American College of Chest Physician score to assess the risk of bleeding during anticoagulation in patients with venous thromboembolism". The goal of this study was to evaluate the ability of the American College of Chest Physicians (ACCP) score to predict the risk of bleeding in an inception cohort of patients belonging to an Italian Register (START2), who had long-term anticoagulation. To do this, 2263 patients participated in the study...
January 28, 2019: Journal of Thrombosis and Haemostasis: JTH
(no author information available yet)
No abstract text is available yet for this article.
January 28, 2019: Journal of Thrombosis and Haemostasis: JTH
Gualtiero Palareti, Alberto Tosetto
We thank Drs Daraz and Shahsavari for their comments on our manuscript. We fully agree that several steps are required to fully validate a prediction model before proposing it for clinical guidance. Indeed, the aim of our study was not to develop a new prediction model to assess the risk of bleeding during anticoagulation, but rather to perform an external validation on an already proposed prediction model. This article is protected by copyright. All rights reserved.
January 28, 2019: Journal of Thrombosis and Haemostasis: JTH
Maha At Elsebaie, Nick van Es, Amelia Langston, Harry R Büller, Manila Gaddh
BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly used in acute and long-term treatment of venous thromboembolism (VTE). However, their role in management of thrombophilia-associated VTE is controversial. METHODS: Through a comprehensive search on MEDLINE, Cochrane Library and Clinicaltrials. gov, we identified 10 eligible studies, 8 of which reporting data on 1,994 thrombophilia patients were included in a random-effects meta-analysis. Eligible studies were phase 2-3 randomized controlled trials comparing DOACs to vitamin K antagonists (VKAs) in patients with VTE, including those with thrombophilia...
January 28, 2019: Journal of Thrombosis and Haemostasis: JTH
Hideo Wada, Takeshi Matsumoto, Yoshiki Yamashita, Kohshi Ohishi, Makoto Ikejiri, Naoyuki Katayama
Emicizumab [1, 2], which is a bispecific antibody for clotting factor X (FX) and FIX, is useful for threating hemophilic patients with inhibitors for FVIII and it can reduce the injection frequency for FVIII products in the treatment of hemophilia A. However, measuring the FVIII activity and inhibitors for FVIII is difficult to carry out in hemophilic patients treated with emicizumab. Although hemophilic patients with inhibitors should be treated with bypass therapy at the time of major surgery or severe bleeding, the inhibitors for FVIII cannot be evaluated in patients treated with emicizumab...
January 23, 2019: Journal of Thrombosis and Haemostasis: JTH
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