Join Mailing List   |   Print Page   |   Contact Us   |   Sign In   |   Join
JTH Editors' Highlights

Read the JTH Editors' Highlights


Links to article abstracts below; for complete ISTH member access to JTH full-text articles:

  1. Sign in to the ISTH website
  2. Select "JTH Member Access" under the "Publications" tab in the top navigation. See here.


2016

Review:

Advances in treatment of bleeding disorders - F. Peyvandi, I. Garagiola and E. Biguzzi
While treatment of common bleeding disorders is well established, with many remedies available, this is not necessarily the case for rare bleeding disorders. A review by Peyvandi and colleagues summarizes which new products are now entering the clinical arena.

Factors influencing adherence to clinical guidelines in the management of cancer-associated thrombosis - I. Mahé, J. Chidiac, H Helfer and S. Noble
Although guidelines for the management of cancer associated thrombosis exist, they are not always followed. Reasons for non-compliance are discussed in a review from Mahé and colleagues.

Coagulation:

Original Article

An allosteric disulfide bond is involved in enhanced activation of factor XI by protein disulfide isomerase - M. Zucker, U. Seligsohn, A. Yeheskel and R. Mor-Cohen
It is known that reduction of factor XI by protein disulfide isomerase enhances its capability to cleave factor IX. A new study by Zucker and colleagues now establishes which disulfide bond in factor XI is involved.

Clinical Hemostasis and Thrombosis:

Commentary
Optimising stroke prevention in elderly patients with atrial fibrillation - G. Y. H. Lip

In Focus 
Reasons for and consequences of vitamin K antagonist discontinuation in very elderly patients with non-valvular atrial fibrillation - G. Bertozzo, G. Zoppellaro, S. Granziera, L. Marigo, K. Rossi, F. Petruzzellis, E. Perissinotto, E. Manzato, G. Nante and V. Pengo
Stroke prevention in very elderly patients with atrial fibrillation is not always easy. An observational study by Bertozzo and colleagues identifies the reasons for suspension of treatment and examines the consequences for clinical outcome.

Review:
Coagulation and non-coagulation effects of thrombin - J. J. N. Posma, J. J. Posthuma and H. M. H. Spronk

Thrombin is the central enzyme of the coagulation system. The actions of thrombin however, are manifold and as explained in this review by Posma and colleagues, not limited to the coagulation system per se.

Clinical Hemostasis and Thrombosis:
Questioning the use of an age-adjusted D-dimer threshold to exclude venous thromboembolism: analysis of individual patient data from two diagnostic studies - S. Takach Lapner, J. A Julian, L. A. Linkins, S. M. Bates and C. Kearon

Lately it was proposed that using an age-adjusted D-dimer threshold improves the exclusion of venous thrombosis. The results of a study by Takach Lapner and colleagues question this proposition.

Coagulation:
Thrombin generation and cell-dependent hypercoagulability in sickle cell disease - M. F. Whelihan, M. Y. Lim, M. J. Mooberry, M. G. Piegore, A . Ilich, A. Wogu, J. Cai, D. M. Monroe, K. I. Ataga, K. G. Mann and N. S. Key

One feature of sickle cell disease is a chronic hypercoagulable state that leads to an increased incidence of thrombotic events. Whelihan and colleagues now present evidence that, paradoxically, whole blood thrombin generation is increased, while plasma thrombin generation is decreased. Acquired protein S deficiency may be part of the explanation of the paradox.

In Focus:
Benefits and Challenges of Going Abroad for Research or Clinical Training - N. Riva, M. Lauw

The first article in the September issue is part of a series of contributions from the Early Careers Task Force and discusses, from the perspective of a young scientist and clinician, the idea of going abroad for training. 

Review:
Current and future perspectives in imaging of venous thromboembolism - C. E. A. Dronkers, F. A. Klok and M. V. Huisman

Protamine (heparin)-induced thrombocytopenia: a review of the serological and clinical features associated with anti-protamine/heparin antibodies - T. Bakchoul, R. Jouni and T. E. Warkentin

The two reviews in this issue are 1) on the current state-of-the-art in imaging venous thrombosis and 2) on protamine-induced thrombocytopenia.

Clinical Haemostasis and Thrombosis:
Commentary
Bleeding Risk Assessment in Atrial Fibrillation: Observations on the Use and Misuse of Bleeding Risk Scores - G. Y. H. Lip and D. A. Lane

In Focus
Low performance of bleeding risk models in the very elderly with atrial fibrillation using vitamin K antagonists - J. Jaspers Focks, S. P. G. van Vugt, M. T. H. Albers-Akkers, E. J. P. Lamfers, L. M. Bloem-de Vries, F. W. A. Verheugt and M. A. Brouwer

Fibrinolysis:
Commentary
Plasminogen and stroke: more is better - R. L. Medcalf

In Focus
Physiologic Variations in Blood Plasminogen Levels Affect Outcomes after Acute Cerebral Thromboembolism in Mice: A Pathophysiologic Role for Microvascular Thrombosis - S. Singh, A. K. Houng, D. Wang and G. L. Reed

There are also two In Focus articles, both accompanied by highly readable commentaries. The first deals with the relatively poor performance of commonly used bleeding risk models in the very elderly. The second In Focus article is more fundamental in nature and examines, in mice, the relationship between plasminogen levels and stroke outcome.


Forum:
Unique Challenges and Experiences of Trainees from Reach the World Countries - J. Etulain

Fibrinolysis:
Commentary
Is resistance futile? The role of TAFIa resistance in bleeding in FXI deficiency - M. B. Boffa

In Focus
Reduced fibrinolytic resistance in Patients with FXI deficiency. Evidence of a thrombin-independent impairment of the TAFI pathway - M. Colucci, F. Incampo, A. Cannavò, M. Menegatti, S.M. Siboni, F. Zaccaria, N. Semeraro and F. Peyvandi

Commentary
Backseat Drivers: Passenger Mutations Take Control of Experimental Phenotypes - B. J. M. van Vlijmen and R. J. Westrick

In Focus
Passenger mutations and aberrant gene expression in congenic tissue plasminogen activator-deficient mouse strains - R. Szabo, A. L. Samson, D. A. Lawrence, R. L. Medcalf and T. H. Bugge

Clinical Hemostasis and Thrombosis:
Case of the Month
Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with fatal outcome – characterization of the antibody - K. Pénzes, K. Rázsó, É. Katona, A. Kerényi, M. Kun and L. Muszbek


Forum:
Early Career Professionals: the Mission of a Task Force - G. D. Barnes and M. N. Lauw

The ISTH has formed a task force with the purpose of assisting early career professionals in hemostasis and thrombosis. This Forum article presents the task force itself and outlines its mission.

Clinical Haemostasis and Thrombosis:
Commentary
Better or worse than the original - F. Bernardi

In Focus
Identification and functional characterization of a novel F5 mutation (Ala512Val, FVBonn) associated with activated protein C resistance - B. Pezeshkpoor, E. Castoldi, A. Mahler, D. Hanel, J. Müller, N.S. Hamedani, A. Biswas, J. Oldenburg and A. Pavlova

An In Focus article, which is accompanied by a commentary, describes a novel F5 mutation (FVBonn) that confers APC resistance.

Recommendations and Guidelines:
Categorization of patients as having provoked or unprovoked VTE: guidance from the SSC of ISTH - C. Kearon, W. Ageno, S.C. Cannegieter, B. Cosmi, G-J. Geersing, P. A. Kyrle and The subcommittees on Control of Anticoagulation and Predictive and Diagnostic Variables in Thrombotic Disease

A Recommendations and Guidelines contribution provides SSC guidance on how to best categorize VTE, as either ‘provoked’ or ‘unprovoked’.

Review:
Gene Therapy for Immune Tolerance Induction in Hemophilia with Inhibitors- V. R. Arruda and B. J. Samelson-Jones

The design and synthesis of new synthetic low molecular weight heparins - K. Chandarajoti, J. Liu and R. Pawlinski

The laboratory's 2015 perspective on direct oral anticoagulant testing - R. C. Gosselin and D. M. Adcock

Clinical Hemostasis and Thrombosis:
Original Article
Impact of Incident Myocardial Infarction on Risk of Venous Thromboembolism. The Tromsø Study - L. B. Rinde, C. Lind, B. Småbrekke, I. Njølstad, E. B. Mathiesen, T. Wilsgaard, M. L. Løchen, E. M. Hald, A. Vik, S. K. Brækkan and J. B. Hansen

This June issue contains two reviews. The first deals with the complexities of immune tolerence induction within the context of gene therapy and hemophilia. The second review is very basic in nature and discusses the state of the art of the design and synthesis of low molecular weight heparins.

This present issue also contains a provocative Forum article that challenges some of the dogmas surrounding the pathogenesis of antiphospholipid syndrome. Topics of the Original Articles in this month’s issue are very varied and range from antiplatelet treatment in cardiovascular patients to the role of microRNAs in the regulation of tissue factor expression.

Review:
Coagulopathy and its Management in Patients with Severe Burns- G.J. Glas, M. Levi and M.J. Schultz

Periprocedural Management of Patients on a Vitamin K Antagonist or a Direct Oral Anticoagulant Requiring an Elective Procedure or Surgery - A.C. Spyropoulos, A. Al-Badri, M.W. Sherwood and J.D. Douketis

The laboratory's 2015 perspective on direct oral anticoagulant testing - R. C. Gosselin and D. M. Adcock

Canine Models of Inherited Bleeding Disorders in the Development of Coagulation Assays, Novel Protein Replacement and Gene Therapies -T. Nichols, C. Hough, M. Ezban, H. Agersø, D. Lillicrap

Transport physics and biorheology in the setting of hemostasis and thrombosis - S. Diamond, L. Brass

Platelet signaling: a complex interplay between inhibitory and activatory networks - A. P. Bye, A. J. Unsworth and J. M. Gibbins

This May issue of JTH is particularly rich in Review articles, of which there are six. These are very varied. Two are basic, and describe the complex signaling pathways in blood platelets and the biophysics of thrombosis and hemostasis in flowing blood. Another two are on laboratory methods and models. The first of these looks at direct oral anticoagulant (DOAC) testing, while the other focuses on models of inherited bleeding disorders in dogs. Finally, the issue starts off with two clinical reviews, with the first on coagulopathy in patients with severe burns, and the second describing how to manage patients who require an invasive procedure while taking oral anticoagulants.

Coagulation:
Commentary
Alzheimer's Disease is In-Part a Thrombo-Hemorrhagic Disorder - A. H. Schmaier

In Focus
The Alzheimer's disease peptide β-amyloid promotes thrombin generation through activation of coagulation factor XII - D. Zamolodchikov, T. Renné and S. Strickland

Commentary
Is Leukocyte Tissue Factor the key to Venous Thrombosis in Antiphospholipid Syndrome? - N. Mackman and R. A. S. Roubey

In Focus
Cofactor Independent Human Antiphospholipid Antibodies Induce Venous Thrombosis in Mice - D. Manukyan, N. Müller-Calleja, S. Jäckel, K. Luchmann, R. Mönnikes,K. Klytaimnistra, C. Reinhardt, K. Jurk, U. Walter and K. J. Lackner

The May issue also includes a Case of the Month article (on abnormal clotting tests in drug addicts), as well as two In Focus articles, accompanied by commentaries providing additional perspectives. The first In Focus article and commentary look at the relationship between Alzheimer’s disease and coagulation activation, and the role of beta-amyloid therein. The second article and commentary pair is on leucocyte tissue factor, antiphospholipid syndrome, and the influence on the occurrence of venous thrombosis.

Review:
Structure-function relationships in Thrombin-activatable Fibrinolysis Inhibitor- T. Plug and J. C. M. Meijers

Platelet immunoreceptor tyrosine-based activation motif (ITAM) and hemITAM signaling and vascular integrity in inflammation and development - R. H. Lee and W. Bergmeier

There are two Review articles in this April issue. The first is on thrombin activatable fibrinolysis inhibitor and summarizes what is known about its structure and how this impacts function. The second review discusses ITAM receptors, their associated signaling pathways in platelets, and how this relates to vascular function in development and in inflammation.

Platelets:
Commentary
How can non-nucleated platelets be so smart? - F. Cognasse, O. Garraud, B. Pozzetto, S. Laradi and H. Hamzeh-Cognasse

In Focus
Escherichia coli induces platelet aggregation in an FcγRIIa-dependent manner - R. D. Moriarty, A. Cox, M. McCall, S. G. J. Smith and D. Cox

The In Focus article, as usual accompanied by a Commentary, is also on platelets, and examines in mechanistic detail, how E. coli induces platelet aggregation.

Coagulation:
Original Article
Site-specific analysis of von Willebrand factor O-glycosylation - B. A. Solecka, C. Weise, M. A. Laffan and C. Kannicht

The final pick is a deep biochemistry study of von Willebrand factor. It examines the details of O-glycosylation and the results provide a new starting point for studies into the influence of this type of glycosylation on functional aspects of von Willebrand factor.

We highlight three contributions in the March issue of the journal. The first is a Forum article that summarizes and discusses biosimilars in the context of low molecular weight heparin, a topic that is timely and important. The second highlighted article is a review of diagnostic procedures for von Willebrand disease. Diagnosis of this disease is far from trivial and the article may help clinicians in their diagnosis and guide researchers in their quest for further improved procedures. The third highlighted contribution is from the SSC and provides guidance on when and how to use antidotes for the direct oral anticoagulants that are now on the market.

Forum:

Biosimilars of low molecular weight heparin (LMWH) products: fostering competition or reducing “biodiversity”?- J. Harenberg, C. Cimminiello, G. Agnelli, G. Di Minno, H. Polo Friz, P. Prandoni and F. Scaglione

Review:

Developments in the diagnostic procedures of von Willebrand disease - A. de Jong and J. Eikenboom

Recommendations and Guidelines:

When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH - J. H. Levy, W. Ageno, N. C. Chan, M. Crowther, P. Verhamme, J. I. Weitz for the Subcommittee on Control of Anticoagulation

Forum:

Shock, acute disseminated intravascular coagulation and microvascular thrombosis: is ‘shock liver’ the unrecognized provocateur of ischemic limb necrosis?- T. E. Warkentin and M. Pai

This Forum article presents an intriguing hypothesis that tries to explain why some critically ill patients are prone to limb necrosis and others are not.

Reviews:

Structural and functional insights into enzymes of the vitamin K cycle - J. K. Tie and D. W. Stafford

A critical appraisal of one-stage and chromogenic assays of factor VIII activity - F. Peyvandi, J. Oldenburg and K. D. Friedman

There are two authoritative reviews in the February issue of JTH. The first presents a detailed overview of what has been accomplished in detailing the complex biochemistry and molecular biology of the enzymes involved in the vitamin K cycle and in the gamma carboxylation of glutamate residues of, among others, coagulation proteins. The second review presents a critical appraisal of assays of factor VIII activity. Understanding the performance of these assays is key to the clinical care of patients who are using factor VIII concentrates.

Special Feature:

ISTH Core Curriculum Project: Core Competencies in Clinical Thrombosis and Haemostasis- C. McLintock, I. Pabinger, K. A. Bauer, M. Laffan, P. Angchaisuksiri, S. M. Rezende, S. Middeldorp and M. Ross

A special feature article summarizes the Haemostasis Core Curriculum Project. This initiative of the ISTH aims to provide a framework of core competences that can be used worldwide to improve and harmonize training of basic scientists and clinicians in our field.

Review:

The Contact Activation and Kallikrein/Kinin Systems: Pathophysiologic and Physiologic Activities - A. H. Schmaier

Actions of Thrombin in the Interstitium - G. G. de Ridder, R. L. L. and S. V. Pizzo

Recent developments on the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles - E. van der Pol, A. N. Böing, E. L. Gool and R. Nieuwland

There are three authoritative review articles in the January issue of JTH. The first is on the contact system and zooms in on current physiologic and pathophysiologic insights. The second article deals with the actions of thrombin in the interstitium and the putative relationship between thrombin and interstitial fibrosis. The third review article is a good read for all those who strive to stay current on many aspects of the fast moving field that investigates the function of microvesicles.

Coagulation:

Commentary
Challenging the anticoagulant paradigm? - H. ten Cate

In Focus
Discovery and characterization of an antibody directed against exosite I of thrombin - H. ten Cate

There are three authoritative review articles in the January issue of JTH. The first is on the contact system and zooms in on current physiologic and pathophysiologic insights. The second article deals with the actions of thrombin in the interstitium and the putative relationship between thrombin and interstitial fibrosis. The third review article is a good read for all those who strive to stay current on many aspects of the fast moving field that investigates the function of microvesicles.

2015

Review:

Platelet secretory behaviour: as diverse as the granules … or not?- H. Heijnen and P. van der Sluijs

This review by Heijnen and van der Sluijs discusses the secretory pattern of the three granule types that are released from platelets: α-granules, dense granules, and lysosomes. The focus is on how secretory processes are regulated, and the way differential secretory patterns impact adhesiveness and other platelet (releasate) functions.

Coagulation:

Original Article
Ex vivo addition of fibrinogen concentrate improves fibrin network structure in plasma samples taken during liver transplantation - D. J. Groeneveld, J. Adelmeijer, G. C. G. Hugenholtz, R. A. S. Ariëns, R. J. Porte and T. Lisman

It is not easy to manage hemostasis in patients undergoing orthotopic liver transplantation. Groeneveld and colleagues suggest, based on an ex vivo study of plasma samples, that the administration of fibrinogen concentrate might become a useful tool to control bleeding complications during the transplantation procedure.

Clinical Haemostasis and Thrombosis:

Commentary
Revisiting the tale of venous thromboembolism in hospitalized medical patients - V. Chopra, S. A. Flanders

In Focus
Central venous catheters and upper extremity deep vein thrombosis in medical inpatients: the Medical Inpatients and Thrombosis (MITH) Study - J. P. Winters, P. W. Callas, M. Cushman, A. B. Repp, N. A. Zakai

This article by Winters and colleagues (accompanied by a commentary from Chopra and Flanders) describes a case-cohort study of hospitalized medical patients and documents the incidence of venous thrombosis. Emphasis is on the proportion of upper versus lower extremity thrombosis and on the role of venous catheters.

Review Articles:

Spatiotemporal regulation of coagulation and platelet activation during the hemostatic response in vivo- T. Stalker and L. Ivanciu

A critical appraissal of point-of-care coagulation testing in critically ill patients- M. Levi and B. J. Hunt

There are two review articles in the November issue. The first, written by Ivanciu and Stalker, is very fundamental and discusses how we currently view the hemostatic response in time and space. Levi and Hunt wrote the second review which summarizes what we now know about the usefulness of point of care testing in critically ill patients.

Cardiovascular Medicine:

Commentary
Stroke in atrial fibrillation and improving the identification of ‘high risk’ patients: the crossroads of immunity and thrombosis - E. Shantsila and G. Lip

In Focus
Neutrophil to lymphocyte ratio and risk of a first episode of stroke in patients with atrial fibrillation: a cohort study - W. Saliba, O. Barnett-Griness, M. Elias and G. Rennert

November's In Focus article, by Saliba and colleagues describes how the neutrophil to lymphocyte ratio – which can be calculated from routine blood cell counts – can become useful as a predictor of stroke in atrial fibrillation.

Review Articles:

New paradigms in sepsis: from prevention to protection of failing microcirculation- J. Hawiger, R. A. Veach and J. Zienkiewicz

Circulatory support devices: fundamental aspects and clinical management of bleeding and thrombosis- S. Susen, A. Rauch, E. Van Belle, A. Vincentelli and P.J. Lenting

This October issue starts with two excellent reviews. Hawiger and colleagues have written a review on sepsis, with a focus on ‘new paradigms’ such as vaccinations to prevent sepsis, role of microvascular endothelial injury, and ‘genome wars’ unleashed by microbial agents. .

The second review is on circulatory support devices and was written by Susen and colleagues. There is good evidence for the clinical benefit of these devices, but thrombotic and bleeding complications remain a problem. The review describes the current state of the art of this field, and also attempts to provide some guidance on how to best prevent and manage complications. .

Clinical Hemostasis and Thrombosis:

Case of the Month
Acquired factor V inhibitor after exposure to topical human thrombin related to an otorhinolaryngological procedure - K. Donohoe and R. Levine

In October's Case of the Month, Donohoe and Levine present a patient who developed an inhibitor against coagulation factor V after exposure to human thrombin..

Vascular Biology

Commentary
More about cellular signaling by antiphospholipid antibodies - K. J. Lackner

In Focus
A novel pathway of cellular activation mediated by antiphospholipid antibody-induced extracellular vesicles - M. Wu, J. Barnard, S. Kundu and K. R. McCrae

The Vascular Biology category contains an In Focus article written by Wu and colleagues, accompanied by an informative commentary contributed by K. Lackner. It is all about the antiphospholipid syndrome and more in particular, about claiming a novel pathway towards cell activation that involves microvesicles. .

Review Article:

Engineering of Plasminogen Activators for Targeting to Thrombus and Heightening Thrombolytic Efficacy- Ahsan, Fakhrul (proxy) (contact); Absar, Shahriar; Gupta, Nilesh; Nahar, Kamrun

The September issue of the journal opens with a review on engineered plasminogen activators. Arterial occlusions are often treated with plasminogen activators in order to lyse the clot. As a side effect of this treatment, bleeding often occurs. The review by Absar and colleagues covers the biotechnological approaches that have been taken to create variants of plasminogen activators, that among others, are all aimed at improving clot specificity and lowering the risk of bleeding..

Clinical Hemostasis and Thrombosis:

Commentary

Prophylaxis in Patients with von Willebrand disease: Who, when, how? - Augusto B. Federici

In Focus

Factor XI and Contact Activation as Targets for Antithrombotic Therapy - T. Abshire, J. Cox-Gill, C.L. Kempton, F.W.G. Leebeek, M. Carcao, P. Kouides, S. Donfield and E. Berntorp

The In Focus article of the September issue also deals with bleeding by describing a study on prophylactic treatment of severe von Willebrand disease. Albeit quite small, the study presented by Abshire and colleagues - on behalf of the ‘von Willebrand Disease Profylaxis Network’ – shows for the first time, that profylaxis with von Willebrand factor concentrates work. The accompanying commentary by A.B. Federici places the Abshire study in a broad

Special Feature:

Global Public Awareness of Venous Thromboembolism- Aaron M Wendelboe, Micah McCumber, Elaine M Hylek, Harry Buller, Jeffrey I Weitz, Gary Raskob and The ISTH Steering Committee for World Thrombosis Day

This is a special feature article on public awareness of venous thrombosis, written by Wendelboe and colleagues from the ‘ISTH Steering Committee for World Thrombosis Day’ (see also the August editorial). The World Thrombosis Day campaign was initiated in 2014 and one of its aims is to increase public awareness of venous thrombosis. The article shows that at present, the awareness of venous thrombosis around the globe is poor indeed. These findings underline the need for the campaign and for everyone involved in our field to become active on 13 October (please go to http://www.worldthrombosisday.org for inspiration). Start preparing now! .

Review Articles:

Venous Thrombosis and Cancer: from Mouse Models to Clinical Trials - Y. Hisada, J. E. Geddings, C. Ay and N. Mackman

Factor XI and Contact Activation as Targets for Antithrombotic Therapy - David Gailani, Charles E. Bane and Andras Gruber

There are two review articles in the August issue that are hot topics in the field. The first is by Hisada and colleagues and is on the relationship between venous thrombosis and cancer. This relationship is quite complicated and the authors systematically review current evidence, both experimental and clinical, for mechanistic involvement of a long list of key components such as platelets, microvesicles and leucocytes (but also many others). The second review article by Gailani and colleagues is on factor XI and the contact system as targets for antithrombotic therapy. Several times the ‘contact system field’ has been declared dead, but the review shows clearly that the field is very much alive and kicking. .

Clinical Haemostasis and Thrombosis:

Another Surprising Finding in Heparin-Induced Thrombocytopenia – Eat Big - A. Greinacher and M. Delcea

Commentary

Heparin enhances uptake of platelet factor 4/heparin complexes by monocytes and macrophages - Manali Joglekar, Sanjay Khandelwal, Douglas B. Cines, Mortimer Poncz, Lubica Rauova and Gowthami M. Arepally

In Focus

Lastly, there is an In Focus article by Joglekar and colleagues, accompanied by a commentary written by Greinacher and Delcea. The focus of the article is on immune mechanisms that lead to heparin-induced thrombocytopenia. In particular the authors show that monocytes take up platelet factor 4-heparin complexes via an active endocytic pathway and then transport these to late endosomes.

Editorial:

Set the record straight- F. R. Rosendaal and P.H. Reitsma

Review Articles:

Management of superficial vein thrombosis - B. Cosmi

Hemophilia B: molecular pathogenesis and mutation analysis - A.C. Goodeve

There are two excellent review articles in the July issue of JTH. The first was written by B. Cosmi and is clinical in nature. It describes the available data on the management of superficial vein thrombosis. A. Goodeve wrote the second review which summarizes the genetic architecture of hemophilia B. .

Coagulation:

Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice - G. M. Thomas, A. Brill, S. Mezouar, L. Crescence, M. Gallant, C. Dubois and D. D. Wagner

Original Article

Cell derived microparticles (often also called micro vesicles or nowadays extracellular vesicles) and their role in hemostasis continue to intrigue many fundamental and clinical researchers. An article by Thomas and colleagues adds further evidence – obtained in an experimental mouse model -  to the existing literature on the importance of these particles, when covered with tissue factor, for cancer related thrombosis. .

Platelets:

The histone deacetylase sirtuin 2 is a new player in the regulation of platelet function - A. Moscardó, J. Vallés, A. Latorre, R. Jover and M.T. Santos

Original Article

The list of proteins that play key roles in platelet function continues to grow. An article by Moscado and colleagues describes the histone deacetylase Sirtuin2 as a new kid on the block. Using an extensive set of specific inhibitors it was possible to show that protein acetylation by Sirtuin2 is central to platelet function..

Clinical Haemostasis and Thrombosis:

Original Article

A prognostic score to identify low-risk outpatients with accute deep vein thrombosis in the upper extremity - V. Rosa-Salazar, J. Trujillo-Santos, J. A. Díaz Peromingo, A. Apollonio, O. Sanz, R. Malý, F. J. Muñoz-Rodriguez, J. Carlos Serrano, S. Soler, M. Monreal for the RIETE Investigators

Consistently, the July issue also contains important clinical papers that offer new insights or are meant to change clinical practice. To name just one example, an article by Rosa-Salazar and colleagues, describes a prognostic score that might become useful for the identification of outpatients with acute upper extremity thrombosis who, at a low risk of adverse events, are eligible for home treatment.

Editorial:

Business, but not as usual - F. Johnstone for the Editorial Office

Review Articles:

Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis - M. Arman and K. Krauel

Original Article (Invited Review)

Antithrombotic Therapy for Left Ventricular Assist Devices in Adults: a Systematic Review - L. Baumann Kreuziger, B. Kim and G. M. Wieselthaler

There are two Review Articles in the June issue of JTH. The first, by Arman and Krauel, is fundamental in nature. It reviews the role of the platelet Fc receptor FcγRIIA in immunity and thrombosis. The second review is by Baumann Kreuziger and colleagues and covers a much more clinical topic through a systematic, rather than a narrative review. It addresses how to prevent thrombosis in adults that are using a left ventricular assists device.

Clinical Haemostasis and Thrombosis:

Case of the Month

Of men and meals - J. Beyer-Westendorf and G. Siegert

JTH rarely publishes case reports. The June issue of JTH is an exception and contains a Case of the Month with the provocative title ‘Of men and meals’. It was written by Beyer-Westendorf and Siegert. The report describes a young patient in whom all the difference was made by taking rivaroxaban with a regular meal.

Fibrinolysis:

In Focus

Generation of a stable thrombin-activatable fibrinolysis inhibitor deletion mutant exerting full carboxypeptidase activity without activation -X. Zhou and P. J. Declerck

Commentary

New clues regarding the mysterious mechanism of activated thrombin-activatable fibrinolysis inhibitor self-destruction -T. Plug and J. C .M. Meijers

The In Focus article in the June issue of JTH is by Zhou and Declerck. The publication of this article is accompanied by a very informative commentary that was written by Plug and Meijers. The topic addressed concerns the enigmatic self destruction of activated thrombin-activatable fibrinolysis inhibitor. The authors’ notable achievement is that they have produced a deletion mutant of the inhibitor that retains activity towards small substrates but does not self destruct.

Editorial:

Mutation goes global - F. R. Rosendaal, P. H. Reitsma

Clinical Haemostasis and Thrombosis:

Original Article

Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial - P. Chowdary, S. Lethagen, U. Friedrich, B. Brand, C. Hay, F. A. Karim, R. Klamroth, P. Knoebl, M. Laffan, J. Mahlangu, W. Miesbach, J. D. Nielsen, M. Martín-Salces, P. Angchaisuksiri

Wouldn’t it be nice to have the same treatment available for hemophilia A and hemophilia B that would work even when inhibitors are present? This possibility is one step closer with the work of Chowdury and colleagues. Their study describes the safety and pharmacokinetics of a monoclonal antibody against the second Kunitz domain of Tissue Factor Pathway inhibitor (TFPI). Moreover, the study claims a dose-dependent procoagulant effect that may be of benefit in patients with hemophilia.

Commentary

NET untangled in TMA? - P. Knöbl

In Focus

Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies - M. Jiménez-Alcázar, M. Napirei, R. Panda, E. C. Köhler, J. A. Kremer-Hovinga, H. G. Mannherz, S. Peine, T. Renné, B. Lämmle and T. A. Fuchs

The In Focus article by Jiménez-Alcázar is on neutrophila extracellular traps (NETs) in acute thrombotic angiopathies (TMA). Dr P. Knöble has contributed a well-written commentary that highlights the most important aspects of the article. These include the seminal observation that patients with TMA are not capable of degrading NETs effectively, which may be due to a lack of DNAse1 activity.

Recommendations and Guidelines:

Recommendations for the use of NOD/SCID mouse model in autoimmune- and drug-induced thrombocytopenia: communication from the SSC of the ISTH -T. Bakchoul, J. Fuhrmann, B. H. Chong, D. Bougie, R. Aster and The Subcommittee of Platelet Immunology of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis

Design of Clinical Trials for New Products in Hemophilia: Communication from the SSC of the ISTH -D. M. Dimichele, S. Lacroix-Desmazes, F. Peyvandi, A. Srivastava, F.R. Rosendaal and The Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders

Diagnosis and Treatment of Incidental Venous Thromboembolism in Cancer Patients: guidance from the SSC of the ISTH -M. Di Nisio, A. Y. Y. Lee, M. Carrier, H. A. Liebman, A. A. Khorana and The Subcommittee on Haemostasis & Malignancy

Almost every issue of the Journal of Thrombosis and Haemostasis contains one or more contribution in the Recommendation and Guidelines section, and with three of these articles, the May issue is no exception. One is on mouse models for thrombocytopenia, one is on diagnosis and treatment of venous thrombosis in cancer patients, and one is on the design of clinical trials for new products for the treatment of hemophilia. The conclusion of the last article states that an innovative approach will increase the feasibility of studying multiple new products.

Editorial:

Statistically Speaking - F. R. Rosendaal, P. H. Reitsma

Cardiovascular Medicine:

Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study - A. Gorst-Rasmussen, F. Skjøth, T. B. Larsen, L. H. Rasmussen, G. Y. H. Lip and D. A. Lane

Physicians fear that patients taking one of the new oral anticoagulants exhibit poor medication adherence due to not being routinely monitored. The paper by Gorst-Rasmussen and colleagues in the April issue of the Journal of Thrombosis and Haemostasis tests the validity of this notion. In order to do this, authors retrieved data from the Nationwide Danish patient and prescription purchase registries. The outcome of the study indicated that over 75% of the patients were adherent with dabigatran more than 80% of the time during the first year of drug usage.

Clinical Haemostasis and Thrombosis:

Commentary

Recombinant soluble thrombomodulin: coagulation takes another chance to reduce sepsis mortality - M. Levi

In Focus

Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis - K. Yamakawa, M. Aihara, H. Ogura, H. Yuhara, T. Hamasaki and T. Shimazu

There are two In Focus articles in the April issue of the Journal of Thrombosis and Haemostasis. The first is a systematic review and meta-analysis by Yamakawa and colleagues with an accompanying commentary by Marcel Levi. The purpose of this analysis was to establish whether the use of recombinant human thrombomodulin, wide in Japanese patients with disseminated intravascular coagulation, is justified by the available scientific evidence. The outcome of the analysis showed a trend in reduced mortality in treated patients, whilst larger and more rigorous trials are needed for a final verdict.

Coagulation:

Commentary

Exposed: the elusive αC regions in fibrinogen, fibrin protofibrils and fibers -M. Rocco and J. W. Weisel

In Focus

Visualization of fibrinogen αC regions and their arrangement during fibrin network formation by high-resolution AFM -A. D. Protopopova, N. A. Barinov, E. G. Zavyalova, A. M. Kopylov, V. I. Sergienko and D. V. Klinov

The second In Focus article is a basic science paper on structural aspects of fibrinogen that was written by Protopopova and colleagues, whilst Mattia Rocco and John Weisel teamed up to write the accompanying commentary. The article contains remarkable images of fibrinogen and fibrin(ogen) fragments at different stages of polymerization that were obtained by atomic force microscopy. From these images, new details emerged about the structure of individual fibrinogen molecules, fibrin monomers, and oligomers during early stages of fibrinogen polymerization.

Editorial:

Love thy neighbors - F. R. Rosendaal, P. H. Reitsma

Review Article:

New explanations for old observations: Marginal band coiling during platelet activation - K. Sadoul

Comment: The review article by Sadoul in the March issue of the Journal of Thrombosis and Haemostasis discusses ‘marginal band coiling’ in detail. Resting platelets are retained in a flat discoid shape by a circumferential bundle of microtubules, known as the ‘marginal band’. Upon activation, these marginal band microtubules are crucial for cytoskeletal and shape changes in the platelet. The review summarizes the molecular mechanisms with emphasis on the coiling of microtubules.

Coagulation:

Commentary

Down in a hole: A new laser ablation model of hemostasis - K. B. Neeves

In Focus

Novel mouse hemostasis model for real-time determination of bleeding time and hemostatic plug composition - T. M. Getz, R. Piatt, B. G. Petrich, D. Monroe, N. Mackman and W. Bergmeier

Comment: The ‘In Focus’ article in the March issue of the Journal of Thrombosis and Haemostasis by Getz et al – accompanied by a commentary written by Keith Neeves – introduces a new model of hemostasis, that uses a laser to reproducibly puncture the saphenous vein of a mouse. The transient accumulation of fluorescently labeled platelets and fibrin is monitored and directly followed. The initial thrombus that is formed can be hit again (up to 5-times) by the laser in order to mimic re-injury which considerably improves the statistical power of the model.

Platelets:

Original Article

Severe Bleeding Events in Adults and Children with Primary Immune Thrombocytopenia: A Systematic Review -C. Neunert, N. Noroozi, G. Norman, G. R. Buchanan, J. Goy, I. Nazi, J. G. Kelton and D. M. Arnold

Comment: Low platelet count in patients with immune thrombocytopenia exposes them to an increased risk of bleeding, however the frequency of bleeding events in children and adults with ITP has not yet been established with certainty. The meta-analysis that is described in the article by Neunert et al in the March issue of the Journal of Thrombosis and Haemostasis tries to fill this void. Authors conclude that ‘these data improve our understanding of the natural history of ITP and help inform patients and physicians about the risks of withholding treatment during periods of observation, which is often indicated in managing ITP patients.

Editorial:

Fundamental - F. R. Rosendaal, P. H. Reitsma

Review Article:

microRNAs in Hemostasis - R. Teruel-Montoya, F. R. Rosendaal and C. Martínez

Comment: RNA inhibition by small, noncoding microRNAS was discovered relatively recently, in the early 2000s. Today, we know thousands of different microRNAs and insight into their profound biological effects is rapidly growing. A review by Teruel-Montoya et al. in the February issue of JTH summarizes what is known to date about the role of microRNAs in regulating the hemostatic system.

Clinical Haemostasis and Thrombosis:

Risks of Venous thromboembolism in Patients with Liver Cirrhosis: A Nationwide Cohort Study in Taiwan - K.-J. Ng, Y.-K. Lee, M.-Y. Huang, C.-Y. Hsu and Y.-C. Su

Comment: Liver cirrhosis leads to many changes in blood coagulation factor levels that seem to translate in both an increased thrombotic and bleeding risk. Most studies investigating this event, were done in Caucasian subjects, but not in other ethnicities. A paper by Ng et al. describes a study of thrombotic risk in Taiwanese patients with liver cirrhosis. Data from 1 million individuals were utilized for this study and the results show that in severe liver cirrhosis, thrombotic risk may be increased by as much as a factor 4.

Platelets:

Commentary

Platelets: the unsung hero of the immune response - M. Koupenova and J. E. Freedman

In Focus

Platelets interact with Coxsackieviruses B and have a critical role in the pathogenesis of virus-induced myocarditis - S. Negrotto, C. Jaquenod de Giusti, L. Rivadeneyra, A. E. Ure, H. A. Mena, M. Schattner and R. M. Gomez

Comment: All readers of JTH will know that blood platelets are crucial for a normal hemostatic response upon vascular injury. Less well defined is the role platelets play in immunology. A paper by Negrotto et al. provides compelling evidence that platelets directly impact the outcome of Coxsackievirus B-induced myocarditis, and the importance of these findings is further explored in the commentary by Koupenova and Freedman.

Editorial:

Winter studies - F. R. Rosendaal, P. H. Reitsma

Cardiovascular Medicine:

Original Article

Prospective study of sickle cell trait and venous thromboembolism incidence - A. R. Folsom, W. Tang, N. S. Roetker, A. V. Kshirsagar, V. K. Derebail, P. L. Lutsey, R. Naik, J. S. Pankow, M. L. Grove, S. Basu, N. S. Key and M. Cushman

Comment: Sickle cell trait, i.e. heterozygosity for hemoglobin S, has not been established as a risk factor for venous thrombosis with certainty. This study provides more proof on this topic and presents compelling evidence that sickle cell trait increases the risk of pulmonary embolism two-fold, whereas risk of deep vein thrombosis was not found to be elevated.

Vascular Biology:

Original Article

Protein S exacerbates alcoholic hepatitis by stimulating liver natural killer T cells - A. L. Chelakkot-Govindalayathil, R. Mifuji-Moroka, C. N. D’ Alessandro-Gabazza, M. Toda, Y. Matsuda, P. Gil-Bernabe, Z. Roeen, T. Yasuma, Y. Yano, E. C. Gabazza, M. Iwasa and Y. Takei

Comment: Protein S is a vitamin K-dependent protein that is best known for its anticoagulant function. Protein S may also exert anti-inflammatory and anti-apoptotic activity through binding to Tyro3, Axl and Mer (TAM) tyrosine kinase receptors. This mouse study hypothesized that protein S might be protective in alcoholic hepatitis, but the opposite appears to be the case. Effects on natural killer T cell apoptosis seem to be at the heart of these findings.

Platelets:

Brief Report

Effect of prasugrel in patients with asthma: results of PRINA, a randomized, double-blind, placebo-controlled, cross-over study - P. M. Zakas, K. Vanijcharoenkarn, R. C. Markovitz, S. L. Meeks and C. B. Doering

Comment: Experimental animal data has suggested that platelet P2Y12 receptors are a key player in bronchial inflammation. Based on this data, a proof-of-concept trial has been done in twenty-six asthmatic patients in order to examine whether treatment with the P2Y12 inhibitor prasugrel improves asthma. The study indeed suggests that prasugrel lowers the bronchial inflammatory burden, but the effect may be limited.

Coagulation:

Original Article

Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors - R. P. Naik, M. B. Streiff, C. Haywood Jr, J. B. Segal and S. Lanzkron

Comment: In 20-30% of cases, treatment of severe hemophilia A, is complicated by the development of inhibitors against the administered factor VIII. There are strategies to bypass inhibitors, such as the use of recombinant factor VIIa. An alternative strategy could be the use of factor VIII from other species that confer reduced antigenicity and inhibition. This paper describes pre-clincal data in a mouse model of hemophiliaA for an ortholog of FVIII derived from sheep, and suggests that there is potential for such a biological.

2014

Editorial:

Another year - F. R. Rosendaal, P. H. Reitsma

Review Article:

Progress and challenges in the development of a cell-based therapy for hemophilia A - Marina E. Fomin, P. P. Togarrati and M. O. Muench

Comment: Alternative strategies for the treatment of hemophila A include gene therapy and cell therapy. This narrative review summarizes the promises, but also the challenges and hurdles, of the cell therapy based approaches.

Platelets:

Commentary

Moonlighting proteins dictate the cross-talk between thrombosis and innate immunity - M. Saffarzadeh and K. T. Preissner

Comment: The commentary helps to appreciate the importance of the In Focus paper by Maugeri et al that examines how activated platelets might play a role in NETosis by neutrophils in the interplay between coagulation and immunity.

In Focus

Activated platelets present High Mobility Group Box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps - N. Maugeri, L. Campana, M. Gavina, C. Covino, M. De Metrio, C. Panciroli, L. Maiuri, A. Maseri, A. D'Angelo, M. E. Bianchi, P. Rovere-Querini and A. A. Manfredi

Comment: The commentary helps to appreciate the importance of the In Focus paper by Maugeri et al that examines how activated platelets might play a role in NETosis by neutrophils in the interplay between coagulation and immunity.

Clinical Haemostasis and Thrombosis:

Original Article

Venous thromboembolism incidence in the Cooperative Study of Sickle Cell Disease - R. P. Naik, M. B. Streiff, C. Haywood Jr, J. B. Segal and S. Lanzkron

Comment: Venous thrombosis was recently recognized as a complication of sickle cell disease. This contribution to JTH attempts to estimate the exact incidence rate of venous thrombosis in sickle cell patients, and the data show these patients are indeed at considerable risk for venous thrombotic events.

Editorial:

5000 years old and still going strong - F. R. Rosendaal, P. H. Reitsma

Review Article:

Platelets in inflammation and immunity - J. M. Herter, J. Rossaint and A. Zarbock

Recommendations and Guidelines:

Prevention of VTE in Cancer Outpatients: guidance from the SSC of the ISTH - A. A. Khorana, H. M. Otten, J. I. Zwicker, G. C. Connolly, D. Farge-Bancel, I. Pabinger and The Subcommittee on Haemostasis Malignancy

Comment: Physicians often struggle with the question which cancer patients need thromboprophylaxis. This important SSC document gives clear guidance in this area.

Vascular Biology:

In Focus

sPLA2-V impairs EPCR-dependent protein C activation and accelerates thrombosis in vivo - I. Tamayo, S. E. Velasco, C. Puy, C. T. Esmon, M. G. Dichiara, R. Montes and J. Hermida

Comment: The interaction between protein C or activated protein C with the endothelial protein C receptor is dependent on phosphatidylcholine. Here it is shown that under inflammatory conditions phosphatidylcholine can become replaced, which impairs protein C activation.

Clinical Haemostasis and Thrombosis:

Original Article

Recombinant factor VIII Fc fusion protein: Extended-interval dosing maintains low bleeding rates and correlates with von Willebrand Factor levels - A. D. Shapiro, M. V. Ragni, R. Kulkarni, J. Oldenberg, A. Srivastava, D. V. Quon, K. J. Pasi, H. Hanabusa, I. Pabinger, J. Mahlangu, P. Fogarty, D. Lillicrap, S. Kulke, J. Potts, S. Neelakantan, I. Nestorov, S. Li, J. A. Dumont, H. Jiang, A. Brennan and G. F. Pierce

Comment: In the past years we have witnessed the development of recombinant factor VIII molecules with an extended plasma half-life. This gave hope that profylactic treatment in hemophilia A might benefit from reduced infusion frequencies with the same clinical outcome. This indeed seems to be the case.

Editorial:

Thrombosis unfurry - F. R. Rosendaal, P. H. Reitsma

Special Feature:

Thrombosis: A major contributor to global disease burden - ISTH Steering Committee for World Thrombosis Day

Comment: From this year onwards, October 13 is the World Thrombosis Day. The global burden of this frequent and dilapidating disease is not widely appreciated. The data presented in the article by the ISTH Steering Committee for World Thrombosis Day will greatly help in increasing the awareness of thrombotic disease among clinicians, scientists, policy makers and the general public.

Review Article:

Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment. - R. E. J. Roach, S. C. Cannegieter and W. M. Lijfering

Comment: Men are at a higher risk of venous thrombosis than women. Much research effort has gone into understanding this sex difference in thrombotic risk. The review by Roach et al summarizes this work, with an emphasis on genes and environment which will help to set the future research agenda on this important topic.

Fibrinolyisis

Enhanced Venous Thrombus Resolution in Plasminogen Activator Inhibitor Type-2 Deficient Mice - S. A. Siefert, C. Chabasse, S. Mukhopadhyay, M. H. Hoofnagle, D. K. Strickland, R. Sarkar and T. M. Antalis

Comment: The real biological role of PAI-2 has been disputable ever since its discovery as an inhibitor of urokinase, even despite the fact that quite a few types of cells are capable of producing large amounts of this protein. What is clear from the study of Siefert et al is that lack of PAI-2 promotes venous thrombus resolution. So PAI-2 may be a real PAI after all.

Editorial:

Questions, questions, questions... - F. R. Rosendaal, P. H. Reitsma

Review Article:

In Focus

Pneumonia, thrombosis and vascular disease. - F. Violi, R. Cangemi and C. Calvieri

Clinical Haemostasis and Thrombosis:

Commentary

Prothrombin Complex Concentrate (PCC) for Non-Vitamin K Oral Anticoagulant (NOAC) reversal: Good enough for now? - M. Makris

In Focus

Comparison of Three- and Four-Factor Prothrombin Complex Concentrates on the Anticoagulant Effects of Rivaroxaban in Healthy Volunteers - M. Levi, K. T. Moore, C. F. Castillejos, D. Kubitza, S. D. Berkowitz, S. Z. Goldhaber, M. Raghoebar, M. R. Patel, J. I. Weitz and J. H. Levy

Commentary

Tailored eculizumab regimen for patients with atypical hemolytic uremic syndrome: requirement for comprehensive complement analysis - C. Wehling and M. Kirschfink

In Focus

Complement Functional Tests For Monitoring Eculizumab Treatment In Patients With Atypical Hemolytic Uremic Syndrome - M. Cugno, R. Gualtierotti, I. Possenti, S. Testa, F. Tel, S. Griffini, E. Grovetti, S. Tedeschi, S. Salardi, D. Cresseri, P. Messa and G. Ardissino

Editorial:

Fast Science - F. R. Rosendaal, P. H. Reitsma

Cardiovascular Medicine:

In Focus

Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case-control study - M. Schmidt, S. C. Cannegieter, S. A. Johannesdottir, O. M. Dekkers, E. Horváth-Puhó and H. T. Sørensen

Commentary

Clots and Cardiac Valve Prostheses - R. Jeffrey

Clinical Haemostasis and Thrombosis:

In Focus

Quantitative impact of using different criteria for the laboratory diagnosis of type 1 von Willebrand disease. - T. Quiroga, M. Goycoolea, S. Belmont, O. Panes, E. Aranda, P. Zúñiga, J. Pereira and D. Mezzano

Editorial:

Meta-analysis - F. R. Rosendaal, P. H. Reitsma

Review Article:

Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation- The View from Japan - Toshiaki Iba, Satoshi Gando and Jecko Thachil

Clinical Haemostasis and Thrombosis:

Original Article

The effect of low-molecular-weight heparin on survival in cancer patients: An updated systematic review and meta-analysis of randomized trials - D. Sanford, A. Naidu, N. Alizadeh and A. Lazo-Langner

Coagulation:

Original Article

Abnormal plasma clot structure and stability distinguish bleeding risk in patients with severe factor XI deficiency - M. Zucker, U. Seligsohn, O. Salomon and Alisa S. Wolberg

Vascular Biology:

In Focus

Neutrophils recruit and activate Human Endothelial Colony Forming Cells at the site of vessel injury via PSGL-1 and L-Selectin - L. Hubert, R. Darbousset, L. Panicot-Dubois, S. Robert, F. Sabatier, K. Fallague, F. Dignat-George and C. Dubois

Commentary

Neutrophils as new conductors of vascular homeostasis - D. Smadja

Editorial:

Terminated - F. R. Rosendaal, P. H. Reitsma

Clinical Haemostasis and Thrombosis:

Commentary

Clinical Trials and Tribulations - M. Greaves

In Focus

Comparison of idrabiotaparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: the Borealis-AF study - H.R. Buller, J. Halperin, G.J. Hankey, G. Pillion, M.H. Prins and G.E. Raskob

Platelets:

In Focus

The Ca2+/calmodulin-dependent kinase kinase β-AMP-activated protein kinase-α1 pathway regulates phosphorylation of cytoskeletal targets in thrombin-stimulated human platelets - M. B. Onselaer, C. Oury, R. W. Hunter, S. Eeckhoudt, N. Barile, Christelle Lecut, Nicole Morel, B. Viollet, L. M. Jacquet, L. Bertrand, K. Sakamoto, J. L. Vanoverschelde, C. Beauloye and S. Horman

Coagulation:

Original Article

Oral gene therapy for hemophilia B using chitosan formulated FIX mutants - P. Quade-Lyssy, P. Milanov, D. Abriss, C. Ungerer, C. Königs, E. Seifried and J. Schüttrumpf

Editorial:

A case of two commentaries - F. R. Rosendaal, P. H. Reitsma

Review Article:

Coronary heart disease: linking pathological, coagulation and epidemiological evidence - H. ten Cate and T. Meade

Cardiovascular Medicine:

Original Article

Influence of Sex on Risk of Bleeding in Anticoagulated Patients: A Meta-analysis - S. Takach Lapner, N. Cohen and C. Kearon

Platelets:

Commentary

The DRY Motif at Work: The P2Y12 Receptor Case - E. G. Rovati, V. Capra

In Focus

A novel mutation in the p2y12 receptor and a function-reducing polymorphism in par-1 in a patient with chronic bleeding - Y. M. Patel, M. Lordkipanidzé, G. C. Lowe, S. P. Nisar, K. Garner, J. Stockley, M. E. Daly, M. Mitchell, S. P. Watson, S. K. Austin and S. J. Mundell

Vascular Biology:

In Focus

NF-B is Activated from Endosomal Compartments in Antiphospholipid Antibodies-treated Human Monocytes - K. J. Brandt, C. Fickentscher, F. Boehlen, E. K. O. Kruithof and P. de Moerloose

Recommendations and Guidelines:

Membership Management Software Powered by YourMembership  ::  Legal