2017 marks a very special year for Thrombosis and Haemostasis: it marked the 60th anniversary of the journal. To commemorate this event, selected
section editors were invited to create a modern portrait of the journal, reflecting
the milestones of the past and encouraging a glance into future across the many topics
of the journal's scope. The main directions reflected in the anniversary editorial[1] are recapitulated in this year's Editors' Choice selection of papers of high interest
or citation.
We traditionally start the New Near with various position and consensus papers and
current state-of-the-art developments, revealing valuable insights for researchers
and clinical specialists. For instance, the role of microvesicles in the pathophysiology
of thrombosis and cardiovascular disease has been intensely investigated in light
of their value as potential biomarkers. We are therefore delighted to publish a relevant
position paper of the European Society of Cardiology Working Group on Atherosclerosis
and Vascular Biology, which comprehensively summarizes the current mechanistic knowledge
on the formation, composition and function of microvesicles with an endothelial, platelet,
red blood cell and leukocyte origin.[2]
In addition, we also published an executive summary of a joint consensus document
from the European Heart Rhythm Association and European Society of Cardiology Working
Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease,
Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS),
Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association
and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE),
addressing the topic of antithrombotic therapy in atrial fibrillation (AF) associated
with valvular heart disease.[3] This document recommends that the term ‘valvular AF’ is outdated and proposes a
new functional Evaluated Heartvalves, Rheumatic or Artificial (EHRA) categorization
in relation to the type of oral anticoagulant use in patients with AF, as follows:
(1) EHRA Type 1 valvular heart disease which refers to AF patients with ‘valvular
heart disease needing therapy with a vitamin K antagonist (VKA)’ and (2) EHRA Type
2 valvular heart disease, which refers to AF patients with ‘valvular heart disease
needing therapy with a VKA or a non-VKA oral anticoagulant (NOAC)’, also taking into
consideration score risk factors.
New Developments in Anticoagulants
New Developments in Anticoagulants
Anticoagulants are the mainstay for the prevention and treatment of thrombosis. In
their joint paper, Weitz and Harenberg highlighted the advances of oral anticoagulant
therapy, referring to safety issues and reviewing some of the ongoing trials with
NOACs, and provided insights into recent research on factors XII and XI inhibitors
as potentially novel anticoagulants.[4]
Poterucha et al in their review focused on heparin interference in the inflammatory
pathophysiology of thrombosis development and tended to advancing treatments based
on heparin derivatives.[5] To complement this, Schulman et al reviewed published as well as ongoing observational
studies with NOACs in VTE and discussed limitations in analysis and interpretation.[6]
With the NOACs, the quest for reversal agents continues, and there was much interest
in the paper by Ansell et al[7] on ciraparantag, a new ‘universal antidote’ and small molecule that potentially
reverses the anticoagulant effects of dabigatran and factor Xa inhibitors.
However, despite the developments with NOACs, the VKAs are not ‘dead’ and we published
interesting papers on the pharmacology of tecarfarin, a novel VKA drug.[8]
[9] This complements the clinical data from the EmbraceAC trial.[10]
Venous Thromboembolism
Venous thromboembolism (VTE) as the third most frequent acute cardiovascular syndrome
is associated with a considerable disease burden. In the anniversary issue, Schulman
et al recalled therapeutic developments focusing on prophylaxis, attending to new
drugs and technical advances in imaging, as well as hospital accreditation and funding
based on evidence-based practice.[11]
Additional analyses from the large trials included a pooled analysis of RE-COVER and
RE-COVER II trials comparing dabigatran versus warfarin for acute venous thromboembolism
in elderly or impaired renal function patients.[12]
Apart from clinical trials, real-world observational data on NOACs are increasingly
evident. As one notable example, Coleman et al assessed the effectiveness and safety
of rivaroxaban versus warfarin in VTE patients in routine practice and came to the
conclusion that it more effectively reduces patients' hazard of both recurrent VTE
and major bleeding.[13] Trujillo-Santos et al investigated the use of NOACs under real-life conditions,
including nonrecommended doses or regimens and unveiled the influence on VTE occurrence
and subsequent outcomes.[14] We also published the design paper for RE-COVERY DVT/PE, a prospective observational
study of acute venous thromboembolism with a focus on dabigatran etexilate.[15]
Metabolic-Vascular Disease
Metabolic-Vascular Disease
Endothelial cell metabolism has emerged as an important regulator of angiogenesis.
In their review, Breier et al provided insights into angiogenesis during obesity-related
metabolic dysfunction and into signaling pathways linking cell metabolism to endothelial
function.[16] A set of publications highlighted the impact of hepatic alterations on thrombosis.
Ambrosino et al figured out the importance of specific VTE prevention strategies for
cirrhotic subjects,[17] whereas an interesting contribution to elucidating the molecular and pathogenic
mechanisms underlying nonalcoholic steatohepatitis (NASH) was provided by Geys et
al, demonstrating that ADAMTS13 deficiency in obese mice induces hepatic microthrombosis.[18]
[19] Lallukka et al demonstrated that obesity and insulin resistance rather than liver
fat increases circulating coagulation factor activities.[20] Finally, adipose tissue inflammation starts with cell accumulation. Having disclosed
a role of leukocyte integrin Mac-1 in macrophage accumulation in adipose tissue in
a murine model, Wolf et al[21] remained sceptical concerning the net effect of integrin blockade in cardiometabolic
disease.
Stroke Prevention in Atrial Fibrillation
Stroke Prevention in Atrial Fibrillation
The evolution of stroke and bleeding risk assessment over the past decades was reviewed
by Lip et al,[22] culminating in a practical management pathway to help streamline and simplify decision
making for stroke prevention in patients with AF with three simple steps and to aid
decision making for stroke prevention in AF (referred to as the Birmingham ‘3-step’).
Biomarker scores represent an attractive prognostic tool for bleeding risk assessment.
The performance of the new ABC-bleeding score was validated and compared with the
HAS-BLED score in a ‘real-world’ setting of anticoagulated AF patients with long-term
follow-up, which concluded that HAS-BLED performed significantly better in predicting
major bleeding.[23] In the largest ‘real-world’ study on apixaban effectiveness and safety to date,
Li et al showed that apixaban significantly attenuates stroke risk and major bleeding
compared with warfarin independent from risk subgroups and dose regimens.[24]
Therapeutic Strategies for Atherosclerosis and Atherothrombosis
Therapeutic Strategies for Atherosclerosis and Atherothrombosis
Atherosclerosis and atherothrombosis continue to be the leading causes of death worldwide.
In their review, Weber et al[25] provided historical overview, spotted the range of currently available state-of-the-art
therapies and highlighted the promising therapeutic strategies aimed at reduction
of the residual risk that still persists despite current therapeutic options. Jamasbi
et al underscored their expectations for novel antiplatelet drugs selectively inhibiting
arterial thrombosis without interfering with normal haemostasis.[26]
The nature of atherosclerosis had been extensively studied through sophisticated transgenic
animal models. As an example, Winkels et al revealed the new atherosclerosis-modulating
properties of CD70 through altering macrophage function.[27] Pointing out the recent failures in translating various anti-inflammatory therapeutic
strategies for use in humans demands to retain a healthy scepticism regarding the
inflammatory causality underlying human atherosclerosis despite the recent success
of the CANTOS trial, Santovito and Weber advised to keep in mind that ‘things may
not always be what they appear’.[28]
Antithrombotic Therapy for Acute Coronary Syndrome
Antithrombotic Therapy for Acute Coronary Syndrome
Plaque erosions and ruptures accompany arterial thrombus formation in the coronary
arteries resulting in acute coronary syndrome. Sibbing et al highlighted a discrepancy
between current guideline recommendations favouring potent platelet inhibition in
ACS and the utilization of the respective drugs in clinical practice and pointed out
the development of optimized antiplatelet treatment strategies and their utilization
in the real world.[29] Standard care for treating non-ST elevation myocardial infarction patients is represented
by dual antiplatelet therapy. Interestingly, chewing versus an equal dose of traditional
oral administration enhances inhibition of platelet aggregation after administering
a ticagrelor.[30]
Beyond Cardiovascular Disease
Beyond Cardiovascular Disease
The biochemical characterization of the proteolytic pathways that constitute blood
coagulation is followed by identifying and validating appropriate targets for improving
global health through their application in haemostasis and thrombosis pathologies.
In their review, Ten Cate et al evaluated the concepts providing a modern vision of
coagulation, illustrating the importance of the coagulation cascade in cardiovascular
pathology through thrombotic as well as atherosclerotic processes and in the response
to ischaemia–reperfusion injury.[31] Severe inflammatory complications often determine the disease progression and outcome.
The evidence from both basic research and clinical studies highlighted the role of
self-extracellular nucleic acids in the crosstalk between immunity and cardiovascular
diseases. Preissner et al delivered a portrait of self-extracellular nucleic acids
with an emphasis on their role in immune response, inflammation, thrombosis and cardiovascular
diseases.[32]
Over the past 60 years, Thrombosis and Haemostasis continues be a platform for exciting developments in vascular biology and medicine,
welcoming next generation of authors with novel and amazing approaches in all aspects
of coagulation, haemostatic and vascular research. We look forward to help you in
sharing and disseminating your knowledge.
