Beauty is in the eye of the beholder
In Molly Brown by Margaret Wolfe Hungerford, 1878
The idiom, in similar wording, actually originates from the old Greek philosophers.
This idiom is often used today to illustrate any experience or perception that is
subjective and personal. The main aim of Seminars in Thrombosis and Hemostasis is to publish reviews, driven by topics related to the themes of ‘thrombosis’ or
‘hemostasis.’ Nevertheless, original peer reviewed research papers are also published
in this journal. It should be recognized that differences exist between personal opinions
on the proportion of original papers vs reviews that should be published in this journal, and differences may also exist
in personal perceptions of what actually constitutes a “review.” In this third part
of the ‘Recent Advances in Thrombosis and Hemostasis’ series, the proportion of original
articles may seem relatively high for what is primarily seen as a review journal.
In the humble opinion of the editor of this issue, of the 10 contributions to this
issue, 3 are purely original research, 2 are a combination of original research and
literature reviews, 3 are review articles, and 2 are systematic reviews and meta-analyses.
The latter articles become particularly problematic to characterize specifically as
original papers or reviews, since they are definitely reviews of the literature and probably more complete
than regular review articles, and given they are based on extensive literature searches
according to a predefined protocol. On the other hand, they do contain original analyses
of the data. However, even a regular review article will contain a Discussion section,
where the author makes a less formal, but still personal and hopefully original (or
else it could be plagiarism) synthesis of the data reviewed. Thus, it seems logical
to acknowledge the systematic reviews as part of the review article ‘count’ for this
issue.
This issue starts with three articles on the epidemiology of venous thromboembolism
(VTE). Deficiency of antithrombin is the hereditary thrombophilic defect with the
highest risk for VTE.[1] In a systematic review and meta-analysis, Croles et al have quantified the risk
of first VTE and of recurrence in patients with congenital antithrombin deficiency,
and their results inform us of the need for indefinite duration of anticoagulation
when they have suffered an episode of VTE.[2] Moving on to the acquired risk factors, it is well established that long-distance
travel by plane is associated with an increased risk of VTE, albeit small in absolute
numbers.[3] The risk is higher for long-haul flights than for long-distance surface travel.[3] Lippi and Favaloro are herein specifically addressing the risk associated with travel
by car, by reviewing available studies and case reports.[4] The risk is not as clear cut as for travel by plane, but the authors end up with
suggestions for VTE prevention, particularly for travelers with additional risk factors.
The last epidemiological contribution addresses the risk of pulmonary embolism (PE)
after surgery for lung cancer, both of which are established risk factors. In a retrospective
cohort study, Li et al analyzed the risk for PE and for fatal PE and independent risk
factors for PE.[5] Although the overall 30-day event rate of PE without prophylaxis is not impressive
(0.57%), the results indicate that in the presence of particularly stage IV of lung
cancer, with or without extensive surgery, extension of prophylaxis up to a month
should be considered.
The characteristics of deep vein thrombosis (DVT) can be associated with outcomes
such as recurrence and mortality. We accept that unprovoked DVT as well as proximal
DVT are associated with a higher risk of recurrence than provoked or distal DVT, respectively.
Bikdeli et al have now analyzed outcomes in relation to the side of the DVT, utilizing
data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) database.[6] Over 30,000 patients were included in this analysis. Whereas differences in outcomes
between DVT in the right or left leg are not sufficiently large to warrant different
management, the few patients diagnosed with bilateral DVT have more comorbidities
and higher risk for PE within 90 days and death within 1 year, justifying special
attention in their management.
The next six contributions to this issue deal with treatment with oral anticoagulants.
Any anticoagulant therapy is associated with an increased risk of bleeding. Whereas
we will hardly ever abstain from anticoagulant treatment of a newly diagnosed VTE,
unless there is active bleeding and a vena cava filter is inserted, we may want to
discontinue treatment after the minimum duration considered acceptable. To this extent,
a risk assessment model can be helpful. The Hypertension, Abnormal Renal/Liver Function,
Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED)
score was developed and validated in patients with anticoagulation for stroke prophylaxis
in atrial fibrillation.[7] Rief et al explored its performance in a prospective cohort study of patients with
VTE.[8] Their results indicate that a HAS-BLED score of 3 or higher could be helpful in
identifying patients at high risk of major bleeding, and it seemed to perform better
than the recently published VTE-bleed score.[9]
Non-vitamin K antagonist oral anticoagulants (NOACs) were studied well in large phase
III trials that addressed efficacy and safety in general, but several subsets of patients
were excluded. Individuals with end-stage renal disease were not included, but based
on pharmacokinetic modeling, there is in some jurisdictions now an expansion of the
indications to these patients. Klil-Drori and Tagalakis are herein reviewing existing
data on warfarin and different NOACs for this patient population.[10] Interestingly, they find that the commonly used warfarin is probably less safe than
some of the NOACs for these patients. Mechanical heart valves are still considered
a contraindication for NOACs based on the RE-ALIGN study with dabigatran that was
prematurely stopped for safety.[11] For patients with bioprosthetic heart valves, the situation is different, since
they do not require vitamin K antagonists, at least not for long-term prophylaxis
against stroke. Russo et al describe the outcomes of 122 patients in their database
that had the combination of atrial fibrillation, bioprosthetic heart valve or valve
repair, and NOAC treatment.[12] They also review the literature and conclude that existing evidence does not support
the exclusion of these patients from use of NOACs. In the following article, they
perform a similar analysis of patients with atrial fibrillation, cancer, and treatment
with NOACs and report very good efficacy in 76 patients.[13] Data from the recently published Hokusai VTE Cancer study also demonstrated good
efficacy of the NOAC edoxaban, in fact not inferior to that of low-molecular-weight
heparin, but with an increased risk of major bleeding, especially among patients with
gastrointestinal or urothelial cancer.[14] This may also pertain to the population with atrial fibrillation. A systematic review
and meta-analysis demonstrated a 10% reduction in all-cause mortality with NOACs compared
with warfarin, which was related to both a reduction in fatal bleeding and lower cardiovascular
mortality.[15] Gomez-Outes et al have here looked further into the causes of death in the NOAC
trials in the VTE-population in systematic review and meta-analysis.[16] The leading cause of death was cancer without a difference between NOACs and vitamin
K antagonists. Continuing on the cancer theme, Tufano et al have reviewed the dilemmas
that face the clinician when ordering both chemotherapy for cancer and anticoagulation
in atrial fibrillation.[17] Cardiotoxicity and optimal choice of antiarrhythmic agents, chemotherapy-induced
liver dysfunction or thrombocytopenia, and sometimes renal failure will definitely
require a multidisciplinary approach.
This issue ends with three Letters to the Editor, (1) discussing the optimal timing
of the vital signs measurement for best risk stratification of PE using the simplified
PE Severity Index,[18] (2) demonstrating a streamlined algorithm for treatment of VTE and its evaluation
at Oregon Health & Science University,[19] and (3) a report on a patient with afibrinogenemia and both bleeding and thrombotic
manifestations, eventually refractory to dual antiplatelet therapy and fibrinogen
replacement but successfully treated with the protease activated receptor 1 antagonist
vorapaxar.[20]
This compilation contains many exciting presentations of the recent advances in our
field and should provide useful reading for many clinicians in our field. I hope you
will enjoy this mixture of reviews, systematic reviews and meta-analyses, original
articles, and letters.
