Venous thromboembolism leads the clinician mainly to think of deep vein thrombosis
in the leg and pulmonary embolism. There are also unusual sites for thrombosis that
the consultant has to deal with not infrequently. The cause of venous thrombosis is
typically a trigger from surgery, trauma, immobilization, or cancer, and if nothing
of this kind is identified it is called “unprovoked.” There are, however, unusual
situations where venous thromboembolism occurs, such as vascular malformations or
rare inflammatory or autoimmune disorders. The mechanism behind thrombus generation
is not always clear, although in case of tissue injury the extrinsic pathway is easily
implicated. There may, however, be other mechanisms involved, for example, when venous
stasis results in hypoxia in the stagnant blood behind the venous valves or in inflammation,
perhaps resulting in neutrophil extracellular trap formation or NETosis. The pathophysiology
may include other alternatives as well. The treatment of venous thromboembolism has
been studied in many randomized clinical trials for the adult population but hardly
at all in children. An often-debated topic is the duration of anticoagulation after
venous thromboembolism, and although the risk of recurrence probably never goes down
to zero, many physicians feel reluctant to treat indefinitely due to the risk of bleeding.
Prediction rules might give some support for decisions in this situation.
Many of these topics are dealt with in this second part of the “Recent advances in
thrombosis and hemostasis” issue theme. We hope that the readers of Seminars in Thrombosis and Hemostasis will find the articles interesting and also helpful for their clinical practice.
Half of the topics were discussed by well-known scientists in the field in association
with a congregation in Stockholm, Sweden, in November 2016, itself the subject of
a separate meeting report in the current issue of the journal.[1] The remaining contributions were selected from other submissions accepted for publication
over recent past months.
Naudin et al begin this issue and provide us with a review of the role of polyphosphate
(polyP), a potent contact activator, and factor XII in the generation of arterial
or venous thrombosis mediated by platelets.[2] This pathway is in fact already being explored as a target for drugs to prevent
or treat thrombosis. In addition, polyP activates the bradykinin-mediated pathway
to inflammation. We will surely learn much more about polyP in the next few years.
A very rare cause of deep vein thrombosis is agenesis of the inferior vena cava, but
its prevalence might be underestimated due to inadequate diagnosis. Tufano et al have
authored a comprehensive description of this condition based on local experience and
a literature review.[3] It is particularly important to keep this vascular malformation in mind when deep
vein thrombosis occurs in a young patient. Venous thrombosis in the distal leg veins,
in other words below the trifurcation, is not captured with the typical compression
ultrasound examination performed in most hospitals. This is not considered a problem
because many consider distal deep vein thrombosis as clinically unimportant and not
necessary to treat. Lim et al have performed a meta-analysis of the randomized controlled
trials and the cohort studies published.[4] They find that this common perception might be wrong and that there probably are
benefits without increased risk of harm to diagnose and treat these patients.
Although the diagnosis of atrial fibrillation almost always justifies anticoagulant
therapy, it is often not realized that there can be concomitant pulmonary embolism,
which sometimes might change the treatment strategy. Bikdeli et al present a systematic
review of the coexistence of these entities.[5] They discuss which one of these could have occurred first, with the alternate pathology
as a consequence, the epidemiology, the prognostic significance, and the therapeutic
options. Interestingly, a clinical prediction rule for risk of stroke in atrial fibrillation
(CHA2DS2-VASc) seems to predict the mortality in pulmonary embolism without coexisting atrial
fibrillation. Continuing on this theme, Tang et al used their historic hospital population
of over 4,000 patients with pulmonary embolism to identify 305 patients with concomitant
atrial fibrillation and then explore the predictive value for in-hospital outcome
with the CHADS2 score, the CHA2DS2-VASc score, and the pulmonary embolism severity index (PESI).[6] Although PESI had the best predictive value, addition of the CHADS2 score seemed to improve it further. Finally, Alatri et al present an analysis of
yet another prediction rule, the modified Ottawa score for hospitalized patients with
cancer and venous thromboembolism.[7] Although the score did not turn out to be useful for the prediction of recurrent
venous thromboembolism, it indicated risk of early mortality.
Thrombosis in neonatal patients is almost always provoked by obvious risk factors,
such as central venous catheters in combination with serious pathological conditions.
Radulescu informs us here of the epidemiology of venous thromboembolism in the pediatric
population and reviews the large number of therapeutic options available, finalizing
with a discussion on the duration of anticoagulation.[8]
The main risk of antithrombotic therapy, in young and old, is hemorrhage. The most
common major hemorrhage is gastrointestinal and the most feared, due to high mortality
and frequent residual neurologic impairment, is intracranial bleeding. Schulman reviews
the management of major bleeding, which differs between the anticoagulants.[9] The non–vitamin K antagonist anticoagulants, often abbreviated NOACs, are progressively
gaining market shares from warfarin and its derivatives and it is useful to be aware
of the currently available options to reverse bleeding, should this occur. Once the
hemorrhagic complication has been controlled, the balance between risk for thromboembolic
events and the risk of recurrent hemorrhage has to be weighed. Studies that support
such a decision after intracranial or gastrointestinal hemorrhage are also discussed
here.
The concluding article in this theme issue may seem a bit off topic, focusing on endovascular
treatment of stroke, that is, intervention on the arterial side to remove clots from
small vessels in the brain. Until recently, this was very uncertain territory and
intravenous thrombolysis was considered the optimal choice unless contraindicated.
Cagnap and Smith are here supporting the recommendation for the endovascular approach
in eligible patients based on results from recent trials.[10] This treatment modality requires expertise but also changes in the logistics for
the emergency management of patients with ischemic stroke.
As mentioned, we are also tying up any remaining loose ends of the first two parts
of the current issue theme with a brief report by the guest editors, but primarily
from the meeting organizer, Md. Shahidul Islam, of the 93rd Berzelius Symposium, the
meeting where most of the contained topics were discussed.[1]
We are pleased to publish this compilation with the conviction that many readers will
find the reviews, as well as the original data presented in some papers, both interesting
and helpful in their decisions as consultants or most responsible physicians. These
articles complement the ones in Part I of this theme issue, published in November
2016.[11] The letter to the editor at the end of this issue,[12] and the response from the original authors,[13] pertains to one of those articles in Part I.[14]
