Written in
Featured research from recent issues of Blood
Superficial Vein Thromboses Put People at Risk
for Subsequent Blood Clots
Until recently, a superficial vein thrombosis (SVT) was seen as a painful
induration of limited clinical significance. New evidence from a large
population-based study published in Blood advises health care providers
to not neglect the prognostic importance of SVTs.
European researchers, led by Suzanne Cannegieter, MD, of Leiden
University Medical Centre in The Netherlands, determined that patients
presenting with SVTs have both higher short- and long-term risk for
venous and arterial thrombotic events.
The results reinforce the importance of following guidelines on
anticoagulant management of SVTs, Dr. Cannegieter told ASH Clinical
News. The research team reviewed the medical records of 10,973 patients
with a first-time diagnosis of SVT over a 32-year period (1980–2012)
in the Danish National Registry of Patients. They compared this group
with medical records from more than 515,000 age- and gender-matched
subjects from the general Danish population.
Outcomes included venous thromboembolism, acute myocardial
infarction (AMI), ischemic stroke, and death. In analyses, the researchers
accounted for factors related to occurrence of SVT – such as cancer,
surgery, pregnancy, autoimmune disease, and fracture – that could also
affect the outcome of interest.
In the SVT cohort, 1,170 people developed deep-vein thromboses
(DVT) over a median follow-up of 6.4 years, for an incidence rate of
12.8 per 1,000 patient-years (95% CI 12.1-13.6). In the comparison
cohort, 6,096 developed DVT during a median follow-up of 8.4 years, an
incidence rate of 1.2 per 1,000 patient-years (95% CI 1.1-1.2).
The age- and gender-adjusted hazard ratio (HR) for developing DVT
was 11.8 (95% CI 11.1-12.6) in patients with SVT. Notably, this risk
was highest in the first three months post-SVT (3.4%; 95% CI 3.0-3.7).
Compared with the general population, the HR for SVT patients was
71.4 (95% CI 60.2-84.7) within this period, decreasing steadily – but
remaining high – five years after SVT (HR=5.1; 95% CI 4.6-5.5).
SVT patients also faced an increased risk of pulmonary embolism
(PE), with an incidence rate of 4.5 per 1,000 patient years (95% CI
4.1-4.9) in the SVT cohort, compared with 0.9 (95% CI 0.9-1.0) in the
general population.
“There is a substantial short-term risk of DVT or PE in the first
months after an SVT,” Dr. Cannegieter told ASH Clinical News. “Most
guidelines now advise anticoagulant treatment of the SVT, in order
to prevent more serious events. This high risk and its implications for
treatment are something clinicians should be aware of.”
As evidenced by the high five-year risk, “the risk remains increased
in the long-run as well, meaning that a patient with a history of SVT
should be carefully advised during high-risk situations for DVT/PE (e.g.,
surgery, plaster cast) ,” she explained. “Anticoagulant prophylaxis should
Adjusted Hazard Ratios for Venous Events,
Stratified by Gender
TABLE.
Men (95% CI)
Women (95% CI)
VTE
11.28 (10.37-12.27)
6.92 (6.40-7.48)
Unprovoked VTE
13.19 (11.93-14.57)
8.05 (7.33-8.84)
7.90 (6.75-9.25)
5.07 (4.38-5.87)
Provoked VTE
DVT
3.83 (3.34-4.40)
1.25 (1.11-1.40)
1.09 (0.96-1.24)
Ischemic stroke
1.36 (1.21-1.53)
1.22 (1.10-1.35)
Death
ASH Clinical News
9.26 (8.41-10.19)
5.81 (4.97-6.80)
AMI
18
14.34 (12.98-15.85)
PE
1.34 (1.28-1.41)
1.22 (1.18-1.27)
be strictly adhered to in these situations.”
SVT patients also faced a higher risk of acute myocardial infarction
(AMI) than the general population: 5.8 (95% CI 5.3–6.3) versus 4.8
(95% CI 4.8–4.9) per 1,000 patient-years, leading to an age- and genderadjusted HR of 1.2 (95% CI 1.1–1.3). In addition, SVT patients had a
higher risk for ischemic stroke and mortality – again, with the greatest
risk closest to the time of SVT.
When the results were stratified by gender, men had a greater relative
risk for thromboembolic outcomes – despite the fact that women
comprised about 60 percent of SVT patients (TABLE). Dr. Cannegieter
attributed this risk to the fact that men have a higher pro-thrombotic
tendency, contributing to the higher risk for DVT development once an
SVT is present.
In the future, Dr. Cannegieter and her research group plan to mine
medical records for further information on the extent or site of the SVT
and treatment options. “The effect of anticoagulant treatment in daily
practice has only been studied in small, randomized control trials, so far,”
she said, citing the need for more data about newer target-specific oral
anticoagulants and the optimal duration of treatment.
“We also need a better understanding of the etiology of SVT, as its
risk factors are not exactly the same as for DVT or PE,” Dr. Cannegieter
added. “If we know more about its causes, some more options on
prevention may also become available.”
Reference
• Cannegieter SC, Horvath-Puho E, Schmidt M, et al. Risk of venous and arterial thrombotic events in patients diagnosed
with superficial vein thrombosis: a nationwide cohort study. Blood. 2015;125(2):229-35.
Brentuximab Vedotin Active
in Relapsed/Refractory
B-Cell Lymphoma
For patients with relapsed/refractory diffuse large B-cell
lymphoma (DLBCL) who are ineligible for transplant
or fail to respond to salvage regimens, treatment with
brentuximab vedotin – alone or in combination with
rituximab – was associated with significant activity and
reduction in tumor volume. According to the report
published in Blood, responses also occurred across a
range of CD30 expression.
There is no standard therapy for DLBCL patients
resistant to frontline treatment and who fail to respond to
salvage regimens or who are ineligible for transplant, lead
author Eric Jacobsen, MD, from the Dana-Farber Cancer
Institute in Boston, and co-authors noted. “Response rates
are poor in this setting and novel approaches are needed.”
Brentuximab vedotin is a CD30-directed antibodydrug conjugate (ADC); data have suggested that, after
binding to CD30 on the tumor cell surface, the ADC
internalizes, leading to induction of cell-cycle arrest and
apoptosis. CD30 is expressed on a variety of malignancies
and is present in 14 to 25 percent of DLBCL cases –
making the antigen, and the tumor cells that express it,
appropriate targets for treatments.
February 2015