TRAINING and EDUCATION
How I Treat In Brief
In “How I Treat In Brief,” we summarize recent “How I Treat” review articles, offering condensed versions of the diagnostic and therapeutic
advice presented by experts in the field published in Blood. Recently, Noémie Kraaijpoel, MD, and Marc Carrier, MD, MSc, FRCPC, discussed
the management of venous thromboembolism in patients with cancer. Below, we summarize their approach.
This material was repurposed from “How I treat cancer-associated venous thromboembolism” published in the January 24, 2019,
edition of Blood.
Treating Cancer-Associated Venous Thromboembolism
Venous thromboembolism (VTE), comprising deep vein
thrombosis (DVT) and pulmonary embolism (PE), is a
common complication of cancer, with an incidence of up
to 15% per year. Several cancer-associated risk factors for
VTE have been identified, including patient-, treatment-,
and tumor-related factors ( TABLE ).
When VTE is diagnosed, anticoagulant therapy is
indicated in almost all cases. In patients with cancer,
though, the risks of recurrent VTE despite anticoagulant
therapy and bleeding complications are particularly chal-
lenging – and higher than in those without cancer.
For many years, low-molecular-weight heparins
(LMWHs) have been the firstline treatment in this
setting. Compared with vitamin K antagonists (VKAs)
such as warfarin, LMWHs have been associated with a
lower risk of recurrent VTE without an associated in-
creased risk of major bleeding complications. Direct oral
anticoagulants (DOACs) have been well established as
first-choice treatment of DVT and PE in patients without
cancer, but there is limited evidence of their efficacy and
safety in the cancer population.
This review will discuss three common cancer-
associated VTE patient scenarios.
Case 1: Deep Vein Thrombosis
A 61-year-old man with a recent diagnosis of stage IIA
prostate carcinoma presents to the emergency room with
a three-day history of acute pain, swelling, and erythema
of the right lower limb. Compression ultrasonography
demonstrates a filling defect consistent with a diagnosis
of a proximal lower-limb DVT. He is not receiving any
cancer-specific therapies, has denied previous bleeding
episodes, and indicated that he would prefer oral over
parenteral therapy. What would be the appropriate anti-
coagulant treatment regimen for this patient?
Commentary on Case 1
Several factors need to be considered when tailoring
anticoagulation management in a patient with cancer-
associated thrombosis.
Patient preference: Qualitative research including pa-
tients with cancer-associated VTE suggests that the most
important consideration of anticoagulant therapy from the
patient’s perspective is related to potential delays or drug-
drug interactions with cancer-related therapies. Route
of administration is another important concern; most
patients find tablets more convenient, but LMWH can be
used in the context of cancer and its treatment.
Drug-drug interactions: Systemic cancer-related therapies
may interfere with DOACs. Potent inhibitors or inducers
of P-glycoprotein and cytochrome p450 CYP3A4 are
known to influence the metabolization of DOACs and
thereby potentially alter their efficacy and/or safety pro-
files. The extent to which these agents influence DOAC
plasma concentrations is unknown, so LMWH might be a
preferred anticoagulant in this situation.
Bleeding risk assessment: The rates of major bleeding and
clinically relevant nonmajor bleeding events seem to be
higher in patients with cancer-associated thrombosis
using DOACs. Unfortunately, no tool can predict the risk
of bleeding episodes in this specific patient population,
although patients with gastrointestinal cancer appear to
have a higher risk. Until we can stratify these patients
according to their underlying risk of bleeding complica-
tions, the use of DOACs should be carefully considered by
balancing patients’ preference and the risk of bleeding, as
well as age, previous bleeding episodes, anemia, thrombo-
cytopenia, and renal function.
The Scientific and Standardization Committee on
Haemostasis and Malignancy of the International Society
on Thrombosis and Haemostasis (SSC-ISTH) suggests:
TABLE.
Risk Factors for Cancer-Associated VTE
Patient-Related
•
•
•
•
•
Advanced age
Comorbidities
Immobilization or hospitalization
Previous VTE
Hereditary thrombophilia
Tumor-Related
• Tumor type
» » Very high risk: gastric, pancreas, brain
» » High risk: lung, hematologic, gynecologic, renal, bladder
• Cancer stage
• Histological tumor grade
• Localized tumor compression
Treatment-Related
• Chemotherapy (e.g., cisplatin-based, anti-angiogenesis
agents)
• Hormonal therapy
• Red blood cell transfusions and erythropoiesis-stimulating
agents
• Surgery
• Radiotherapy
• Central venous catheters
ASHClinicalNews.org
• specific DOACs (edoxaban or rivaroxaban) for
cancer patients with an acute diagnosis of VTE, a
low bleeding risk, and no drug-drug interactions
• LMWH for those with a high risk of bleeding,
including those with thrombocytopenia
• VKAs reserved for patients for whom LMWHs/
DOACs are contraindicated, unaffordable, or un-
available or in those patients already treated with
and stable on this agent
Case 1: Follow-Up
The patient was treated with five days of therapeutic
LMWH (enoxaparin 1 mg/kg subcutaneously, twice daily),
followed by edoxaban 60 mg once daily for a planned
minimal duration of six months. At outpatient follow-up,
he denied any recurrent VTE or bleeding episodes and
remained on anticoagulant treatment. However, recent
laboratory investigations demonstrated that his cancer had
progressed; androgen-deprivation therapy and docetaxel
were initiated. Is extended anticoagulant therapy indicated
for this patient with advanced-stage cancer?
Commentary: Most clinical practice guidelines recom-
mend a minimum of three to six months of anticoagulant
therapy and suggest extending treatment duration in
patients with active cancer because they are considered
at high risk of recurrent VTE. These recommendations
are based largely on expert opinion; most high-quality
controlled studies have evaluated anticoagulant therapy
for a duration of six months.
The decision to stop or continue anticoagulation
therapy after an initial treatment period of three to six
months should be based on the balance between the
risk of recurrent VTE and bleeding complications in
combination with patient preference, life expectancy,
and treatment costs.
Although data on extended therapy with DOACs are
lacking, one can assume that there is no need to change
the choice of anticoagulant after the initial three to six
months of anticoagulation therapy. We recommend con-
tinuing anticoagulant treatment for this patient, as there
are no significant drug-drug interactions with his cancer
medications and his bleeding risk is low.
Case 2: Incidental Pulmonary Embolism
A 72-year-old woman diagnosed with stage IIIA distal
esophageal carcinoma is started on neoadjuvant radiation
therapy and chemotherapy with carboplatin and paclitaxel.
Two months later, a CT scan for treatment response detect-
ed a filling defect in a segmental pulmonary artery of the
right lower lobe. The patient reported no dyspnea, chest
pain, or hemoptysis. She had an active lifestyle and denied
exertional dyspnea. Should this patient with incidentally
detected PE receive anticoagulant treatment?
Commentary: Up to 50% of all PEs in patients with
cancer are incidentally detected, and the prevalence of
incidental PE diagnosis has been reported to be between
1% and 15% in this patient population. Given that the
signs and symptoms of PE are not specific, they are often
attributed by both the clinician and the patient to the
cancer itself or its underlying treatment – not immedi-
ately leading to suspicion of PE.
In clinical practice, most clinicians would anti-
coagulate patients with cancer and isolated symptom-
atic subsegmental PE. However, the decision to start
anticoagulant treatment in patients with an isolated
incidental single subsegmental PE is more nuanced as it
could unnecessarily expose patients to a risk of bleeding.
Therefore, the SSC-ISTH recommends the follow-
ing diagnostic workup: Review imaging results with an
experienced thoracic radiologist, then perform bilateral
compression ultrasonography of the lower extremities
to detect possible incidental DVT. In patients with con-
comitant proximal DVT, standard-of-care anticoagulant
therapy should be initiated. In patients with no DVT,
the decision to prescribe anticoagulation should be in-
dividualized according to the risk of recurrent VTE and
bleeding and the patient’s performance status and prefer-
ence. If anticoagulation is withheld, clinical monitoring
ASH Clinical News
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