TRAINING and EDUCATION
How I Treat In Brief
Fast Facts
can include serial ultrasonography in those with distal DVT to assess
thrombus extension.
For this patient with a segmental incidental PE in the context
of esophageal carcinoma, bleeding risk was considered high. After
discussion, the patient was started on therapeutic doses of LMWH
(dalteparin 200 IU/kg once-daily followed by 150 IU/kg once daily
after the first month) and a follow-up appointment was scheduled to
monitor for bleeding complications.
✓ ✓ Venous thromboembolism (VTE), including deep vein thrombosis (DVT)
and pulmonary embolism (PE), is a common complication of cancer and
is associated with significant morbidity and mortality.
✓ ✓ Several factors need to be considered when tailoring anticoagulation
management in a patient with cancer-associated thrombosis, including
patient preference, drug-drug interactions, and bleeding risk.
✓ ✓ Low molecular-weight heparins (LMWHs) have been the firstline
treatment of cancer-associated thrombosis. 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 on their
efficacy and safety in patients with cancer.
Case 3: Catheter-Related Thrombosis
A 58-year-old man with stage IIB non–small cell lung cancer presents
with a four-day history of pain, swelling, and redness in his left arm.
One week after initiating chemotherapy through a peripherally inserted
central catheter (PICC) line, the patient started having progressive
symptoms but denied worsening of dyspnea or chest pain. Examination
reveals redness and edema of the entire left arm. Ultrasonography identi-
fied obstructive nonfilling defects in the axillary and brachial veins, and
Doppler showed no flow within the subclavian vein. How should this
patient with catheter-related proximal upper-extremity DVT be treated?
Commentary: Central venous catheters (CVCs; implanted port,
centrally inserted catheter, or PICC) are often used for long-term
chemotherapy or parenteral nutrition in patients with cancer and
may be complicated by catheter-related thrombosis, mostly in the
upper extremities. Risk factors for catheter-related DVT may include
intrinsic factors such as CVC size and type, tip location, side of
placement, and extrinsic factors including inherited thrombophilia,
previous VTE, and metastasized cancer.
Recent guidelines from the American College of Chest Physicians
recommend that the catheter should remain in situ as long as it is
functional and there is an ongoing need for it. Anticoagulant therapy is
recommended for three to six months, regardless of whether the catheter
is removed, and continued treatment is recommended for as long as the
catheter remains.
However, if the catheter is not functional or is improperly positioned,
or in most cases of infection, removal of the catheter is recommended
and a short duration of anticoagulation (3-5 days) is suggested prior to
removal (if possible). Again, anticoagulant therapy is recommended for
a minimum of three months and for as long as the catheter remains.
Based on data supporting LMWHs for the management of lower-
extremity DVT and PE in patients with cancer, most guidance docu-
ments and expert consensus suggest LMWHs over VKAs for managing
cancer-associated, catheter-related, upper-extremity DVT. Evidence on
the efficacy and safety of DOACs in this patient population is emerg-
ing, with a prospective pilot study of rivaroxaban demonstrating recur-
rence and bleeding event incidence rates of 1.43 percent and 12.85
percent, respectively.
For this patient, the catheter remained in place as it was func-
tional, and he needed ongoing chemotherapy. He was started on
therapeutic LMWH (enoxaparin 1.5 mg/kg once-daily dose) for at
least three months.
Future Directions
VTE is a common complication of cancer, and different manifestations
require specific treatment approaches. LMWHs are the recommended
firstline anticoagulant treatment, but ongoing studies are evaluating the
safety and efficacy of DOACs in patients with cancer-associated thrombo-
sis. Future trials should focus on stratifying patients at low and high risk
of major bleeding complications with DOACs to provide clinicians with
guidance on how to better tailor individual treatment regimens.
Furthermore, the efficacy and safety of extended anticoagulant
treatment beyond six months has not yet been determined. Although
evidence on the clinical outcomes of patients with cancer with incidental
VTE is emerging, future studies need to include assessment of the safety
of withholding anticoagulant therapy in those with single subsegmental
PE without proximal DVT, as the risks of anticoagulant treatment may
outweigh the benefits in these patients.
Finally, there are limited data to guide treatment decisions on catheter-
related thrombosis in patients with cancer. Management studies random-
izing patients with cancer to LMWHs or DOACs for this indication are
needed to compare the safety of both regimens. ●
42
ASH Clinical News
✓ ✓ Patients diagnosed with cancer and incidental PE should be treated
with a similar approach as patients with symptomatic PE.
✓ ✓ In managing catheter-related thrombosis, keep the catheter in place if
it is functional and there is an ongoing need for the catheter to deliver
medication.
✓ ✓ Future directions of research include risk-stratifying patients for
bleeding complications with DOACs and determining the safety of
extended anticoagulant treatment beyond 6 months.
Suggested treatment algorithms for symptomatic
and incidental DVT or PE in patients with cancer.
FIGURE 1A.
Cancer patient with symptomatic or incidental DVT or PE 1
Does the patient have
(1) drug-drug interactions with DOACs; or
(2) a high risk of bleeding?
No
*
Yes
Initiate anticoagulant treatment with
DOAC (edoxaban or rivaroxaban) 2
*
Initiate anticoagulant
treatment with LMWH
Consider extended anticoagulant treatment beyond 6 months if the
cancer is still active 3
Suggested treatment algorithm for catheter-related
thrombosis in patients with cancer.
FIGURE 1B.
Cancer patient with catheter-related DVT
Is the central venous catheter
infected, improperly positioned,
or not functional?
Yes
Remove catheter and
complete 3-month
anticoagulant treatment
No
3-month anticoagulant treatment
without catheter removal 4
Consider extended anticoagulant treatment
beyond 3 months if the catheter is still in situ
*Assess drug-drug interactions and bleeding risk during follow-up and consider changing the anticoagulant
treatment regimen accordingly.
1. In patients with isolated single subsegmental PE without concomitant DVT, consider withholding anticoagulant
therapy in patients at high risk of bleeding.
2. Edoxaban is initiated after an LMWH lead-in of at least 5 days.
3. The decision to continue anticoagulant treatment beyond 6 months should also balance the risk of recurrent VTE
and bleeding complications in combination with patients’ preference, life expectancy, and treatment costs.
4. LMWH is currently the preferred treatment option.
DOAC = direct oral anticoagulant; LMWH = low-molecular-weight heparin
June 2019