José Antonio Páramo is a Professor of Hematology at the University Clinic of Navarra, University of Navarra, Pamplona, Spain, where he studies hemostasis and thrombosis.
During the 10th ICTHIC, he co-chaired a session regarding the differences in thromboprophylaxis between hospitalized patients with solid or hematological malignancies. We had a talk with him on this matter.
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Do people with hematologic cancer have less risk of developing venous thromboembolism compared with patients with solid tumors?
“Patients with cancer, in general, have a 4–7-fold increase of venous thromboembolism (VTE), and approximately 20% of VTE is the first clinical manifestation of malignancy. Both solid tumors and hematological cancer have an important risk of VTE, but prophylaxis is underused in these latter patients because of the concern of thrombocytopenia. In general, the impact of thrombosis is more or less the same in solid tumor and hematological cancer,” replied Prof. Páramo.
Limited data are available regarding the epidemiology of thrombotic events and their clinical management in patients with hematological malignancies. In addition, the treatment of thrombosis in these patients is often complicated because of disease- or therapy-related thrombocytopenia .
A recent study investigated the risk of myocardial infarction, ischemic stroke (IS), VTE and bleeding (requiring hospital contact) in patients with hematological cancers. The 10‐year absolute risk of any thromboembolic or bleeding events following hematological cancers was 19%. Overall, patients with hematological cancer were at increased risk for acute myocardial infarction, IS, VTE and bleeding general population .
In patients with acute lymphoblastic leukemia (ALL), one of the main risk factors for VTE development is the use of L-asparaginase, which can help to predict the VTE risk and identify patients who should receive prophylaxis .
In acute myeloid leukemia (AML), the predictors are less clear. Recently, fibrinogen, D-dimer, alpha-2-antiplasmin, antithrombin, prothrombin time and platelet count have been proposed as parameters useful to predict the thrombotic risk in AML patients .
For chronic myeloid leukemia, very little data are available. Still, the use of tyrosine kinase inhibitors (particularly ponatinib) seems to be a risk factor for venous and arterial vascular events .
In patients with multiple myeloma, a high rate of VTE was associated with immunomodulatory therapies. Thalidomide and lenalidomide, both immunomodulatory drugs, were associated with a marked increase in VTE risk. These drugs increase plasma levels of factor VIII and von Willebrand factor, induce protein C resistance, and reduce soluble thrombomodulin, contributing to increased thrombotic events. In these patients, the use of thromboprophylaxis is mandatory .
What are the differences in thromboprophylaxis between hospitalized patients with solid or hematological malignancies?
“It is well known that prophylaxis should be started in all hospitalized patients with cancer because of the high risk of VTE. However, from our study, we know that the rate of prophylaxis administration was lower in hematological cancer,” replied Prof. Páramo.
In one of his latest studies, Prof. Paramo and colleagues evaluated the rate of thromboprophylaxis use and outcome in daily clinical practice in consecutive hospitalized cancer patients. They focused on the differences between patients with solid or hematologic cancer. A total of 15.2% of patients with hematologic cancer presented thrombocytopenia <50 × 109/L, compared with 3.5% of those with solid neoplasm. Using the PRETEMED score, 93% of patients were at high risk. During admission, the rate of low-molecular-weight heparin (LMWH) thromboprophylaxis was 43.3 and 73.8% in patients with hematologic and solid cancer, respectively .
In addition, a survey showed that 40% of patients with hematologic tumors were not receiving LMWH prophylaxis during admission, compared to just 10% of inpatients with solid tumors. The reason behind this difference seems to be the physician’s opinion that the hematological patient’s risk was not high .
“People need to be aware that the risk of VTE in hematological patients exists; the underuse of thromboprophylaxis is an important concern. We must implement the thromboprophylaxis strategy because the risk VTE in hematological patients occurs despite the thromboprophylaxis. We need to keep studying the ideal thromboprophylaxis strategy in hematological patients,” continued Prof. Páramo.
Is there a specific subset of people with hematological cancer that would benefit from extended prophylaxis after discharge?
The pathogeneses of thrombosis in cancer patients are multifactorial. There are some disease-specific factors of thrombosis in cancer patients. Three hematological conditions have a particularly high risk: lymphoma, myeloma and acute leukemia, especially ALL in pediatric patients who receive asparagine, which increases the risk,” replied Prof. Páramo.
Patients with aggressive lymphomas have a high incidence of VTE. In contrast, patients with indolent lymphomas are likely at lower VTE risk, unless associated with other patient factors, such as high prognostic risk index, high BMI and older age .
Patients with multiple myeloma and receiving immunomodulatory agents (such as thalidomide or lenalidomide) have the highest VTE risk, exacerbated by the concomitant use of high-dose steroids .
Finally, the overall risk of VTE in patients with ALL and acute promyelocytic leukemia is close to 10% at 6 months from diagnosis. The major risk factors in this setting are L-asparaginase, older age, comorbidities and central venous catheters increase the risk of VTE in these patients. Patients with AML have a VTE incidence of 5–8%, and patient factors, such as older age, hormonal therapy for women and central venous catheters increase VTE risk .
Is the use of direct oral anticoagulants recommended for people with hematological malignancies?
The standard treatment of CAT prevention is LMWH, even though most of the trials have been conducted in patients with solid tumors.
The International Clinical Practice Guidelines recommend a once-daily regimen of LMWH. After 3–6 months, termination or continuation of anticoagulation should be based on individual assessment . The use of direct oral anticoagulants (DOACs) in the CAT setting is still under investigation, and, when used, their potential interaction with anti-cancer treatment should be considered. Imatinib, crizotinib and other tyrosine kinase inhibitors, vinblastine and doxorubicin may reduce the effect of DOACs in the plasma .
“We don’t have a standard thromboprophylaxis in hematological cancer patients, but we know it should be applied in hospitalized patients. LMWH and DOACs seem to be both ok, but we need to take into consideration the personal risk of each patient,” concluded Prof. Páramo.
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