Managing the competing risks of thrombosis, bleeding, and anticoagulation in patients with malignancy

Abstract

The association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patients with hematologic malignancies and those treated with intensive myelosuppressive chemotherapy regimens. Despite the advancements in cancer-directed therapy made over the past 15 years, numerous large studies have confirmed that bleeding and VTE recurrence rates remain high in cancer patients. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult, because management of cancer-associated thrombosis requires anticoagulation despite known increased risks for bleeding. In the context of challenging illustrative cases, this review will describe management approaches to clinical scenarios in which data are sparse: cancer patients with recurrent VTE despite anticoagulation and cancer patients with a new VTE in the setting of severe thrombocytopenia.

Impact of Tumor Genomic Mutations on Thrombotic Risk in Cancer Patients

“…Balancing the scales of bleeding and thrombotic risk in the cancer patient presents unique challenges [ 83 ]. Although we have the various cancer-associated VTE risk stratification scores, the present and future bleeding risk must be considered, including risks associated with radiation therapy, chemotherapy-induced thrombocytopenia and other concerns.…”

Hemostasis Laboratory Diagnostics: Characteristics, Communication Issues, and Current Challenges Resulting from Centralization of Laboratory Medicine

“…6,8 In accord with the stepwise analytic procedures (stages 1 through 5), algorithms exist that guide the testing pathway and allow a rational diagnostic workup. These algorithms encompass both bleeding [9][10][11][12][13][14][15][16] and thrombotic 15,[17][18][19][20][21][22] disorders or abnormal findings in laboratory hemostasis. For example, in case of a prolonged aPTT, a rather frequent and multicausal finding in hemostasis laboratory diagnostics, 23 the algorithms direct the type and sequence of tests to permit a clear differential diagnosis and to identify the precise cause of the abnormality, including rare clinical conditions.…”

Navigating in the labyrinth of thrombotic and bleeding risks in patients with malignancies – how to make the most reasonable choices for personalized anticoagulation?

“…Balancing the scales of thrombotic and bleeding risks, in the oncology patient population presents unique challenges [45].…”

“…In fact, large observational or retrospective cohort studies have shown an elevated risk of thrombosis in patients with ALK and ROS1 rearranged non-small-cell lung cancer (NSCLC) compared to those without such rearrangements. Therefore, clinicians should consider a lower threshold to apply thromboprophylaxis in patients with NSCLC and ALK or ROS1 rearrangements, who otherwise have traditional VTE risk scores in the intermediate risk range [45]. Similarly, in the case of molecular aberrations in other tumors, the knowledge that a patient may be at increased thrombotic risk due to the underlying tumor genotype is another valid piece of information that the clinician should consider when determining if a patient can possibly benefit from thromboprophylaxis [45].…”

“…Therefore, clinicians should consider a lower threshold to apply thromboprophylaxis in patients with NSCLC and ALK or ROS1 rearrangements, who otherwise have traditional VTE risk scores in the intermediate risk range [45]. Similarly, in the case of molecular aberrations in other tumors, the knowledge that a patient may be at increased thrombotic risk due to the underlying tumor genotype is another valid piece of information that the clinician should consider when determining if a patient can possibly benefit from thromboprophylaxis [45]. In the future, studies on incorporating tumor molecular aberrations into traditional risk scores may enhance the ability of risk scores to identify the patients, who would most likely take advantage of the primary thromboprophylaxis.…”