Srikanth Nagalla, MD, director of the Hematology Oncology Fellowship Program at Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine at UT Southwestern Medical Center, discusses efforts to predict which patients with myeloproliferative neoplasms will develop thrombosis.

Similar to other diseases, investigators are working on putting together an algorithm to predict what patients with MPNs are going to develop thrombosis, says Nagalla. If the risk of developing thrombosis can be predicted, that could prevent unnecessary use of certain drugs.

Investigators are not only examining clinical factors; they are also looking at next-generation sequencing data as a way to identify genes that are being overexpressed or under expressed to see whether that can be used to predict which patients with a particular cancer might develop thrombosis. As science continues to evolve, investigators might be able to do a better job of predicting which patients are at risk of recurrent clots and be able to treat them accordingly with better drugs that have lower rates of bleeding, concludes Nagalla.

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Dr. Nagalla on Efforts to Predict Risk of Thrombosis in Patients With MPNs

Srikanth Nagalla, MD, director of the Hematology Oncology Fellowship Program at Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine at UT Southwestern Medical Center, discusses the utility of direct oral anticoagulants (DOACs) in cancer-associated thrombosis.

Oncologists are already using DOACS such as dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis), in cancer-associated thrombosis, says Nagalla. Trials have been published or are ongoing to evaluate thrombosis prevention, mainly for patients with cancer who have an intermediate to high risk of developing thrombosis while receiving chemotherapy. These agents have also demonstrated benefit in patients who have already experienced a clot, says Nagalla.

Data have suggested that DOACs are effective in preventing thrombosis in patients with cancer or a history of cancer and for treatment of an active clot in a patient with active cancer, concludes Nagalla.

Srikanth Nagalla, MD, discusses the utility of direct oral anticoagulants in cancer-associated thrombosis.

Dr. Nagalla on the Utility of DOACs in Cancer-Associated Thrombosis

Srikanth Nagalla, MD, director of the Hematology Oncology Fellowship Program at Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine at UT Southwestern Medical Center, discusses research efforts dedicated to the development of timely assays for direct oral anticoagulants (DOACs) in myeloproliferative neoplasms (MPNs).

Investigators at UT Southwestern Medical Center are trying to get testing for DOACs. To have an assay for rivaroxaban (Xarelto) or apixaban (Eliquis) that could feasibly be performed in a more timely manner would be beneficial, says Nagalla.

Such assays could help inform treatment selection for patients better. Specifically, these assays could help inform more judicious use of some of the more expensive drugs, such as andexanet alfa (Ondexxya), ensuring that they’re only given in patients in whom we feel bleeding is mainly because of rivaroxaban, apixaban, or edoxaban (Savaysa), adds Nagalla.

That being said, if a patient is bleeding, it would be difficult to wait for assay results to come back; these tests could take at least 30 minutes and if someone is experiencing a brain bleed, treatment cannot wait, says Nagalla. As such, work is being done to improve turnaround times of such assays.

This work is necessary so that treatment can become more personalized for patients with MPNs, and thus more effective. Timely assays can ensure that newer drugs are used appropriately in the right patient population; these agents shouldn’t just be used in anyone who is taking a DOAC, as the DOAC may not even be the cause of current bleeding, concludes Nagalla.

Srikanth Nagalla, MD, discusses research efforts dedicated to the development of timely assays for direct oral anticoagulants in myeloproliferative neoplasms.

Dr. Nagalla on Need for Timely Assays for DOACs in MPNs

Srikanth Nagalla, MD, director, Hematology Oncology Fellowship Program, Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine, UT Southwestern Medical Center, discusses aspirin recommendations for patients with myeloproliferative neoplasms (MPNs) who are receiving direct oral anticoagulants (DOACs).

When aspirin is used for something without an indication in patients who are already taking a DOAC, the risk of bleeding is increased, explains Nagalla. Three articles published in the New England Journal of Medicine in 2018 stated that aspirin should not be used if no clear indication for primary prophylaxis exists.

Previously, it was assumed that any patient with a MPN above age 40 could take a baby aspirin, but the field has since have moved away from that assumption, says Nagalla. Patients who are on a DOAC should not receive aspirin if there is no clear indication for it. In the MPN study that examined the use of aspirin concomitantly with a DOAC, 3 patients experienced bleeding. DOACs, at least in this small retrospective study, were effective in preventing thrombosis in patients with MPNs, concludes Nagalla.

Srikanth Nagalla, MD, discusses aspirin recommendations for patients with myeloproliferative neoplasms who are receiving direct oral anticoagulants.

Dr. Nagalla on Aspirin Use During DOAC Treatment for MPNs

Srikanth Nagalla, MD, director, Hematology Oncology Fellowship Program, Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine, UT Southwestern Medical Center, discusses the challenges of managing thrombocytopenia in patients with myeloproliferative neoplasms (MPNs).

Patients with MPNs who are receiving chemotherapy may develop concomitant thrombocytopenia due to decreased platelets, says Nagalla. In turn, they are at a higher risk of bleeding.

Additionally, these patients may have decreased renal function. This may limit which agents can safely be used to manage concurrent thrombocytopenia, says Nagalla. Warfarin, while not a preferred anticoagulant for patients with cancer, can be used as an alternative for those with low creatinine clearance, concludes Nagalla.

Srikanth Nagalla, MD, discusses the challenges of managing thrombocytopenia in patients with myeloproliferative neoplasms.

Dr. Nagalla on the Challenges of Managing Thrombocytopenia in MPNs

Srikanth Nagalla, MD, director, Hematology Oncology Fellowship Program, Harold C. Simmons Comprehensive Cancer Center, and associate professor of medicine, UT Southwestern Medical Center, discusses the utility of direct oral anticoagulants (DOACs) in patients with a myeloproliferative neoplasm (MPN)—associated venous thromboembolism (VTE).

Historically, DOACs have been used to treat portal vein thrombosis or cerebral venous thrombosis associated with 

-negative MPNs, including polycythemia vera, essential thrombocytopenia, and myelofibrosis, says Nagalla.

In a retrospective analysis that was presented at the 2019 ASH Annual Meeting, 102 patients who had an MPN-associated VTE were identified, 24 of which received a DOAC. Of the 24 patients, 18 were 

-positive and had increased thrombogenicity, says Nagalla.

At a median follow-up of 2.2 years, findings revealed that there were no VTE recurrences in 23 patients who received a DOAC. One patient had indeterminate imaging. Additionally, there were no major bleeding episodes in this patient population.

Clinically relevant non-major bleeding occurred in 2 patients who were taking aspirin in addition to a DOAC. As such, these data suggest that patients without cardiovascular risk factors can forego daily aspirin if they are receiving a DOAC, Nagalla concludes.

Srikanth Nagalla, MD, discusses the utility of direct oral anticoagulants in patients with a myeloproliferative neoplasm–associated venous thromboembolism.

Srikanth Nagalla, MD

Articles

Dr. Nagalla on Efforts to Predict Risk of Thrombosis in Patients With MPNs

Dr. Nagalla on the Utility of DOACs in Cancer-Associated Thrombosis

Dr. Nagalla on Need for Timely Assays for DOACs in MPNs

Dr. Nagalla on Aspirin Use During DOAC Treatment for MPNs

Dr. Nagalla on the Challenges of Managing Thrombocytopenia in MPNs

Dr. Nagalla on the Utility of DOACs in MPN-Associated Thrombosis