Anticoagulation in Cancer Patients With Thrombocytopenia

Roxanne Nelson, BSN, RN

December 15, 2015

ORLANDO, Florida — Cancer patients often need therapeutic anticoagulation for venous thromboembolism (VTE), but they often have coexisting chemotherapy-induced thrombocytopenia (CIT). "This is clinically very important," commented Gerald Soff, MD, chief of the Hematology Service at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York.

"Every day, in every cancer clinic around the world, the question comes up on how to manage blood thinners and how to manage cancer patients with severely reduced platelet counts, " he said here at a press briefing during the American Society of Hematology (ASH) 57th Annual Meeting.

The current standard of care for preventing blood clots in a cancer setting includes treatment with low-molecular-weight heparin (LMWH), but use of LMWH in the setting of CIT is empirical, and there is published evidence on its use in that setting.

In 2010, MSKCC implemented treatment guidelines for the use of anticoagulation in this population. The guidelines called for modifying the dose on the basis of platelet count.

This approach has now been validated prospectively.

New data presented here at the meeting support the safety and efficacy of following the MSKCC guidelines for therapeutic LMWH dose modification, which balances the dual risks of recurrent thrombosis and potential bleeding during periods of CIT in cancer patients, Dr Soff reported. There was a 95% level of compliance with the guidelines among physicians at MSKCC. "We were gratified that the doctors at MSKCC were adhering to the guidelines," said Dr Soff. "And the outcomes were exactly were what we hoped for, and there were no recurrent VTEs or major bleeds."

The take-home message was that MSKCC was following the guidelines, he noted. "Many institutions use similar guidelines for therapeutic LMWH dose modification in the setting of chemotherapy- induced thrombocytopenia, but guidelines are only useful if doctors pay attention to them."

Dr Soff added that this was the first validation, but he cautioned that the results could not be extrapolated to oral anticoagulants or to other anticoagulants. In addition, he noted that conducting a randomized trial would be "highly impractical."

Study Details

The MSKCC guidelines call for a full dose of LMWH to be administered for patients with a platelet count >50,000/μL, a half dose for patients with a platelet count 25,000/μL to 50,000/μL, and for LMWH to be temporarily withheld when platelets dropped to <25,000/μL.

In a quality assessment project, Dr Soff and colleagues evaluated the efficacy, safety, and physician adherence to their guidelines. Patients at MSKCC who were receiving a therapeutic dose of enoxaparin (Lovenox, sanofi-aventis) for VTE during the period from 2011 through 2013 and who experienced at least one episode of thrombocytopenia (platelet count ≤50,000/μL) for at least 7 days were included in the analysis.

Adherence to the LMWH dose modification guidelines was assessed on the basis of dose reduction and/or temporary withholding of LMWH for existing or anticipated thrombocytopenia. Major bleeding events, clinically relevant nonmajor bleeding events, recurrent VTE events, and deaths occurring in association with episodes of thrombocytopenia were recorded.

Dr Soff and colleagues identified 102 patients with a total of 143 episodes of thrombocytopenia and an average duration of 21.3 days per episode.

The LMWH dose was modified in 137 episodes (95%), which reflects adherence to the institutional guidelines, Dr Soff noted.

The LMWH doses were reduced in 20 (14%) episodes, withheld in 89 (62%) episodes, and managed with combination of reduction/withholding in 27 (18.9%) episodes. The dose remained unchanged in seven patients (4.9%).

In general, the more severe thrombocytopenic episodes were managed by withholding LMWH as opposed to dose reduction. The unweighted mean platelet count during episodes managed by withholding LMWH was 27,000/μL with a standard deviation (STD) of 16,000/μL. The mean platelet count during episodes of dose reduction was 36,000/μL with a STD of 15,000.

Strategy Helps Providers

Cancer patients receiving anticoagulants are closely monitored, commented Mary Cushman, MD, professor of medicine, Division of Hematology/Oncology, University of Vermont College of Medicine, Burlington. "But I think the nice thing about this study is that the group decided that they were going to put together a strategy and then expected all providers to adhere to it.

"When you're thinking about improving quality of care, the best thing is to have a standardized strategy," Dr Cushman told Medscape Medical News. "This way, it's the same for every patient, of course within vagaries of the individual patient.

"I really love this because it's a way to take a drug that has a lot of potential danger and really have a strategy to help providers take better care of the patients," Dr Cushman added.

One coauthor received research funding from Janssen Pharmaceuticals. Neither Dr Cushman nor any other coauthors have disclosed any relevant financial relationships.

American Society of Hematology (ASH) 57th Annual Meeting. Abstract 429. Presented December 7, 2015.

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