LMWH dose-reduction guidelines appear safe, effective for chemotherapy-induced thrombocytopenia

Issue: January 10, 2016

ORLANDO, Fla. — Current guidelines for low–molecular-weight heparin dose reduction appeared safe and effective for patients with cancer and chemotherapy-induced thrombocytopenia, according to study results presented at the ASH Annual Meeting and Exposition.

Perspective from Annemarie Fogerty, MD

However, the researchers noted it remains to be determined if established guidelines would be appropriate for the newer generation of oral anticoagulants.

Gerald A. Soff

Patients with cancer commonly develop chemotherapy-induced thrombocytopenia when receiving therapeutic anticoagulation for venous thromboembolism. However, the current approach to low–molecular-weight heparin (LMWH) dosing in this setting is based on little published experience and has not been prospectively validated, according to study background.

“We try to balance the need for anticoagulation and the concomitant risk for thrombocytopenia,” Gerald A. Soff, MD, chair of hematology service at Memorial Sloan Kettering Cancer Center, said during a press conference. “About 5 to 7 years ago, a number of institutions began to implement guidelines. There was no prospective data that led to these guidelines, and there has been no validations of these guidelines. So, when we implemented the guidelines [at Memorial Sloan Kettering Cancer Center] in 2010, we followed them fairly vigorously, which gave us the opportunity to validate both adherence and adequacy.”

The current guidelines recommend a full dose of heparin for patients with a platelet count greater than 50,000 µL, a half dose for patients with a platelet count between 25,000 and 50,000 µL, and a temporary holding for patients with a platelet count lower than 25,000 µL.

Soff and colleagues performed a quality assessment study of patients treated at Memorial Sloan Kettering Cancer Center who received enoxaparin for VTE between 2011 and 2013, and who experienced at least one period of thrombocytopenia (platelet count ≤ 50,000 µL) for at least 7 days.

The researchers assessed the adherence of the LMWH dose modification guidelines reflected by dose reduction and/or temporary hold for existing or anticipated thrombocytopenia.

Further, the researchers recorded major bleeding events, clinically relevant nonmajor bleeding, recurrent VTE events and death.

Soff and colleagues identified 101 patients with 144 episodes of thrombocytopenia. The average episode duration was 21.3 days.

Ninety-five percent (n = 137) of patients received a LMWH dose modification, reflecting widespread institutional adherence to guidelines. The researchers observed 20 instances of dose reduction, 90 instances of dose holding and 27 instances of combined reduction/holding.

Dose holding generally occurred in more severe episodes of thrombocytopenia.

The unweighted mean platelet count during episodes managed with holding LMWH was 27,000 µL (standard deviation [SD] = 16,000), whereas the mean platelet count during dose reduction episodes was 36,000 µL (SD = 15,000).

The researchers did not observe recurrent VTE events or major bleeding episodes when the LMWH dose was reduced or held.

One major bleeding episode — a trauma-associated retroperitoneal hemorrhage caused by an accidental fall — occurred in the cohort, on the third day of a thrombocytopenic episode and prior to dose reduction. The patient had a platelet count of 28,000 µL at the time of the event.

Further, the researchers recorded 14 clinically relevant nonmajor bleeding episodes, half of which consisted of ecchymosis, epistaxis or gingival bleeding.

Ten patients died during a thrombocytopenic episode, according to the researchers.

“Our institution followed the guidelines with approximately 95% adherence, and when adhered to appropriately, we saw very gratifying safety and efficacy results,” Soff said. “Our experience is the first validation of the guidelines, which we think will have an impact on practices around the country and the world. We would emphasize that education of the practitioners is important, because guidelines are only useful if the doctors adhere to them.”

However, Soff cautioned these data may not be applicable to newer direct oral anticoagulants.

“Their safe and acceptable use needs to be prospectively validated,” he said. “One would acknowledge that the highest quality of data are always in a randomized clinical trial. However, the nature of this kind of event in patients with thrombosis would not lend itself to a clinical trial.” – by Cameron Kelsall

Reference:

Miao Y, et al. Abstract 429. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Lee AYY, et al. J Clin Oncol. 2009;doi:10.1200/JCO.2009.22.3958.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Annemarie Fogerty, MD

This study highlights a concern that all centers have, because there really are no international standards for what platelet thresholds should be. What Memorial Sloan Kettering Cancer Center has done — and what many of us are trying to do — is establish institutional guidelines, where locally you would have an expert opinion saying, “These are the platelet counts we are going to use.” There is a lot of concern among providers about patients who are at a bleeding risk for a perceived or actual low platelet count, but who also have a blood clot. Based on other published consensus guidelines, Miao and colleagues established the threshold of platelets and found that with good provider education, they could achieve 95% compliance and prevent bleeding complications. What remains to be seen is what we do with patients once they recover from their platelet counts. Did they go back and institute the full therapeutic guidelines? All institutions should have a local consensus on platelet thresholds.

Annemarie Fogerty, MD

Massachusetts General Hospital Cancer Center

Disclosures: Fogerty reports no relevant financial disclosures.