Is it safe to use conditionally ordered LMWH in cancer patients with VTE?

Conditional orders of low molecular weight heparin (LMWH) based on platelet values appears safe and effective in the treatment of venous thromboembolism (VTE) in patients with malignant haematology (MH) experiencing thrombocytopenia, a study has shown. In addition, worsening or new VTE has not been reported among study participants.

“The safety and efficacy demonstrated in the study provide reassurance for [the] practice of LMWH conditional orders based on platelet values,” said the investigators.

The investigators screened the electronic records of MH inpatients admitted to Princess Margaret Cancer Centre in Toronto, Canada, between January 2017 and December 2019. Eligible patients received at least one dose of an LMWH for the treatment of VTE.

A total of 108 inpatients were screened, of whom 50 (median age 59 years) met the eligibility criteria. Acute lymphoblastic leukaemia (30 percent) was the most common MH diagnosis. [J Oncol Pharm Pract 2024;doi:10.1177/10781552231189695]

Thirty of the eligible patients (60 percent) received conditional orders of LMWH. Overall, 571 administrations had been carried out, of which 543 (95 percent) were administered concordantly (Χ², 472; p<0.0001).

Of note, eight patients experienced bleeding or a decrease in haemoglobin >10 g/L within 3 days. None of the patients, however, had a recurrent VTE during treatment, with a duration of up to 40 days following hospital admission.

Conditional order

“This study revealed the use of conditional orders with a variation in the platelet threshold cutoffs as well as the number of platelet threshold cutoffs for a single conditional order,” the investigators said. “The most common ordering scenario utilized three conditional orders/platelet threshold cutoffs.”

This gradated conditional order may follow from existing guidelines, but there remains no published comparison of efficacy or safety between conditional orders with varying numbers of threshold cutoffs (eg, one condition [“LMWH dose” if platelets >50 × 10⁹/L] vs two conditions [“LMWH dose” if platelets >50 × 10⁹/L, then “LMWH dose” if platelets 30‒50 × 10⁹/L]). [J Thromb Haemost 2018;16:1246-1249; Curr Oncol 2015;22:144]

There are some disadvantages to gradated orders with additional conditions, such as increasing the risk of the patients receiving an incorrect LMWH dose if the order was misinterpreted, more entries for the prescriber to order, and an increase in the workload of nurses.

“Although our study did not investigate if there was a difference in outcomes between orders with a single condition versus multiple conditions, it is reasonable to assume that standardizing platelet conditions and dose reductions should reduce administration errors,” the investigators said. “A study into the benefit of additional conditions for conditional orders may be a future direction.”

Guidelines set by the American Society of Clinical Oncology, International Initiative on Thrombosis and Cancer, and American Society of Hematology recommend initial treatment either with LMWH or direct oral anticoagulant (DOAC) for cancer patients with an established VTE.

Such recommendation was based on meta-analyses that revealed increased efficacy of LMWH or DOACs relative to vitamin K antagonists at lowering the incidence of recurrent VTEs in cancer patients. [J Clin Oncol 2019;38:496-520; N Engl J Med 2003;349:146-153; Blood Adv 2021;5:927-974]