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Secondary Prophylaxis With Full-Dose Anticoagulation Significantly Reduces Recurrent CVC-VTE in Children

January 31, 2022

February 2022

In children who underwent central venous catheter (CVC) placement following a CVC-associated venous thromboembolism (VTE), secondary prophylaxis with full-dose anticoagulation was associated with a 65% reduction in the odds of recurrent CVC-associated thrombotic events, according to research findings published in Blood.

These findings offer hope for these children, explained corresponding study author Char Witmer, MD, of the Children’s Hospital of Philadelphia (CHOP), given that CVC-associated thrombosis is the most common cause of VTE in hospitalized children and is a significant source of harm.

“Currently, due to a lack of data, there are no clinical guidelines regarding secondary prophylaxis for patients who have a history of a CVC-VTE with subsequent CVC placement leading to significant variation in practice,” Dr. Witmer added. “But debate remains about the efficacy of anticoagulation to prevent CVC-VTE in pediatric patients.”

In the study, Dr. Witmer and colleagues retrospectively assessed electronic medical records in a clinical thrombosis database within the CHOP Division of Hematology and an inpatient database for hospital-acquired VTE. The investigators only included records of patients who were younger than age 19 at their first CVC-VTE event between 2003 and 2013. Additionally, researchers collected details on subsequent CVCs placed after the index CVC-VTE event, including data on use of anticoagulation for secondary prevention.

Secondary prophylaxis with full-dose anticoagulation included warfarin, enoxaparin, heparin, and bivalirudin. In contrast, those who received a prophylactic dose of anticoagulation received warfarin, enoxaparin, and low-dose heparin. Some patients received both full and prophylactic dosing while a CVC was in place. The researchers assessed the rates of recurrent CVC-VTE events, defined as a VTE diagnosed at least seven days after the thrombotic event, as well as bleeding events.

A total of 373 patients had an index CVC-VTE during the study period. Patients had a median follow-up of 688 days. The majority of patients were younger than age 1 (59%). Approximately 64% of the overall cohort had 550 additional CVCs placed, reflecting a median of two additional CVCs per patient.

The median interval between the index CVC-VTE event to subsequent CVC placement was four days. Fifty-three percent of patients received full-dose anticoagulation, 14% received a prophylactic dose, and 3% received both full and prophylactic doses. Nearly one-third (31%) of patients received no anticoagulation.

Approximately 17% of patients experienced a recurrent VTE, and 90.8% of events were associated with CVC placement. According to a multivariable survival analysis, variables significantly associated with an increased hazard of VTE recurrence included each additional CVC (hazard ratio [HR] = 12.00; 95% CI 2.78-51.91), congenital heart disease (HR=3.70; 95% CI 1.97-6.95), and total parenteral nutrition (TPN) dependence (HR=4.02; 95% CI 2.23-7.28).

“These results provide further data to support thromboprophylaxis for pediatric patients with TPN dependence and a prior history of CVC-VTE,” Dr. Witmer said.

Additionally, the use of full-dose anticoagulation was significantly associated with decreased odds of recurrent CVC-VTE (odds ratio [OR] = 0.35; 95% CI 0.19-0.65), but this association did not hold true for prophylactic dosing (OR=0.61; 95% CI 0.28-1.30). Major bleeding was observed in only 1.3% of CVCs with prophylactic or full-dose anticoagulation.

Limitations of the study included its single-center design and retrospective nature.

“While we were able to demonstrate recurrent VTE reduction with full-dose anticoagulation, this benefit needs to be weighed against the potential harm,” Dr. Witmer added. “While we found a low rate of bleeding, this was determined by chart review and bleeding events could have been missed.”

Despite these limitations, Dr. Witmer noted that the study “lays the groundwork for a prospective clinical trial to assess the efficacy of secondary prophylaxis in patients with a prior history of CVC-VTE with subsequent line placement.”

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Clark HH, Ballester L, Whitworth HB, Raffini L, Witmer C. Prevention of recurrent thrombotic events in children with central venous catheter-associated venous thrombosis [published online ahead of print, 2021 Nov 2]. Blood. doi: 10.1182/blood.2021013453.

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