ASH panel provides ‘weak’ recommendations for thrombophilia testing
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Key takeaways:
- ASH panel recommends thrombophilia testing for multiple patient populations.
- Indefinite anticoagulant treatment advised for multiple patient populations that test positive.
Women with venous thromboembolism associated with pregnancy, the postpartum period or combined oral contraceptives who have finished primary short-term treatment may be considered for thrombophilia testing.
An ASH panel recommended this testing for thrombophilia to guide treatment duration.
The multidisciplinary guideline panel, working with the McMaster University GRADE Centre, made 23 total recommendations for thrombophilia testing — most of which were labeled conditional based on very low certainty of evidence about — as part of a special interest session on Clinical Practice Guidelines on Venous Thromboembolism at ASH Annual Meeting and Exposition.
“This is a weak recommendation with a lot of uncertainty surrounding it. In this guideline, I think the big change is that we have specified clinical situations — particularly for patients with an episode of venous thromboembolism — where patients may benefit from testing for thrombophilia to guide the duration of anticoagulation or make other treatment decisions,” Saskia Middeldorp, MD, PhD, professor of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, told Healio.
Background
Thrombophilia, hereditary or acquired, is a risk factor for VTE.
Antithrombin, protein C, protein S, and the gain-of-function mutations factor V Leiden and prothrombin G20210A mutation are “the most commonly tested” hereditary thrombophilias, background information on the report stated.
Lupus anticoagulants, anticardiolipin antibodies, and anti–beta-2-glycoprotein 1 antibodies — “laboratory features of the acquired thrombophilic antiphospholipid syndrome” — are usually tested for as well.
However, thrombophilia testing can cause overdiagnosis and overtreatment, resulting in physical, mental and financial harm for patients.
The ASH panel, with help from McMaster GRADE Centre, set out to determine when thrombophilia testing can be considered based on models that assess the effect of testing and subsequent management decisions on recurrent VTE and bleeding using previously conducted systematic reviews and studies.
Key recommendations
The panel gave a conditional recommendation that women with VTE associated with pregnancy, the postpartum period or combined oral contraceptives who tested positive for thrombophilia might consider indefinite anticoagulant treatment.
The panel made the same conditional recommendation for patients with VTE associated with a “nonsurgical major transient risk factor.”
“When we did math in the models and saw the results of testing on recurrent VTE, we were very hesitant — but this is what came out of the data,” Middeldorp said. “We were already thinking that, ‘Wow, this is going to raise some turmoil,’ which indeed happened. I literally remember one of the panel members saying, ‘Oh my goodness. Are we going to suggest testing in this situation because of the data?’ So, yes, I do understand people who read this for the first time are also a little bit surprised.”
The panel gave a conditional recommendation that patients with unusual site thrombosis, such as cerebral venous thrombosis or splanchnic venous thrombosis, who have finished their primary treatment and who would stop anticoagulation could be considered for thrombophilia testing, followed by indefinite anticoagulations in those patients with positive test results.
The panel conditionally recommended testing for thrombophilia for asymptomatic individuals with a family history of protein C, protein S or antithrombin VTE, in order to use thromboprophylaxis during high-risk situations or to avoid hormone use that increases thrombosis risk.
The panel also conditionally recommended testing for ambulatory patients with cancer who have a family history of VTE, are receiving systemic treatment and have a low to moderate thrombosis risk. Patients who test positive would be eligible for thromboprophylaxis.
“It’s a weak recommendation, but imagine you’re a patient, you have cancer, you’re going to undergo systemic anticancer therapy, and you have a brother with VTE. What can you do to reduce VTE risk? These questions actually happen all the time,” Middeldorp said. “Now we can say that what we could do is test you for inherited thrombophilia, and if you have a defect, then we can suggest using thromboprophylaxis. That’s fairly new.”
Most of the recommendations are conditional because of the lack of randomized control trials, Middeldorp said.
“We really need trials that randomize between strategies,” she said, stressing that these recommendations are suggestions and doctors should have conversations with their patients about their options.
“It’s not written in stone,” she said. “It’s not a strong recommendation for various reasons ... but it gives you a bit more room to discuss this aspect with your patients and then decide whether or not a thrombophilia test would change management.”
References:
- Middeldorp S, et al. ASH Guidelines on Venous Thromboembolism (VTE): What’s new. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023; San Diego.
- Middeldorp S, et al. Blood Adva. 2023;doi:10.1182/bloodadvances.2023010177.
For more information:
Saskia Middeldorp, MD, PhD, can be reached at saskia.middeldorp@radboudumc.nl.
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Middeldorp S, et al. ASH Guidelines on Venous Thromboembolism (VTE): What’s new. Presented at: ASH Annual Meeting and Exhibition; Dec. 9-12, 2023; San Diego.
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