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Unprovoked VTE, thrombosis at young age increased risk among first-degree relatives
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The development of unprovoked venous thromboembolism or thrombosis at a young age independently predicted venous thromboembolism risk in those patients’ first-degree relatives, according to study results.
Professor Francis Couturaud, MD, PhD, of the department of internal medicine and chest diseases at University Hospital Centre La Cavale Blanche at European Brittany University in France, and colleagues previously established a correlation between unprovoked venous thromboembolism (VTE) and risk in first-degree relatives if the index patient had prothrombin 20210A gene variant or Factor V Leiden. However, the risk associated with provoked VTE was unknown, according to background information provided by the researchers.
Researchers hypothesized that thrombosis risk was higher in first-degree relatives of patients with unprovoked VTE than provoked VTE.
To investigate this theory, they assessed thrombosis risk in first-degree relatives of patients with provoked VTE, then compared that risk to what they previously observed in first-degree relatives of patients with unprovoked VTE.
The analysis included 138 patients with provoked VTE and 915 of their first-degree relatives, plus 378 patients with unprovoked VTE and 1,752 of their first-degree relatives.
Researchers observed 123 total VTE case in the entire cohort of 2,617 first-degree relatives, equating to an incidence of 0.12 per 100 person-years.
First-degree relatives were more likely to experience VTE if the index patient developed unprovoked VTE (OR=2.38; 95% CI, 1.43-3.85) or if the index patient was younger (OR=.97 per year older; 95% CI, 0.96-0.99). First-degree relatives of patients aged younger than 45 years were at nearly five times the risk for VTE than first-degree relatives of patients aged older than 72 years (OR=4.97; 95% CI, 1.24-19.99).
The risks associated with unprovoked VTE and younger age were additive for first-degree relatives, according to researchers.
VTE risk also increased for those individuals who had two or more first-degree relatives develop VTE (OR=2.71; 95% CI, 2.22-3.31). This association persisted regardless of whether the index patient had provoked (adjusted OR=2.78; 95% CI, 1.79-4.33) or unprovoked (adjusted OR=2.53; 95% CI, 2.02-3.18) VTE.
VTE risk among first-degree relatives also was higher if the index patient had Factor V Leiden or prothrombin 20210A gene variant (OR=4.42; 95% CI, 1.35-14.38). The presence of these abnormalities was higher in patients with unprovoked vs. provoked VTE (28.4% vs. 14.5%; P˂.001).
“The risk of VTE in the first-degree relatives of patients with a first VTE is strongly influenced by whether the VTE was provoked or unprovoked, the patient’s age when the VTE occurred, and the number of relatives who have had thrombosis,” the researchers concluded. “This information complements the results of thrombophilia testing when counseling family members about their risk of thrombosis.”
Disclosure: The study was supported by grants from Programme Hospitalier de Recherche Clinique and the Heart and Stroke Foundation of Ontario.
Perspective
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Mary Cushman, MD, MSc
This paper builds on prior data and teaches us that detailed knowledge of family history of thrombosis is important to patients, but also that characteristics of the thrombosis in the affected family member may modulate the risk for thrombosis in their relatives. The results will be helpful to me because, when I am seeing a relative of a patient with thrombosis, I will adopt a standard set of questions to ask and also will try to determine — if possible — which thrombophilia their relative had in order to perform only the needed laboratory testing in that relative. The results of this evaluation will help me counsel the patient about what they might expect in terms of their individual risk for thrombosis.The major interesting findings of this study are that, among first-degree relatives of probands with VTE, those at higher risk of
VTE were those where the proband was younger (vs. older), the proband had unprovoked (vs. provoked VTE), there were increasing numbers of relatives with VTE, and when the proband and first-degree relative both had Factor V Leiden or the prothrombin variant (results would be expected to be the same for other thrombophilias but they weren’t evaluated in this study). When considering evaluation of relatives in primary care or specialty clinics, this information should be sought in order to best educate the relative and implement prevention strategies.
I can envision three future studies that would be helpful. First, as always, a confirmatory study of these findings is needed. Second is an assessment of the accuracy of family history information provided by patients about their family history of VTE in primary care settings. Can physicians elicit the correct history in relation to either presence or absence of thrombosis, but also whether that thrombosis was provoked or unprovoked, or even more difficult, associated with genetic thrombophilia? Finally, a management study of first-degree relatives of those with confirmed VTE would be an ideal next step. Such a study would perform risk assessment and then intervene in the high-risk subset to reduce risk of VTE. Optimally, the intervention would be in the form of a randomized trial.
The challenge here is that the general population is not very aware of venous thrombosis, so they can’t provide this history accurately to their physicians. It also is unlikely that primary care physicians routinely ask their patients about family history of venous thrombosis.
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