Genetic risk factors, family history predict venous thrombosis in older patients

Genetic factors that predicted venous thrombosis in younger patients remained predictive in older cohorts, according to results of a case–control study.

A positive family history for venous thrombosis (VT) also served as an important risk factor in older age groups.

The risk for VT is associated with environmental and genetic risk factors. Recognized risk factors in young and middle-aged patients include factor V Leiden and prothrombin mutations, non-O blood group and family history.

“Limited information is available regarding genetic risk factors for VT in the elderly,” Astrid van Hylckama Vlieg, PhD, assistant professor in the department of clinical epidemiology at Leiden University Medical Center in the Netherlands, and colleagues wrote. “Elderly persons are often excluded from clinical studies into etiology and management because of comorbidities, short life expectancies and logistical difficulties. Furthermore, it is unknown whether a positive family history of VT is predictive of a venous thrombotic event at an older age.”

van Hylckama Vlieg and colleagues sought to determine whether common genetic risk factors affected the risk for first VT in individuals aged older than 70 years.

The analysis included data from 401 older patients (mean age, 78.7 years; range, 70-101) presenting with a first VT, as well as 431 controls (mean age, 77.5 years; range, 70-96) without VT.

Fifty-nine percent of patients with VT (n = 235) had a pulmonary embolism, with or without deep vein thrombosis. The remaining 41% (n = 166) had an isolated DVT.

Information on potential genetic risk factors came from patient and control interviews. The researchers had access to data on factor V Leiden and prothrombin G20210A mutations in 98% of patients (n = 394 for both mutations) and 99% of controls (factor V Leiden, n = 426; prothrombin, n = 427).

Blood group data were available from 94% (n = 376) of patients and 97% (n = 416) of controls.

Twenty-five patients (6%) and 13 controls (3%) did not know their family history; the researchers classified these individuals as having a negative family history.

Thirty-four patients (8.6%) and 18 (4.2%) controls carried factor V Leiden. Patients who carried factor V Leiden had a 2.2-fold (OR = 2.2; 95% CI, 1.2-3.9) increased overall risk for VT. The risk for VT associated with factor V Leiden appeared greater for unprovoked VT (OR = 2.4; 95% CI, 1.2-4.5) than provoked VT (OR = 1.6; 95% CI, 0.7-3.7).

Nine patients (2.3%) and seven controls (1.6%) harbored prothrombin G20210A mutations (OR = 1.4; 95% CI, 0.5-3.9). The risk for VT associated with prothrombin G20210A mutations appeared comparable for provoked (OR = 1.2; 95% CI, 0.3-4.9) and unprovoked (OR = 1.5; 95% CI, 0.5-4.7) VT.

A total of 231 patients (61.4%) and 232 controls (55.8%) had a non-O blood group (OR = 1.3; 95% CI, 1-1.8). A non-O blood group did not increase the risk for provoked VT; however, it resulted in a 1.5-fold increase (OR = 1.5; 95% CI, 1.1-2.1) in the risk for unprovoked VT.

Ninety-seven patients (24.2%) and 54 controls (12.5%) reported a family history of VT in a first-degree relative. The presence of VT in a first-degree relative correlated with a 2.1-fold increase (OR = 2.1; 95% CI, 1.5-3.1) in VT risk compared with individuals without a family history.

The risk remained similar when the researchers excluded individuals who did not know their family histories (OR = 2.2; 95% CI, 1.5-3.2).

A positive family history increased the risk of provoked (OR = 1.7; 95% CI, 1-2.8) and unprovoked (OR = 2.4; 95% CI, 1.6-3.6) VT.

The researchers observed the greatest risk increase among individuals who carried a prothrombotic variant and had a family history of VT (OR = 7.6; 95% CI, 1.6-35.7).

The researchers acknowledged study limitations, including the potential for selection bias, as individuals with a family history of VT may have been more willing to enroll in a study of the condition than those without.

They further noted that patients with VT might be more likely to learn of their family history after experiencing VT themselves, which may bias results toward overestimation.

“Our results may have clinical implications,” van Hylckama Vlieg and colleagues wrote. “A positive family history of VT doubled the risk [for] VT in the elderly. In clinical practice this information is easy to obtain; however, it is not implemented in clinical decision rules of VT risk. In the elderly, these clinical decision rules show a high failure rate. Potentially, obtaining information on family history of VT in individuals aged 70 years or older could improve prediction of VT in the elderly.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.