Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden

Abstract

Zöller B, Li X, Sundquist J, Sundquist K. (Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA). Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. J Intern Med 2011; 270: 158–165. Abstract. Objective. This is the first nationwide study to determine familial risks of unusual forms of venous thrombosis amongst offspring of affected parents and amongst siblings. Design and settings. The Swedish Multigeneration Register of 0‐ to 75‐year‐old subjects was linked to the Hospital Discharge Register for the period 1987–2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for venous thromboembolism (VTE), as determined by the International Classification of Diseases, compared to those whose relatives were not affected by VTE. Results. The total number of hospitalized patients with VTE was 45 362, of which 1824 (4.0%) were affected by a rare thrombotic condition. The familial SIRs in cases with a history of VTE in parents or siblings were significantly increased for migrating thrombophlebitis (1.81; 95% confidence interval (CI) 1.40–2.31), portal vein thrombosis (2.35; 95% CI 1.77–3.06), vena cava thrombosis (1.96; 95% CI 1.42–2.64) and cerebral venous thrombosis (1.74; 95% CI 1.30–2.28). Budd–Chiari syndrome (SIR, 0.92; 95% CI 0.24–2.38) and renal vein thrombosis (SIR, 1.72; 95% CI 0.62–3.77) were not significantly associated with parental or sibling history of VTE; however, these two conditions were very rare, and therefore, we cannot draw any definite conclusions from this finding. Conclusions. Family history is an important risk factor for most unusual forms of VTE. Moreover, even the paraneoplastic phenomenon, migrating thrombophlebitis (Trousseau’s syndrome), is associated with a family history of VTE. Thus, our data suggest that most rare forms of VTE have a familial background.

Familial Transmission of Venous Thromboembolism

“…In contrast, the overall risk in adoptees with ≥1 adoptive parent with VTE was not increased. The importance of family history in the development of VTE has been demonstrated in previous studies, which have 18,44 Although it is well established that genetic factors contribute to the risk of VTE, our finding that genetic factors seem to be more important for the familial transmission of VTE than family environmental factors is novel. The potential to disentangle the contributions of genetic and family environmental factors to the familial transmission of VTE stems from the fact that adoptees do not share the same family environment as their biological parents.…”

“…This is in-line with previously published nationwide family studies. 17,18,[40][41][42][43][44] A further observation is that the biological familial risk (SIR=1.51) was slightly lower than previously published (familial risk ≈2).…”

“…12, [14][15][16][17][18][19][40][41][42][43][44] The explanation may, however, simply be because of the relatively lower power in a study only including adoptees. However, a possible hypothesis for the modest familial risk of 1.51 is that the higher familial transmission observed in nonadopted offspring 17,18,[40][41][42][43][44] is because of the sum of interactions between familial genetic and environmental factors.…”

“…12,[14][15][16][17][18][19] Although a familial risk of 2 might seem modest, it does suggest that uncovering genetic and nongenetic sources of familial aggregation might be worthwhile. 13 However, if familial environmental effects are strong, this might not be the case.…”

Venous Thromboembolism Does Not Share Strong Familial Susceptibility With Ischemic Stroke

“…16 Even rare forms of VTE have a familial background. 31 Because no strong risk for stroke among relatives to probands with VTE was observed in our study, it is unlikely that any shared strong genetic risk factors exist between ischemic stroke and VTE. In addition, meta-analysis have found only weak or no associations between factor V Leiden Gln506 (rs6025) and prothrombin G20210A (rs1799963), both important risk factors for VTE and ischemic stroke.…”