The value of family history as a risk indicator for venous thrombosis

Irene D Bezemer ¹, Felix J M van der Meer, Jeroen C J Eikenboom, Frits R Rosendaal, Carine J M Doggen

PMID: 19307525. DOI: 10.1001/archinternmed.2008.589

Abstract

Background: A positive family history of venous thrombosis may reflect the presence of genetic risk factors. Once a risk factor has been identified, it is not known whether family history is of additional value in predicting an individual’s risk. We studied the contribution of family history to the risk of venous thrombosis in relation to known risk factors.

Methods: In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis, a population-based case-control study, we collected blood samples and information about family history and environmental triggers from 1605 patients with a first venous thrombosis and 2159 control subjects.

Results: A total of 505 patients (31.5%) and 373 controls (17.3%) reported having 1 or more first-degree relatives with a history of venous thrombosis. A positive family history increased the risk of venous thrombosis more than 2-fold (odds ratio [95% confidence interval], 2.2 [1.9-2.6]) and up to 4-fold (3.9 [2.7-5.7]) when more than 1 relative was affected. Family history corresponded poorly with known genetic risk factors. Both in those with and without genetic or environmental risk factors, family history remained associated with venous thrombosis. The risk increased with the number of factors identified; for those with a genetic and environmental risk factor and a positive family history, the risk was about 64-fold higher than for those with no known risk factor and a negative family history.

Conclusions: Family history is a risk indicator for a first venous thrombosis, regardless of the other risk factors identified. In clinical practice, family history may be more useful for risk assessment than thrombophilia testing.

Reference:

Arch Intern Med. 2009 Mar 23;169(6):610-5. doi: 10.1001/archinternmed.2008.589.

Familial risk of venous thromboembolism in first-, second- and third-degree relatives: a nationwide family study in Sweden

Bengt Zöller ¹, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist

PMID: 23348971. DOI: 10.1160/TH12-10-0743

Erratum in

Thromb Haemost. 2013 Jul 1;110(1):204

Abstract

Venous thromboembolism (VTE) clusters in families, but the familial risk of VTE has only been determined in first-degree relatives. This nationwide study aimed to determine the familial risk of VTE in first-, second- and third-degree relatives of affected individuals. The Swedish Multi-Generation Register was linked to Hospital Discharge Register data for the period 1987-2009. This was a case-cohort study. Odds ratios (ORs) for VTE were calculated for individuals whose relatives were hospitalised for VTE, as determined by the International Classification of Diseases (ICD), and those whose relatives were unaffected by VTE. The familial OR for VTE was 2.49 in siblings (95% confidence interval [CI] 2.40-2.58), 2.65 in children (2.50-2.80), 2.09 in parents (2.03-2.15), 1.52 in maternal half-siblings (1.26-1.85), 2.34 in paternal half-siblings (2.00-2.73), 1.69 in nieces/nephews (1.57-1.82), 1.47 in cousins (1.33-1.64), and 1.14 in spouses of individuals diagnosed with VTE (1.09-1.18). Familial clustering was stronger at young ages. The familial transmission was slightly stronger for males compared with females but was only significant for siblings 1.13 (1.05-1.22) and parents 1.11 (1.05-1.78) of probands. The present data showing an increased VTE risk among not only first-degree relatives but also second- and third-degree relatives indicate that the genetic component of the familial clustering of VTE is strong. Family history is a potentially useful genetic surrogate marker for clinical VTE risk assessment, even in second- and third degree-relatives.

Reference:

Thromb Haemost. 2013 Mar;109(3):458-63. doi: 10.1160/TH12-10-0743. Epub 2013 Jan 24.

Hypercoagulability Is a Stronger Risk Factor for Ischaemic Stroke than for Myocardial Infarction: A Systematic Review

Alberto Maino ¹, Frits R Rosendaal ², Ale Algra ³, Flora Peyvandi ⁴, Bob Siegerink ⁵

PMID: 26252207. PMCID: PMC4529149. DOI: 10.1371/journal.pone.0133523

Abstract

Background and purpose: Hypercoagulability increases the risk of arterial thrombosis; however, this effect may differ between various manifestations of arterial disease.

Methods: In this study, we compared the effect of coagulation factors as measures of hypercoagulability on the risk of ischaemic stroke (IS) and myocardial infarction (MI) by performing a systematic review of the literature. The effect of a risk factor on IS (relative risk for IS, RRIS) was compared with the effect on MI (RRMI) by calculating their ratio (RRR = RRIS/RRMI). A relevant differential effect was considered when RRR was >1+ its own standard error (SE) or <1-SE.

Results: We identified 70 publications, describing results from 31 study populations, accounting for 351 markers of hypercoagulability. The majority (203/351, 58%) had an RRR greater than 1. A larger effect on IS risk than MI risk (RRE>1+1SE) was found in 49/343 (14%) markers. Of these, 18/49 (37%) had an RRR greater than 1+2SE. On the opposite side, a larger effect on MI risk (RRR<1-1SE) was found in only 17/343 (5%) markers.

Conclusions: These results suggest that hypercoagulability has a more pronounced effect on the risk of IS than that of MI.

Reference:

PLoS One. 2015 Aug 7;10(8):e0133523. doi: 10.1371/journal.pone.0133523.eCollection 2015.