Thrombocytopenia as a thrombotic risk factor in patients with antiphospholipid antibodies without disease criteria

SummaryDespite many reports of individuals with congenital plasminogen deficiency and thrombosis, there is still uncertainty whether heterozygous deficiency represents a real thrombophilic risk factor or simply a coincidental finding. We have addressed this issue by testing for plasminogen deficiency in a cohort of 9611 blood donors. Out of 66 donors with reduced plasminogen activity on two occasions 28 were shown to have a familial deficiency state (including 3 with dysplasminogen-aemia). Our observed prevalence rate for familial plasminogen deficiency, calculated at 2.9/1000 (95% Cl = 1.9-4.2 per 1000), was not significantly different from that calculated from published reports of congenital plasminogen deficiency in thrombotic cohorts (5.4/1000). Furthermore, with only two exceptions, all 80 donors and relatives with familial deficiency were asymptomatic with regard to thrombosis -including a 29 year old donor with suspected compound heterozygous hypoplasminogenaemia. These findings add further weight to the argument that familial heterozygous plasminogen deficiency, at least in isolation, does not constitute a significant thrombotic risk factor. However, it remains uncertain whether plasminogen deficiency, when combined with other thrombophilic conditions, may become more clinically important.

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APC resistance as an additional thrombotic risk factor in a patient suffering from polycythemia vera and recurrent thrombosis

Annals of Hematology ◽

10.1007/s002770050256 ◽

1997 ◽

Vol 74 (1) ◽

pp. 49-50 ◽

Cited By ~ 5

Author(s):

S. Lamparter ◽

M. Schuermann ◽

H.-H. Heidtmann

Keyword(s):

Risk Factor ◽

Polycythemia Vera ◽

Recurrent Thrombosis ◽

Thrombotic Risk ◽

Thrombotic Risk Factor ◽

Apc Resistance

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Factor V Leiden in Women: A Thrombotic Risk Factor or an Evolutionary Advantage?

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0031-1273091 ◽

2011 ◽

Vol 37 (03) ◽

pp. 275-279 ◽

Cited By ~ 7

Author(s):

Massimo Franchini ◽

Giuseppe Lippi

Keyword(s):

Risk Factor ◽

Factor V Leiden ◽

Factor V ◽

Thrombotic Risk ◽

Thrombotic Risk Factor ◽

Evolutionary Advantage

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Intermediate and Severe Hyperhomocysteinemia with Thrombosis: A Study of Genetic Determinants

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613862 ◽

2000 ◽

Vol 83 (04) ◽

pp. 554-558 ◽

Cited By ~ 29

Author(s):

Mette Gaustadnes ◽

Niels Rüdiger ◽

Karsten Rasmussen ◽

Jørgen Ingerslev

Keyword(s):

Risk Factor ◽

Methylenetetrahydrofolate Reductase ◽

Missense Mutations ◽

Strongly Correlated ◽

Genetic Determinants ◽

Thrombotic Risk ◽

Genotype Combination ◽

Thrombotic Risk Factor ◽

Plasma Thcy ◽

Total Homocysteine

SummaryHyperhomocysteinemia is an independent risk factor for cardiovascular disease. In search of genetic factors causing elevated levels of total homocysteine in plasma (tHcy), we investigated a cohort of consecutively identified, unrelated thrombosis patients (n = 28) having intermediate or severe hyperhomocysteinemia (30 µmol/l<tHcy ≤100 µmol/l, and tHcy >100 µmol/l, respectively). The methylenetetrahydrofolate reductase (MTHFR) 677C→T genotype, and the complete cystathionine β-synthase (CBS) genotype was determined in all patients. We found that the MTHFR T/T genotype was strongly correlated with intermediate hyperhomocysteinemia, being present in 73.9 % of those cases (17 of 23). In three of five patients with severe hyperhomocysteinemia, compound heterozygosity for CBS mutations was detected. Among the mutations, two novel missense mutations: 1265C→T (S422L) and 1397C→T (S466L) were detected. The phenotype in those patients was quite mild, thromboembolism apart. This indicates that a search for CBS mutations in patients with severe hyperhomocysteinemia is important to ensure the detection of a possible CBS deficiency, thus enabling treatment. Co-existence of the MTHFR T/T genotype and the common CBS 844ins68 variant was significantly higher among patients (10.7%) as compared to controls (1.2%), indicating that this genotype combination is a thrombotic risk factor (P <0.05). In a few patients, hyperhomocysteinemia could not be explained by this genetic approach, suggesting that other genetic risk factors were implicated.Abbreviations: MTHFR, methylenetetrahydrofolate reductase; CBS, cystathionine β-synthase; tHcy, total homocysteine in plasma.

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The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors

Blood ◽

10.1182/blood-2013-07-518159 ◽

2013 ◽

Vol 122 (26) ◽

pp. 4264-4269 ◽

Cited By ~ 30

Author(s):

Rachel E. J. Roach ◽

Willem M. Lijfering ◽

Astrid van Hylckama Vlieg ◽

Frans M. Helmerhorst ◽

Frits R. Rosendaal ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thrombosis ◽

Superficial Vein ◽

Thrombotic Risk ◽

Vein Thrombosis ◽

Thrombotic Risk Factor ◽

Key Points ◽

Superficial Vein Thrombosis ◽

History Of

Key Points Superficial vein thrombosis combined with an acquired thrombotic risk factor increases the risk of venous thrombosis 10- to 100-fold. If confirmed, these findings have important implications for the future prevention of venous thrombosis.

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The Homozygous Leu Variant of the Factor XIII Val34Leu Polymorphism as a Risk Factor for the Manifestation of Thrombotic Microangiopathies

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607304723 ◽

2007 ◽

Vol 15 (2) ◽

pp. 197-200 ◽

Cited By ~ 1

Author(s):

Christoph Sucker ◽

Firuseh Farokhzad ◽

Christine Kurschat ◽

Bernd Grabensee ◽

Rudiger E. Scharf ◽

...

Keyword(s):

Risk Factor ◽

Odds Ratio ◽

Factor Xiii ◽

Genetic Variant ◽

Thrombotic Microangiopathies ◽

Thrombocytopenic Purpura ◽

Thrombotic Risk ◽

Thrombotic Risk Factor ◽

Uremic Syndrome

The 34 Leu (100T) variant of the factor XIII Val34Leu (G100T-) polymorphism slows down fibrinolysis and has been proposed as a thrombotic risk factor. In this pilot study, we enrolled 40 patients (mean age ± SD = 38 ± 11 years) and 728 controls to assess the role of this genetic variant for the manifestation of thrombotic microangiopathies. From the genotype prevalences, an increased manifestation risk for carriers of the TT genotype (homozygous Leu variant) of the factor XIII Val34Leu (G100T-) polymorphism was calculated (odds ratio [OR] = 2.44; 95% confidence interval [CI] = 0.8-7.6; P = .11). This association was statistically significant for patients with thrombotic thrombocytopenic purpura—hemolytic-uremic syndrome (TTP-HUS) (OR = 6.6; 95% CI = 1.7-25.9; P = .006). Our data suggest a role of the homozygous Leu variant of the factor XIII Val34Leu polymorphism in the manifestation of thrombotic microangiopathies. Decreased fibrinolysis in the presence of this genetic variant provides a plausible explanation for this association.

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