Thrombophilia testing. Useful or hype?

Lippi, Giuseppe

doi:10.1515/cclm-2013-0561

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…The assessment of thrombin generation is currently regarded as an useful tool for screening, diagnosis, and therapeutic monitoring of a variety of hemostatic disorders, both hemorrhagic and prothrombotic. 82 At variance with global coagulation assays such as the aPTT and the prothrombin time, or specific tests such as those used for the screening of thrombophilia, [83][84][85] thrombin generation is believed to more closely reflect an impairment between procoagulant and anticoagulant forces in vivo. 86 Thrombin generation also seems more sensitive to fluctuations of clotting function in a major area of clinical interest, that is the population of subjects with normal values for routine clotting tests.…”

Section: Fibrinolytic System Proteins and Agingmentioning

confidence: 99%

Aging Hemostasis: Changes to Laboratory Markers of Hemostasis As We Age—A Narrative Review

Favaloro

Franchini

Lippi

2014

Semin Thromb Hemost

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110

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The incidence of venous thromboembolism (VTE) is well recognized to increase with aging. Concurrently, the plasma concentrations of many coagulation factors (e.g., fibrinogen, factor [F] V, FVII, FVIII, and FIX) increase with aging, as does von Willebrand factor (VWF), thrombin generation, and platelet activation. Data are conflicting regarding age-related changes in the natural anticoagulants, including protein C, protein S, and antithrombin. Changes are also observed with components of the fibrinolytic pathway. All in all, aging is associated with a variety of hemostasis changes that on balance reflects a heightened procoagulant status compared with earlier age. It has to be recognized that as this occurs in the otherwise normal general population, this can also be considered a normal phenomenon of progressive life. An element of this heightened procoagulant status may reflect ongoing inflammatory processes, given some markers, notably FVIII and fibrinogen, are acute phase reactants. A variety of acquired prothrombotic risk factors (e.g., cancer, autoimmune disorders, and diabetes) also gradually develop with aging, some of which may induce profound abnormalities of hemostasis, and confound the age-related changes in hemostasis, as well as their influence on thrombotic risk. In this article, we review the changes in hemostasis markers measurable within many hemostasis laboratories, and consider many of the important implications for clinical and laboratory practice. Apart from representing an increased thrombotic risk, additional considerations entail the potential need (1) to utilize age-adjusted normal ranges (e.g., for D-dimer), (2) to consider the consequence on previous diagnoses (e.g., "mild type 1" von Willebrand disease [VWD], where VWF test results may "normalize" with aging), and (3) to consider the effect of these changes of risk factors on the (perceived) therapeutic efficacy of antithrombotic medications such as aspirin.

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Section: Fibrinolytic System Proteins and Agingmentioning

confidence: 99%

Aging Hemostasis: Changes to Laboratory Markers of Hemostasis As We Age—A Narrative Review

Favaloro

Franchini

Lippi

2014

Semin Thromb Hemost

Self Cite

110

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“…There are several reasons for these discordances: (1) heterogeneous criteria have been used to define RPL and RIF in most studies to date; (2) some studies compared the frequency of prothrombotic gene variants in patients and controls of different geographical areas; and (3) most studies analyzed a scarce number of cases. Finally, in the clinical context, the ordering of tests for thrombophilia is strongly heterogeneous and not supported by evidence‐based results 20–22 . Moving on from the idea that prothrombotic status may impair the outcome of the pregnancy, the tendency is to widely investigate thrombophilia in all women who experience obstetric complications and RIF.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, in the clinical context, the ordering of tests for thrombophilia is strongly heterogeneous and not supported by evidence-based results. [20][21][22] Moving on from the idea that prothrombotic status may impair the outcome of the pregnancy, the tendency is to widely investigate thrombophilia in all women who experience obstetric complications and RIF. Nevertheless, information from adequately sized subgroups of patients is lacking.…”

Section: Introductionmentioning

confidence: 99%

The relevance of prothrombotic genetic variants in women who experienced pregnancy loss or embryo implantation failure: A retrospective analysis of 1922 cases

Cernera,

Liguori,

Bruzzese

et al. 2023

Intl J Gynecology & Obste

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ObjectiveThe aim of our study was that to assess the allelic and genotype frequencies of nine prothrombotic gene variants in patients with a history of pregnancy loss and recurrent pregnancy loss (RPL). Women who underwent assisted reproductive technology (ART) with ongoing pregnancy and those with recurrent implantation failure (RIF) were also included.MethodsNine prothrombotic gene variants were evaluated: factor V Leiden (FVL), factor V, H1299R variant (FVR2), factor II (FII) G20210A, methylene‐tetrahydrofolate reductase (MTHFR) C677T and A1298C, beta‐fibrinogen ‐455G>A, factor XIII (FXIII) V34L, human platelet antigen‐1 (HPA‐1) L33P variants, and plasminogen activator inhibitor‐1 (PAI‐1) 4G/5G. The following study groups were assessed: (1) women who experienced one (n = 334) or two (n = 264) episodes of pregnancy loss; (2) 468 women who experienced RPL; (3) 214 women who underwent ART followed by ongoing pregnancies; and (4) 282 women who experienced RIF after ART, that is, three or more consecutive implantation failures following high‐quality embryo transfers to the uterus with an appropriate endometrium. As control group, 430 subjects from the general population were enrolled.ResultsFVL, the ‐455G>A variant of beta‐fibrinogen, and PAI‐1 4G were associated with a higher risk of developing RPL compared with the general population. Furthermore, FVL, FVR2, FII G20210A and MTHFR C677T conferred a significantly higher risk of RIF in women who performed ART compared with the general population. No statistical differences between the general population and other study groups were observed.ConclusionsSpecific prothrombotic genetic variants are more frequently expressed in women with RPL and RIF, supporting their role in the development of polimicrothrombosis and impairing the invasion during embryo implantation.

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“…Discordant results were reported so far on the role of such variants as risk factors for venous thrombosis, mainly because: i) heterogeneous criteria have been used so far to select the patients; ii) most studies pooled male and female patients and women are frequently underrepresented [10] thus obscuring eventual sex differences [7,11]; iii) some studies compared the frequency of prothrombotic gene variants in patients and controls of different geographical areas. Finally, as regards the clinical context, the ordering of tests for thrombophilia is strongly heterogeneous [12] and scarcerly respective of guidelines [13].…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of prothrombotic gene variants in venous thrombotic diseases. Different risk factors in different sex and clinical forms.

Cernera¹,

Amato²,

Elce³

et al. 2019

Preprint

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Background The role of prothrombotic gene variants as risk factors for venous thrombotic diseases is controversial and the ordering of tests for thrombophilia in the clinical context is scarcerly respective of evidence-based data. Methods We studied FVL, FVR2, FII G20210A, MTHFR C677T and A1298C, beta-fibrinogen -455 G>A, FXIII V34L, HPA-1 L33P variants and PAI-1 4G/5G alleles in: 343 patients with deep vein thrombosis (DVT), 164 with pulmonary embolism (PE), 126 with superficial vein thrombosis (SVT), 118 with portal vein thrombosis (PVT), 75 with cerebral vein thrombosis (CVT), 119 with retinal vein thrombosis (RVT) in comparison with 430 subjects from the general population (GP) of the same geographical area (Southern Italy). Results About 40% of patients with DVT, PE and SVT have a prothrombotic predisposition represented by FVL, FVR2 and FII G20210A variants (significantly more frequent than in the general population), significantly higher in PE males. While, in patients with PVT and CVT only FII G20210A variant is more frequent particularly in females. Finally, RVT is poorly related to prothrombotic risk factors, confirming that local vascular and other factors have a pivotal role in its pathogenesis. Conclusions Our data indicate that only FVL, FVR2 and FII G20210A are related to vein thrombotic diseases while all the other gene variants, frequently ordered in the clinical context, do not have a role as risk factors. Furthermore, the evidence of a sex difference for some variants, once confirmed in larger populations, may help to promote sex-specific prevention of such diseases.

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Thrombophilia testing. Useful or hype?

Cited by 6 publications

References 13 publications

Aging Hemostasis: Changes to Laboratory Markers of Hemostasis As We Age—A Narrative Review

Aging Hemostasis: Changes to Laboratory Markers of Hemostasis As We Age—A Narrative Review

The relevance of prothrombotic genetic variants in women who experienced pregnancy loss or embryo implantation failure: A retrospective analysis of 1922 cases

Molecular analysis of prothrombotic gene variants in venous thrombotic diseases. Different risk factors in different sex and clinical forms.

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