Testing for Thrombophilia in Young Cryptogenic Stroke Patients: Does the Presence of Patent Foramen Ovale Make a Difference?
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Hart, R.G.; Diener, H.-C.; Coutts, S.B.; Easton, J.D.; Granger, C.B.; O’Donnell, M.J.; Sacco, R.L.; Connolly, S.J.; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: The case for a new clinical construct. Lancet Neurol. 2014, 13, 429–438. [Google Scholar] [CrossRef]
- Overell, J.R.; Bone, I.; Lees, K.R. Interatrial septal abnormalities and stroke: A meta-analysis of case-control studies. Neurology 2000, 55, 1172–1179. [Google Scholar] [CrossRef] [PubMed]
- Koutroulou, I.; Tsivgoulis, G.; Tsalikakis, D.; Karacostas, D.; Grigoriadis, N.; Karapanayiotides, T. Epidemiology of Patent Foramen Ovale in General Population and in Stroke Patients: A Narrative Review. Front. Neurol. 2020, 11, 281. [Google Scholar] [CrossRef] [PubMed]
- Pristipino, C.; Sievert, H.; D’Ascenzo, F.; Mas, J.L.; Meier, B.; Scacciatella, P.; Hildick-Smith, D.; Gaita, F.; Toni, D.; Kyrle, P.; et al. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. Eur. Heart J. 2019, 40, 3182–3195. [Google Scholar] [CrossRef] [PubMed]
- Mas, J.-L.; Derex, L.; Guérin, P.; Guillon, B.; Habib, G.; Juliard, J.-M.; Marijon, E.; Massardier, E.; Meneveau, N.; Vuillier, F. Transcatheter closure of patent foramen ovale to prevent stroke recurrence in patients with otherwise unexplained ischaemic stroke: Expert consensus of the French Neurovascular Society and the French Society of Cardiology. Arch. Cardiovasc. Dis. 2019, 112, 532–542. [Google Scholar] [CrossRef] [PubMed]
- Messé, S.R.; Gronseth, G.S.; Kent, D.M.; Kizer, J.R.; Homma, S.; Rosterman, L.; Carroll, J.D.; Ishida, K.; Sangha, N.; Kasner, S.E. Practice advisory update summary: Patent foramen ovale and secondary stroke prevention: Report of the Guideline Subcommittee of the American Academy of Neurology. Neurology 2020, 94, 876–885. [Google Scholar] [CrossRef] [PubMed]
- Morris, J.G.; Singh, S.; Fisher, M. Testing for inherited thrombophilias in arterial stroke: Can it cause more harm than good? Stroke 2010, 41, 2985–2990. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kleindorfer, D.O.; Towfighi, A.; Chaturvedi, S.; Cockroft, K.M.; Gutierrez, J.; Lombardi-Hill, D.; Kamel, H.; Kernan, W.N.; Kittner, S.J.; Leira, E.C.; et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke 2021, 52, e364–e467. [Google Scholar] [CrossRef] [PubMed]
- Ridker, P.M.; Miletich, J.P.; Hennekens, C.H.; Buring, J.E. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 1997, 277, 1305–1307. [Google Scholar] [CrossRef] [PubMed]
- Carroll, B.J.; Piazza, G. Hypercoagulable states in arterial and venous thrombosis: When, how, and who to test? Vasc. Med. 2018, 23, 388–399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Den Heijer, M.; Koster, T.; Blom, H.J.; Bos, G.M.; Briët, E.; Reitsma, P.H.; Vandenbroucke, J.P.; Rosendaal, F.R. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N. Engl. J. Med. 1996, 334, 759–762. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sofi, F.; Marcucci, R.; Abbate, R.; Gensini, G.F.; Prisco, D. Lipoprotein (a) and Venous Thromboembolism in Adults: A Meta-Analysis. Am. J. Med. 2007, 120, 728–733. [Google Scholar] [CrossRef] [PubMed]
- Connors, J.M. Thrombophilia Testing and Venous Thrombosis. N. Engl. J. Med. 2017, 377, 1177–1187. [Google Scholar] [CrossRef] [PubMed]
- Chiasakul, T.; De Jesus, E.; Tong, J.; Chen, Y.; Crowther, M.; Garcia, D.; Chai-Adisaksopha, C.; Messé, S.R.; Cuker, A. Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis. J. Am. Heart Assoc. 2019, 8, e012877. [Google Scholar] [CrossRef] [PubMed]
- Jauss, M.; Zanette, E. Detection of Right-to-Left Shunt with Ultrasound Contrast Agent and Transcranial Doppler Sonography. Cerebrovasc. Dis. 2000, 10, 490–496. [Google Scholar] [CrossRef] [PubMed]
- Den Heijer, M.; Rosendaal, F.R.; Blom, H.J.; Gerrits, W.B.; Bos, G.M. Hyperhomocysteinemia and venous thrombosis: A meta-analysis. Thromb. Haemost. 1998, 80, 874–877. [Google Scholar] [CrossRef] [PubMed]
- Toole, J.F.; Malinow, M.R.; Chambless, L.E.; Spence, J.D.; Pettigrew, L.C.; Howard, V.J.; Sides, E.G.; Wang, C.-H.; Stampfer, M. Lowering homocysteine in patients with ischemic stroke to recurrent stroke, myocardial infarction, and death: The vitamin intervention for stroke prevention (VISP) randomized controlled trial. JAMA 2004, 291, 565–575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rose, D.; Kasner, S. Forge AHEAD with stricter criteria in future trials of embolic stroke of undetermined source. Neural Regen. Res. 2022, 17, 1009. [Google Scholar] [CrossRef] [PubMed]
Laboratory Test | Number of Patients Tested, n (%) | Thrombophilia Diagnosis, n |
---|---|---|
Antiphospholipid antibodies | 154 (95.7%) | 6 ** |
Homocysteine | 139 (86.3%) | 43 *** |
Factor V Leiden mutation | 131 (81.4%) | 2 **** |
Prothrombin mutation * | 131 (81.4%) | 3 **** |
Factor VIII activity | 122 (75.8%) | 4 |
Antithrombin | 121 (75.2%) | - |
Protein C | 116 (72.1%) | 1 |
Protein S | 113 (70.2%) | 1 |
Lipoprotein a | 49 (30.4%) | 4 |
APS (+), n = 6 | APS (-) | p | PTM or FVL (+), n = 5 | PTM or FVL (-) | p | HHcy (+), n = 43 | HHcy (-) | p | MTHFR (+), n = 21 | MTHFR (-) | p | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Positive personal history of thrombosis | 4 (66.7%) | 33 (21.3%) | 0.025 | 1 (20%) | 30 (19.2%) | 1 | 6 (14.0%) | 31 (26.3%) | 0.100 | 3 (14.3%) | 34 (24.3%) | 0.411 |
Positive family history of thrombosis | 2 (33.3%) | 23 (14.7%) | 0.234 | 2 (40%) | 23 (14.7%) | 0.172 | 6 (14.0%) | 19 (16.1%) | 0.739 | 3 (14.3%) | 22 (15.7%) | 1 |
Positive personal or family history of thrombosis | 4 (66.7%) | 51 (32.9%) | 0.182 | 3 (60%) | 52 (33.3%) | 0.339 | 12 (27.9%) | 43 (36.4%) | 0.352 | 6 (28.6%) | 49 (35.0%) | 0.630 |
Thrombophilia | Shunt (-) | Shunt (+) | p | Shunt at Rest (-) | Shunt at Rest (+) | p |
---|---|---|---|---|---|---|
Increased activity of FVIII | 2 | 2 | 0.281 | 2 | 2 | 1 |
Prothrombin mutation | 2 | 1 | 0.165 | 3 | 0 | 0.101 |
Leiden V mutation | 2 | 0 | 0.066 | 2 | 0 | 0.218 |
Protein C deficit | 0 | 1 | 1 | 1 | 0 | 0.400 |
Protein S deficit | 0 | 1 | 1 | 0 | 1 | 1 |
Total | 6 | 5 | 0.092 | 8 | 3 | 0.140 |
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Jokubaitis, M.; Mineikytė, R.; Kryžauskaitė, L.; Gumbienė, L.; Kaplerienė, L.; Andruškevičius, S.; Ryliškienė, K. Testing for Thrombophilia in Young Cryptogenic Stroke Patients: Does the Presence of Patent Foramen Ovale Make a Difference? Medicina 2022, 58, 1056. https://doi.org/10.3390/medicina58081056
Jokubaitis M, Mineikytė R, Kryžauskaitė L, Gumbienė L, Kaplerienė L, Andruškevičius S, Ryliškienė K. Testing for Thrombophilia in Young Cryptogenic Stroke Patients: Does the Presence of Patent Foramen Ovale Make a Difference? Medicina. 2022; 58(8):1056. https://doi.org/10.3390/medicina58081056
Chicago/Turabian StyleJokubaitis, Mantas, Rūta Mineikytė, Lina Kryžauskaitė, Lina Gumbienė, Lina Kaplerienė, Saulius Andruškevičius, and Kristina Ryliškienė. 2022. "Testing for Thrombophilia in Young Cryptogenic Stroke Patients: Does the Presence of Patent Foramen Ovale Make a Difference?" Medicina 58, no. 8: 1056. https://doi.org/10.3390/medicina58081056