Skip to main content

Advertisement

SpringerLink
Log in

Fibrinogen depletion and intracerebral hemorrhage after thrombolysis for ischemic stroke: a meta-analysis

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Purpose

Intracerebral hemorrhage (ICH) can be a fatal complication of intravenous thrombolysis (IVT) for acute ischemic stroke. An early coagulopathy can develop after IVT, in relation to a significant fibrinogen depletion, increasing the risk of ICH. This systematic review and meta-analysis aimed at defining the role of fibrinogen depletion after IVT on the risk of ICH after IVT.

Methods

Protocol was registered with PROSPERO (CRD42020124241) and followed PRISMA and MOOSE guidelines. We systematically searched English studies reporting rates of post-IVT ICH depending on fibrinogen depletion until 7/1/2021. Primary outcome was symptomatic ICH (sICH). Meta-analysis followed random-effects model to account for heterogeneity in design and timing of ascertainments. Biases were assessed via the Newcastle–Ottawa Scale.

Results

Overall, among 352 records identified, 5 observational studies were eligible for quantitative synthesis (n = 2142), all of fair quality. Considering sICH within 24–36 h post-IVT, pooling data from 4 studies (n = 1753), fibrinogen depletion consistently increased the risk of sICH (OR 3.67, 95%CI 2.28–5.90, pheterogeneity = 0.55). Pooling adjusted estimated for age, gender, and NIHSS from 3 studies (n = 723), fibrinogen depletion was confirmed to significantly increase the risk of ICH after IVT (OR 5.41, 95%CI 2.96–9.89).

Conclusions

Fibrinogen depletion significantly increases the risk of ICH after IVT for acute ischemic stroke. Routine fibrinogen assessment might be considered to identify people at higher risk of ICH. As fibrinogen repletion is feasible, trials should investigate its efficacy in preventing ICH, potentially increasing the net benefit profile of IVT in acute ischemic stroke.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Data will be shared upon reasonable request from the corresponding author.

Code availability

Data will be shared upon reasonable request from the corresponding author.

References

  1. NINDS rtPA Study Group (1997) Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 28:2109–2118

    Article  Google Scholar 

  2. Hacke W, Kaste M, Fieschi C, Von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P (1998) Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 352:1245–1251

    Article  CAS  Google Scholar 

  3. Vandelli L, Marietta M, Trenti T, Varani M, Bigliardi G, Rosafio F, Dell’Acqua ML, Picchetto L, Nichelli P, Zini A (2019) Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment. Adv Clin Exp Med 28:219–222

    Article  Google Scholar 

  4. Schlemm L, Endres M, Werring DJ, Nolte CH (2020) Benefit of intravenous thrombolysis in acute ischemic stroke patients with high cerebral microbleed burden. Stroke 51:232–239

    Article  Google Scholar 

  5. Bagoly Z, Szegedi I, Kálmándi R, Tóth NK, Csiba L. Markers of coagulation and fibrinolysis predicting the outcome of acute ischemic stroke thrombolysis treatment: a review of the literature. Front Neurol 2019; 10.

  6. Trouillas P, Derex L, Philippeau F, Nighoghossian N, Honnorat J, Hanss M, Ffrench P, Adeleine P, Dechavanne M (2004) Early fibrinogen degradation coagulopathy is predictive of parenchymal hematomas in cerebral rt-PA thrombolysis: a study of 157 cases. Stroke 35:1323–1328

    Article  CAS  Google Scholar 

  7. Sun X, Berthiller J, Trouillas P, Derex L, Diallo L, Hanss M (2015) Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis. J Neurol Sci 351:109–14

    Article  CAS  Google Scholar 

  8. Matosevic B, Knoflach M, Werner P, Pechlaner R, Zangerle A, Ruecker M, Kirchmayr M, Willeit J, Kiechl S (2013) Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology 80:1216–1224

    Article  CAS  Google Scholar 

  9. Vandelli L, Marietta M, Gambini M, Cavazzuti M, Trenti T, Cenci MA, Casoni F, Bigliardi G, Pentore R, Nichelli P, Zini A (2015) Fibrinogen decrease after intravenous thrombolysis in ischemic stroke patients is a risk factor for intracerebral hemorrhage. J Stroke Cerebrovasc Dis 24:394–400

    Article  Google Scholar 

  10. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther 89:873–80

    Article  Google Scholar 

  11. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–12

    Article  CAS  Google Scholar 

  12. Romoli M, Paciaroni M, Tsivgoulis G, Agostoni EC, Vidale S. Mothership versus drip-and-ship model for mechanical thrombectomy in acute stroke: a systematic review and meta-analysis for clinical and radiological outcomes. J Stroke 2020; 22.

  13. Romoli M, Mosconi MG, Pierini P, Alberti A, Venti M, Caso V, Vidale S, Lotti EM, Longoni M, Calabresi P, Tsivgoulis G, Paciaroni M. Reperfusion strategies in stroke due to isolated cervical internal carotid artery occlusion: systematic review and treatment comparison. Neurol Sci 2020; .

  14. Viechtbauer W (2010) Conducting meta-analyses in R with the metafor. J Stat Softw 36:1–48

    Article  Google Scholar 

  15. Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  Google Scholar 

  16. Higgins JPT (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  Google Scholar 

  17. Yan S, Zhang X, Zhang R, Xu J, Lou M (2019) Early fibrinogen depletion and symptomatic intracranial hemorrhage after reperfusion therapy. Stroke 50:2716–2721

    Article  CAS  Google Scholar 

  18. Lee VH, Conners JJ, Cutting S, Song SY, Bernstein RA, Prabhakaran S (2014) Elevated international normalized ratio as a manifestation of post-thrombolytic coagulopathy in acute ischemic stroke. J Stroke Cerebrovasc Dis 23:2139–2144

    Article  Google Scholar 

  19. Barra ME, Feske SK, Sylvester KW, Ong C, Culbreth SE, Krause P, Henderson G V., Rybak E. Fibrinogen concentrate for the treatment of thrombolysis-associated hemorrhage in adult ischemic stroke patients. Clin Appl Thromb 2020; 26.

  20. Szabo S, Letsch R, Ehlers R, Walter T, Kazmaier S, Helber U, Hoffmeister HM (2002) Absence of paradoxical thrombin activation by fibrin-specific thrombolytics in acute myocardial infarction: comparison of single-bolus tenecteplase and front-loaded alteplase. Thromb Res 106:113–119

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. IRCCS Istituto delle Scienze Neurologiche di Bologna, Neurology and Stroke Center, Ospedale Maggiore, Bologna, Italy

    Michele Romoli & Andrea Zini

  2. Neurology Clinic, University of Perugia – S. Maria della Misericordia Hospital, Perugia, Italy

    Michele Romoli

  3. Neurology and Stroke Unit, “Maurizio Bufalini” Hospital, Cesena, Italy

    Michele Romoli

  4. Neurology and Stroke Unit, Gubbio-Gualdo Tadino Hospital, Gubbio, Italy

    David Giannandrea

Authors
  1. Michele Romoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Giannandrea
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Zini
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MR and DG performed systematic review and drafted the manuscript. MR completed statistical analysis. AZ critically reviewed the manuscript for scientific content.

Corresponding author

Correspondence to Michele Romoli.

Ethics declarations

Ethical approval

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (545 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Romoli, M., Giannandrea, D. & Zini, A. Fibrinogen depletion and intracerebral hemorrhage after thrombolysis for ischemic stroke: a meta-analysis. Neurol Sci 43, 1127–1134 (2022). https://doi.org/10.1007/s10072-021-05441-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-021-05441-6

Keywords

Search

Navigation