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

Neurol Sci. 2022 Feb;43(2):1127-1134. doi: 10.1007/s10072-021-05441-6. Epub 2021 Jul 2.

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.

Keywords: Fibrinogen; Hemorrhage; Stroke; Thrombolytic therapy.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Brain Ischemia* / complications
  • Brain Ischemia* / drug therapy
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / drug therapy
  • Fibrinogen
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Ischemic Stroke*
  • Stroke* / complications
  • Stroke* / drug therapy
  • Thrombolytic Therapy / adverse effects
  • Tissue Plasminogen Activator / therapeutic use
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Fibrinogen
  • Tissue Plasminogen Activator