Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA

Neurology. 2019 Aug 27;93(9):e851-e863. doi: 10.1212/WNL.0000000000007997. Epub 2019 Jul 31.

Abstract

Objective: To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.

Methods: We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.

Results: Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10-6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10-4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009).

Conclusion: The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / epidemiology*
  • Factor XII / genetics
  • Female
  • Finland / epidemiology
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests*
  • Retrospective Studies
  • Risk Factors
  • Spain / epidemiology
  • Stroke / drug therapy
  • Thrombectomy / adverse effects
  • Thrombectomy / statistics & numerical data
  • Thrombolytic Therapy / adverse effects
  • Time Factors
  • Tissue Plasminogen Activator / adverse effects*
  • Tissue Plasminogen Activator / therapeutic use
  • alpha-Macroglobulins / genetics

Substances

  • A2M protein, human
  • alpha-Macroglobulins
  • Factor XII
  • Tissue Plasminogen Activator