4.7 Article

Factors Affecting Clot Lysis Rates in Patients With Spontaneous Intraventricular Hemorrhage

Journal

STROKE
Volume 43, Issue 5, Pages 1234-+

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.111.641050

Keywords

acute care; critical care; drug trials; intracerebral hemorrhage; neurocritical care; randomized controlled trials; thrombolysis; treatment

Funding

  1. Eleanor Naylor Dana Fellowship
  2. American Academy of Neurology
  3. Office of Orphan Products Development, Food and Drug Administration [FD-R-001693, FD-R 002018]
  4. National Institutes of Health/National Institute of Neurological Disorders and Stroke [U01NS062851, RO1NS046309]
  5. Jeffry and Harriet Legum Endowment
  6. France Merrick Foundation
  7. Genentech, Inc.

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Background and Purpose-In the treatment of severe intraventricular hemorrhage (IVH), thrombolytic use and clot size are known to influence clot lysis rates. We evaluated the effect of other variables on IVH clot lysis rates among patients treated with recombinant tissue-type plasminogen activator or placebo. Methods-One hundred patients with IVH and intracerebral hemorrhage volume < 30 mL requiring emergency external ventricular drainage from 2 multicenter trials were treated with intraventricular administration of recombinant tissue-type plasminogen activator (n=78; 53 males, 25 females) or placebo (n=22; 7 males, 15 females). IVH volume was quantified daily by head CT. A segmented linear regression using an optimized spline knot for each patient was fit. Random effects linear regression was used to estimate the effect of prespecified patient characteristics on clot lysis rates over the first 6 days. Results-Stability IVH volumes were larger in males (N=60; 54 +/- 5 mL) than females (N=40; 36 +/- 5 mL; P=0.01). Intraventricular thrombolytic treatment was associated with an increase in clot lysis rate of 14.6% of stability IVH volume/day before the spline knot compared with the placebo group (P < 0.001). After adjustment for thrombolytic, higher baseline serum plasminogen and lower baseline platelet count were independently associated with an increase in clot lysis of 1.28%/day per 10-g/dL increase (P < 0.001) and 0.70% /day per 10x10(3)/uL decrease (P < 0.001) before the knot, respectively. Conclusions-Although thrombolysis remains the major determinant of IVH clot lysis rate, higher baseline serum plasminogen and lower platelet count also predict faster clot lysis. Further studies are needed to confirm whether plasminogen availability and thrombus structure impact IVH clot removal. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT00650858. (Stroke. 2012; 43:1234-1239.)

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