Factors affecting clot lysis rates in patients with spontaneous intraventricular hemorrhage

Abstract

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 10×10(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: https://ichgcp.net/clinical-trials-registry/NCT00650858" title="See in ClinicalTrials.gov">NCT00650858.

Conflict of interest statement

Conflicts of Interest/Disclosures

Dr. Hanley has received research support as PI of the CLEAR IVH trial.

Figures

Figure 1:

IVH Clot volume remaining over time as a percentage of stability CT clot volume in one rt-PA treated patient, showing the initial designation of the spline knot for this patient.

Figure 2:

Estimated IVH clot volume remaining over time as a percentage of stability CT clot volume for placebo and rtPA patients by quartile of baseline serum plasminogen level.