Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke

Abstract

Objective: Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke.

Approach and results: We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro. The main finding is that clot contraction from the blood of stroke patients was reduced compared with healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis, and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke pathogenesis suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke.

Conclusions: The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction need further exploration.

Keywords: blood coagulation; clot retraction; stroke; thrombosis.

Figure 1. Optical tracking system used for measurements of clot contraction

(A) Depicts the optical analyzer (side view) used to measure light scattering during the process of clot contraction. (B) The changes in relative clot size are converted into a kinetic curve that can be analyzed for (a) the extent of clot contraction at 20 minutes, (b) the lag time or the time to 5% contraction, and (c) the area over the curve (AOC) that characterizes the entire process of clot contraction and integrates the extent and rate of contraction and the lag time. Optical tracking was used to assess differences in between healthy subjects and stroke patients (A) extent of clot contraction, (B) average velocity of contraction, (C) AOC and (D) lag time. Parameters for healthy subjects and stroke patients were compared using an unpaired, two-tailed Student’s t-test. ****P<0.0001.

Figure 2. Averaged kinetic clot contraction curves obtained in the blood of stroke patients (n=85) and healthy subjects (n=79)

Optical tracking was used to measure the relative changes in clot size over 20 minutes with 15-second intervals. Data is represent at mean ± SEM.

Figure 3. Clot contraction parameters in the blood of two groups of ischemic stroke patients segregated based on the NIH Stroke Score values: <15 (minor to moderate stroke) and >15 (severe stroke)

Optical tracking was used to assess differences in (A) extent of clot contraction, (B) average velocity of contraction, (C) AOC and (D) lag time. Parameters for stroke patients were compared using an unpaired, two-tailed Student’s t-test. *P<0.05, **P<0.01

Figure 4. Clot contraction parameters in the blood of patients of clinical subpopulations of ischemic stroke as defined by TOAST

The extent of clot contraction is reduced in patients with cardioembolic type strokes (n=33) compared to atherothrombotic type strokes (n=45). *P<0.05