Endothelial markers are associated with thrombolysis resistance in acute stroke patients.
OBJECTIVE
The endothelium is crucial in maintaining the haemostatic balance between pro- and anti-thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke (AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt-PA).


METHODS
Sixty-four AIS patients treated with rt-PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble endothelial protein C receptor (sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0-2 at 90 days.


RESULTS
Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml, P = 0.008; median sEPCR, 78 vs. 114 ng/ml, P = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome.


CONCLUSIONS
Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt-PA thrombolysis who could benefit from a modified recanalization therapy.
INSERM U698, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Hematology, Bichat-Claude Bernard Hospital, AP-HP, Paris, France.
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D
Faille
J
J
Labreuche
E
E
Meseguer
M-G
MG
Huisse
N
N
Ajzenberg
M
M
Mazighi
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood*; D002408:Catheters, Indwelling; D002533:Cerebral Angiography; D000074283:Endothelial Protein C Receptor; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D020521:Stroke / Q000188:drug therapy*; D018180:Thrombomodulin / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism*
D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D005343:Fibrinolytic Agents; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator
endothelial markers; ischaemic stroke; recanalization; thrombolysis