D-dimer predicts outcome after aneurysmal subarachnoid hemorrhage: no effect of thromboprophylaxis on coagulation activity.
OBJECTIVE
Approximately one-third of all patients with acute nontraumatic subarachnoid hemorrhage (SAH) experience complications owing to delayed ischemic deficit. We reported recently that enoxaparin 40 mg once daily for 10 days seems safe and demonstrates thromboprophylactic efficacy, but it failed to improve outcome in a randomized SAH trial. In the present study, we assessed hemostatic variables associated with clinical status and outcome of SAH. We also monitored the effect of enoxaparin on activation of coagulation and fibrinolysis after closure of the ruptured aneurysm.


METHODS
Blood samples to measure activation of coagulation and fibrinolysis were collected from 42 patients participating in the enoxaparin trial for acute aneurysmal SAH at four time points: 1) at hospital admission; 2) 12 to 24 hours after aneurysm surgery but before initiation of enoxaparin therapy; 3) 3 hours after the first dose; and 4) at the conclusion of treatment.


RESULTS
At admission, several variables of coagulation and fibrinolysis were elevated and correlated well with clinical status. Specifically, D-dimer levels at all four time points correlated with patients' long-term outcomes. A single dose of enoxaparin suppressed early coagulation activity, but thrombin generation was not inhibited during thromboprophylaxis. However, PAI-1 activity was suppressed.


CONCLUSIONS
D-dimer offers a useful laboratory tool for assessing early and late clinical severity of SAH. A thromboprophylactic dose of enoxaparin inhibited PAI-1 activity but failed to down-regulate coagulation activity and D-dimer. These findings are compatible with the lack of efficacy of enoxaparin in reducing ischemic deficit after SAH.
Wihuri Research Institute, Department of Hematology, Helsinki University Central Hospital, Helsinki, Finland.
Sorella
S
Ilveskero
Seppo
S
Juvela
Jari
J
Siironen
Riitta
R
Lassila
D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000379:methods; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000627:therapeutic use; D011237:Predictive Value of Tests; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; C036309:fibrin fragment D