Platelet Dysfunction Is Commonly Detected in Patients with Acute Intracerebral Hemorrhage

Introduction: The role of platelet dysfunction and other hemostatic functions in Intracerebral hemorrhage (ICH) have not yet been clearly defined. Improving patient outcomes who present with ICH depends on our understanding of platelet function and hemostatic mechanisms to limit ICH hematoma expansion (HE). We hypothesize that changes in platelet function, coagulation and fibrinolytic system activation will reveal important biomarkers for the progress of HE, and lead to targeted interventions to improve patient outcomes. We performed platelet function, coagulation and fibrinolysis assays to determine hemostatic mechanisms occurring in patients presenting with ICH.

Methods: Platelet function is measured in patients with acute ICH by Thromboelastography (TEG) and Thromboelastometry (ROTEM) viscoelastic assays (VEA) and by platelet function analyzer PFA-100®, and VerifyNow® Aspirin and P₂Y₁₂ point-of-care (POC) assays within the first 12 hours of symptom onset and at 24 hours. Coagulation activation is measured by Thrombin Generation Assay (TGA) and Tissue Factor activity at same time points. Plasmin/antiplasmin (PAP) complex, Fibrinogen, D-Dimer and PAI-1 antigen and activity assays are used to simultaneously assess fibrinolysis activity.

Results: Thirty-eight patients who presented with acute ICH and hypertension were consented. Platelet dysfunction with inhibited ADP-induced aggregation early after symptom onset was shown by TEG platelet mapping in 21/35 patients (60%), with mean inhibition of 34.5% (range 4.0 - 96.5%). At 24 hours, platelet ADP-induced aggregation was inhibited in 16/31 (51.6%) of patients. VerifyNow detected aspirin-effect on platelet function in 20 of 36 patients (56%) at admission and 10 of 25 patients at 24 hours post-admission. The VerifyNow P2Y12 assay detected ADP receptor inhibition in 9/36 patients (25%) at admission and 0/25 patients at 24 hours. The number and percent of patients with platelet dysfunction decreased at 24 hours (see Table). In contrast, the platelet function analyzer (PFA-100) detected platelet dysfunction in 8/33 patients (24%) on admission and 3/24 patients (12.5%) at 24 hours. Viscoelastic tests detected increased fibrinolysis in 4/34 patients (11.7%) on admission which reduced to 2/24 (8.3%) at 24 hours. Thirteen of 31 patients (42%) tested had elevated D-dimer, mean 553 ng/mL D-DU (range 150 to 3205) while fibrinogen levels were in the normal range. Increased Tissue Factor expression and fibrinolysis markers (tPA, PAI-1 and plasmin antiplasmin complex (PAP)) were also found in the ICH group when compared with healthy controls. Overall, platelet dysfunction was the most common finding, detected in 34/38 (89%) of patients presenting with ICH while increased fibrinolysis and elevated D-dimer levels were seen in fewer patients presenting with ICH.

Conclusions: Platelet dysfunction is very commonly detected in patients presenting with acute ICH using TEG platelet mapping and POC testing. Coagulation activation, elevated D-dimers and increased fibrinolysis were detected less frequently. Platelet dysfunction, and hemostasis parameters are investigated and discussed as potential biomarkers for ICH hematoma expansion.

No relevant conflicts of interest to declare.