Coagulation abnormalities associated with severe isolated traumatic brain injury: cerebral arterio-venous differences in coagulation and inflammatory markers.
Although coagulopathy is known to be the major contributor to a poor outcome of traumatic brain injury (TBI), the mechanisms that trigger coagulation abnormalities have not been studied in detail. We undertook a prospective observational study at a neurosurgical ICU (NICU) in a university hospital. We examined 11 patients with severe isolated TBI, at admittance to the hospital and during the next 3 days. We collected cerebrovenous blood samples from a jugular bulb catheter, arterial blood, and cerebrospinal fluid (CSF) samples. We measured concentrations of thrombin-antithrombin complex (TAT), fibrin D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), interleukin-6 (IL-6), and complement complex (C5b-9). All patients had some degree of consumption coagulopathy at the study start and a tendency to thrombocytopenia during the next few days. Levels of DD (3.6 +/- 2.7 mg/L), TAT (86 +/- 72 microg/L) and F1 + 2 (5.9 +/- 6.8 nmol/L) were significantly increased shortly after the trauma compared to reference values, with considerable transcranial gradients for TAT (49 microg/L) and F1 + 2 (3.2 nmol/L). Compared to controls, IL-6 levels were increased more than a hundredfold in both blood (283 +/- 192 ng/L) and CSF (424 +/- 355 ng/L) samples, with a transcranial gradient at the study start (107 ng/L). C5b-9 levels were moderately increased in blood samples, 270 +/- 114 microg/L, versus controls, 184 +/- 39 (p < 0.05). We conclude that activation of the coagulation system takes place during the passage of blood through the damaged brain, and is already evident hours after the trauma. IL-6 and activation of the complement system (C5b-9) co-vary with hemostatic parameters in TBI patients.
Nekludov
Michael
M
Department of Anesthesiology and Intensive Care, Karolinska University Hospital and Institutet, 17176 Stockholm, Sweden. michael.nekludov@karolinska.se
Antovic
Jovan
J
Bredbacka
Sixteen
S
Blombäck
Margareta
M
D000059:Accidents; D000328:Adult; D000991:Antithrombins / Q000737:chemistry; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000209:etiology*; D001780:Blood Coagulation Tests; D001930:Brain Injuries / Q000097:blood* / Q000150:complications*; D015938:Complement Membrane Attack Complex / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D015600:Glasgow Coma Scale; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D011516:Prothrombin; D013917:Thrombin / Q000737:chemistry
D000991:Antithrombins; D015415:Biomarkers; D015938:Complement Membrane Attack Complex; D015850:Interleukin-6; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D005337:Fibrin; D013917:Thrombin