No abstract

Coagulopathy is a common phenomenon in traumatic brain injury (TBI) and a major contributor to a poor outcome. Thrombocytopenia is a strong negative prognostic factor in TBI, but bleeding tendency can be present even with a normal platelet count. We investigated platelet function in patients with TBI by means of modified thromboelastography (i.e., platelet mapping [TEG-PM]). Four groups were studied: (1) patients with severe isolated TBI (n = 20), (2) patients with general trauma without TBI (the ICU group, n = 10), (3) patients with chronic alcohol abuse (n = 7; as alcohol abuse is common in patients with TBI), and (4) healthy volunteers (n = 10). We measured platelet counts in venous blood (Plt), Ivy bleeding time, standard TEG parameters, and platelet responses to arachidonic acid (AA) and adenosindiphosphate (ADP), using TEG-PM. TBI patients had a lower Plt (180 +/- 68 x 10(9) ; mean +/- SD) and a longer bleeding time (674 +/- 230 sec) than healthy controls, (256 +/- 43 x 10(9), p < 0.01) and (320 +/- 95 sec, p < 0.005), respectively. TBI patients had dramatically lower platelet responses to AA (0-86%, mean 22%) compared to healthy controls (57-89%, mean 73%), the ICU group (4-75%, mean 49%), and the alcohol abusers (17-88%, mean 64%; p < 0.001). Responses to ADP did not differ significantly between the groups. Patients with low responsiveness to AA at admittance to the hospital were likely to develop bleeding complications later. Patients with TBI develop platelet dysfunction, which most likely contributes to bleeding complications. The observed platelet dysfunction appears to involve the cyclooxygenase pathway. TEG-PM analysis can be used to identify patients with a high risk of bleeding complications.

The potential pathophysiological role of circulating microparticles (MPs) has been recognized in various conditions, such as cardiovascular and thrombotic diseases. Traumatic brain injury (TBI) has a complex pathophysiology that involves coagulopathy and inflammation. We investigated endothelial-, platelet-, and leukocyte-derived microparticles (EMPs, PMPs, and LMPs, respectively) in 16 patients with severe isolated TBI. Arterial and cerebrovenous samples were taken repeatedly, during 1-72 h after injury. Subpopulations of MPs, exposing tissue factor (TF) and P-selection, were also studied. MP counts in cerebrovenous samples, irrespective of cellular origin, were higher in TBI cases, compared to healthy controls (peak levels of EMPs were approximately 7 times higher, PMPs 1.4 times higher, and LMPs 2 times higher, respectively; p<0.001 for all). MP counts declined sharply from high levels shortly after the trauma toward slightly elevated levels 72 h later. EMPs and PMPs exposing TF, as well as PMPs exposing P-selection, showed a transcranial gradient with higher concentration in cerebrovenous, compared to arterial, samples. In contrast, LMPs exposing TF were higher in arterial samples, suggesting accumulation of LMPs in the brain. We conclude that the pattern of circulating MPs is altered after TBI. PMPs exposing P-selection and EMPs exposing TF seem to be generated in the injured brain, whereas LMPs exposing TF are accumulated. The pathophysiological significance of these changes in MP pattern in TBI should be further investigated. Including MPs exposing brain-specific antigens in the assessment of brain injury would give further information of origin and likely give additional information of the size of the injury, given that the MP phenotypes investigated in the present study are not brain-specific markers.