Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients - a retrospective study.

BACKGROUND: Fibrinogen-based clot firmness is reported as the maximum amplitude (MA) when using the citrated functional fibrinogen (CFF) assay in thrombelastography (TEG), and as the maximum clot firmness (MCF) together with several clot amplitude parameters when using the FIBTEM assay in thromboelastometry (ROTEM). Concern is currently being raised that these two tests have different platelet inhibiting performance and consequently provide different values. This is relevant for the clinical setting of fibrinogen replacement. We aim herein to compare the parameters of these two fibrinogen-based clot quality tests and their correlation with the plasma fibrinogen level as determined by the Clauss method. METHODS: In total 261 whole blood samples taken from 163 clinical routine surgical patients were analyzed with TEG 5000 and ROTEM tests, and correlation with Clauss fibrinogen level was assessed. RESULTS: Using TEG, the overall fibrin-based clot firmness measured in the CFF assay was significantly higher than the MCF measured by FIBTEM assay. Both assays showed significantly positive correlations with the fibrinogen levels measured using the Clauss method. However, individual values of Clauss fibrinogen concentration corresponded with different values for the two viscoelastometric tests; e.g. within the range of 1.9-2.1 g/L Clauss fibrinogen the median of CFF MA was 16.3 mm whereas FIBTEM MCF was 12.0 mm. CONCLUSIONS: We showed herein by measurements of citrated whole blood samples from surgical patients that CFF MA values were different from FIBTEM MCF values measured in the same sample. Awareness that these whole blood assays provide different clot amplitude results is mandatory, particularly if they are being considered as tools for guiding fibrinogen supplementation. Thromboembolic side effects caused by a potentially too high fibrinogen substitution must also kept in mind in this context.

The effect of intracerebroventricular application of the caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after global cerebral ischaemia due to cardiac arrest in rats.

BACKGROUND: Global cerebral ischaemia after cardiac arrest (CA) leads to programmed cell death (PCD) with characteristic signs of apoptosis in selectively vulnerable areas of the brain. The activation of caspase-3, an executioner caspase, plays a key role in the apoptotic cascade. We, therefore, studied the effects of the application of the specific caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after experimental CA in rats. METHODS: A 6-min CA was induced in anaesthetised and mechanically ventilated male Wistar rats. After cardiopulmonary resuscitation (CPR) and restoration of spontaneous circulation (ROSC) the animals were randomised to two groups to receive a continuous intracerebroventricular (i.c.v.) infusion for 7 days of zDEVD-FMK or placebo (artificial cerebrospinal fluid, CSF). At 24h, 3 and 7 days after ROSC, animals were tested according to a neurological deficit score (NDS). Seven days after ROSC, coronal sections of the brain were taken at the dorsal hippocampal level and analysed with cresyl-violet staining, the TUNEL technique and a caspase activity assay. Viable and TUNEL-positive neurons were counted in the hippocampal CA-1 sector. RESULTS: The NDS demonstrated severe deficits 1 and 3 days after ROSC, which resolved by 7 days with no difference between the two groups. At 7 days after ROSC neuronal death could be detected using cresyl-violet and TUNEL staining with no difference between the groups. CONCLUSION: We conclude that zDEVD-FMK administration has no effect on neurological outcome and PCD after global cerebral ischaemia following CA in rats. Other mechanisms or pathways must be identified in the pathophysiology of PCD after CA.

Improved resuscitation after cardiac arrest in rats expressing the baculovirus caspase inhibitor protein p35 in central neurons.

BACKGROUND: Global cerebral ischemia is associated with delayed neuronal death. Given the role of caspases in apoptosis, caspase inhibitors may provide neuronal protection after cardiac arrest. To this end, the authors generated a transgenic rat line expressing baculovirus p35, a broad-spectrum caspase inhibitor, in central neurons. Its effects were evaluated on neuronal cell death and outcome after global cerebral ischemia. METHODS: Global cerebral ischemia was induced by cardiocirculatory arrest. After 6 min, animals were resuscitated by controlled ventilation, extrathoracic cardiac massage, epinephrine, and electrical countershocks. Neuronal death was assessed after 7 days by histologic evaluation of the hippocampal cornu ammonis 1 sector. Postischemic outcome was assessed by determination of overall survival and according to neurologic deficit scores 24 h, 3 days, and 7 days after resuscitation. RESULTS: The rate of 7-day survival after cardiac arrest for the transgenic rats (85%) was significantly higher than that for the nontransgenic controls (52%; P < 0.05). However, no differences were observed either in the number of terminal deoxynucleotidyltransferase-mediated d-uracil triphosphate-biotin nick end-labeling-positive cells or viable neurons in the cornu ammonis 1 sector or in the neurologic deficit score when comparing surviving transgenic and nontransgenic rats. These findings suggest that neuronal apoptosis after cardiac arrest is not primarily initiated by activation of caspases. CONCLUSION: Expression of baculovirus p35 can improve survival after cardiac arrest in rats, but the mode and site of action remain to be elucidated.