Platelet reactivity in thromboelastometry. Revision of the FIBTEM test: a basic study.

This study aimed to investigate modifications to the FIBTEM test to better assess fibrinogen levels and the quality of fibrin polymerization in citrated blood using Multiplate impedance aggregometry to verify platelet inhibition. Blood samples from 26 healthy volunteers were subjected to thromboelastometry studies (EXTEM/FIBTEM tests) in accordance with the standard study protocol (cytochalasin D) and according to a modified protocol (synthetic IIbIIIa receptor antagonist vs. acetylsalicylic acid [ASA] + synthetic IIbIIIa receptor antagonist instead of cytochalasin D). Independent of thromboelastometry, Multiplate impedance aggregometry was used to assess the degree of restriction by the platelet blocked with the following treatments: (1) cytochalasin D, (2) synthetic IIbIIIa antagonist or (3) ASA + synthetic IIbIIIa antagonist to assess the aggregation response to activation with an agonist (ADP, collagen, thrombin receptor activating peptide-6 [TRAP-6], and arachidonic acid). Via aggregometry, cytochalasin D more weakly inhibited platelet aggregation than simultaneous administration of the -IIbIIIa receptor antagonist with ASA. However, total platelet aggregation inhibition was observed after simultaneous administration of cytochalasin D combined with a synthetic IIbIIIa receptor antagonist. In the thromboelastometry, a significant decrease of the A10, A20 and MCF parameters were observed in the EXTEM/FIBTEM tests after they were modified by the addition of a synthetic IIbIIIa receptor antagonist alone or in combination with ASA. In conclusion, in this Multiplate- and ROTEM-based laboratory approach, a two-way blockade (IIbIIIa-antagonist + cytochalasine D) was sufficient to completely inhibit procoagulant platelet function as observed by aggregometry and thromboelastometry.

Assessment of subclinical acute kidney injury after abdominal aortic aneurysm surgery using novel markers: L-FABP and H-FABP.

BACKGROUND: One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Even small rises in serum creatinine are associated with increased mortality. The aim of this study was to assess the dynamics of AKI after elective AAA surgery using novel markers. METHODS: The study group consisted of 22 patients with AAA. We measured urinary liver- (u-L-FABP) and heart-type fatty acid-binding proteins (u-H-FABP) before, during and within 3 days after surgery. RESULTS: We found an abrupt and significant elevation of both urine FABPs normalized to urinary creatinine; u-L-FABP reached its peak value 2 hours after aortic clamp release {137.79 (38.57-451.79) vs. 9.94 (6.82-12.42) ng/mg baseline value, p<0.05; values are medians (lower-upper quartile)}. The peak value of u-H-FABP was reported 72 hours after aortic clamp release {16.462 (4.182-37.595) vs. 0.141 (0.014-0.927) ng/mg baseline value, p<0.05}. The serum creatinine level did not changed significantly during the investigation period. CONCLUSIONS: The significant rise of both u-L-FABP and u-H-FABP after AAA surgery indicates renal proximal and distal tubule injury in this population. Our results suggest that, after AAA surgery, the distal tubules could be more affected than the proximal ones. u-FABPs could serve as sensitive biomarkers of kidney tubular injury and may allow to detect the very early phases of AKI.

Endothelium injury and inflammatory state during abdominal aortic aneurysm surgery: scrutinizing the very early and minute injurious effects using endothelial markers - a pilot study.

INTRODUCTION: One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Acute kidney injury is an inflammatory process whose pathogenesis involves endothelial cells (EC). The aim of this study was to assess the dynamics of endothelium injury markers measured during elective AAA surgery which might confirm the inflammatory character of AKI. MATERIAL AND METHODS: The study group consisted of 14 patients with AAA. We measured plasma soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin as well as the levels of von Willebrand factor (vWF) before, during (including intra-abdominal vein levels before and after aortic clamp removal) and within 2 days after surgery. RESULTS: We have found a biphasic response of ICAM-1, VCAM-1 and P-selectin with an initial fall and subsequent rise. However, only VCAM-1 changes were significant compared to its baseline value. The maximum decrease of VCAM-1 was observed in the renal vein 5 min after aortic clamp removal (335.42 ±129.63 ng/ml vs. 488.90 ±169.80 ng/ml baseline value, p < 0.05), and the highest rise 48 h after aortic clamp removal (721.46 ±333.99 vs. baseline, p < 0.05). CONCLUSIONS: Vascular cell adhesion molecule-1 turned out to be the most sensitive indicator of EC injury and inflammatory status after AAA surgery. During AAA surgery, soluble forms of P-selectin, ICAM-1 and VCAM-1 demonstrate a biphasic response with an initial fall and subsequent rise. These soluble forms could have a modulatory effect on the development of inflammation.

Acute kidney injury after abdominal aortic aneurysm surgery: detailed assessment of early effects using novel markers.

INTRODUCTION:  One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Even small rises in serum creatinine after surgery are associated with increased mortality. OBJECTIVES:  The aim of the study was to assess the dynamics of AKI after elective AAA surgery using novel markers. PATIENTS AND METHODS:  The study group consisted of 14 patients with AAA. We measured serum neutrophil gelatinase­associated lipocalin (NGAL) before, during (including intra­abdominal vein levels before and after removal of aortic clamp), and within 2 days after surgery.  Moreover, we assessed urinary NGAL, interleukin 18 (IL­18), and liver­type fatty acid­binding protein (L­FABP) before, during, and within 3 days after surgery. RESULTS:  We observed a marked but nonsignificant increase in serum NGAL directly after clamp removal (75.21 ±55.83 vs. 46.37 ±21.60 ng/ml baseline value, P >0.05) and significantly elevated plasma NGAL at 2 hours (91.54 ±76.54 vs. baseline, P <0.05), 12 hours (100.78 ±44.92 vs. baseline, P <0.05) and 24 hours (89.46 ±94.18 vs. baseline, P <0.05) after clamp release. There was also significant elevation of urinary IL­18 at 2 hours (51.60 [12.12-527.16] vs. 25.99 [9.34-187.80] pg/ml at baseline, P <0.05); L­FABP at 2 hours (47.10 [5.40-500.00] vs. 5.50 (2.20-27.20) ng/ml at baseline, P <0.05) and 12 hours (39.00 [5.20-500.00] vs. baseline, P <0.05); NGAL at 12 hours (20.75 [5.00-176.10] vs. 5.85 [1.40-16.00] ng/ml at baseline, P <0.05) and 24 hours (13.95 [3.90-163.30] vs. baseline, P <0.05) after clamp release. CONCLUSIONS:  Elective AAA surgery may induce AKI. Novel markers can facilitate early detection of AKI, thus allowing to start therapy at an appropriate time point.