Activation of Blood Coagulation After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Trial of Rotational Thromboelastometry.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) has been reported to actuate blood coagulation. Rotational thromboelastometry (ROTEM) is a dynamic hemostatic test that can differentiate various coagulation abnormalities. For example, increased coagulation activity can be detected as a wider amplitude of tracing (maximal clot firmness [MCF]). ROTEM had not been used to evaluate coagulation changes after aSAH. We evaluated the on-going coagulation process in patients with aSAH in a prospective, observational study to compare their ROTEM assay results with the control values obtained from patients undergoing clipping of nonruptured aneurysms. METHODS: ROTEM analyses were performed at 12, 24, 48, and 72 hours after the onset of aSAH and compared with the preoperative analyses from the control group. A total of 17 patients with aSAH treated in the intensive care unit and 16 control patients were enrolled. RESULTS: At 72 hours, EXTEM-MCF was significantly greater in patients with aSAH compared with the baseline values of the control group (68.0 mm [interquartile range (IQR), 66.0-71.0] versus 64.5 mm [IQR, 59.5-66.8]; P = 0.024). This was mainly due to increased fibrin formation and fibrin polymerization. The same comparison in the FIBTEM-MCF analysis yielded similar results (aSAH group, 23.0 mm [IQR, 19.0-25.0] vs. control group, 15.4 mm [IQR, 12.5-17.8], respectively; P = 0.001). CONCLUSIONS: Blood coagulation is activated at 72 hours after aSAH onset, which can be detected by ROTEM EXTEM-MCF analysis. Also, the FIBTEM-MCF was elevated, implying that the relative contribution of fibrin formation and fibrin polymerization is essential.

Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting.

In a previous study, preoperative levels of activated protein C (APC) were associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the cofactor of activated protein C, has activated protein C-independent anticoagulant activity and cytoprotective effects. Therefore, the objective of this study was to test whether preoperative, baseline levels of either thrombin or protein S were associated with hemodynamic performance or markers of myocardial damage after CABG. One hundred patients undergoing elective on-pump CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin generation) and free protein S were measured preoperatively and cardiac index, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were measured serially thereafter at fixed time points. Cardiac biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse correlation between preoperative F1+2 and free protein S levels (r= -0.30, p=0.003). High preoperative F1+2 and low preoperative protein S levels were associated with a less favorable hemodynamic profile postoperatively. Patients with F1+2 in the highest decile (≥0.85 nmol/l) and patients with preoperative protein S in the lowest decile (≤63%) had lower CI values, and higher pulmonary and systemic vascular resistance index values postoperatively than comparison patients. Preoperative F1+2 or protein S did not correlate with postoperative cardiac biomarker levels. Baseline activation of coagulation and the balance between pro-coagulant and anti-coagulant factors preoperatively might have implications for postoperative hemodynamic recovery after CABG.

Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery.

BACKGROUND AND AIMS: The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer's acetate on cardiac and stroke volume index after cardiac surgery. MATERIAL AND METHODS: Three consecutive boluses (each 7 mL·kg(-1)) of either 6% HES 130/0.4, 4% gelatine, or Ringer's acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg(-1)) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg(-1). RESULTS AND CONCLUSION: Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min(-1)·m(-2) (0.7), 34.1 (6.7) ml·m( -2)] than in the gelatine group [2.2 L·min(-1)·m( -2) (0.6), 25.8 (7.2) ml·m(-2)] after completion of 7 mL·kg(-1) of study solution. At this stage, the effect of gelatine did not differ from Ringer's acetate. After completion of 14 mL·kg(-1) and 21 mL·kg(-1) of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer's acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer's acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer's acetate group.

Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation.

Severe sepsis induces coagulopathy, which may lead to disseminated intravascular coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation monitor, which has been validated in human endotoxemia model. We assessed thromboelastometry in severe sepsis and overt DIC and investigated its applicability in differentiating sepsis-related coagulation disturbances. Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria of overt DIC on admission. Ten healthy persons served as controls. Coagulation parameters, clotting time, clot formation time (CFT), alpha angle, maximal clot firmness (MCF) and lysis index at 60 min, were registered. In patients with overt DIC, EXTEM MCF, CFT and alpha angle differed from that in both healthy controls and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT 184, 88 and 73 s; and alpha angle 58, 72 and 76 degrees , respectively, P < 0.01 for all). In patients without DIC, the trend was toward hypercoagulation in EXTEM and FIBTEM MCF (68 vs. 63 mm, P = 0.042 and 23 vs. 15 mm, P = 0.034, respectively). Receiver operating characteristic curves showed that MCF, CFT and alpha angle discriminated patients with overt DIC moderately (area under curve 0.891, 0.815 and 0.828, respectively, P < 0.001 for all). Traditional coagulation assays showed progressively worsening coagulopathy from controls to septic patients without DIC and further to those with overt DIC. We conclude that thromboelastometry may be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.

Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function.

BACKGROUND: Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties. METHODS: This prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2 microg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted. RESULTS: The groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9 (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112). CONCLUSIONS: Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased.

Rapidly degradable hydroxyethyl starch solutions impair blood coagulation after cardiac surgery: a prospective randomized trial.

BACKGROUND: There is continuing concern about the effect of hydroxyethyl starch (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more favorable effects on clot strength have therefore been developed. Because the risk of bleeding is increased after cardiopulmonary bypass, we examined whether these types of HES solutions could be administered after cardiac surgery without an alteration of coagulation. METHODS: Two new rapidly degradable HES solutions were compared with human albumin in 45 patients scheduled for elective primary cardiac surgery. After admission to the cardiac surgical intensive care unit, the patients were allocated in random order to receive either 15 mL/kg of HES solution with low molecular weight and low molar substitution (either 6% HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70-240 min) infusion. RESULTS: Clot formation time was prolonged and maximum clot firmness was decreased in thromboelastometry tracings after infusion of both HES solutions. This impairment in thromboelastometry tracings partly recovered (using InTEM and ExTEM coagulation activators) at 2 h after the completion of the study infusion. Platelet contribution to maximum clot firmness remained unaffected in all of the study groups. HES did not induce fibrinolysis. No changes in thromboelastometry tracings were observed after human albumin infusion. Chest tube drainage was comparable in the study groups. CONCLUSIONS: We conclude that a short-time infusion of rapidly degradable HES solutions after cardiac surgery produces impairment in fibrin formation and clot strength in thromboelastometry tracings. In this clinical setting, human albumin does not impair hemostasis.

Tranexamic acid does not correct the haemostatic impairment caused by hydroxyethyl starch (200 kDa/0.5) after cardiac surgery.

We investigated the effect of intravenous tranexamic acid on hydroxyethyl starch (HES)-induced clot strength impairment after cardiac surgery. Patients were randomized to receive either 1 g tranexamic acid or the same volume of 0.9% saline after administration of 15 ml/kg of 6% HES (molecular weight, 200 kDa; degree of substitution, 0.5) in the immediate postoperative period. Modified thromboelastometry (ROTEM) using different activators [intrinsic ROTEM (InTEM), extrinsic ROTEM (ExTEM), fibrinogen ROTEM (FibTEM)] was carried out to evaluate clot formation and lysis. The clot formation time was prolonged, and the maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF / (100-MCF), dynes/cm(2)] decreased (all activators of ROTEM) after completion of HES (P < 0.001, two-factor analysis of variance). These abnormalities in blood coagulation persisted despite tranexamic acid. Maximal lysis (FibTEM), indicative of fibrinolytic activity, was increased after HES but no effect of tranexamic acid was observed. The cumulative chest tube drainage until the first postoperative morning was not different between the groups (1008 +/- 251 and 1081 +/- 654 ml, P = 0.698, respectively). We conclude that after cardiopulmonary bypass, HES-induced impairment in clot formation and strength, or increased fibrinolytic capacity, is not reversed by the administration of tranexamic acid.

Treatment of abdominal compartment syndrome with subcutaneous anterior abdominal fasciotomy in severe acute pancreatitis.

BACKGROUND: Managing the abdominal compartment syndrome associated with severe acute pancreatitis by the open abdomen method is associated with considerable morbidity and resource utilization. METHODS: A technique of subcutaneous anterior abdominal fasciotomy is described for the first time in two patients with severe acute pancreatitis. RESULTS: Following the procedure, the intra-abdominal pressure decreased from 30 mmHg immediately to 23 mmHg and to a sustained level of 12-14 mmHg in the first patient, and from 35 mmHg immediately to 23 mmHg and to a sustained level of 14-19 mmHg in the second patient. CONCLUSIONS: The subcutaneous anterior abdominal fasciotomy is a promising method for safe and effective abdominal decompression with sustained effect and avoiding the morbidity associated with the alternative open abdomen techniques.

Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery.

We investigated the effect of postoperative administration of colloids on hemostasis in 45 patients after cardiac surgery. Patients were randomized to receive 15 mL kg(-1) of either 4% albumin, 4% succinylated gelatin, or 6% hydroxyethyl starch (molecular weight of 200 kDa/degree of substitution 0.5) as a short-term infusion. There was a comparable decrease in maximum clot firmness of thromboelastometry tracings in gelatin and hydroxyethyl starch groups immediately after completion of the infusion, whereas these values remained unchanged in the albumin group. The impairment in clot strength persisted up to 2 h, although the values partly recovered. Postoperative bleeding correlated inversely with the clot strength in pooled data of the artificial colloids. Fibrin formation (clot formation time, alpha-angle) and fibrinogen-dependent clot strength (maximum clot firmness and shear elastic modulus) were more disturbed in the hydroxyethyl starch group than in the gelatin group. We conclude that after cardiopulmonary bypass surgery, both gelatin and hydroxyethyl starch impair clot strength and fibrin buildup, which may predispose patients to increased blood loss. The greatest impairment in hemostasis was seen after hydroxyethyl starch administration, whereas albumin appeared to have the least effect on hemostatic variables.

Recombinant factor VIIa in the treatment of postoperative hemorrhage after cardiac surgery.

BACKGROUND: A generalized coagulation disorder after cardiac surgery that is associated with massive postoperative hemorrhage is not completely understood. Recombinant factor VIIa (rFVIIa) has emerged as a possible "salvage" medication. Limited experience reported in the literature and fears of possible thromboembolic complications make the use of rFVIIa in the treatment of bleeding after cardiac surgery controversial. METHODS: We analyzed retrospectively all consecutive cardiac surgical patients who have received rFVIIa in the Helsinki University Hospital in order to evaluate the safety and efficacy of rFVIIa after cardiac surgery in our institution. Altogether, 16 patients were identified from operating room and intensive care unit (ICU) databases. Patient records and operating room and ICU databases were reviewed. RESULTS: In this series of high risk patients hospital mortality was high (25%). A definite hemostatic effect was seen after rFVIIa administration in all but three patients (82%). Mean amount of bleeding and amount of platelet and fresh frozen plasma transfusions decreased significantly after rFVIIa administration. Four patients had serious postoperative thromboembolic complications. CONCLUSIONS: Recombinant factor VIIa was effective in restoring hemostasis, but thromboembolic complications occurred after rFVIIa use. They may be related to the underlying pathologies and surgery performed. It is possible, however, that rFVIIa treatment contributed to their occurrence.

Hydroxyethyl starch as a priming solution for cardiopulmonary bypass impairs hemostasis after cardiac surgery.

UNLABELLED: We investigated the influence of hydroxyethyl starch (HES) as a priming solution for the cardiopulmonary bypass (CPB) circuit on postoperative hemostasis in 45 patients undergoing elective coronary artery bypass grafting. In a randomized sequence, 20 mL/kg of low-molecular-weight HES (HES 120; molecular weight 120,000 daltons), high-molecular-weight HES (HES 400; molecular weight 400,000 daltons), or 4% human albumin (ALB) was used as the main component of the CPB priming solution. The thromboelastographic values indicating the speed of solid clot formation (alpha-angle) and the strength of the fibrin clot (maximum amplitude and shear elastic modulus) were decreased up to 2 h after CPB in both HES groups. Four hours after the operation, blood loss through the chest tubes had increased in the HES groups: HES 120, mean 804 mL (range, 330-1390 mL); HES 400, mean 1008 mL (range, 505-1955 mL); and ALB, mean 681 mL (range, 295-1500 mL) (P < 0.05 between the HES 400 and ALB groups). We conclude that HES solutions, when given in doses of 20 mL/kg in connection with the CPB prime, compromise hemostasis after cardiac surgery. This effect appears related to formation of a less stable thrombus compared with that formed in the presence of ALB. IMPLICATIONS: The influence of hydroxyethyl starch (HES) on postoperative hemostasis was investigated in cardiac surgery. The thromboelastographic values indicated that HES solutions, when given in connection with the cardiopulmonary bypass prime, compromise hemostasis after cardiac surgery. This effect seems to occur through the formation of a less stable clot.