Corinna Velik-Salchner

Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration.

BACKGROUND:To explore whether disturbed fibrin polymerization is the main problem underlying dilutional coagulopathy and can be reversed by fibrinogen administration, we conducted a prospective study using modified thrombelastography (ROTEM®). METHODS:Sixty-six orthopedic patients randomly received modified gelatin solution, hydroxyethyl starch 130/0.4, or exclusively Ringer lactate solution. ROTEM® analysis was performed, concentrations of coagulation factors and markers of thrombin generation were measured. Fibrinogen concentrate (Hemocomplettan®) was administered (30 mg/kg) when thrombelastographically measured fibrinogen polymerization was critically decreased. RESULTS:The α angle, clot firmness, and fibrinogen polymerization (median [min to max]) significantly decreased in the patients receiving hydroxyethyl starch (area under the curve minus baseline (−5 [−9 to −2]), followed by gelatin solution (−3 [−8 to 0]), with the least reductions seen for Ringer lactate solution (−2 [− 4 to 1]) (colloids versus Ringer lactate P < 0.0001). Thirteen patients in the colloid groups but none in the Ringer lactate group needed fibrinogen concentrate to maintain borderline clot firmness. Activity of FVII, FVIII, FIX, and von Willebrand ristocetin activity decreased significantly with colloids. Thrombelastographically measured coagulation time, molecular markers of thrombin generation, and activity of all other coagulation factors were comparable in all groups. CONCLUSION:Disturbance of fibrinogen/fibrin polymerization is the primary problem triggering dilutional coagulopathy during major orthopedic surgery. The magnitude of clot firmness reduction is determined by the type of fluid used, with hydroxyethyl starch showing the most pronounced effects. These undesirable effects of intravascular volume therapy can be reversed by increasing fibrinogen concentration by administering fibrinogen concentrate, even during continuing blood loss and intravascular volume replacement.

The Effect of Fibrinogen Substitution on Reversal of Dilutional Coagulopathy: An In Vitro Model

Colloids and crystalloids are usually administered as treatment for hypovolemia in severely injured patients. However, dilution of clotting factors and platelets together with impaired fibrinogen polymerization are associated with fluid therapy and may aggravate hemorrhage, thus worsening final outcome of these patients. We investigated, in an in vitro model, whether the addition of fibrinogen to diluted blood samples can reverse dilutional coagulopathy. Blood from 5 healthy male volunteers was diluted by 60% using lactated Ringers solution, 4% modified gelatin solution, or 6% hydroxyethyl starch 130/0.4, as well as the combination of lactated Ringers solution with either of the 2 colloid solutions. Thereafter, aliquots of diluted blood samples were incubated with 3 different concentrations of fibrinogen (0.75, 1.5, and 3.0 mg/mL). Measurements were performed by modified thrombelastography (ROTEM®; Pentapharm, Munich, Germany). After 60% dilution, clotting times increased, whereas clot firmness and fibrin polymerization decreased significantly. After administration of fibrinogen, clotting times decreased and clot firmness, as well as fibrin polymerization, increased in all diluted blood samples. The effect of in vitro fibrinogen substitution on ROTEM® variables was dependent on the fibrinogen dosage and the type of solution used to dilute the blood samples.

Fibrinogen in Craniosynostosis Surgery

BACKGROUND: During craniosynostosis repair, massive blood loss, consumption and dilution of clotting factors often result in coagulopathy, for which cryoprecipitate, fresh frozen plasma (FFP), and platelets are recommended for treatment. However, cryoprecipitate is not available in most European countries, and the efficacy of FFP in correcting fibrinogen deficiency is limited. We report our experience with human fibrinogen concentrate (Hemocomplettan®) used to improve impaired fibrinogen polymerization in children. METHODS: Results of routine coagulation tests, thrombelastometry (ROTEM®), transfusion requirements, administration of fibrinogen concentrate, and data on the postoperative course of nine consecutive children undergoing major craniofacial surgery were retrospectively collected from anesthesia protocols, medical charts, laboratory and ROTEM® databases. RESULTS: The nine children aged 12 (8, 22) mo (median [25th, 75th percentile]), weighing 9.5 (9, 10) kg had a calculated blood loss of 80 (49, 92)% of calculated blood volume during the surgery lasting 6.4 (4.5, 7.2) h. Impaired fibrinogen polymerization detected by ROTEM® was the main problem underlying dilutional coagulopathy. In all cases, sufficient hemostasis was achieved without adverse effects by administering (if necessary), repeated doses of fibrinogen concentrates (each single dose 30 mg/kg) without FFP or platelet transfusions. All children were successfully weaned from mechanical ventilation within a few hours and were able to be discharged early from the Intensive Care Unit. CONCLUSIONS: Administration of fibrinogen concentrate effectively improves fibrinogen polymerization and total clot strength, which were the main underlying problems of dilutional coagulopathy in children undergoing craniosynostosis surgery.

Point-of-care whole blood impedance aggregometry versus classical light transmission aggregometry for detecting aspirin and clopidogrel: the results of a pilot study.

BACKGROUND:We determined whether whole blood impedance aggregometry using the Multiplate® detects the effects of antiplatelet drugs as reliably as does classical light transmission aggregometry (LTA) or the platelet function analyzer PFA-100®. METHODS:Multiplate (M) assays, measuring changes in electrical resistance as aggregation units over time (AU*min), and LTA assays induced by collagen (COL), adenosine diphosphate (ADP) or arachidonic acid (AA) and PFA-100 testing, using epinephrine (PFA100-EPI) or ADP (PFA100-ADP) cartridges, were performed simultaneously using arterial blood samples obtained before induction of anesthesia in 70 consecutive patients scheduled for elective coronary artery bypass grafting. Patients in group A (n = 48) served as controls, patients in group B (n = 11) received aspirin 100 mg/d and those in group C (n = 11) aspirin 100 mg/d and clopidogrel 75 mg/d until the day before surgery. RESULTS:In controls the median (1st, 3rd quartiles) change in impedance AU*min for M-COL (374 [231–469]) was significantly greater than in patients receiving aspirin (164 [86–211], P = 0.0009) or receiving aspirin and clopidogrel (118 [101–244], P = 0.004). M-ADP values in controls were 258 (158–389), in patients receiving aspirin 261 (159–393), and in patients receiving aspirin and clopidogrel 88 (48–231, P = 0.054). M-AA values were significantly lower in patients receiving aspirin alone (45 [28–60], P = 0.0004) or aspirin and clopidogrel (44 [26–221], P = 0.008) than in controls (200 [86–345]). The areas under the receiver operating characteristic curves indicating the ability to discriminate patients taking aspirin from those not taking aspirin were comparable for COL and AA assays using whole blood impedance aggregometry or classical LTA (M-COL 0.84 [P = 0.001], LTA-COL 0.85 [P = < .001], M-AA 0.84 [P = < .001] and LTA-AA 0.87 [P = < .001]), but only 0.74 for PFA-100-EPI (P = 0.03). Similarly, for discrimination of patients not taking antiplatelet drugs from patients taking clopidogrel and aspirin the areas under the receiver operating characteristic curve were also comparable for both aggregometry methods M-COL 0.77 (P = 0.006), LTA-COL 0.78 (P = 0.004), M-ADP 0.74 (P = 0.015), LTA-ADP 0.73 (P = 0.018). CONCLUSION:Results achieved with the bedside Multiplate assays were not different than those obtained with classical aggregometry for detecting the effects of aspirin and clopidogrel in preoperative patients scheduled for elective cardiac surgery.

Sixty-four slice CT evaluation of aortic stenosis using planimetry of the aortic valve area.

OBJECTIVE The purpose of our study was to evaluate planimetry of the aortic valve area with 64-slice CT in comparison with transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in patients with aortic stenosis. MATERIALS AND METHODS Thirty-six patients with aortic valve disease referred for coronary 64-slice CT angiography were examined. Planimetry of the aortic valve area with 64-slice CT was compared with TTE using the Doppler continuity equation for calculation of the aortic valve area and with planimetric measurement of the aortic valve area using TEE. RESULTS Planimetry of the aortic valve area with CT (1.11 +/- 0.42 cm2) showed a good correlation with TTE (1.05 +/- 0.42 cm2) (r = 0.88, p < 0.001) in 32 patients and a good correlation with TEE (1.41 +/- 1.61 cm2) (r = 0.99, p < 0.0001) in 10 patients. The mean and maximum transvalvular pressure gradients were correlated with the aortic valve area as measured with CT (r = -0.68, p = 0.0001; and r = -0.67, p = 0.0001, respectively). Beta-blockers were not given (mean heart rate, 62.5 +/- 10.7 beats per minute). CONCLUSION MDCT allows accurate planimetry of the aortic valve area in patients with aortic stenosis. In patients referred for 64-slice CT coronary angiography, concomitant aortic stenosis can be identified and evaluated.

The in vitro effects of fibrinogen concentrate, factor XIII and fresh frozen plasma on impaired clot formation after 60% dilution.

BACKGROUND:Previous investigations have shown that increasing fibrinogen concentration improves dilution-dependent impairment of clot formation. We conducted an in vitro study to explore whether substitution with fibrin-stabilizing factor XIII (FXIII) combined with fibrinogen promotes further improvement of clot formation, and whether fibrinogen administration as concentrate or fresh frozen plasma (FFP) results in comparable effects. METHODS:Blood from six healthy donors was diluted by 60% using lactated Ringer’s solution. Aliquots of diluted blood samples were incubated with two different doses of fibrinogen concentrate, FXIII concentrate, the combination of both, or with two different doses of FFP. Using thrombelastometry (ROTEM®) blood samples were analyzed at baseline (undiluted), after dilution and after supplementation. Variables were analyzed for changes from baseline, and effects of fibrinogen concentrate alone or combined with FXIII were compared with effects observed with corresponding FFP doses. RESULTS:After 60% in vitro dilution of blood all ROTEM parameters and global coagulation tests changed significantly. Among the substitutes tested FXIII alone had no effect, the combination with fibrinogen improved coagulation time, &agr; angle and fibrinogen/fibrin polymerization significantly more than did small-dose fibrinogen alone. After substituting fibrinogen, median values of all ROTEM variables were within the normal range, thereby showing dose dependency but also significant differences (P = 0.027) from corresponding FFP doses (EXTEM MCF FFP small dose [38 (35, 40.3) mm)], which enabled only coagulation time to be shortened to baseline levels. CONCLUSIONS:Supplementation of fibrinogen restored all ROTEM parameters after dilution. This effect was partially enhanced by adding FXIII and was significantly stronger than for FFP substitution.

Quality of Life Improvement after Robotically Assisted Coronary Artery Bypass Grafting

Objectives: Coronary artery bypass grafting (CABG) is associated with long rehabilitation periods and slow quality of life (QOL) improvement. Totally endoscopic coronary artery bypass grafting (TECAB) can be performed using robotic technology and remote access perfusion. The aim of this study was to evaluate whether TECAB leads to accelerated QOL improvement as compared to standard CABG. Methods: We included 120 patients who had received robotically assisted CABG, 56 of whom were operated on using standard sternotomy. These patients were compared to 55 patients who underwent the TECAB procedure and to 9 TECAB patients who required conversion to conventional sternotomy. QOL evaluation was performed before the operation and 1, 3 and 6 months after the procedure using the SF-36 health survey and a standardized questionnaire. Results: All quality of life aspects improved significantly in all study patients. At 3 months, TECAB patients showed significantly better QOL scores related to bodily pain and physical health. Hospital stay and time to restoration of daily activities were significantly shorter. Converted patients experienced similar courses to sternotomy patients in terms of QOL. Conclusions: TECAB using robotic technology leads to improved physical health, shorter hospital stay and a more rapid restoration of daily activities. Conversion from TECAB to sternotomy does not lead to QOL impairment as compared to primary sternotomy.

An assessment of cardiopulmonary bypass-induced changes in platelet function using whole blood and classical light transmission aggregometry: the results of a pilot study.

BACKGROUND: In this study, we explored whether antiplatelet medications impair whole blood impedance aggregometry after cardiac surgery and cardiopulmonary bypass (CPB) compared with classical light transmission aggregometry (LTA). METHODS: Multiplate® (M) assays measuring changes in electrical resistance as aggregation units over time, and LTA assays (% aggregation) induced by collagen (COL), adenosine diphosphate (ADP), or arachidonic acid were performed simultaneously using arterial blood samples obtained before induction of anesthesia, 15 min and 3 h after neutralization of heparin in 70 consecutive patients scheduled for elective coronary artery bypass grafting. Patients in Group A (n = 48) discontinued intake of antiplatelet drugs for at least 7 days and served as controls, patients in Group B (n = 11) received aspirin 100 mg/d and those in Group C (n = 11) aspirin 100 mg/d and clopidogrel 75 mg/d (dual antiplatelet therapy) until the day before surgery. RESULTS: In patients without antiplatelet therapy, 15 min and 3 h after protamine a significant decrease in platelet aggregation was observed with all three agonists and both aggregation methods. In patients receiving aspirin alone, LTA-COL, LTA-ADP and M-ADP changed significantly over time, and ADP assays of both aggregation methods showed a significant decrease in platelet aggregation 15 min after protamine in patients receiving dual antiplatelet therapy. When calculating the areas under the receiver-operating characteristic curves for discrimination of antiplatelet agents, LTA-COL was able to discriminate between controls and patients receiving aspirin or dual antiplatelet therapy 15 min and 3 h after CPB and the M-ADP assay was able to discriminate between controls and patients receiving dual antiplatelet therapy 3 h after protamine. CONCLUSION: Whole blood and classical LTA performed with all commonly used agonists enable detection of CPB-induced changes in platelet aggregation in patients not taking antiplatelet medication, whereas in patients receiving antiplatelet therapy, ADP-induced antiplatelet assays are preferable for detecting CPB-induced impairment of platelet aggregation.

Functional Recovery of a Human Neonatal Heart After Severe Myocardial Infarction

RATIONALE Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, cardiac regeneration has been demonstrated in fish and newborn mice after apex resection or cardiac infarctions. Two key issues remain to translate findings in model organisms to future therapies in humans: what is the mechanism and can cardiac regeneration indeed occur in newborn humans? OBJECTIVE To assess whether human neonatal hearts can functionally recover after myocardial infarction. METHODS AND RESULTS Here, we report the case of a newborn child having a severe myocardial infarction due to coronary artery occlusion. The child developed massive cardiac damage as defined by serum markers for cardiomyocyte cell death, electrocardiograms, echocardiography, and cardiac angiography. Remarkably, within weeks after the initial ischemic insult, we observed functional cardiac recovery, which translated into long-term normal heart function. CONCLUSIONS These data indicate that, similar to neonatal rodents, newborn humans might have the intrinsic capacity to repair myocardial damage and completely recover cardiac function.

Less impairment of hemostasis and reduced blood loss in pigs after resuscitation from hemorrhagic shock using the small-volume concept with hypertonic saline/hydroxyethyl starch as compared to administration of 4% gelatin or 6% hydroxyethyl starch solution.

BACKGROUND: Small-volume resuscitation using hypertonic saline/hydroxyethyl starch 200/0.62 (HS-HES) has been shown to be an effective alternative to the administration of crystalloids or colloids in trauma patients. All IV fluids cause dose-related dilutional coagulopathy and show intrinsic effects on the hemostatic system, but only few data refer to functional consequences after small-volume resuscitation. METHODS: Using thrombelastometry (ROTEM®), we studied 30 pigs (weighing 35–45 kg) after withdrawal of 60% of blood volume [1484 mL (1369–1624 mL)] and receiving 4 mL/kg HS-HES for compensation of blood loss or 4% gelatin or 6% HES 130/0.4 in a 1:1 ratio to lost blood volume. To compare the ROTEM variables (coagulation time, clot formation time, α angle, clot firmness, and fibrinogen polymerization) with bleeding tendency, a hepatic incision was made and blood loss was measured. RESULTS: Median (25th, 75th percentile) fibrinogen polymerization was significantly higher after HS-HES infusion [11 mm (10, 11), P = 0.0034] when compared with administration of 4% gelatin [4.5 mm (3.0, 5.8)] or HES 130/0.4 [3.5 mm (2.3, 4.0)]. Median blood loss after liver incision was 725 mL (900, 375) after HS-HES, 1625 mL (1275, 1950) after 4% gelatin, and 1600 mL (1500, 1800) after 6% HES 130/0.4 (P = 0.004). Hemodynamic stabilization was traceable in all groups but showed differences regarding filling pressures. CONCLUSIONS: Resuscitation from hemorrhagic shock with HS-HES 200/0.62 results in less impairment of clot formation when compared with compensation of blood loss by administering 6% HES 130/0.4 or 4% gelatin.