Michael Adamzik

Perioperative Coagulation Management and Control of Platelet Transfusion by Point-of-Care Platelet Function Analysis

About one third of all blood components transfused intraoperatively is used in cardiac surgery, whereas mortality of cardiosurgical patients correlates nearly linear with the number of transfused units of packed red blood cells. Acquired platelet function disorders play a major role in perioperative bleeding in cardiac surgery. Therefore, the use of point-of-care-suitable platelet function analyzers seems to be reasonable in this field. Methods: Platelet function analyzer PFA-100®, rotational thrombelastometry (ROTEM®), and multiple platelet function analyzer (Multiplate®) are in principle applicable for point-of-care testing. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. Results: Perioperative use of platelet function analyzers is helpful in prediction of blood loss in cardiac surgery. Perioperative usage of blood components and their respective costs can be reduced by an appropriate coagulation management. Conclusion: Algorithms for perioperative coagulation management based on point-of-care testing permit a fast diagnostic and goal-directed therapy of coagulation and functional platelet disorders. The possibility to reduce the mortality of patients and the overall cost for hospital stay is subject of further studies.

Conservative treatment of tracheal injuries.

Tracheal injuries, independent of their origin, may be life-threatening. Surgical repair is regarded as the treatment of choice but has not been compared with other approaches. We hypothesized that defects bridgeable by an artificial airway may enable conservative treatment. We report on five patients with tracheal injuries, two in the trachea’s upper third resulting from trauma and intubation and three in its middle third after percutaneous dilational tracheostomy. Tracheal defects were bridged by endotracheal or tracheostomy tubes under bronchoscopic guidance and the cuff was inflated distal to the lesion. Air leakage stopped immediately and all tracheal defects healed without further interventions. No case of stenosis or mediastinitis was observed. These results suggest that treating tracheal injuries conservatively by placing an artificial airway under bronchoscopic guidance may be effective and offers a convenient starting position for secondary surgical repair in selected patients when conservative treatment fails.

Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome

IntroductionHemolysis can be induced in sepsis via various mechanisms, its pathophysiological importance has been demonstrated in experimental sepsis. However, no data on free hemoglobin concentrations in human sepsis are available. In the present study we measured free hemoglobin in patients with severe sepsis as well as in postoperative patients using four methods. It was our aim to determine the potential value of free hemoglobin as a biomarker for diagnosis and outcome of severe sepsis in critical illness.MethodsPlasma concentration of free hemoglobin was determined in patients with severe sepsis (n = 161) and postoperative patients (n = 136) on day 1 of diagnosis and surgery. For the measurement of free hemoglobin, an enzyme linked immunosorbent assay and three spectrophotometric algorithms were used. Moreover, SAPS II- and SOFA scores as well as procalcitonin concentration and outcome were determined. Kaplan-Meier analysis was performed and odds ratios were determined after classification of free hemoglobin concentrations in a high and low concentration group according to the median. For statistical evaluation the Mann-Whitney test and logistic regression analysis were used.ResultsIn non-survivors of severe sepsis, free hemoglobin concentration was twice the concentration compared to survivors. Thirty-day survival of patients, as evidenced by Kaplan-Meier analysis, was markedly lower in patients with high free hemoglobin concentration than in patients with low free hemoglobin concentration. Best discrimination of outcome was achieved with the spectrophotometric method of Harboe (51.3% vs. 86.4% survival, p < 0.001; odds ratio 6.1). Multivariate analysis including free hemoglobin, age, SAPS II- and SOFA-score and procalcitonin demonstrated that free hemoglobin, as determined by all 4 methods, was the best and an independent predictor for death in severe sepsis (p = 0.022 to p < 0.001). Free hemoglobin concentrations were not significantly different in postoperative and septic patients in three of four assays. Thus, free hemoglobin can not be used to diagnose severe sepsis in critical illness.ConclusionsFree hemoglobin is an important new predictor of survival in severe sepsis.

Comparison of thromboelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critically ill adults

IntroductionEstablished biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults.MethodsIn the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated.ResultsIn comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838 - 0.964) for the lysis index, and 0.756 (CI 0.666 - 0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7 - 334.5).ConclusionsThe thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.

Comparison of thrombelastometry with simplified acute physiology score II and sequential organ failure assessment scores for the prediction of 30-day survival: a cohort study.

Disseminated intravascular coagulation contributes to mortality of sepsis. The study was performed to investigate thromboelastometry as a potential predictor of 30-day survival in severe sepsis and to compare thromboelastometry to Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores. Ninety-eight patients with severe sepsis were included in the cohort study. Thromboelastometry clotting time, clot formation time (CFT), maximum clot firmness (MCF), and &agr; angle as well as SAPS II and SOFA scores were determined at the day of diagnosis. Thromboelastometry variables differed in survivors and nonsurvivors. Mean CFT was prolonged (276 ± 194 vs. 194 ± 109 s, P = 0.021; mean ± SD), and both MCF (52.7 ± 12.1 mm vs. 57.3 ± 11.5 mm, P = 0.042) and &agr; angle (53.4 ± 12.8 degrees vs. 58.9 ± 11.8 degrees, P = 0.028) were reduced in nonsurvivors. Clotting time and SAPS II and SOFA scores were not different. Thromboelastometry values were classified as normal and pathological, respectively, using the median of the variables as the cutoff. Thromboelastometry values were normal if CFT was less than 185 s, MCF was greater than 55 mm, and &agr; was greater than 57.5 degrees. Thirty-day survival was 85.7% when all thromboelastometry variables were normal, but 58.7% when at least one variable was pathological (P = 0.005). Multivariate analysis revealed that the absence or presence of at least one pathological thromboelastometry variable allows for better prediction of 30-day survival in severe sepsis than the SAPS II and SOFA scores (P = 0.01; odds ratio, 4.1), respectively, emphasizing the importance of the coagulation system in sepsis.

Aquaporin 1 (AQP1) expression is a novel characteristic feature of a particularly aggressive subgroup of basal-like breast carcinomas

Aquaporin1 (AQP1) is a water channel protein that facilitates water flux across cell membranes. It is widely expressed in epithelial and endothelial cells in several tissues. AQP1 is also associated with angiogenesis, cell migration and metastasis in some human malignancies. In this study the immunohistochemical expression of AQP1 in 203 invasive breast carcinomas with long-term follow up was investigated. AQP1 expression was demonstrated in 11 tumours (5.4%) and showed highly significant correlation with high tumour grade, medullary-like histology, “triple-negativity”, cytokeratin 14 and smooth muscle actin expression. In univariate analysis, AQP1 was significantly associated with poor prognosis. In multivariate analysis, AQP1 expression proved to be an independent prognostic marker if stratified by age, tumour size, lymph node status, histological grade, ER status and CMF therapy. Our results strongly suggest that AQP1 expression is a new characteristic feature of a particularly aggressive subgroup of basal-like breast carcinomas.

Alveolar extracellular 20S proteasome in patients with acute respiratory distress syndrome.

RATIONALE Repair mechanisms resulting in alveolar protein degradation in acute respiratory distress syndrome (ARDS) are largely unknown. OBJECTIVES To test whether the 20S proteasome is present and functional in the alveolar space in patients with ARDS. METHODS Proteasome antigenic concentration in bronchoalveolar lavage (BAL) supernatants was measured by ELISA in patients with ARDS (n = 64), acute lung injury (ALI) (n = 8), sarcoidosis (n = 13), and in healthy subjects (n = 8). Cleavage of specific fluorogenic substrates (+/-epoxomicin), I(125) albumin degradation rate, and gel filtration were used to quantify and characterize proteasomal activity. The presence of proteasomes was confirmed independently by electron microscopic techniques. MEASUREMENTS AND MAIN RESULTS Proteasome concentrations in patients with ARDS were markedly increased (1,069 +/- 1,194 ng/ml) in comparison to healthy subjects (60.8 +/- 49.8; P < 0.001), ALI (154 +/- 43; P = 0.006), and sarcoidosis (97.6 +/- 42.2; P = 0.037). All fluorogenic substrates were hydrolyzed (Suc-LLVY-AMC, 3.6 +/- 8.8 pkat/mg; BZ-VGR-AMC, 1.8 +/- 3.1; Suc-LLE-AMC, 1 +/- 1.7) by BAL supernatants of patients with ARDS, with inhibition by epoxomicin (P = 0.0001), and the majority of proteolytic activity was detected in BAL supernatant. Maximum hydrolyzing activity occurred at 660 kD and 20S proteasome was seen microscopically after purification and being released by pneumocytes type II. Proteasomal activity and albumin degradation rate in patients with ARDS were approximately 17-fold lower than in healthy subjects. Proteasomal activity in normal BAL was inhibited by BAL aliquots from patients with ARDS but not by denatured BAL, and returned to normal by purification. CONCLUSIONS For the first time, we identified extracellular, biologically active 20S proteasome in the alveolar space of patients with ARDS in concentrations much higher than in normal subjects or in those with ALI.

Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis

See related Letter by Hartmann et al.http://ccforum.com/content/17/2/427IntroductionSepsis leads to an activation of the immune system and hemostatis. However, studies on platelet aggregation in severe sepsis using impedance aggregometry have not been performed and the diagnostic and prognostic capabilities are unknown. In the present study we hypothesized that impedance aggregometry findings might serve as a biomarker for the diagnosis and prognosis of severe sepsis.MethodsEighty patients with severe sepsis and 50 postoperative patients were included in the prospective observational study. Platelet function was determined at the first day of severe sepsis and surgery, respectively, using impedance aggregometry (Multiplate®). Moreover, platelet count, procalcitonin, interleukin 6, C-reactive protein and 30-day mortality were determined.ResultsCompared to postoperative patients, platelet aggregation was significantly reduced in patients with severe sepsis (collagen-test: 70.8 (44.4, 83.2) arbitrary units (A.U.) vs. 26.8 (12.7, 45.8) A.U.; P <0.001; median and quartiles). Furthermore, marked differences in platelet function were observed in survivors and non-survivors of severe sepsis (collagen-test: 33.4 (10.9, 48.8) A.U. vs. 12.4 (6.5, 25.0) A.U.; P = 0.001). Kaplan-Meier analysis demonstrated that higher platelet function was associated with a mortality of 10%, while mortality was 40% when platelet function was low (collagen-test; P = 0.002). The odds ratio was 6.0. In both univariate and multivariate analyses (including procalcitonin, IL6, C-reactive protein and platelet count) impedance aggregometry using collagen as the activator proved to be the best and an independent predictor for the diagnosis and prognosis of severe sepsis in critical illness.ConclusionsIn severe sepsis, impedance aggregometry allows better prediction of diagnosis and survival than conventional biomarkers and platelet count.

[Platelet function analysis with point-of-care methods].

BACKGROUND More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance. METHODS Platelet function analyzer (PFA-100), multiple platelet function analyzer (Multiplate), and rotational thrombelastometry (ROTEM) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. RESULTS PFA-100 enables a sensitive detection of von Willebrands syndrome. Multiplate is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction. CONCLUSION Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.ZusammenfassungHintergrund:Immer mehr Patienten werden heutzutage mit Thrombozytenaggregationshemmern behandelt. Dabei ist eine suffiziente Blockade der Thrombozytenaggregation einerseits von entscheidender Bedeutung für die Effektivität einer Herzinfarkt- oder Schlaganfallprophylaxe, insbesondere bei Patienten mit medikamentenbeschichteten Stents. Andererseits kann diese Medikation aber auch perioperativ zu einem wesentlich erhöhten Blutungsrisiko führen. Für beide Situationen ist eine Kontrolle der Effektivität der Therapie bzw. eine Beurteilung der Beeinträchtigung des Hämostasesystems von entscheidender Bedeutung.Methodik:Mit dem Platelet Function Analyzer (PFA-100®), dem Multiple Platelet Function Analyzer (Multiplate®) und der Rotationsthrombelastometrie (ROTEM®) stehen zurzeit leicht zu bedienende und verlässliche Point-of-Care-(POC-)taugliche Geräte zur Verfügung, die jedoch unterschiedliche Aspekte der Thrombozytenfunktion untersuchen und auch unterschiedliche Limitationen aufweisen. Daher hängt die Auswahl des richtigen Testsystems von der jeweiligen Fragestellung ab.Ergebnisse:Der PFA-100® ermöglicht einen sensitiven Nachweis eines Von-Willebrand-Syndroms. Der Multi plate®-Analyzer eignet sich zur Kontrolle der Effektivität einer Therapie mit Thrombozytenaggregationshemmern, wie z.B. Acetylsalicylsäure, Clopidogrel und Glykoprotein-IIb/IIIa-Rezeptor-Antagonisten. Die ROTEM®-Analyse ermöglicht eine ganzheitliche Beurteilung des Hämostasesystems und erfasst dabei insbesondere eine Hyperfibrinolyse, Heparineffekte und die Fibrinogen-Thrombozyten-Interaktion.Schlussfolgerung:Aufgrund ihrer einfachen Handhabbarkeit sind die beschriebenen POC-Geräte sowohl für den Einsatz im Operationssaal oder auf der Intensivstation als auch im Herzkatheterlabor oder in der kardiologischen Praxis geeignet. Sie ermöglichen dort eine schnelle Erfassung der Thrombozytenfunktion und eine individuell gesteuerte Therapie.AbstractBackground:More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance.Methods:Platelet function analyzer (PFA-100®), multiple platelet function analyzer (Multiplate®), and rotational thrombelastometry (ROTEM®) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question.Results:PFA-100® enables a sensitive detection of von Willebrands syndrome. Multiplate® is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM® analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM® analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction.Conclusion:Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.

Messung der Thrombozytenfunktion mit Point-of-Care-Methoden

BACKGROUND More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance. METHODS Platelet function analyzer (PFA-100), multiple platelet function analyzer (Multiplate), and rotational thrombelastometry (ROTEM) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. RESULTS PFA-100 enables a sensitive detection of von Willebrands syndrome. Multiplate is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction. CONCLUSION Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.ZusammenfassungHintergrund:Immer mehr Patienten werden heutzutage mit Thrombozytenaggregationshemmern behandelt. Dabei ist eine suffiziente Blockade der Thrombozytenaggregation einerseits von entscheidender Bedeutung für die Effektivität einer Herzinfarkt- oder Schlaganfallprophylaxe, insbesondere bei Patienten mit medikamentenbeschichteten Stents. Andererseits kann diese Medikation aber auch perioperativ zu einem wesentlich erhöhten Blutungsrisiko führen. Für beide Situationen ist eine Kontrolle der Effektivität der Therapie bzw. eine Beurteilung der Beeinträchtigung des Hämostasesystems von entscheidender Bedeutung.Methodik:Mit dem Platelet Function Analyzer (PFA-100®), dem Multiple Platelet Function Analyzer (Multiplate®) und der Rotationsthrombelastometrie (ROTEM®) stehen zurzeit leicht zu bedienende und verlässliche Point-of-Care-(POC-)taugliche Geräte zur Verfügung, die jedoch unterschiedliche Aspekte der Thrombozytenfunktion untersuchen und auch unterschiedliche Limitationen aufweisen. Daher hängt die Auswahl des richtigen Testsystems von der jeweiligen Fragestellung ab.Ergebnisse:Der PFA-100® ermöglicht einen sensitiven Nachweis eines Von-Willebrand-Syndroms. Der Multi plate®-Analyzer eignet sich zur Kontrolle der Effektivität einer Therapie mit Thrombozytenaggregationshemmern, wie z.B. Acetylsalicylsäure, Clopidogrel und Glykoprotein-IIb/IIIa-Rezeptor-Antagonisten. Die ROTEM®-Analyse ermöglicht eine ganzheitliche Beurteilung des Hämostasesystems und erfasst dabei insbesondere eine Hyperfibrinolyse, Heparineffekte und die Fibrinogen-Thrombozyten-Interaktion.Schlussfolgerung:Aufgrund ihrer einfachen Handhabbarkeit sind die beschriebenen POC-Geräte sowohl für den Einsatz im Operationssaal oder auf der Intensivstation als auch im Herzkatheterlabor oder in der kardiologischen Praxis geeignet. Sie ermöglichen dort eine schnelle Erfassung der Thrombozytenfunktion und eine individuell gesteuerte Therapie.AbstractBackground:More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance.Methods:Platelet function analyzer (PFA-100®), multiple platelet function analyzer (Multiplate®), and rotational thrombelastometry (ROTEM®) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question.Results:PFA-100® enables a sensitive detection of von Willebrands syndrome. Multiplate® is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM® analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM® analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction.Conclusion:Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.