Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany.

BACKGROUND: There are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50-97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19. OBJECTIVES: The aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV. METHODS: A multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated. RESULTS: A total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58-77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3-9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5-24), and the duration of MV was 15 days (8-25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients. CONCLUSION: In this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.

The effect of the interruption of agitation, temporary cooling, and pneumatic tube transportation on platelet quality during storage for transfusion.

BACKGROUND: Conditions during blood product storage and transportation should maintain quality. The aim of this in vitro study was to investigate the effect of interruption of agitation, temporary cooling (TC), and pneumatic tube system transportation (PTST) on the aggregation ability (AA) and mitochondrial function (MF) of platelet concentrates (PC). STUDY DESIGN AND METHODS: A PC was divided equally into four subunits and then allocated to four test groups. The control group (I) was stored as recommended (continuous agitation, 22 ± 2°C) for 4 days. The test groups were stored without agitation (II), stored as recommended, albeit 4°C for 60 minutes on day (d)2 (III) and PTST (IV). Aggregometry was measured using Multiplate (RocheAG; ADPtest, ASPItest, TRAPtest, COLtest) and MF using Oxygraph-2k (Oroboros Instruments). The basal and maximum mitochondrial respiratory rate (MMRR) were determined. AA and MF were measured daily in I and II and AA in III and IV on d2 after TC/PTST. Statistical analysis was performed using tests for matched observations. RESULTS: Eleven PCs were used. TRAP-6 induced AA was significantly lower in II when compared to I on d4 (P = 0.015*). In III the ASPItest was significantly lower (P = 0.032*). IV showed no significant differences. The basal and MMRR were significantly reduced over 4 days in I and II (for both rates in both groups: P = <0.0001*). No significant differences occurred on d4 (P = 0.495). CONCLUSION: Our results indicate that ex vivo AA and MF of PCs are unaffected, even in no-ideal storage and transport circumstances with respect to agitation, temperature, and force.

[Point of Care 2.0: Coagulation Monitoring Using Rotem® Sigma and Teg® 6S]. / Point of Care 2.0: Gerinnungsdiagnostik mit ROTEM® sigma und TEG® 6s.

New-generation methods for point of care based coagulation monitoring enable fully automated viscoelastic analyses for the assessment of particular parts of hemostasis. Contrary to the measuring techniques of former models, the viscoelastic ROTEM® sigma and TEG® 6s analyses are performed in single-use test cartridges without time- and personnel-intensive pre-analytical procedures. This review highlights methodical strengths and limitations of the devices and meets concerns associated with their integration in routine clinical practice.

Microparticles from stored red blood cells enhance procoagulant and proinflammatory activity.

BACKGROUND: The pathomechanisms of morbidity due to blood transfusions are not yet entirely understood. Elevated levels of red blood cell-derived microparticles (RMPs) are found in coagulation-related pathologies and also in stored blood. Previous research has shown that RMPs mediate transfusion-related complications by the intrinsic pathway. We hypothesized that RMPs might play a role in post-transfusion thrombotic complications by enhancing procoagulant activity also through the extrinsic pathway of coagulation. STUDY DESIGN AND METHODS: In this laboratory study, blood from 18 healthy volunteers was stimulated with microparticles from expired stored red blood cells. Various clotting parameters were recorded. Flow cytometry, enzyme-linked immunosorbent assays, and real-time polymerase chain reaction were used to investigate possible mediating mechanisms. RESULTS: The addition of RMPs shortened the clotting time from 194 to 161 seconds (p < 0.001). After incubation with RMPs, there was increased expression of tissue factor (TF) on monocytes and in plasma. TF messenger RNA expression increased in a time-dependent and concentration-dependent manner. There was a significant induction of interleukin-1ß and interleukin-6. After stimulation with RMPs, there was a significant increase in the number of activated platelets, an increased percentage of PAC-1/CD62P (procaspase activating compound-1/platelet surface P-selectin) double-positive platelets, and an increased number of platelet-neutrophil duplets and platelet-monocyte duplets, indicating enhanced interaction of platelets with neutrophils and monocytes. Levels of CXCL-8 (C-X-C motif chemokine ligand 1) and interleukin-6 were significantly higher after treatment with RMPs. CONCLUSION: Our results suggest that RMPs trigger coagulation through TF signaling, induce the secretion of proinflammatory cytokines, and induce cell-cell interaction between platelets and neutrophils. Thus, under certain conditions, RMPs could play a role in post-transfusion complications through these mechanisms.

Antifactor Xa Activity for the Management of Anticoagulation during Cardiac Surgery.

Background In patients with autoimmune diseases associated with antiphospholipid antibodies, precise management of anticoagulation during extracorporeal circulation (ECC) is complicated. It was the aim of the present study to determine whether antifactor Xa (aXa) activity is useful in guiding heparin therapy during ECC. Methods In 15 patients undergoing cardiac surgery, anticoagulation with unfractionated heparin (UFH) and its reversal with protamine were guided using activated clotting time (ACT) (>400 second during ECC; ≤100 second for UFH reversal). For each ACT, the corresponding aXa activity levels were measured. Results A total of 144 blood samples were obtained. ACT and aXa activity were significantly correlated (r = 0.771, p< 0.0001, Spearman rank-order correlation). Using receiver operating characteristic curve (ROC) analyses, the cutoffvalues for aXa activity were 1.14 IU/mL (area under the ROC curve [AUC]: 0.89; inaccuracy rate: 9.4%) to predict ACT > 400 seconds and 0.55 IU/mL (AUC: 0.85; inaccuracy rate: 13.3%) for ACT ≤ 100 seconds. Conclusion AXa activity is strongly correlated with ACT, and therefore may be feasible for managing anticoagulation with UFH during ECC.

Coagulation management in trauma-associated coagulopathy: allogenic blood products versus coagulation factor concentrates in trauma care.

PURPOSE OF REVIEW: Coagulation management by transfusion of allogenic blood products and coagulation factors are competing concepts in current trauma care. RECENT FINDINGS: Rapid and adequate therapy of trauma-associated coagulopathy is crucial to survival of severely injured patients. Standard coagulation tests such as prothrombin time and activated partial thromboplastin time are commonly used, but these tests are inappropriate for monitoring and guiding therapy in trauma patients. Coagulation factor-based treatment showed promising results, but randomized trials have not yet been performed. In addition, viscoelastic tests are needed to guide therapy, although there is in fact limited evidence for these in tests in trauma care. Regarding transfusion therapy with allogenic blood products, plasma transfusion has been associated with improved survival in trauma patients following massive transfusion. In contrast, patients not requiring massive transfusion seem to be at risk for suffering complications with increasing volumes of plasma transfused. SUMMARY: The collective of trauma patients is heterogeneous. Despite the lack of evidence, there are strong arguments for individualized patient treatment with coagulation factors for some indications and to abstain from the use of fresh frozen plasma. In patients with severe trauma and major bleeding, plasma, platelets, and red blood cells should be considered to be administered at a ratio of 1 : 1 : 1.

Assessment of hemostatic changes after initiation of continuous venovenous hemodialysis.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a standard therapy in critically ill patients suffering from acute kidney injury (AKI). Extracorporeal circulation and exposure to foreign surfaces during CRRT may induce disturbances in hemostasis, particularly in platelet function. The present study described the hemostatic changes associated with CRRT and aimed to identify the independent predictors of premature clotting of the circuit. METHODS: In a prospective cohort mono-center study, patients were assessed for eligibility if they were i) diagnosed with AKI and ii) assigned to receive CRRT for the first time. Patients were included in the study if their platelet count was greater than 100/nL prior to inclusion in the study. After initiation of CRRT, aggregometric [Multiplate, Roche, Grenzach, Germany: Arachidonic acid (ASPItest)-, ADP (ADPtest)- and Thrombin (TRAPtest)-induced platelet aggregation] and viscoelastic (ROTEM; TEM International, Munich, Germany) analyses were performed immediately before (Baseline, T1) and 6 hours (T2), 12 hours (T3), 24 hours (T4), and 48 hours (T5) after initiation of CRRT. Conventional laboratory coagulation analyses were routinely performed twice a day. Arachidonic acid- and ADP-induced platelet aggregations were defined as primary endpoints. RESULTS: A total of 127 patients were screened for eligibility, and 50 patients were enrolled in this study. Aggregometric analyses showed that arachidonic acid-induced platelet aggregation was significantly reduced at T2 [532 (210/1105) median (25th/75th percentile) AU*min] compared to the Baseline at T1 [780 (297/1156), p = 0.007] and remained unchanged from T2 onward. Platelet aggregation in the ADPtest and TRAPtest remained unchanged during the study period. Viscoelastic and conventional coagulation analyses indicated a progredient increase of clot firmness. In total, 76 filter sets (an average of 1.5 per patient) were used, and 26 filter sets occluded prematurely after an average treatment time of 17 ± 12 hours. No predictors for premature clotting of the circuit were identified. CONCLUSIONS: The results of the present study indicate that CRRT may lead to impaired primary hemostasis as shown by a decrease in ex vivo arachidonic acid-induced platelet aggregation. Moreover, viscoelastic measure indicate a fibrinogen-associated trend of increasing clot firmness during the study period. Further studies are needed to analyze whether these findings are of hemostatic relevance.

Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation.

BACKGROUND: There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. PATIENTS AND METHODS: The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. RESULTS: A total of n = 40 patients were assessed for eligibility and n = 25 patients were finally enrolled into the study (hypothermic ECC group: n = 20; normothermic ECC group: n = 5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. CONCLUSION: Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction.

Hematologic Effects of Heart Valve Prostheses and Vascular Grafts after Aortic Root Replacement.

BACKGROUND: Heart valve prosthesis as well as vascular grafts cause changes in blood parameters. This may correlate with valve-related complications, less frequently observed after repair surgery. We thus studied changes in rheology after Bentall, Ross, or Tirone David (TD) procedure. METHODS: Seventeen patients underwent a TD, 17 patients underwent a Ross, and 16 patients underwent a Bentall procedure. Venous blood samples were collected 4 ± 3 (TD), 4 ± 3 (Ross), and 6 ± 3 years mean (Bentall) postoperatively. Concentrations of fibrinogen, leucocytes, platelets, haptoglobin, hemoglobin, lactate dehydrogenase (LDH), bilirubin, hematocrit, and ß-thromboglobulin were determined. Platelet function and activity were analyzed. Results were compared with those of healthy control subjects. RESULTS: Level of fibrinogen was higher in the Bentall than in the other two groups (338 ± 63 vs. 298 ± 43 Ross and 308 ± 48 mg/dL TD, p > 0.05). LDH was also elevated in the Bentall group (311 ± 45 vs. 205 ± 30 Ross, p < 0.01 and 203 ± 34 U/l TD, p < 0.01). Platelet count and haptoglobin levels were significantly reduced in the Bentall (190 ± 43/nL, 2.4 ± 1 mg/dL) and TD groups (183 ± 52/nL, 89 ± 57 mg/dL) in comparison to the control group (250 ± 86/nL, 140 ± 53 mg/dL) with p < 0.05, whereas there were no significant differences in the Ross group (214 ± 47/nL and 129 ± 54 mg/dL) in comparison to the control group. Leucocyte count and platelet function showed no significant differences between the groups. CONCLUSION: Polyester ascending aortic prostheses and more pronounced when combined with a prosthetic aortic valve cause hematologic changes compared with minimal deviations in Ross patients. We observed mild hemolysis, a decreased platelet count, and an increase in fibrinogen level in patients after conduit root replacement compared with procedures retaining an autologous aortic valve at midterm follow-up.

[Coagulation factor XIII ­ Pathophysiology, clinic and therapy of factor XIII deficiency]. / Der Gerinnungsfaktor XIII ­ Pathophysiologie, Klinik und Therapie von Mangelzuständen.

The complex activity of the transglutaminase factor XIII (FXIII) comprises central functions in secondary hemostasis. Congenital or acquired FXIII deficiencies may be associated with habitual abortions, impaired wound healing, coagulopathy and fatal hemorrhage. The present review describes physiological functions of FXIII, as well as pathophysiology, diagnostic and therapeutic options of FXIII deficiencies.

Aggregometric assessment of clonidine's impact on the efficacy of dual platelet inhibition.

BACKGROUND: Clonidine is commonly used as a calmative and antihypertensive agent in perioperative care. Due to the drug's alpha-2-agonistic effects, it has recently been hypothesised that clonidine may affect platelet aggregability. The present investigation aimed to study the potential impact of clonidine on the efficacy of dual antiplatelet therapy. METHODS: In this prospective, observational, single-centre study, patients treated with dual antiplatelet therapy were screened for eligibility. The patients were enrolled in the study if ex vivo thrombin-induced (TRAPtest), arachidonic acid-induced (ASPItest) and adenosine diphosphate-induced (ADPtest) platelet aggregation, as measured using multiple electrode aggregometry (MEA; Multiplate, Roche AG, Grenzach, Germany), confirmed efficient dual platelet inhibition. Ex vivo induced platelet aggregation was assessed before (baseline) and 3 minutes after (T1) spiking blood samples with either 1 ng/mL clonidine or sodium chloride 0.9% (control group). RESULTS: In total, 34 patients were finally enrolled in the study. Compared with baseline, platelet aggregation in the ASPItest and ADPtest was significantly increased at T1 in both groups. Platelet aggregation in the TRAPtest remained unchanged between baseline and T1 in both groups. Comparing platelet aggregation at T1, we detected no differences between blood samples that were spiked with clonidine and blood samples that were spiked with sodium chloride 0.9% in the TRAPtest, the ASPItest, or the ADPtest. CONCLUSIONS: The results of this study indicate that clonidine does not affect platelet aggregability in patients treated with dual antiplatelet therapy. The findings of the study also indicate that ex vivo induced platelet aggregation in the ASPItest and ADPtest increases with the duration between blood drawing and MEA analyses.

Hemotherapy algorithms for coagulopathic cardiac surgery patients.

In patients undergoing cardiac surgery, perioperative coagulopathy and the use of allogenic blood products are independently associated with increased mortality and major perioperative cardiac and non-cardiac adverse events. Hemotherapy should be based on specific hemotherapy algorithms rather than "clinical judgments". However, whether hemotherapy should be based on "classical" conventional laboratory coagulation analyses or Point-of-Care (POC) measures is discussed controversially. There is very good evidence from retrospective studies and prospective randomized controlled trials that the implementation of viscoelastic and aggregometric measurements in hemostatic therapy algorithms may reduce the transfusion rate of allogenic blood products. Furthermore, data suggest improved clinical outcome. Unfortunately, the studied hemotherapy--algorithms are very complex and thus hard to integrate into daily practice. In close cooperation of three German University Hospitals, the authors developed and implemented two more comprehensive and practical hemotherapy algorithms that are based on either POC measures or conventional coagulation testing. Here we present and discuss the structure and limitations of these algorithms.

Response to dual antiplatelet therapy in patients with peripheral artery occlusive disease suffering from critical limb ischemia.

BACKGROUND: Failure to reach the level of therapeutic anticoagulation represents a risk factor for occlusive events in patients suffering from peripheral arterial disease. Our study aimed to analyze the prevalence of nonresponse to dual antiplatelet therapy in a group of patients admitted to our hospital with critical limb ischemia (CLI) following stent-thrombosis. METHODS: This prospective study was approved by the local Ethics Review Board. Patients with critical limb ischemia following stent thrombosis were included if dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel per day had been administered over three months prior to enrollment. The antiaggregatory effects were analyzed using the Multiple Electrode Aggregometry (MEA, Multiplate®, Roche AG, Grenzach, Germany). The primary endpoints were the area under the aggregation curve (AUC) of the ex-vivo-induced platelet aggregation following stimulation with adenosine diphosphate (ADP, ADPtest) and arachidonic acid (ASPItest). RESULTS: Sixty patients were enrolled in this study. Platelet aggregation was 39.6 (24/54) [median (25th/75th percentile)] U in the ADPtest and 22.4 (13/35) U in the ASPItest. Effective aspirin- and ADP-induced therapeutic inhibition of platelet aggregation was confirmed in 78% and 53% of our patients, respectively. Effective dual platelet inhibition was achieved in 27 patients (45%). A non-response to both of the antiaggregatory drugs was found in 14% of the patients. CONCLUSIONS: The results of the present study indicate a high prevalence of nonresponse to antiaggregatory medication in our study collective. Further studies are needed to confirm our hypothesis that individual adjustments of both aspirin and clopidogrel dosages may potentially reduce the incidence of CLI in patients suffering from peripheral arterial occlusive disease.

Safety and effectiveness of a Patient Blood Management (PBM) program in surgical patients--the study design for a multi-centre prospective epidemiologic non-inferiority trial.

BACKGROUND: Preoperative and hospital-acquired anaemia is common among surgical patients. It is associated with an increased risk of morbidity and mortality and a strong risk factor for allogeneic blood transfusions with their own inherent risks. Patient Blood Management (PBM) concepts aim to increase and preserve autologous erythrocyte volume and to optimise haemotherapy. They thus have great potential to benefit patients. METHODS/DESIGN: This prospective, multi-centre clinical trial tests the hypothesis that PBM programs are safe and effective in the care of adult surgical patients. Primary outcome is a composite endpoint of adverse events and in-hospital mortality. DISCUSSION: This trial will determine whether the implementation of a PBM program is safe and effective in terms of clinical outcome compared to a pre-implementation cohort. This trial is registered at www.clinicaltrials.gov (NCT01820949).

[Hemorrhage after accidental overdosage of enoxaparin: monitoring and therapy]. / Kasuistik - Hämorrhagie nach akzidenteller Überdosierung mit Enoxaparin: Monitoring und Therapie.

At the morning of the sixth postoperative day after a complex cardiac surgery procedure, a patient accidentally received a subcutaneous injection of 450 mg Enoxaparin sodium (Clexane®, Sanofi GmbH, Frankfurt, Germany). A few hours later an excessive coagulopathy developed and necessitated the transfusion of allogenic blood products. The present case report describes and discusses our diagnostic and therapeutic approaches.

A novel method for the direct determination of heparin concentration during cardiopulmonary bypass surgery.

BACKGROUND: Heparin is the standard drug for anticoagulation treatment and is used in many cardiac surgical interventions to prevent blood clotting. The anticoagulation status is controlled by various clotting tests. However, these tests depend on parameters like temperature, hemodilution etc. and are thus not applicable for a direct monitoring of the heparin concentration. The aim of this prospective study was to test a novel light scattering assay (LiSA) for the direct determination of heparin concentration during cardiopulmonary bypass (CPB) surgery and to compare the heparin concentrations with routinely determined activated clotting time (ACT). METHODS: The patient group consisted of 50 patients undergoing coronary bypass surgery with CPB. The coagulation status was monitored by the measurement of ACT, which was performed approximately every 30 min during surgery. Parallel to each ACT measurement, the heparin concentration was measured by LiSA. RESULTS: For 70% of the patients, ACT and heparin concentration measured by LiSA correlated reasonably over the entire time course of the intervention. For 30% of the patients, an insufficient correlation or even no correlation at all was observed. CONCLUSIONS: This study showed that LiSA enables the determination of intra-operative heparin levels. The lack of correlation between ACT and heparin concentration in a substantial group of patients shows that monitoring of heparin concentration is important. A more precise blood coagulation management, in particular, a precise administration of heparin and protamine, should be based on a combination of the measurement of heparin concentration and of ACT, but not on ACT alone.

Investigation of acquired dysfibrinogenaemia in adult patients with sepsis using fibrinogen function vs. concentration ratios: a cross-sectional study.

Introduction: Inherited or acquired molecular abnormalities form a clinically heterogeneous group of fibrinogen disorders called dysfibrinogenaemia. Apart from a pediatric case report and in contrast to other clinical conditions, acquired dysfibrinogenaemia has not been previously reported in septic patients. Methods: In an observational cohort study, 79 adult septic patients were investigated for the presence of acquired dysfibrinogenaemia at the time of their admission to the intensive care unit (ICU) of the University Hospital Frankfurt. Following established recommendations, fibrinogen clotting activity vs. antigen ratios were analyzed using Clauss fibrinogen, prothrombin-derived fibrinogen, and radial immunodiffusion (RID) fibrinogen concentration. Results: Prothrombin-derived fibrinogen levels were highest (527 ± 182 mg/dL) followed by Clauss fibrinogen (492 ± 209 mg/dL) and radial immunodiffusion fibrinogen (426 ± 159 mg/dL). Very few cases demonstrated hypofibrinogenaemia making overt disseminated intravascular coagulation (DIC) unlikely in the cohort investigated. Clauss/RID fibrinogen ratios were lower (1.17 ± 0.19) compared to prothrombin time-derived/RID ratios (1.35 ± 0.33). Using the Clauss/RID dataset, 21% of patients (16/76 patients) demonstrated values below a threshold ratio for suspected acquired dysfibrinogenaemia arbitrarily set at 1.0. In contrast, prothrombin-derived ratios were below the threshold in only 7% (4/58 patients). Discussion: The results point to the presence of acquired dysfibrinogenaemia in part of adult septic patients. If confirmed in further studies, this may form part of a specific laboratory signature of a sepsis-associated coagulation phenotype.

Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients.

INTRODUCTION: The current investigation aimed to study the efficacy of hemostatic therapy guided either by conventional coagulation analyses or point-of-care (POC) testing in coagulopathic cardiac surgery patients. METHODS: Patients undergoing complex cardiac surgery were assessed for eligibility. Those patients in whom diffuse bleeding was diagnosed after heparin reversal or increased blood loss during the first 24 postoperative hours were enrolled and randomized to the conventional or POC group. Thromboelastometry and whole blood impedance aggregometry have been performed in the POC group. The primary outcome variable was the number of transfused units of packed erythrocytes during the first 24 h after inclusion. Secondary outcome variables included postoperative blood loss, use and costs of hemostatic therapy, and clinical outcome parameters. Sample size analysis revealed a sample size of at least 100 patients per group. RESULTS: There were 152 patients who were screened for eligibility and 100 patients were enrolled in the study. After randomization of 50 patients to each group, a planned interim analysis revealed a significant difference in erythrocyte transfusion rate in the conventional compared with the POC group [5 (4;9) versus 3 (2;6) units [median (25 and 75 percentile)], P<0.001]. The study was terminated early. The secondary outcome parameters of fresh frozen plasma and platelet transfusion rates, postoperative mechanical ventilation time, length of intensive care unit stay, composite adverse events rate, costs of hemostatic therapy, and 6-month mortality were lower in the POC group. CONCLUSIONS: Hemostatic therapy based on POC testing reduced patient exposure to allogenic blood products and provided significant benefits with respect to clinical outcomes.

[Modern coagulation management reduces the transfusion rate of allogenic blood products]. / Rationaler Einsatz von Blutprodukten - Reduzierung des Blutprodukteverbrauchs durch ein modernes Gerinnungsmanagement.

Evaluating the patient's individual bleeding history with a standardized questionnaire, using "point-of-care" - methods for coagulation analyses and providing autologous transfusion techniques are preconditions of a modern coagulation management. Therapy of coagulopathic patients should be based on structured hemotherapy algorithms. Surgical haemostasis and the maintenance of the basic conditions for haemostasis are elementary requirements for an effective therapy. In cases of diffuse bleeding, early antifibrinolytic therapy should be considered. Coagulation factor deficiencies should be corrected "goal-directed" using coagulation factor concentrates. Transfusion of fresh frozen plasma is only indicated in the clinical setting of massive transfusions. DDAVP and transfusion of platelet concentrates are options to optimize primary haemostasis. In cases of on-going bleeding, recombinant activated coagulation factor VII represents an option for "ultima-ratio" therapy.