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.

New Insights in the Occurrence of Venous Thromboembolism in Critically Ill Patients with COVID-19-A Large Postmortem and Clinical Analysis.

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41-4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.

The Pre- and Postoperative Prevalence and Risk Factors of ASA Nonresponse in Vascular Surgery.

BACKGROUND: An antiplatelet therapy with acetylsalicylic acid (ASA) is prescribed in the prevention of cardiovascular events, but around 24% of ASA takers are resistant to the treatment. AIM: In this prospective, observational cohort study, we aimed to identify the prevalence and risk factors of ASA nonresponse in patients who underwent vascular surgery. METHODS: The study was conducted in the University hospital in Frankfurt am Main. In total, 70 patients were pre-treated with 100 mg of ASA per day and underwent either elective carotid thromboendarterectomy, femoral thromboendarterectomy or endovascular aneurysm repair of the abdominal aorta. The platelet function was measured on the first preoperative and the second or fourth postoperative day with the multiple electrode aggregometry by in-vitro stimulation with arachidonic acid (ASPItest) and thrombin receptor activating peptide 6 (TRAPtest). The primary end point was the in-vitro induced platelet aggregation in the ASPItest. If the ASPItest amounted ≥400 AU × min, the patients were categorized as ASA nonresponders. RESULTS: The total prevalence of ASA nonresponse in our study was 20% preoperatively and 35.7% postoperatively (p = 0.005). As significant predictors for ASA nonresponse, we demonstrated the area under the aggregation curve in the TRAPtest preoperatively (p = 0.04) and postoperatively (p = 0.02), and the two comorbidities arterial hypertension (P < .001; rho 0.44) and diabetes mellitus (p = 0.04; rho 0.39), which are already well known to be associated with ASA nonresponse. CONCLUSION: In conclusion, data of the study indicate a high incidence of perioperative, laboratory ASA nonresponse in patients undergoing vascular surgery.

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.

Prospective Evaluation of the Pre-, Intra-, and Postoperative Kinetics of ADAMTS-13, von Willebrand Factor, and Interleukin-6 in Vascular Surgery.

Postoperative thrombotic thrombocytopenic purpura (TTP) shows clinical presentation similar to classical TTP, whereas exact pathophysiological contexts remain unexplained. In this study, we investigated intraoperative and postoperative changes in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13), von Willebrand factor (VWF), large VWF multimers, and interleukin-6 (IL-6) in vascular surgery patients. The objective was to compare the impact of endovascular, peripheral, and aortic surgery on target parameters which are supposed to play a role in surgery-associated TTP. A total of 93 vascular surgery patients were included and divided into 4 groups according to the specific type of intervention they underwent. Blood samples were taken preoperatively, intraoperatively, and postoperatively on days 2 and 4. The ADAMTS-13 activity decreased significantly in 3 of the 4 groups during surgery (from median 81% to 49%, P < .001, in the group undergoing aortoiliacal interventions), whereas the percentage of large VWF multimers increased in all groups of patients. von Willebrand factor antigen increased significantly in all groups on postoperative day 2 and IL-6 increased significantly in the intraoperative and early postoperative period. There was no significant correlation between the intraoperative decrease in ADAMTS-13 and the increase in VWF or IL-6. No patient in this study showed clinical picture of TTP; the precise cause and clinical significance of moderately reduced ADAMTS-13 activity in the perioperative setting have not yet been definitely determined.

Assessment of hemostatic profile in patients with mild to advanced liver cirrhosis.

BACKGROUND: Hemostasis of patients suffering from liver cirrhosis is challenging due to both, pro- and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation. Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients. However, conventional coagulation analysis and platelet count do not reflect in-vivo coagulation status or platelet function. The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis. AIM: To assess the hemostatic profile of cirrhotic patients according to model for end-stage liver disease (MELD) score. METHODS: Our study included both in- and outpatients suffering from liver cirrhosis attending the out- and inpatient care of the department of hepatology. Demographic and biochemical data as well as medical history including cause of liver cirrhosis, end stage kidney failure and medication with anticoagulants were recorded. To assess the hemostatic profile, platelet function was analyzed by multiple electrode aggregometry (MEA) using Multiplate® (ADP-, ASPI- and TRAP-test) and thrombelastometry using ROTEM® (EXTEM, INTEM, FIBTEM). Data were compared using Mann-Whitney U- or χ 2-test. Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA. RESULTS: A total of 68 patients attending the out- and inpatient care suffering from liver cirrhosis were screened. Of these, 50 patients were included and assigned to groups according to MELD score 6 to 11 (n = 25) or ≥ 17 (n = 25). Baseline patient characteristics revealed significant differences for MELD score (8 vs 22, P < 0.0001) and underlying laboratory parameters (international normalized ratio, bilirubine, creatinine) as well as fibrinogen level (275 mg/dL vs 209 mg/dL, P = 0.006) and aPTT (30 s vs 35 s, P = 0.047). MEA showed a moderately impaired platelet function (medians: AUCADP = 43U, AUCASPI = 71U, AUCTRAP = 92U) but no significant differences between both groups. Thrombelastometry using ROTEM® (EXTEM, INTEM, FIBTEM) revealed values within normal range in both groups. No significant correlation was observed between MELD score and results of MEA/thrombelastometry. CONCLUSION: Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score. An individual assessment of a potential coagulopathy should therefore be considered.

[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.

The Prevalence and Clinical Relevance of ASA Nonresponse After Cardiac Surgery: A Prospective Bicentric Study.

We aimed to identify the prevalence of acetylsalicylic acid (ASA) nonresponse in patients after coronary artery bypass graft (CABG) surgery and the possible consequences for the rate of major cardiovascular events. This prospective, observational, bicentric cohort study was conducted in two German University hospitals. A total of 400 patients (200 in each study center) undergoing elective CABG surgery were enrolled after written informed consent. Platelet function was analyzed on day 3 (d3) and day 5 (d5) postoperatively following stimulation with arachidonic acid (ASPItest) and with thrombin receptor-activating peptide 6 (TRAPtest) using multiple electrode aggregometry (Multiplate). Individuals with an ASPItest ≥40 AU·min were categorized as ASA nonresponders. A 1-year follow-up recorded the combined end point of cardiovascular events, hospital admissions, or deaths related to cardiovascular disease. The prevalence of ASA nonresponse was 51.5% on d3, and it significantly increased to 71.3% on d5 ( P = .0049). The area under the aggregation curve in the TRAPtest ( P < .0001), the platelet count on d5 ( P = .009), and the cardiopulmonary bypass time ( P = .01) were identified as independent predictors of an ASA nonresponse. A 1-year follow-up recorded 54 events fulfilling criteria for the combined end point with no difference between ASA responders and nonresponders. This study indicates a high incidence of perioperative ASA nonresponse in patients following CABG. No effect on the incidence of cardiovascular events was recorded in the 1-year follow-up. Therefore, a randomized dosage adjustment trial should elucidate whether a tailored ASA treatment after CABG surgery represents a useful concept.

Laryngeal tube suction for airway management during in-hospital emergencies.

OBJECTIVE:: The role of supraglottic airway devices in emergency airway management is highlighted in international airway management guidelines. We evaluated the application of the new generation laryngeal tube suction (LTS-II/LTS-D) in the management of in-hospital unexpected difficult airway and cardiopulmonary resuscitation. METHODS:: During a seven-year period, patients treated with a laryngeal tube who received routine anesthesia and had an unexpected difficult airway (Cormack Lehane Grade 3-4), who underwent cardiopulmonary resuscitation, or who underwent cardiopulmonary resuscitation outside the operating room and had a difficult airway were evaluated. Successful placement of the LTS II/LTS-D, sufficient ventilation, time to placement, number of placement attempts, stomach content, peripheral oxygen saturation/end-tidal carbon dioxide development (SpO2/etCO2) over 5 minutes, subjective overall assessment and complications were recorded. RESULTS:: In total, 106 adult patients were treated using an LTS-II/LTS-D. The main indication for placement was a difficult airway (75%, n=80), followed by cardiopulmonary resuscitation (25%, n=26) or an overlap between both (18%, n=19). In 94% of patients (n=100), users placed the laryngeal tube during the first attempt. In 93% of patients (n=98), the tube was placed within 30 seconds. A significant increase in SpO2 from 97% (0-100) to 99% (5-100) was observed in the whole population and in cardiopulmonary resuscitation patients. The average initial etCO2 of 39.5 mmHg (0-100 mmHg) decreased significantly to an average of 38.4 mmHg (10-62 mmHg) after 5 minutes. A comparison of cardiopulmonary resuscitation patients with non-cardiopulmonary resuscitation patients regarding gastric contents showed no significant difference. CONCLUSIONS:: LTS-D/LTS-II use for in-hospital unexpected difficult airway management provides a secure method for primary airway management until other options such as video laryngoscopy or fiber optic intubation become available.

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.

Laryngeal tube suction for airway management during in-hospital emergencies

OBJECTIVE: The role of supraglottic airway devices in emergency airway management is highlighted in international airway management guidelines. We evaluated the application of the new generation laryngeal tube suction (LTS-II/LTS-D) in the management of in-hospital unexpected difficult airway and cardiopulmonary resuscitation. METHODS: During a seven-year period, patients treated with a laryngeal tube who received routine anesthesia and had an unexpected difficult airway (Cormack Lehane Grade 3-4), who underwent cardiopulmonary resuscitation, or who underwent cardiopulmonary resuscitation outside the operating room and had a difficult airway were evaluated. Successful placement of the LTS II/LTS-D, sufficient ventilation, time to placement, number of placement attempts, stomach content, peripheral oxygen saturation/end-tidal carbon dioxide development (SpO2/etCO2) over 5 minutes, subjective overall assessment and complications were recorded. RESULTS: In total, 106 adult patients were treated using an LTS-II/LTS-D. The main indication for placement was a difficult airway (75%, n=80), followed by cardiopulmonary resuscitation (25%, n=26) or an overlap between both (18%, n=19). In 94% of patients (n=100), users placed the laryngeal tube during the first attempt. In 93% of patients (n=98), the tube was placed within 30 seconds. A significant increase in SpO2 from 97% (0-100) to 99% (5-100) was observed in the whole population and in cardiopulmonary resuscitation patients. The average initial etCO2 of 39.5 mmHg (0-100 mmHg) decreased significantly to an average of 38.4 mmHg (10-62 mmHg) after 5 minutes. A comparison of cardiopulmonary resuscitation patients with non-cardiopulmonary resuscitation patients regarding gastric contents showed no significant difference. CONCLUSIONS: LTS-D/LTS-II use for in-hospital unexpected difficult airway management provides a secure method for primary airway management until other options such as video laryngoscopy or fiber optic intubation become available.

Patient Blood Management Bundles to Facilitate Implementation.

More than 30% of the world's population are anemic with serious economic consequences including reduced work capacity and other obstacles to national welfare and development. Red blood cell transfusion is the mainstay to correct anemia, but it is also 1 of the top 5 overused procedures. Patient blood management (PBM) is a proactive, patient-centered, and multidisciplinary approach to manage anemia, optimize hemostasis, minimize iatrogenic blood loss, and harness tolerance to anemia. Although the World Health Organization has endorsed PBM in 2010, many hospitals still seek guidance with the implementation of PBM in clinical routine. Given the use of proven change management principles, we propose simple, cost-effective measures enabling any hospital to reduce both anemia and red blood cell transfusions in surgical and medical patients. This article provides comprehensive bundles of PBM components encompassing 107 different PBM measures, divided into 6 bundle blocks acting as a working template to develop institutions' individual PBM practices for hospitals beginning a program or trying to improve an already existing program. A stepwise selection of the most feasible measures will facilitate the implementation of PBM. In this manner, PBM represents a new quality and safety standard.

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.

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 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.

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.

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.