Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

OBJECTIVES: Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. MATERIALS AND METHODS: We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/µL. RESULTS: Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. CONCLUSIONS: End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.

Delayed surgery for acute type A aortic dissection: a retrospective review of an alternative surgical strategy in the COVID-19 era.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, medical resources have often been limited to emergency surgeries. This study aimed to evaluate our experience with delayed surgery for acute type A aortic dissections (ATAADs). METHODS: A retrospective study was conducted on 33 patients who underwent surgery for ATAADs between January 2020 and December 2021. The patients were divided into two groups: patients treated within 12 h of arrival (E group; N = 21) and those treated > 12 h after arrival (D group; N = 12) with strict antihypertensive therapy until surgery. RESULTS: The plasma fibrinogen levels on arrival were lower in the D group than in the E group (174.3 ± 109.1 vs 293.4 ± 165.4, p = 0.038). The time to surgery from symptom onset was longer in the D group than in the E group (4 ± 1 h vs. 86 ± 108 h, p < 0.001). There was one case (3%) of mortality and seven cases (21%) of cerebral infarctions in the E group. There was no significant difference in the intraoperative data and quantity of blood transfused between the two groups. CONCLUSION: Thus, delayed surgery for ATAAD with appropriate preoperative management may be an alternative surgical strategy in the COVID-19 era.

Assessing hypercoagulability and VTE risk using thromboelastography and Khorana score in women with cancers receiving chemotherapy.

Venous thromboembolism (VTE) is a common occurrence in cancer and chemotherapy increases thrombosis risk. Current risk assessment models such as the Khorana score (KS) and its modifications have limitations in female cancers. We assessed the coagulation profile of a group of women cancer patients under chemotherapy using thromboelastography (TEG) to determine if this can inform VTE risk assessment. Cancer patients who planned to receive chemotherapy were recruited. Baseline demographics, cancer data, BMI, Khorana Score (KS), and VTE risk factors were recorded and patients were followed for 6 months, for any thrombotic events. A total of 36 patients aged 35-85 (18 breast, 11 endometrial, 7 ovarian cancer) were evaluated. Hypercoagulability was detected in 63% of patients post-chemo cycle 1 and 75% post-cycle 2, with a significant increase in MA (maximum amplitude) and CI (clotting index), reduction in R (reaction time), K (clot kinetics), and LY30 (lysis time after 30 min of MA). KS showed only 7% of patients were high risk, 23% were low, and 70% were intermediate risk. MA and CI significantly increased in patients with intermediate and high-risk KS when compared with the low-risk patients and MA was positively correlated with KS. Five patients developed actual VTE; 100% of the tested ones were hypercoagulable either post-cycle 1 or 2 and 80% were KS intermediate risk. TEG is a hypercoagulability marker and TEG-MA and CI can potentially assess VTE risk. Larger studies are needed to assess the utility of TEG as an adjuvant to KS to better predict VTE in specific female cancers.

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan-1 study.

OBJECTIVE: The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow's triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation. METHODS: With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM Sigma, and the concentration of syndecan-1 was determined by ELISA. RESULTS: In the ROTEM analyses, the A5, A10, and maximum clot firmness (MCF) values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays, indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p < .026) and controls (p < .03), suggesting differences in the state of endothelium. CONCLUSIONS: For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Diagnostic value of clot formation parameters determined by rotational thromboelastometry in 63 patients with congenital dysfibrinogenemia.

Rotational thromboelastometry (ROTEM) is a global hemostasis assay. The diagnosis added value of ROTEM in congenital dysfibrinogenemia remains to be established. The aim of this study was to analyze clot formation by ROTEM in a cohort of dysfibrinogenemic patients and to establish correlations with genotype, clinical features, and coagulation parameters. The study included genetically confirmed congenital dysfibrinogenemia cases (n = 63) and healthy controls ( n  = 50). EXTEM, INTEM, FIBTEM tests were used to measure ROTEM parameters, that is, clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and amplitude 10 min after CT (A10). The ISTH bleeding assessment tool was used to determine bleeding episodes. CT (INTEM) was statistically significantly shorter in congenital dysfibrinogenemia patients compared to controls while CFT (EXTEM) was prolonged. Patients's MCF in EXTEM, INTEM, and FIBTEM were similar to controls while A10 (FIBTEM) was statistically significantly lower. Fibrinogen activity was positively correlated with fibrinogen antigen, A10 and MCF in all three assays. Bleeding phenotypes were observed in 23 (36.5%) patients. Only CFT in EXTEM and CT in INTEM were statistically different in patients with bleeding phenotype versus controls. Carriers of the FGA mutation p.Arg35His had a CT (EXTEM) slightly prolonged and a reduced A10 (FIBTEM) compared to controls. Some ROTEM parameters were able to distinguish congenital dysfibrinogenemia patients from controls, and patients with a bleeding phenotype. Prolonged CFT in EXTEM were associated with congenital dysfibrinogenemia and bleeding phenotype. Bleeding episodes in most patients were generally mild and prevalence of thrombosis was very low.

Description of an In Vitro Platelet Function Analyzer-PFA-100™.

This manuscript represents a republication of a manuscript originally published in STH in 1995. This republication is to help celebrate 50 years of publishing for STH. The original abstract follows.A new in vitro system for the detection of platelet dysfunction, PFA-100®, has been developed. It provides a quantitative measure of platelet function in anticoagulated whole blood. The system comprises a microprocessor-controlled instrument and a disposable test cartridge containing a biologically active membrane. The instrument aspirates a blood sample under constant vacuum from the sample reservoir through a capillary and a microscopic aperture cut into the membrane. The membrane is coated with collagen and epinephrine or adenosine 5'-diphosphate. The presence of these biochemical stimuli, and the high shear rates generated under the standardized flow conditions, result in platelet attachment, activation, and aggregation, slowly building a stable platelet plug at the aperture. The time required to obtain full occlusion of the aperture is reported as the "closure time." We have found that impairment of von Willebrand factor, or inhibition of platelet receptors glycoprotein Ib or IIb/IIIa with monoclonal antibodies or peptides, resulted in abnormal closure times. An antifibrinogen antibody, in contrast, failed to show any effect. The test appears to be sensitive to platelet adherence and aggregation abnormalities. The PFA-100® system has potential applications in routine evaluation of platelet function in the clinical setting because of its accuracy, case of operation, and rapid turnaround of results.

Comparisons between diluted thrombin time, ecarin chromogenic assays, and UPLC-MS for plasma level dabigatran quantification: Results from DRIVING study.

INTRODUCTION: The knowledge of dabigatran levels is helpful for decision-making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high-performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30-50 ng/mL clinically relevant thresholds. METHODS: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300-mg dabigatran etexilate dose. Serial blood samplings were performed at pre-defined time points (0 to 24 h). We analyzed plasma samples using ultra-performance-liquid chromatography coupled with tandem mass spectrometry (UPLC-MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot-DTI-Hyphen-Biomed); iii/ecarin-based chromogenic assay (ECA-II-Stago). RESULTS: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA-II values were highly correlated with those of UPLC-MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA-II compared to UPLC-MS: biases were constant, +14% and +16% with dTT and ECA-II, respectively (Bland-Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30-50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA-II was of 90.6% [88.4-92.5] (Cohen's kappa coefficient 0.84). CONCLUSION: dTT and ECA-II assays rapidly provide accurate dabigatran-level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites.

Global hemostasis assays in acute myeloid leukemia: results of an observational prospective study.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by a complex spectrum of coagulopathy ranging from hemorrhagic to thrombotic symptoms. To date, platelet count (PLT) and conventional coagulation tests (CCTs) cannot predict hemorrhagic events and thrombotic risk. Thromboelastography (TEG) measures the viscoelastic properties of the clot, thus providing information on the entire process of blood coagulation. The primary aim of the study was to assess the hemostatic balance from AML diagnosis to the end of chemotherapy (CHT) by TEG. MATERIAL AND METHODS: Here we present the results of a prospective study enrolling newly diagnosed AML patients treated with chemotherapy. Patients had complete blood counts (CBCs), TEG and CCTs performed at three time points: 1) diagnosis (T0); 2) during the first cycle of CHT (T1); and 3) at the end of CHT (T2). An algorithm of TEG indirectly calculated thrombin generation (TG). Patients underwent daily follow-up for bleeding and thrombotic episodes up to the time of hospital discharge or death. RESULTS: Eighty consecutive patients were evaluated; forty were eligible for the study, and 21 completed the entire study. At T1, maximum amplitude (MA), TG and K-time were significantly shifted toward a hypocoagulability state compared to T0 (p<0.05), while a hypercoagulable state at T2 was shown by changes in α-angle, MA and TG values. Otherwise, there were no statistically significant differences in CCTs between the evaluated time points. DISCUSSION: Overall, TEG revealed complex and dynamic coagulation abnormalities in patients with AML according to both the course of disease and therapy. Further studies are needed to investigate more fully the role of TEG in defining the hemostatic profile in patients with AML.

Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration.

ABSTRACT: Transglutaminase factor XIII (FXIII) is essential for hemostasis, wound healing, and pregnancy maintenance. Plasma FXIII is composed of A and B subunit dimers synthesized in cells of hematopoietic origin and hepatocytes, respectively. The subunits associate tightly in circulation as FXIII-A2B2. FXIII-B2 stabilizes the (pro)active site-containing FXIII-A subunits. Interestingly, people with genetic FXIII-A deficiency have decreased FXIII-B2, and therapeutic infusion of recombinant FXIII-A2 (rFXIII-A2) increases FXIII-B2, suggesting FXIII-A regulates FXIII-B secretion, production, and/or clearance. We analyzed humans and mice with genetic FXIII-A deficiency and developed a mouse model of rFXIII-A2 infusion to define mechanisms mediating plasma FXIII-B levels. Like humans with FXIII-A deficiency, mice with genetic FXIII-A deficiency had reduced circulating FXIII-B2, and infusion of FXIII-A2 increased FXIII-B2. FXIII-A-deficient mice had normal hepatic function and did not store FXIII-B in liver, indicating FXIII-A does not mediate FXIII-B secretion. Transcriptional analysis and polysome profiling indicated similar F13b levels and ribosome occupancy in FXIII-A-sufficient and -deficient mice and in FXIII-A-deficient mice infused with rFXIII-A2, indicating FXIII-A does not induce de novo FXIII-B synthesis. Unexpectedly, pharmacokinetic/pharmacodynamic modeling of FXIII-B antigen after rFXIII-A2 infusion in humans and mice suggested FXIII-A2 slows FXIII-B2 loss from plasma. Accordingly, comparison of free FXIII-B2 vs FXIII-A2-complexed FXIII-B2 (FXIII-A2B2) infused into mice revealed faster clearance of free FXIII-B2. These data show FXIII-A2 prevents FXIII-B2 loss from circulation and establish the mechanism underlying FXIII-B2 behavior in FXIII-A deficiency and during rFXIII-A2 therapy. Our findings reveal a unique, reciprocal relationship between independently synthesized subunits that mediate an essential hemostatic protein in circulation. This trial was registered at www.ClinicalTrials.com as #NCT00978380.

Thrombin generation assay in platelet-poor plasma in children with iron deficiency anemia.

OBJECTIVES: Iron deficiency anemia (IDA) is the most common type of anemia in childhood and it leads to a hypercoagulable state. We investigated endogenous thrombin production in platelet-poor plasma before and after oral iron replacement in children with IDA using the thrombin generation assay (TGA). METHODS: A total of 72 children diagnosed with IDA (IDA group) and 60 healthy children (control group) were included in the study. Blood samples were collected from the patients before and 1 month after oral iron replacement. TGA parameters [lag time, time to peak, peak height, endogenous thrombin potential (ETP)] were studied. RESULTS: In the IDA group, the lag time and time to peak decreased by 8.3% and 10.6%, respectively, and the endogenous thrombin potential (ETP) and peak height both increased by 30% compared to those of the control group. Compared to the values before iron replacement, 1 month after iron replacement, the lag time and time to peak increased by 8.7% and 5%, respectively, and the ETP and peak height decreased by 31% and 31.3%, respectively, and became similar to those of the control group. CONCLUSION: Children with IDA have increased endogenous thrombin production in platelet-poor plasma and a tendency for hypercoagulability. These changes are reversible, and the ETP values become similar to those of healthy children 1 month after iron replacement.

Exploration of rotational thromboelastometry (ROTEM) to characterize the coagulation profiles of newly diagnosed pediatric leukemia patients.

BACKGROUND: Viscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. OBJECTIVES: Analyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT's and Rotational Thromboelastometry (ROTEM). METHODS: Pediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. RESULTS: Sixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/µL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). CONCLUSION: Fibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement.

Clot waveform analysis in acute promyelocytic leukemia.

The aim of this study was to evaluate the activated partial thromboplastin time (APTT) and prothrombin time (PT)-based clot waveform analysis (CWA) in patients diagnosed with acute promyelocytic leukemia (APL). APTT-based and PT-based CWA parameters of patients diagnosed with APL were analyzed and compared with healthy volunteers. Four APTT-CWA parameters were noted, maximum velocity corresponding to the first peak of the first derivative (max1), maximum acceleration corresponding to the first peak of the second derivative (max2) and the corresponding peak times of max1 and max2 (Tmax1, Tmax2). For the PT-CWA, two PT-CWA parameters were noted, maximum velocity (max1') and the corresponding timing (Tmax1'). The results were expressed in medians. Mann-Whitney U test was used to compare the CWA parameters. Correlations were examined using the Spearman correlation test. Tmax1 and Tmax2 were significantly prolonged in patients with APL in comparison with healthy volunteers. Although max1 and max2 were lower in APL patients compared with healthy volunteers, no significant difference was noted. There was a strong and significant correlation between the DIC score and the parameters max1, max2 and max1' and a very strong and significant correlation between fibrinogen levels and max1, max2 and max1'. When comparing DIC patients with hypofibrinogenemia and DIC without hypofibrinogenemia, a significant difference was noted in max1, max2, Tmax1 and Tmax2. The APTT and PT-based CWA analysis is a good tool to evaluate the bleeding tendency in APL, as it offers a novel approach for evaluating global hemostasis, predicting the bleeding risk and delivering improvements to APL patients management.

Trauma-induced coagulopathy: What you need to know.

ABSTRACT: Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, which occurs after traumatic injury. It occurs in approximately 25% of severely injured patients, and its incidence is directly related to injury severity. The mechanism of TIC is multifaceted; proposed contributing factors include dysregulation of activated protein C, increased tPA, systemic endothelial activation, decreased fibrinogen, clotting factor consumption, and platelet dysfunction. Effects of TIC include systemic inflammation, coagulation derangements, acidemia, and hypothermia. Trauma-induced coagulopathy may be diagnosed by conventional coagulation tests including platelet count, Clauss assay, international normalized ratio, thrombin time, prothrombin time, and activated partial thromboplastin time; viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastography; or a clinical scoring system known as the Trauma Induced Coagulopathy Clinical Score. Preventing TIC begins in the prehospital phase with early hemorrhage control, blood product resuscitation, and tranexamic acid therapy. Early administration of prothrombin complex concentrate is also being studied in the prehospital environment. The mainstays of TIC treatment include hemorrhage control, blood and component transfusions, and correction of abnormalities such as hypocalcemia, acidosis, and hypothermia. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Clues of incomplete reversal of heparin in cardiac surgery.

OBJECTIVES: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. METHODS: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. RESULTS: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p < .0001) and 0.95 (p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]. CONCLUSION: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin.

[Does a preoperative coagulation sheet change the postoperative bleeding rate after adenoidectomy?] / Verändert die Einführung eines präoperativen Gerinnungsbogens die Nachblutungsrate nach Adenotomie?

BACKGROUND: Adenoidectomy (AT) represents one of the first and most common surgeries in childhood. A joint statement of the German Society for Anesthesiology & Intensive Care Medicine as well as Pediatric & Adolescent Medicine and Otolaryngology, Head and Neck Surgery was published in 2006 to prevent of a possibly life-threatening postoperative bleeding after AT in Child age. Routine blood sampling should be avoided during preoperative preparations and instead a standardized coagulation questionnaire (GB) should be performed to clarify a coagulation disorder (GS). If the GB is abnormal, there is an indication for coagulation diagnostics (GD). MATERIALS AND METHODS: This unicenter, nonrandomized, retrospective study compared the rate of bleeding after AT and Re-AT without (2011 to early 2014) and with (early 2014 to 2018) the use of a GB. 2633 children aged one to six years, were included in the statistical analysis to assess whether the introduction of GB in early 2014 was able to reduce the rate of bleeding after AT and Re-AT. RESULTS: Of the 2633 children, 1451 had GB and 1182 did not. Without GB, there was a bleeding rate of 0.83% and 2,08% with GB. 174 GB were abnormal and 169 GD were performed, 164 of these were unremarkable, 2 resulted in a confirmed mild type 1 von Willebrand syndrome as well as 2 suspected vWS and 1 suspected factor VII deficiency. The sensitivity of the GB was 16% and the specificity was 87.5%. The positive predictive value was 2.8% and the negative predictive value was 98%. CONCLUSION: The GB is a tool for detecting possible GS, but is not useful for reducing the rate of postoperative bleeding.

Evaluation of coagulopathy in cirrhotic patients: A scoping review of the utility of viscoelastic testing.

BACKGROUND: Cirrhosis causes significant coagulopathy. Traditional coagulation tests may not accurately measure coagulopathy in well-compensated patients with cirrhosis. Viscoelastic tests are functional tests that may better assess coagulopathy in cirrhotic patients. METHODS: We searched PubMed, ScienceDirect, Google Scholar, and grey literature using terms meaning viscoelastic testing and cirrhosis. After reviewing over 500 titles and abstracts, 40 full-text papers met inclusion criteria. RESULTS: Twenty-two papers found viscoelastic testing was a better indicator of baseline coagulation than traditional testing in cirrhosis. Nineteen additional papers evaluated the utility of peri-procedural viscoelastic testing and found they led to a reduction in blood product administration without increasing risk of hemorrhage, thrombotic events, or other complications. CONCLUSIONS: The usage of viscoelastic testing in patients with cirrhosis allows for better assessment of coagulopathy, resulting in improved outcomes. Educating physicians to optimize care of this high-risk group is necessary to further improve their treatment.

Analysis of fibrinolytic shutdown in trauma patients with traumatic brain injury.

BACKGROUND: Coagulation profiles following major trauma vary depending on injury pattern and degree of shock. The physiologic mechanisms involved in coagulation function at any given time are varied and remain poorly understood. Thromboelastography (TEG) has been used evaluate coagulation profiles in the trauma population with some reports demonstrating a spectrum of fibrinolysis to fibrinolytic shutdown on initial presentation. The objective of this study was to evaluate the fibrinolytic profile of patients with TBI using thromboelastography (TEG). We hypothesized that patients with TBI would demonstrate low fibrinolytic activity. METHODS: All trauma activations at an ACS-verified level 1 trauma center received a TEG analysis upon arrival from December 2019 to June 2021. A retrospective review of the results and outcomes was conducted, and TBI patients were compared to patients without TBI. Linear regression was used to evaluate the effect of patient and injury factors on fibrinolysis. Hyperfibrinolysis was defined as LY30 â€‹> â€‹7.7%, physiologic fibrinolysis as LY30 0.6-7.7%, and fibrinolytic shutdown as LY30 â€‹< â€‹0.6%. RESULTS: A total of 1369 patients received an admission TEG analysis. Patients with TBI had a significantly higher median ISS (16 vs. 8, p â€‹< â€‹0.001), lower median admission Glasgow Coma Scale (14 vs. 15, p â€‹< â€‹0.001), longer intensive care unit length of stay (3 vs. 2 days, p â€‹< â€‹0.0001), increased ventilator days (216 vs. 183, p â€‹< â€‹0.001), higher mortality (14.6% vs. 5.1%, p â€‹< â€‹0.001), but lower shock index (0.6 vs. 0.7, p â€‹< â€‹0.0001) compared to those without TBI. Median LY30 was found to be decreased in the TBI group (0.1 vs. 0.2, p â€‹= â€‹0.0006). Patients with TBI were found to have a higher rate of fibrinolytic shutdown compared those without TBI (68.7% vs. 63.5%, p â€‹= â€‹0.054). ISS, sex, and shock index were found to be predictive of LY30 on linear regression, but TBI was not (Β: 0.09, SE: 0.277, p â€‹= â€‹0.745). The rate of DVT/PE did not appear to be elevated in patients with TBI (0.8%) and without TBI (1.2%). CONCLUSIONS: Trauma patients with and without TBI were found to have high rates of fibrinolytic shutdown. Although there was a high incidence of fibrinolytic shutdown, it did not appear to have an impact on the rate of thrombotic complications. The clinical significance of these results is unclear and differs significantly from recent reports which demonstrated that TBI is associated with a 25% rate of fibrinolytic shutdown. Further investigation is needed to better define the fibrinolytic pathway in patients with trauma and TBI to develop optimal treatment algorithms.

[Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome].

OBJECTIVE: To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome. METHODS: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis. RESULTS: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%. CONCLUSION: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

Systemic anticoagulation in ECMO.

While unfractionated heparin (UFH) remains the mainstay of anticoagulation during pediatric extracorporeal life support, direct thrombin inhibitors (DTIs) are increasingly used. In this article, we will review most recent evidence regarding utilization of both UFH and DTIs and compare their known advantages and disadvantages. We will present anticoagulation monitoring strategies during ECMO and outline the most recent Extracorporeal Life Support Organization's anticoagulation guidelines, however with the caveat that there are no true consensus recommendations for anticoagulation management in pediatric ECMO. With these updates, we will serve as the bedside clinician's refresher on common practices for anticoagulation during "routine" ECMO. We will additionally highlight special circumstances, including high risk surgical procedures during ECMO, in which adjustments in anticoagulation and/or addition of antifibrinolytic therapy might mitigate risk.