Non-bleeding Patients Research Articles

Severe bleeding events among critically ill patients with haematological malignancies

BackgroundBleeding events are common complications in critically ill patients with haematological malignancies. The objective of this study was to assess the incidence and identify determinants of ICU-acquired severe bleeding events in critically ill patients with haematological malignancies. We conducted a single-center retrospective study including all adult patients with a history of haematological malignancy requiring unplanned ICU admission over a 12-year period (2007–2018). The primary endpoint was the occurrence of ICU-acquired (i.e. after the first 24 h in the ICU) severe bleeding events, as defined as grades 3 or 4 of the World Health Organization classification.ResultsA total of 1012 patients were analysed, mainly with a diagnosis of lymphoma (n = 434, 42.9%) and leukaemia or myelodysplastic syndrome (n = 266, 26.3%). Most patients were recently diagnosed (n = 340, 33.6%) and under active cancer treatment within the last 3 months (n = 604, 59.7%). The main cause for admission was infection (n = 479, 47.3%), but a significant proportion of patients were admitted for a primary haemorrhage (n = 99, 10%). ICU-acquired severe bleeding events occurred in 109 (10.8%) patients after 3.0 days [1.0–7.0] in the ICU. The main source of bleeding was the gastrointestinal tract (n = 44, 40.3%). Patients experiencing an ICU-acquired severe bleeding event displayed prolonged in-ICU length of stay (9.0 days [1.0–6.0] vs. 3.0 [3.5–15.0] in non-bleeding patients, p < 0.001) and worsened outcomes with increased in-ICU and in-hospital mortality rates (55% vs. 18.3% and 65.7% vs. 33.1%, respectively, p < 0.001). In multivariate analysis, independent predictors of ICU-acquired severe bleeding events were chronic kidney disease (cause-specific hazard 2.00 [1.19–3.31], p = 0.008), a primary bleeding event present at the time of ICU admission (CSH 4.17 [2.71–6.43], p < 0.001), non-platelet SOFA score (CSH per point increase 1.06 [1.01–1.11], p = 0.02) and prolonged prothrombin time (CSH per 5-percent increase 0.90 [0.85–0.96], p = 0.001) on the day prior to the event of interest.ConclusionsMajor bleeding events are common complications in critically ill patients with haematological malignancies and are associated with a worsened prognosis. We identified relevant risk factors of bleeding which may prompt closer monitoring or preventive measures.

Use of half red blood cell units in oncology patients during severe shortages to extend hospital supply.

The COVID-19 pandemic exerted an unprecedented impact on the blood supply from 2020 through 2022. As a result, throughout 2021 there were months our hospital had less than one-day supply of type O RBCs. To meet transfusion needs, whole RBC units were split into half units and issued to stable, non-bleeding patients. This single-institution, retrospective study examines time intervals to subsequent transfusion and total numbers of RBC units subsequently transfused after the first half or whole RBC unit. Patients who were transfused RBC between May 21, 2021 and November 1, 2021 were divided into in- and outpatient groups, then based on whether they received at least 1 half RBC unit or only whole RBC units during the study period. The time interval between this first half unit transfusion, or first whole unit transfusion in those who did not receive half units, and the subsequent RBC transfusion within 90 days was calculated and compared, as well as the total number of RBC units transfused 30 days after the first unit. In general, patients transfused with half units received a subsequent transfusion significantly earlier than those transfused with whole units. Additionally, receiving an index half unit was associated with more RBC transfusions in the following 30 days (p = .001). Transfusion of half RBC units during a severe RBC blood shortage can temporarily decrease RBC usage but will result in a shorter interval to the next transfusion and greater total number of RBC units transfused in subsequent days.

Correction of Warfarin Coagulopathy for Non-bleeding Patients in the Outpatient Setting at an Ambulatory Care Organization: Application of Vitamin K Guidance

Background: Warfarin is an effective anticoagulant but requires close International Normalized Ratio (INR) monitoring and may occasionally require correction of excessive anticoagulation. Current guidelines provide limited practical guidance on the administration of vitamin K for the management of supratherapeutic INR levels ≥ 5.0 in non-bleeding outpatients. Objective: Based on expert consensus and guidelines, the Atrius Health Anticoagulation Management Services (AMS) has developed internal guidance for oral vitamin K use in highly selected populations. This study will describe the internal guidance for oral vitamin K use and present associated results and clinical outcomes Methods: Episodes with INR &gt; 5.0 were included, with vitamin K considered for episodes with INR ≥ 6. Moreover, compelling indications and exclusions to select ideal patients for vitamin K intervention were also defined Results: Overall, episodes were managed conservatively; of the 246 collected episodes of excessive anticoagulation, in 18 episodes (7%), patients received vitamin K, and in 228 (93%) episodes, patients did not receive vitamin K. The mean index INR was 6.0 (range 5.0 – 10.5, SD 1.07), with nearly 57% of episodes achieving INR correction and 15% of episodes developing INR overcorrection. High thrombotic risk patients, regardless of hemorrhagic risk, were less likely to receive vitamin K. Three episodes (1.2%) resulted in bleeding complications. No thrombotic complications occurred during the 30-day follow-up of the index INR value ≥ 5.0. Conclusion: Our internal guidance is a novel, standardized approach that serves as a decision support tool for the management of warfarin-associated coagulopathy and vitamin K intervention using patient-specific characteristics and index INR values. This guidance may assist other anticoagulation management services with practical applications and require validation in a prospective clinical trial.

Updated review on malignancy-associated venous thromboembolism: Pathogenesis and comparison between various therapeutic modalities

Venous thromboembolism (VTE) is one of the life-threatening complications in cancer patients, the incidence of which is affected by the patient and malignancy-related variables. Location, type, therapeutic route, stage, grade, and non-supportive treatment of the cancer are the most important VTE risk factors. Patient age, ethnicity, and concomitant genetic or acquired comorbidities or thrombophilias are known risk factors for VTE in cancer. All high-risk cancer patients admitted to hospitals or treated as outpatients should receive VTE prophylaxis. Low molecular weight heparin is the main treatment for active malignant VTE. Vitamin K antagonists and non-Vitamin K-dependent oral anticoagulants are used in stable, non-bleeding cancer patients. Anticoagulation should be continued until the cancer is treated or at least controlled. Over the past two decades, randomized clinical and observational trials have improved the pathogenesis and therapeutic knowledge of VTE, but many challenges remain. The lack of an optimal primary prophylaxis method for inpatients and outpatients in oncology and the care of cancer-associated VTE in standard and high-bleeding risk groups are examples for which more clinical research on cancer-associated thrombosis is necessary to address these issues. In this review, we describe the pathogenesis, factors that increase the risk of VTE, and the comparison between the effectiveness of available anticoagulants in the treatment and prevention of VTE in cancer patients.

Fibrinolysis as a Causative Mechanism for Bleeding Complications on Extracorporeal Membrane Oxygenation: A Pilot Observational Prospective Study.

Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers-i.e., changes over time-in the context of bleeding events in patients on ECMO. Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter. The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin-antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin-antiplasmin, tPA, PAI-1, and tPA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. -440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049). Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives.

In-hospital bleeding occurring while treating ST-segment elevation myocardial infarction during the COVID-19 pandemic: STEMI during the COVID-19 pandemic

Pursose. Our purpose was to evaluate less well known factors and outcome associated to bleeding in STEMI patients after primary PCI and concomitant antithrombotic therapy during Covid-19 pandemic.&#x0D; Methods. This was a retrospective, observational study of the prevalence and factors associated to hospital bleeding in 317 STEMI patients (74.8% men, mean age 65.7±11.9 years) and of the impact of bleeding on 30-day and 6-month survival in STEMI patients during the Covid-19 pandemic from January-October 2021. The leading reperfusion strategy was primary PCI; we registered all significant bleeding events. &#x0D; Results: Concomittant Covid-19 was observed in 3.2% of STEMI patients. Primary PCI was performed in 94.3% of all cases, but only in 17% within the first 3 hours of chest pain. Bleeding was observed in 11.4% of all STEMI patients and was associated significantly with out-of-hospital cardiac arrests (OHCA), hospital complications and mortality. In bleeding and nonbleeding patients the prevalence of age, sex, comorbidities, Covid-19 cases, the use and start of primary PCI was similar.&#x0D; Conclusions: The prevalence of hospital bleeding in treatment of STEMI patients during Covid-19 pandemic was 11.4% and was associated significantly to OHCA, hospital complications and early mortality of STEMI patients.

Machine learning model for predicting physical activity related bleeding risk in Chinese boys with haemophilia A

BackgroundPhysical activity is a crucial part of an active lifestyle for haemophiliac children. However, the fear of bleeds has been identified as barriers to participating physical activity for haemophiliac children even with prophylaxis. Lack of evidence and metrics driven by data is key problem. ObjectivesWe aim to develop machine learning models based on clinical data with multiple potential factors considered to predict risk of physical activity bleeding for haemophilia children with prophylaxis. MethodsFrom this cohort study, we collected information on 98 haemophiliac children with adequate prophylaxis (trough FVIII:C level > 1 %). The involved potential predictor variables include demographic information, treatment information, physical activity, joint evaluation, and pharmacokinetic parameters, etc. We applied CoxPH, Random Survival Forests (RSF) and DeepSurv to construct prediction models for the risk of bleeding during physical activities. All three survival analysis models were internally and externally validated. ResultsA total of 98 patients were enrolled in this study. Their median age was 7.9 (5.5, 10.2) years. The CoxPH, RSF and DeepSurv models' discriminative and calibration abilities were all high, and the RSF model had the best performance (Internal validation: C-index, 0.7648 ± 0.0139; Brier Score, 0.1098 ± 0.0015; External validation: C-index, 0.7260 ± 0.0154; Brier Score, 0.0930 ± 0.0018). The prediction curves demonstrated that the developed RSF model can distinguish the risks well between bleeding and non-bleeding patients, as well as patients with different levels of physical activity. Meanwhile, the feature importance analysis confirmed that physical activity bleeding was deduced by comprehensive effects of various factors, and the importance of different factors on bleeding outcome is discrepant. ConclusionsThis study revealed from the mechanism that it is necessary to incorporate multiple factors to accurately predict physical activity related bleeding risk. In clinical practice, the designed machine learning models can provide guidance for children with haemophilia A to positively participate in physical activity.

Transfusion increased skin blood flow when initially low in volume-resuscitated patients without acute bleeding.

Alterations in skin blood flow is a marker of inadequate tissue perfusion in critically ill patients after initial resuscitation. The effects of red blood cell transfusions (RBCT) on skin perfusion are not described in this setting. We evaluated the effects of red blood cell transfusions on skin tissue perfusion in critically ill patients without acute bleeding after initial resuscitation. A prospective observational study included 175 non-bleeding adult patients after fluid resuscitation requiring red blood cell transfusions. Using laser Doppler, we measured finger skin blood flow (SBF) at skin basal temperature (SBFBT), together with mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb), central venous pressure (CVP), lactate, and central or mixed venous oxygen saturation before and 1 h after RBCT. SBF responders were those with a 20% increase in SBFBT after RBCT. Overall, SBFBT did not significantly change after RBCT [from 79.8 (4.3-479.4) to 83.4 (4.9-561.6); p = 0.67]. A relative increase equal to or more than 20% in SBFBT after RBCT (SBF responders) was observed in 77/175 of RBCT (44%). SBF responders had significantly lower SBFBT [41.3 (4.3-279.3) vs. 136.3 (6.5-479.4) perfusion units; p < 0.01], mixed or central venous oxygen saturation (62.5 ± 9.2 vs. 67.3% ± 12.0%; p < 0.01) and CVP (8.3 ± 5.1 vs. 10.3 ± 5.6 mmHg; p = 0.03) at baseline than non-responders. SBFBT increased in responders [from 41.3 (4.3-279.3) to 93.1 (9.8-561.6) perfusion units; p < 0.01], and decreased in the non-responders [from 136.3 (6.5-479.4) to 80.0 (4.9-540.8) perfusion units; p < 0.01] after RBCT. Pre-transfusion SBFBT was independently associated with a 20% increase in SBFBT after RBCT. Baseline SBFBT had an area under receiver operator characteristic of 0.73 (95% CI, 0.68-0.83) to predict SBFBT increase; A SBFBT of 73.0 perfusion units (PU) had a sensitivity of 71.4% and a specificity of 70.4% to predict SBFBT increase after RBCT. No significant differences in SBFBT were observed after RBCT in different subgroup analyses. The skin blood flow is globally unaltered by red blood cell transfusions in non-bleeding critically ill patients after initial resuscitation. However, a lower SBFBT at baseline was associated with a relative increase in skin tissue perfusion after RBCT.

Prediction of Mid-term Platelet Transfusion in Stable Trauma Patients Using Rotational Thromboelastometry.

Rotational thromboelastometry (ROTEM; TEM International GmbH, Munich, Germany) is a global coagulation test that guides evidence-based platelet transfusion in trauma patients. We evaluated ROTEM parameters for predicting mid-term (five days) platelet transfusion in trauma patients. Maximum clot firmness and clot amplitudes after 5, 10, and 15 mins (A5, A10, and A15, respectively) of fibrin-specific ROTEM (FIBTEM) and extrinsically activated ROTEM (EXTEM) were retrospectively collected from 82 hospitalized, stable, non-bleeding trauma patients after successful initial resuscitation. Platelet-specific ROTEM (PLTEM) was calculated by subtracting FIBTEM from EXTEM. Platelet transfusions were reviewed for five days after ROTEM. The areas under the curve for FIBTEM, EXTEM, and PLTEM predicting platelet concentrate transfusion of >12 U at mid-term were 0.915-0.923, 0.878-0.896, and 0.551-0.735, respectively. FIBTEM and EXTEM parameters were comparable to those of fibrinogen, fibrin/fibrinogen degradation products, D-dimer, and antithrombin III. Strong correlations (r>0.7) were noted between platelet count and EXTEM (A5, A10, and A15) or PLTEM (A5), platelet function (per platelet count) and EXTEM (A10 and A15), and fibrinogen levels and all FIBTEM parameters. FIBTEM and EXTEM can reliably predict mid-term platelet transfusion in trauma patients. FIBTEM, EXTEM, and PLTEM parameters correlate with conventional coagulation tests (platelets and fibrinogen).

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study

BackgroundThrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO.MethodsThis was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018–Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100–150·109/L), moderate (50–100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models.ResultsOf the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9–56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34–360).ConclusionsThrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding.Trial registration: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Assessment of bleeding risk in cancer patients treated with anticoagulants for venous thromboembolic events.

Anticoagulant is the cornerstone of the management of VTE at the cost of a non-negligible risk of bleeding. Reliable and validated clinical tools to predict thromboembolic and hemorrhagic events are crucial for individualized decision-making for the type and duration of anticoagulant treatment. We evaluate the available risk models in real life cancer patients with VTE. The objectives of the study were to describe the bleeding of cancer patients with VTE and to evaluate the performance of the different bleeding models to predict the risk of bleeding during a 6-month follow-up. VTE-diagnosed patient's demographic and clinical characteristics, treatment regimens and outcomes for up to 6 months were collected. The primary endpoint was the occurrence of a major bleeding (MB) or a clinically relevant non major bleeding (CRNMB) event, categorized according to the ISTH criteria. During the 6-months follow-up period, 26 out of 110 included patients (26.7%) experienced a bleeding event, with 3 recurrences of bleeding. Out of the 29 bleeding events, 19 events were CRNMB and 10 MB. One patient died because of a MB. Bleeding occurred in 27 % of the patients treated with DOACs and 22% of the patients treated with LMWH. Most of the bleedings were gastrointestinal (9 events, 31%); 26.9% of the bleedings occurred in patient with colorectal cancer and 19.6% in patients with lung cancer. In our cohort, none of the 10 RAMs used in our study were able to distinguish cancer patients with a low risk of bleeding, from all bleeding or non-bleeding patients. The Nieto et al. RAM had the best overall performance (C-statistic = 0.730, 95% CI (0.619-0.840)). However, it classified 1 out of 5 patients with major bleeding in the low risk of bleeding group. The rest of the RAMs showed a suboptimal result, with a range of C-statistic between 0.489, 95%CI (0.360-0.617)) and 0.532, 95%CI (0.406-0.658)). The management of CAT patients is challenging due to a higher risk of both recurrent VTE and bleeding events, as compared with non-cancer patients with VTE. None of the existing RAMs was able to consistently identify patients with risk of anticoagulant associated bleeding events.

An instrument to measure atrial fibrillation knowledge in Chinese patients: validation of the Jessa Atrial fibrillation Knowledge Questionnaire.

Background: There is no validated tool to assess patients' knowledge of oral anticoagulant therapy in atrial fibrillation in China. Methods: Using a standard translation program, the Jessa Atrial fibrillation Knowledge Questionnaire (JAKQ) was translated into Chinese. The reliability of the JAKQ was assessed by internal consistency (Cronbach's α coefficient), repeatability (test-retest reliability), and sensitivity tests. Effectiveness was assessed by hypothesizing that a lower JAKQ score was a risk factor for bleeding. A total of 447 patients with atrial fibrillation (AF) who were hospitalized between July 2019 and December 2021 were studied and followed up. Participants were followed up 1, 3, 6, and 12 months after enrollment. Bleeding during follow-up was recorded. Data were obtained from hospital databases and telephone follow-up. Result: A total of 447 patients with AF completed JAKQ. The mean age of patients was 67.7 ± 10.2years. The median JAKQ score was 31.3% (12.5-43.8). The Cronbach's α coefficient of JAKQ was 0.616-0.637, and the test-retest reliability value was 0.902 (p < 0.001). Multivariate logistic regression showed that the higher knowledge level of AF was associated with secondary education or above, an income of more than 2000 yuan, and a history of AF of more than 1year. Bleeding was associated with a lower JAKQ score, hypertension, and a history of bleeding. Non-bleeding patients on VKA had a better understanding of how often INR should be monitored and what to do if an OAC dose was missed. Conclusion: The Chinese version of JAKQ shows good reliability and validity, indicating that it is a valuable tool for AF and oral anticoagulation (OAC) knowledge assessment. It can be used in clinical practice to guide educational activities and improve the effectiveness and safety of treatment. It was shown that Chinese patients with AF have insufficient knowledge about AF and OAC. Lower JAKQ scores are associated with bleeding, so targeted education is necessary. Targeted educational efforts should focus on patients recently diagnosed with AF and those with lower formal education and income.

The bleeding risk and safety of multiple treatments by bronchoscopy in patients with central airway stenosis

Background Central airway obstruction (CAO) are common abnormality that usually needing interventional bronchoscopy, and sometimes multiple rounds of treatment. However, there were few studies explore the safety of it. Research design & methods The records of patients who underwent interventional bronchoscopy because of CAO at Respiratory department between January 1, 2010, and December 31, 2020 were revised. The patients’ clinical characteristics, information about bronchoscopy and incidence of complications were collected and analyzed. Results There were totally 1,482 bronchoscopy procedures conducted in the 733 CAO patients. And the incidence of major complications in the retreatment group was significantly lower than that in the first treatment group ((4.77% vs. 1.87%, χ2=9.78, df=1, p<0.01), so did the incidence of severe bleeding (2.46% vs. 0.40%, χ2=11.20, df=1, p<0.01). However, there was some variability between the two groups in age and anesthesia type. A short interval time, more treatment times, and general anesthesia were related to a lower incidence of hemorrhage. For patients who were previously bleeding, the incidence of hemorrhage was significantly higher than the incidence in the non-bleeding patients (42.93% vs. 16.33%, respectively; χ2=57.54, df=1, p<0.01). Conclusion For the patients with CAO, repeated interventional bronchoscopy treatment was safe, and it should be treated with discretion when retreat the patients once bleeding during previous therapeutic bronchoscopy.

Comparison of the effects of different treatment protocols on mortality in patients presenting with an INR≥10 due to warfarin-associated over-anticoagulation

One of the most anticipated adverse effects of warfarin is over-anticoagulation. There is little to no evidence on the treatment that should be administered in patients with an international normalized ratio (INR)≥10. The primary outcome of this study is to analyze the effects of various treatments on 30-day mortality in patients with INR≥10 and without major bleeding on 30-day all-cause mortality. The secondary outcome is to propose a model that predicts 30-day all-cause mortality in the same patient group. Patients older than 18 years of age using warfarin and who had an INR≥10 were included in this retrospective cohort study. Patients with major bleeding on admission were excluded. Patients treated with only cessation of warfarin were named as "Group-1", patients who were treated with vitamin-K in addition to cessation of warfarin were named as "Group-2", and patients who were treated with cessation of warfarin and vitamin-K and fresh frozen plasma or prothrombin complex concentrate were named as "Group-3". 190 patients were included in the analysis. Seven (38.9%) patients in the first group, 3 (8.6%) in the second group, and 21 (15.3%) in the third group died within 30-days(p=0.015). In the post-hoc analysis, the difference between Group-1 and Group-2 was found to be significant(p=0.036, OR:0.147, 95%CI=0.032 to 0.671).The performance of the model in predicting 30-day all-cause mortality was high (AUC=0.818 (95%CI=0.716 to 0.920) and found to be compatible with the validation dataset 0.806 (95%CI=0.631 to 0.981). Administration of vitamin K in addition to the cessation of warfarin was found to be a strong contributor to the model and an independent predictor of survival within 30 days(p=0.006). Until randomized controlled studies are conducted, it may be reasonable to administer vitamin-K in addition to cessation of warfarin in non-bleeding patients with INR≥10.

Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study.

In hemodynamically stable patients, both anemia and red blood cell (RBC) transfusion may be detrimental to patients; hence, a decision regarding RBC transfusion should be based on thorough risk-benefit assessment. According to hematology and transfusion medicine organizations, RBC transfusion is indicated when recommended hemoglobin (Hb) triggers are met, and symptoms of anemia are present. The aim of our study was to examine the appropriateness of RBC transfusions in non-bleeding patients at our institution. We performed a retrospective analysis of all RBC transfusions performed between January 2022 and July 2022. The appropriateness of RBC transfusion was based on the most recent Association for the Advancement of Blood and Biotherapies (AABB) guidelines and some additional criteria. The overall incidence of RBC transfusions at our institution was 10.2 per 1000 patient-days. There were 216 (26.1%) RBC units appropriately transfused and 612 (73.9%) RBC units that were transfused with no clear indications. The incidence of appropriate and inappropriate RBC transfusions were 2.6 and 7.5 per 1000 patient-days, respectively. The most frequent clinical situations when RBC transfusion was classified as appropriate were: Hb < 70 g/L plus cognitive problems/headache/dizziness (10.1%), Hb < 60 g/L (5.4%), and Hb < 70 g/L plus dyspnea despite oxygen therapy (4.3%). The most frequent causes of inappropriate RBC transfusions were: no Hb determination pre-RBC transfusion (n = 317) and, among these, RBC transfused as a second unit in a single-transfusion episode (n = 260); absence of anemia sings/symptoms pre-transfusion (n = 179); and Hb concentration ≥80 g/L (n = 80). Although the incidence of RBC transfusions in non-bleeding inpatients in our study was generally low, the majority of RBC transfusions were performed outside recommended indications. Red blood cell transfusions were evaluated as inappropriate mainly due to multiple-unit transfusion episodes, absence of anemia signs and/or symptoms pre- transfusion, and liberal transfusion triggers. There is still the need to educate physicians on appropriate indications for RBC transfusion in non-bleeding patients.

Performance of the ATRIA Bleeding Score in Predicting the Risk of In-Hospital Bleeding in Patients with ST-Elevation or Non-ST-Elevation Myocardial Infarction.

A clear assessment of the bleeding risk score in patients presenting with myocardial infarction (MI) is crucial because of its impact on prognosis. The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA score is a validated risk score to predict bleeding risk in atrial fibrillation (AF), but its predictive value in predicting bleeding after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) patients receiving antithrombotic therapy is unknown. Our aim was to investigate the predictive performance of the ATRIA bleeding score in STEMI and NSTEMI patients in comparison to the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) and ACUITY-HORIZONS (Acute Catheterization and Urgent Intervention Triage strategY-Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) bleeding scores. A total of 830 consecutive STEMI and NSTEMI patients who underwent PCI were evaluated retrospectively. The ATRIA, CRUSADE, and ACUITY-HORIZONS risk scores of the patients were calculated. Discrimination of the three risk models was evaluated using C-statistics. Major bleeding occurred in 52 (6.3%) of 830 patients during hospitalization. Bleeding scores were significantly higher in the bleeding patients than in non-bleeding patients (all P<0.001). The discriminatory ability of the ATRIA, CRUSADE, and ACUITY-HORIZONS bleeding scores for bleeding events was similar (C-statistics 0.810, 0.832, and 0.909, respectively). The good predictive value of all three scores for predicting the risk of bleeding was observed in NSTEMI and STEMI patients as well (C-statistics: 0.820, 0.793, and 0.921 and 0.809, 0.854, and 0.905, respectively). This study demonstrated that the ATRIA bleeding score is a useful risk score for predicting major in-hospital bleeding in MI patients. This good predictive value was also present in STEMI and NSTEMI patient subgroups.

Performance assessment of unfractionated heparin protocol in pediatric patients supported on extracorporeal membrane oxygenation

Abstract Background Using extracorporeal membrane oxygenation in critical care setting is evolving. Unfractionated heparin is the most commonly used anticoagulant and a well-designed protocol is needed. However, there is no consensus from any organization regarding standard protocol. We developed UFH protocol taking into consideration best available evidence and anecdotal ECMO data. This study aims to assess ability of current protocol to achieve anti-Xa assay therapeutic target. Methods Prospective cohort, single-arm study conducted in Pediatric Cardiac Surgery Intensive Care Unit. Twenty patients were required. Anti-Xa assay therapeutic range is 0.1–0.3 U/mL for bleeding and 0.3–0.7 U/mL for non-bleeding patients. The protocol was developed after comprehensive literature review and continuous strict review process by a multidisciplinary ECMO team. It identifies initial UFH infusion dosing and subsequent adjustment, frequency of monitoring Anti-Xa assay, and other laboratory parameters. To ensure protocol adherence, teaching sessions were provided. Finally, we explored survival to discharge rate. The study was approved by the Office of Research Affairs with verbal consent. Results Twenty patients were included, half of them were female. Mean age of 35 months ± SD 52.5 and mean weight of 5.7 kg ± SD 3.8–14.1. Mean estimated glomerular filtration rate using schwartz equation was 80 mL/min/1.73 m2 ± SD 34.7. Main indications of ECMO use were failure to wean after surgery (45%). Median ECMO duration was 6 days+ (IQR: 4.5–7.5). Baseline Anti-Xa assay before cannulation was 0.1 IU/mL. Another important baseline laboratory value was antithrombin III, the mean was 21.1 ± SD 14.3. Selection of bleeding protocol is based on a set of criteria in the bleeding section (Appendix 1). Pre-canulation heparin bolus of 50–100 units/kg was given if ACT is &amp;lt;300 seconds for 11 patients (55%). Holding unfractionated heparin was required in 8 patients (40). Median time UFH was on-hold 13.5 hours (IQR: 10.5–27.5). Achieving Anti-Xa assay therapeutic target thorough out study period was reported in 70% of patients. Median time to achieve target was 41 hours (IQR: 0–91.5) and maintained for 8 hours (IQR: 0–22). Hemorrhagic complications were reported in 8 patients (40%) while thrombotic complications in 5 patients (25%). Both peripheral cannulation site bleeding and gastrointestinal bleeding occurred in 5%. Surgical exploration was needed in 6 patients (30%). Median time to first replacement was 80.5 hours (IQR: 19.5–228.5). Median hospital length of stay was 37 + IQR: 43–22 with survival rate at discharge of 75%. Conclusion Implemented UFH protocol in pediatric ECMO failed to achieve target in early hours after cannulation. However, the majority of those critically ill patients achieved Anti-Xa assay target and maintained it after the third day until day ten. Thromboembolic, hemorrhagic complications, and survival rates were consistent with the reported data Funding Acknowledgement Type of funding sources: None.

Plasma transfusion practices: A multicentre electronic audit.

Plasma is often transfused to patients with bleeding or requiring invasive procedures and with abnormal tests of coagulation. Chart audits find half of plasma transfusions unnecessary, resulting in avoidable complications and costs. This multicentre electronic audit was conducted to determine the proportion of plasma transfused without an indication and/or at a sub-therapeutic dose. Data were extracted on adult inpatients in 2017 at five academic sites from the hospital electronic chart, laboratory information systems and the Canadian Institute for Health Information Discharge Abstract Database. Electronic criteria for plasma transfusion outside recommended indications were: (1) international normalized ratio (INR) < 1.5 with no to moderate bleeding; (2) INR ≥ 1.5, with no to mild bleeding and no planned procedures; and (3) no INR before or after plasma infusion. Sub-therapeutic dose was defined as ≤2units transfused. In 1 year, 2590 patients received 6088 plasma transfusions encompassing 11,490 units of plasma occurred at the five sites. 77.7% of events were either outside indications or under-dosed. Of these, 34.8% of plasma orders had no indication identified, and 62% of these occurred in non-bleeding patients and no planned procedure with an isolated elevated INR. 70.7% of transfusions were under-dosed. Most plasma transfusions occurred in the intensive care unit or the operating room. Inter-hospital variability in peri-transfusion testing and dosing was observed. The majority of plasma transfusions are sub-optimal. Local hospital culture may be an important driver. Electronic audits, with definitions employed in this study, may be a practical alternative to costly chart audits.

Prothrombin complex concentrates for the urgent reversal of apixaban and rivaroxaban: an Australian retrospective cohort study.

Direct acting oral anticoagulants (DOAC) are now commonly prescribed medications. Urgent reversal of their anticoagulant effect is sometimes required in emergency situations. In Australia, a specific reversal agent for factor Xa (FXa)-inhibitor DOAC is not available. Instead, two non-specific haemostatic agents, activated prothrombin complex concentrate (aPCC) and 3 factor-prothrombin complex concentrate (3F-PCC), are used off-label despite a paucity of evidence for their effectiveness or safety. To provide further insight into the efficacy and safety of 3F-PCC and aPCC for the reversal of the anticoagulant effect of FXa inhibitor DOACs. We conducted a single-centre retrospective cohort study to investigate the use of aPCC and 3F-PCC for patients on FXa-inhibitor DOAC who present with a significant bleeding event or who require urgent surgery. The primary outcome was haemostatic efficacy according to prespecified criteria. Safety outcomes included the thromboembolic event rate and all-cause mortality during the hospital admission. A total of 51 patients was included in the study (36 patients who had a spontaneous bleeding event and 15 non-bleeding patients who required urgent perioperative management). Thirty-one patients received aPCC and 20 patients received 3F-PCC. Haemostasis was adjudicated as effective in all assessable patients (n = 50; 100%). Thromboembolic events occurred in three patients who received aPCC and one patient who received 3F-PCC. All-cause mortality was 7.8% (four patients). Both aPCC and 3F-PCC are useful adjuncts for the management of patients who require urgent reversal of the anticoagulant effect of FXa-inhibitor DOAC. However, the risk of thromboembolism in this patient group requires careful consideration. Prospective, comparator studies are needed along with the development of guidelines that reflect the availability of haemostatic agents in Australia.

Predicting organ functioning with and without blood transfusion in critically ill patients with anemia.

BackgroundTo develop a model for the prediction of the (most likely) effect of red blood cell (RBC) transfusion on subsequent organ functioning in nonbleeding critically ill patients with hemoglobin concentrations between 6 and 9 g/dL.Study Design and MethodsWe conducted a retrospective cohort study using electronic health care data of nonbleeding patients admitted between November 2004 and May 2016 at the intensive care unit (ICU) of the Leiden University Medical Center, The Netherlands. We analyzed the associations between transfusion (yes/no) and next‐day SOFA scores (Sequential Organ Failure Assessment—as a measure for organ functioning) for all observed combinations of hemoglobin values (between 6 and 9 g/dL) and concurrent clinical variables.ResultsData of 6425 ICU admission of 5756 critically ill patients with 28,702 hemoglobin values between 6 and 9 g/dL (transfusion decision moments) of which 22.1% were followed by a transfusion were analyzed. The adjusted average difference between the next‐day SOFA score of transfused versus not‐transfused patients was 0.08 (95% confidence interval [CI] −0.03 to 0.18). At singular transfusion decision moments, the score predicted a beneficial effect of transfusion on next‐day SOFA score for some subgroups and medical conditions and a harmful effect in other occasions.ConclusionsAmong these critically ill patients with hemoglobin concentrations between 6 and 9 g/dL the population average effect of transfusion on the next SOFA score was negligible. Further, our results support caution in clinical decision‐making regarding transfusion of critical ill, nonbleeding ICU patients.