Impact of introduction of a goal directed transfusion strategy in a patient blood management program: A single cardiac surgery centre experience.

BACKGROUND: The aim of this retrospective and observational study was to analyse the impact of the introduction of a goal directed transfusion (GDT) strategy based on a viscoelastic test (ROTEM®) and specific procoagulant products in a patient blood management (PBM) Program on blood product use and perioperative bleeding in a single cardiac surgery centre. STUDY DESIGN AND METHODS: Patient population underwent cardiac surgery from 2011 to 2021 was divided in two groups based on PBM protocol used (G#11-14, years 2011-2014, G#15-21, years 2015-2021) and compared for the following variables: intraoperative and postoperative transfusions of packed red blood cell and any procoagulant products, postoperative drain blood loss volume and rate of re-exploration surgery. The second program was defined after the introduction of a GDT protocol based on viscoelastic tests and specific procoagulant products. RESULTS: After the introduction of a GDT protocol, about 80% less amongst patients were transfused with fresh frozen plasma and any procoagulant product (p < 0.001 for both phases). Moreover, similar results were obtained with PRBC transfusions (p < 0.001) and drain blood loss volume (p = 0.006) in the postoperative phase. The main factors affecting the use of any procoagulant and PBRC transfusion in the multivariate logistic regression analysis was Group (2 versus 1, OR 0.207, p < 0.001) and preoperative haemoglobin (OR 0.728, p < 0.001), respectively. DISCUSSION: In our experience, a GDT strategy for the diagnosis and treatment of the coagulopathy in patients undergone cardiac surgery led to a significant reduction in bleeding and transfusion.

Iatrogenic anaemia and transfusion thresholds in ICU patients with COVID-19 disease at a tertiary care hospital.

BACKGROUND: Patients with severe COVID-19 disease frequently develop anaemia as the result of multiple mechanisms and often receive transfusions. The aims of this study were to assess the impact of repeated blood samplings on patients' anaemic state using standard-volume tubes, in comparison with the hypothetical use of low-volume tubes and to evaluate the transfusion policy adopted. STUDY DESIGN AND METHODS: Transfusion data of mechanically ventilated non-bleeding patients with COVID-19 disease hospitalized in ICU for a minimum of 20 days were recorded. The total volume of blood drawn for samplings with standard-volume tubes and the corresponding red blood cell mass (RBCM) removed during hospitalization for each patient were calculated and compared with the hypothetical use of low-volume tubes. RESULTS: Twenty-four patients fulfilled the inclusion criteria. Ten patients were anaemic at ICU admission (41.7 %). Overall, 6658 sampling tubes were employed, for a total of 16,786 mL of blood. The median RBCM subtracted by blood samplings per patient accounted for about one third of the total patients' RBCM decrease until discharge. The use of low-volume tubes would have led to a median saving of about one third of the drawn RBCM. Eleven patients were transfused (45.8 %) at a mean Hb value of 7.7 (± 0.5) g/dL. CONCLUSION: The amount of blood drawn for sampling has a significant role in the development of anaemia and the use of low-volume tubes could minimize the problem. Large high-powered studies are warranted to assess the more appropriate transfusion thresholds in non-bleeding critically ill patients with COVID-19 disease.

Attitude changes in prescribing intravenous iron supplementation in different settings at a hospital consortium in Italy.

BACKGROUND: Iron deficiency anaemia is a public health problem. In case oral iron treatment is ineffective, poorly tolerated or contraindicated, the intravenous route becomes the first choice. The aim of the study was to evaluate the shift between ferrous gluconate (FG) and ferric carboxymaltose (FCM) usage at our hospitals over the years. We also performed a cost comparison between pre and post-FCM availability periods, taking into account the acquisition costs of both intravenous iron and red blood cell units (PRBC). STUDY DESIGN AND METHODS: The amount and costs of FG and FCM released by hospital Pharmacy Services from 2010 to 2019 were analysed, along with the number of transfused PRBC units in the same timeframe. RESULTS: Overall, the proportion of FCM usage rose from 8.6 % in 2014 to 71.9 % in 2019, as percentage of total intravenous iron released. After exclusion of haemodialysis, where FG is still widely used, the FCM use in the last four years raised from 12.9% to 92.5%. Despite the higher FCM cost, the mean yearly expenditure for intravenous iron plus PRBC units did not differ between pre- and post-FCM eras (2010-2013, € 2,396,876 € versus 2014-2019, € 2,307,875 - p = 0.234), as a result of a net decrease of PRBC usage, namely from 15,083 to 12,654 (-16.1 %), respectively. DISCUSSION: Intravenous iron has a major role in treating iron deficiency anaemia in several settings. Third generation compounds are paving the way to more updated and safer treatments.

Efficacy and safety of high-dose intravenous iron as the first-choice therapy in outpatients with severe iron deficiency anemia.

BACKGROUND: Asymptomatic severe iron deficiency anemia is a common finding in subjects admitted to the outpatient anemia clinic. Although the condition can be easily be reversed with intravenous iron (IVI) therapy and several guidelines have suggested a restrictive threshold for using transfusion in hemodynamically stable patients, transfusion is often the rule in clinical practice. This study describes clinical practice results of IVI therapy without transfusion. STUDY DESIGN AND METHODS: In this multicenter retrospective observational study, data of severely anemic outpatients treated only with high-dose IVI with ferric carboxymaltose were collected. Inclusion criteria were hemoglobin (Hb) level of less than 7.0 g/dL and ferritin level of less than 30 ng/mL or mean corpuscular volume of less than 75 fL. RESULTS: Overall, 303 patients referred to the anemia clinic mainly from primary health care centers (46.2%) or the emergency department (28.7%) met the inclusion criteria. Median (interquartile range [IQR]) age was 47 (37-62) years and 84.5% were female. The median (IQR) Hb concentration at first visit was 6.5 (6.1-6.8) g/dL, 64 patients (21.1%) presented with a Hb level of less than 6.0 g/dL at diagnosis, and 11 of them (3.6%) had extreme anemia (Hb ≤ 5 g/dL). Gynecologic and gastroenteric bleeding were the main cause. After a mean IV administration of 1500 mg of iron, the Hb increased by a median of 5.7 g/dL. Thirteen patients experienced only mild side effects. CONCLUSIONS: In chronic very severe sideropenic anemias, third-generation IVI is effective and safe for quick correction and avoidance of red blood cell transfusion. These results suggest that more specific guidelines for this clinical setting are warranted.

Prevalence of anemia and therapeutic behavior in the emergency department at a tertiary care Hospital: Are patient blood management principles applied?

BACKGROUND: The aim of this study was to assess the general prevalence and the treatment policy of anemic patients referring to the Emergency Department (ED) of a tertiary care Hospital during 2015. STUDY DESIGN AND METHODS: The full blood cell count data from patients admitted to the ED for any reason,excepted for those with massive hemorrhage and multiple trauma, were studied. The prevalence of anemic patients and the degree of anemia were recorded, along with the transfusion policy applied. Transfusion appropriateness was retrospectively evaluated with a specific algorithm, that also considered the administered volume of red blood cells. A particular focus was made on patients with microcytosis about the physicians' awareness of the underlying iron deficiency and the consequent iron prescription. RESULTS: In a group of 22,329 patients the overall prevalence of anemia was 27.5% (6144 patients). Among the anemic patients, 281 / 6144 (4.6%) were transfused. The applied transfusion policy, as evaluated with the algorithm showed an overall good level of appropriateness (74.5% of transfusion episodes) but the appropriateness of the administered red blood cell mass was low (8.8%), due to over-transfusion. In microcytic transfused patients (mean MCV 69.0 ± SD 9.1), the iron balance tests were rarely ordered (22 patients out of 98-22.2%) and intravenous iron was prescribed in only 9 patients out of the 98 eligible (9.2%). CONCLUSION: The Patient Blood Management principles should be applied also in the ED setting, to promote a more appropriate and effective clinical approach to anemic patients.

Efficacy of a strict surveillance policy towards inappropriateness of plasma transfusion.

BACKGROUND: Plasma transfusion is not without risks. Despite a limited spectrum of indications, plasma is frequently used as prophylaxis in non-bleeding patients, to correct altered coagulation tests. A high rate of inappropriate use of plasma transfusion is frequently reported, as well as underdosage. STUDY DESIGN AND METHODS: Since 2010 we started an education program that occurred in several phases to disseminate the knowledge of plasma transfusion guidelines. Since 2014 a 'zero tolerance' policy was applied: except for massive bleedings, plasma requests were prospectively evaluated, rejecting those without an appropriate indication. When indicated, at least 10 mL/Kg b.w.were issued. The previous five year period (2005-2009) served as control. RESULTS: The number of patients transfused/year decreased by 67.6% vs the control period (149 vs 460), and the liters of plasma issued/year decreased by 70.4% (233 vs 795). The deepest fall was observed in acute care wards (-70.8%). The mean volume transfused per episode raised from 731 mL ±â€¯70 to 879 mL ±â€¯154. The Prothrombin Time ratio at the moment of transfusion request increased from a mean of 1.35 (Interquartile range 1.20-2.64) in the control period to 1.62 (Interquartile range 1.43-1.98) in the last period (p < 0.001). CONCLUSION: With a proactive educational approach a remarkable reduction of plasma order and administration has been obtained, without any consequence on morbidity and mortality and with an estimated saving since 2014 of 750,000 €. A 'zero tolerance' policy can be effectively implemented only with a thorough workup with the local physicians, including repeated rounds of information and refreshing of the updated transfusion practice and knowledge of the established guidelines over the time.

Extreme anemia (Hb 33 g/L) in a 13-year-old girl: Is the transfusion always mandatory?

Iron-deficiency anemia is a frequent condition in women and adolescent girls often caused by heavy menstrual bleeding. Sometimes the level of chronic anemia, although well tolerated, can be very severe. The recently introduced Patient Blood Management guidelines and the availability of effective and safe intravenous iron preparations may question transfusion as the traditional option. We describe here the case of a 13 years old girl with extreme iron-deficiency chronic anemia (Hb 33 g/L) that was successfully treated with i.v. Ferric Carboxymaltose (FCM). After the administration of 2 g of FCM in three refracted doses, in association with folic acid 5 mg/day for two weeks, the hemoglobin raised to 79 g/L in 12 days and to 144 g/L after about 7 months without any undesired effect recorded. Intravenous FCM can be an effective and safe alternative to blood transfusion also in selected cases of severe iron-deficiency anemia in children.

Impact of gender parity on preoperative anaemia prevalence and Patient Blood Management practice.

BACKGROUND: Anaemia is a common finding in the preoperative setting, affecting around one-third of patients for whom major surgery is programmed. Moreover, preoperative anaemia has been shown to worsen patient outcome and increase length of hospital stay and costs. In the field of preoperative anaemia correction, a recent Consensus statement suggested reviewing the classic World Health Organization (WHO) criteria in adults by aligning the haemoglobin cut-off to 13 g/dL for both genders. The aim of our study was to assess the differences in terms of prevalence, transfusion rate, transfusion trigger, and blood losses according to gender in a mixed population of surgical patients. MATERIAL AND METHODS: We reviewed data of 610 consecutive patients undergoing elective major surgery at a tertiary care hospital during a 9-month period. Transfusion rate and transfusion triggers were recorded, analysed and stratified by haemoglobin class, with a particular focus on the 12.0-12.9 g/dL range. RESULTS: Since the anaemia threshold was redefined at 13 g/dL for both genders, its prevalence rose from 26.4 to 39.5% (161/610 vs 241/610; p<0.001) in the overall population and from 22.7 to 49.3% (68/300 vs 148/300; p<0.001) in women. Eighty women (26.7%) fell in the haemoglobin 12.0-12.9 g/dL range, and this category was the most represented among transfused women (34.0%). There was no statistical difference in transfusion triggers or overall transfusion rate between genders. Subjects of both genders were transfused at the same haemoglobin level (8.1 g/dL), but women reached the transfusion trigger after less red cell mass loss than men, i.e. 377 mL (249-472 mL) vs 528 mL (356-717 mL), respectively (p<0.001). DISCUSSION: Treatment of pre-surgical anaemia is one of the core principles of Patient Blood Management. Aligning the haemoglobin threshold between genders in the management of pre-surgical anaemia may result in a lower transfusion rate, but in an increased workload for medical staff in the preoperative phase.

Organizational Strategies for the Management of Intravenous Iron Therapy in Non-Hospitalized Settings: A Safe Opportunity to Implement Patient Blood Management in Italy.

This article analyzes the recommendations issued by the Emilia Romagna region in July 2020 on "Organizational strategies for the safe management of intravenous iron therapy in patients in non-hospitalized settings". The objective of these recommendations is to set up safe intravenous iron administration sites outside the hospital environment across the national territory. The document facilitates the organization of methods for intravenous iron infusion that are safe for the patient and correct from a medico-legal perspective. In addition, it opens the way for the widespread use of iron infusion in the field, providing benefits to patient quality of life. This program prevents unnecessary transfusions, reduces costs, prevents overcrowding in hospitals in the event of a pandemic, and enables patient treatment in the field, thus, saving on the use of personnel.

Heparin dosage, level, and resistance in SARS-CoV2 infected patients in intensive care unit.

INTRODUCTION: Patients with COVID-19 frequently exhibit a hypercoagulable state with high thrombotic risk, particularly those admitted to intensive care units (ICU). Thromboprophylaxis is mandatory in these patients; nevertheless, thrombosis still occurs in many cases. Thus, the problem of assessing an adequate level of anticoagulation in ICU patients becomes evident during the COVID-19 pandemic. The aim of this study was to evaluate the heparin resistance and the efficacy of heparin monitoring using an anti-Xa activity assay. METHODS: Thirty-seven heparin-treated patients admitted to ICU for SARS-CoV-2 pneumonia were retrospectively studied for antifactor Xa activity (anti-Xa), activated partial thromboplastin time (APTT), Antithrombin, Fibrinogen, D-Dimer, Factor VIII, von Willebrand Factor, and the total daily amount of heparin administered. The correlation between APTT and anti-Xa was evaluated for unfractionated heparins (UFH). The correlations between the daily dose of UFH or the dosage expressed as IU/kg b.w. for low molecular weight heparin (LMWH) and anti-Xa were also evaluated. RESULTS: Twenty-one patients received calcium heparin, 8 sodium heparin, and 8 LMWH. A moderate correlation was found between APTT and anti-Xa for UFH. APTT did not correlate with coagulation parameters. 62% of UFH and 75% of LMWH treated patients were under the therapeutic range. About 75% of patients could be considered resistant to heparin. CONCLUSIONS: SARS-COV2 pneumonia patients in ICU have frequently heparin resistance. Anti-Xa seems a more reliable method to monitor heparin treatment than APTT in acute patients, also because the assay is insensitive to the increased levels of fibrinogen, FVIII, and LAC that are common during the COVID-19 inflammatory state.

Inhibitory anti ADAMTS13 antibodies with a new rapid fully automated CLiA assay.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterized by severe ADAMTS13 deficiency. The acquired form is associated with autoantibodies directed against ADAMTS13. Both noninhibitory and inhibitory autoantibodies can be detected by ELISA assay, while only inhibitory autoantibodies are detected by Bethesda assay. Due to its short TAT and good performance, chemiluminescence (CliA) ADAMTS13 activity (HemosIL Acustar) has proven to be a good choice in the diagnosis of TTP in emergency settings. Aim of this study was to analyse the performance of the CliA ADAMTS13 activity assay in detecting inhibitory ADAMTS13 antibodies using the Bethesda assay. METHODS: A method comparison study was performed on 69 stored samples: 11 acute TTPs, 38 TTP follow-ups, 5 TTP relapses, 1 congenital TTP, 10 HUS, 4 suspected TTPs. We retrieved the results of tests previously run in ELISA for both activity and autoantibodies. At the same time, we reran new tests including ELISA and CliA activity, ELISA autoantibodies, and ELISA and CliA Bethesda assays on thawed frozen samples. RESULTS: Very good correlation was observed between ELISA and CliA activity assay results (r = 0.96) and between archived ELISA and CliA activity results (r = 0.93). Agreement between the anti-ADAMTS13 assays ranged from good (k = 0.63) to very good (k = 0.92). CONCLUSIONS: CliA and ELISA Bethesda assays showed very good agreement with samples run at the same time using ELISA ADAMTS13-autoantibody assay. Albeit more expensive, the CliA Bethesda assay identified inhibitory anti-ADAMTS13 within almost the same TAT as ELISA, but with better automation and limited operator involvement.

Early intravenous iron administration in the Emergency Department reduces red blood cell unit transfusion, hospitalisation, re-transfusion, length of stay and costs.

BACKGROUND: Moderate to severe iron deficiency anaemia is a common finding in patients admitted to the Emergency Department (ED). According to Patient Blood Management principles, intravenous iron should be the therapy of choice instead of blood transfusion for selected cases affected by chronic iron deficiency anaemia. However, this option is only rarely taken into account by physicians in the ED. As a result, in many circumstances, treatment of iron deficiency anaemia in the ED can differ from that of the Anaemia Clinic. With the aim of reducing inappropriate transfusions, and to implement intravenous iron usage, we shared a specific protocol with the ED. MATERIAL AND METHODS: We reviewed the medical records of all subjects admitted to the ED (n=267, Post-protocol group) with hemoglobin ≤9.0 g/dL and mean corpuscular volume <80 fL in a 13-month period, except if the massive transfusion protocol was activated, and results were compared with an equivalent Pre-protocol historical cohort (n=226). RESULTS: In comparison with the Pre-protocol series, the number of patients transfused did not change, but the appropriateness in terms of transfusion and red blood cell volume transfused improved sharply (87.0 vs 13.3%; p<0.001) with a significant increase in intravenous iron administration (50.2 vs 4.4% of cases; p<0.001). As a positive consequence, both the time spent in the ED by patients who were then directly discharged and costs per subject treated dropped by 37.9% and 59.0%, respectively. Treatment with infusion only in comparison with transfusion only led to a statistically significant Relative Risk reduction in transfusion on the ward and post-discharge transfusion of 55.6% and 44.4%, respectively. DISCUSSION: The implementation of Patient Blood Management principles and early intravenous iron therapy in the Emergency Department have proved to be effective tools to optimise resources both in terms of units transfused and costs.

Granulocyte-Monocyte Apheresis in Steroid-Dependent, Azathioprine-Intolerant/Resistant Moderate Ulcerative Colitis: A Prospective Multicenter Study.

BACKGROUND: Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. AIM: To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. METHODS: Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. RESULTS: From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved. CONCLUSIONS: Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.