Arturo Campos

Identification of preanalytical mistakes in the stat section of the clinical laboratory.

In the era of total quality management, detection and correction of mistakes at all stages of laboratory testing is of outstanding interest, although most attention has been directed towards detecting and correcting errors in the analytical portion of the testing process (1). One of the reasons for this, in addition to the lack of focus on the problem, is the practical difficulty in reporting and measuring the number of errors (1). This situation especially applies to the stat department of the laboratory, due to the huge pressure of demands for an almost immediate response, which may influence the quality (accuracy) of test results. However, as preanalytical mistakes may account for up to 80% of overall mistakes in laboratory testing (2, 3), their detection and prevention are key strategies to improve laboratory quality, and the greatest reduction in the number of laboratory errors is likely to result from improving the quality of specimen collection (4). The University Hospital ‘‘Virgen de la Victoria’’ is a 720-bed teaching hospital with specialised care units that serves an area with a population of 300,000 served by 19 community health centres attended by general practitioners. Some 4500 blood specimens from inpatients and outpatients are processed daily in the clinical laboratory, and approximately 30% of these are referred to the stat section. As an initial step towards the identification and prevention of preanalytical mistakes in the stat section of our clinical laboratory, we retrospectively assessed the number of

Utilidad de la administración de hierro sacarosa intravenoso para la corrección de la anemia preoperatoria en pacientes programados para cirugía mayor

BACKGROUND AND OBJECTIVE There is a high incidence of perioperative anemia among surgical patients (20%-70%). Preoperative anemia has been linked to an increased postoperative morbidity and mortality, as well as a decreased quality of life of surgical patients. In addition, a low preoperative hemoglobin constitutes an important predictive factor of allogeneic blood transfusion in major surgery. We evaluated the efficacy of intravenous iron sucrose (IVIS) administration for correction of anemia in these patient populations. PATIENTS AND METHOD Data from 84 patients with anemia who were scheduled for major elective surgery (30 colon cancer resections, 33 abdominal hysterectomies, 21 lower limb arthroplasties) and who received preoperative IVIS during 3-5 weeks were propectively collected. RESULTS Administration of IVIS -mean dose (standard deviation): 1000 (440)mg- caused a significant increase of hemoglobin levels -2.0 (1.6)g/dl (p<0.001)- and anemia was resolved in 58% of patients. No life-threatening adverse effect was witnessed. CONCLUSIONS Because of the low incidence of side effects and the rapid increase of hemoglobin levels, IVIS emerges as a safe, effective drug for treating preoperative anemia in these patient populations.

The cost of post-operative shed blood salvage after total knee arthroplasty: an analysis of 1,093 consecutive procedures

BACKGROUND Requirements for allogeneic red cell transfusion after total knee arthroplasty are still high (20-50%), and salvage and reinfusion of unwashed, filtered post-operative shed blood is an established method for reducing transfusion requirements following this operation. We performed a cost analysis to ascertain whether this alternative is likely to be cost-effective. MATERIALS AND METHODS Data from 1,093 consecutive primary total knee arthroplasties, managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged blood (control group, n=330), were retrospectively reviewed. The costs of low-vacuum drains, shed blood collection canisters (Bellovac ABT, Wellspect HealthCare and ConstaVac CBC II, Stryker), shed blood reinfusion, acquisition and transfusion of allogeneic red cell concentrate, haemoglobin measurements, and prolonged length of hospital stay were used for the blood management cost analysis. RESULTS Patients in the reinfusion group received 152±64 mL of red blood cells from postoperatively salvaged blood, without clinically relevant incidents, and showed a lower allogeneic transfusion rate (24.5% vs. 8.5%, for the control and reinfusion groups, respectively; p =0.001). There were no differences in post-operative infection rates. Patients receiving allogeneic transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate, both reinfusion systems may provide net savings in different cost scenarios (€ 4.6 to € 106/patient for Bellovac ABT, and € -51.9 to € 49.9/patient for ConstaVac CBCII). DISCUSSION Return of unwashed salvaged blood after total knee arthroplasty seems to save costs in patients with pre-operative haemoglobin between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin <12 g/dL, although cost-saving, its efficacy could be increased by associating some other blood-saving method.

Original breveUtilidad de la administración de hierro sacarosa intravenoso para la corrección de la anemia preoperatoria en pacientes programados para cirugía mayorUsefulness of the administration of intravenous iron sucrose for the correction of preoperative anemia in major surgery patients

BACKGROUND AND OBJECTIVE There is a high incidence of perioperative anemia among surgical patients (20%-70%). Preoperative anemia has been linked to an increased postoperative morbidity and mortality, as well as a decreased quality of life of surgical patients. In addition, a low preoperative hemoglobin constitutes an important predictive factor of allogeneic blood transfusion in major surgery. We evaluated the efficacy of intravenous iron sucrose (IVIS) administration for correction of anemia in these patient populations. PATIENTS AND METHOD Data from 84 patients with anemia who were scheduled for major elective surgery (30 colon cancer resections, 33 abdominal hysterectomies, 21 lower limb arthroplasties) and who received preoperative IVIS during 3-5 weeks were propectively collected. RESULTS Administration of IVIS -mean dose (standard deviation): 1000 (440)mg- caused a significant increase of hemoglobin levels -2.0 (1.6)g/dl (p<0.001)- and anemia was resolved in 58% of patients. No life-threatening adverse effect was witnessed. CONCLUSIONS Because of the low incidence of side effects and the rapid increase of hemoglobin levels, IVIS emerges as a safe, effective drug for treating preoperative anemia in these patient populations.

Impact of Postoperative Unwashed Shed Blood Retrieved after Total Knee Arthroplasty on Endotoxin-stimulated Tumor Necrosis Factor α Release In Vitro

Background:Allogeneic or autologous blood seems to have an immunosuppressive effect that is largely attributable to storage-dependent factors. However, transfusion of postoperative unwashed shed blood (USB) after elective total knee replacement does not undergo storage. Therefore, the authors explored the effects of USB on the mitogen-driven cytokine synthesis by the patient’s peripheral blood mononuclear cells. Methods:Perioperative blood samples were obtained from 12 total knee replacement patients with and 5 without reinfusion of leukoreduced USB, and from USB reinfusion line, before and after leukoreduction. Venous blood obtained at 4–6 postoperative hours was coincubated with USB. Endotoxin-stimulated release of tumor necrosis factor &agr; and interleukin 10 was measured after 24 h of culture by solid-phase enzyme-labeled chemiluminescent immunometric assay. Results:Coincubation of postoperative venous blood with USB, USB cells, or USB plasma resulted in a significant depression of tumor necrosis factor-&agr; synthesis, without significant effects on interleukin-10 synthesis. However, no differences were observed for endotoxin-stimulated cytokine release in perioperative blood samples from patients receiving or not receiving USB. Conclusion:These data suggest that USB seemed to contain an antiinflammatory agent. However, at the actual retransfusion rate, USB does not seem to further enhance the immunosuppression that follows knee replacement surgery.

Incidencia y mortalidad de la transfusión masiva en un hospital universitario: estudio del período 2001-2005

Fundamento y objetivo: Existen pocos estudios epidemiologicos sobre la transfusion masiva (TM), a pesar de su importancia para evaluar posibles estrategias que reduzcan el numero de concentrados de hematies (CH) transfundidos y sus efectos adversos. Por ello evaluamos retrospectivamente la incidencia de TM en nuestra institucion (un hospital universitario con 700 camas) durante un periodo de 5 anos. Pacientes y metodo: Se revisaron los registros del deposito de hemoderivados para identificar los episodios de TM ocurridos entre enero de 2001 y diciembre de 2005. La TM se definio como la transfusion de como minimo 8 unidades de CH en 24 h. Los datos clinicos se obtuvieron exclusivamente de las peticiones de transfusion. Resultados: Se identificaron 304 episodios de TM en 288 pacientes (un episodio por semana), que recibieron 4.845 CH (3.515 durante las primeras 24 h), debido a rotura de aneurisma aortico (n = 62), politraumatismo (n = 57), hemorragia digestiva alta (n = 51) o cirugia cardiaca (n = 41), electiva (n = 36), urgente (n = 30) u oncologica (n = 27). La mortalidad fue del 48%, y el analisis multivariante identifico la edad (odds ratio [OR] = 1,023; intervalo de confianza [IC] del 95%, 1,006-1,040) y el numero de CH en 24 h (OR = 1,094; IC del 95%, 1,0032-1,160) como predictores independientes de mortalidad, mientras que el politraumatismo aparecia como factor protector (OR = 0,325; IC del 95%, 0,112-0,940). Conclusiones: La mortalidad entre los pacientes con TM fue alta y en ella influyeron el numero de CH, la edad y el diagnostico. Dado que la mayoria de los episodios de TM ocurren en cirugia y politraumatismos, se discuten algunas estrategias para reducir el volumen de la TM.

Pre-operative anaemia: prevalence, consequences and approaches to management

Prevalence of pre-operative anaemia A recent study, using public data from 187 countries worldwide and World Health Organization (WHO) definitions of anaemia (Table I), found a significant decrement in the global prevalence of anaemia, which decreased from 40.2% in 1990 to 32.9% in 2010, though the prevalence varied widely across regions1. However, a lower prevalence of mild and moderate anaemia accounted for most of the reduction, while the prevalence of severe anaemia remained largely unchanged1. Previously, the third US National Health and Nutrition Examination Survey (NHANES III, Phases 1&2, 19881994; 26,372 individuals), showed an average prevalence of anaemia of 7% in the 1to 64-year old age group, with the prevalence being slightly higher among females2. In people 65 years old or more, the prevalence of anaemia increased progressively with age (13% in subjects aged 75-84, 23% in those over 85 years) and the condition was more common among males2. However, analysing the distribution of haemoglobin (Hb) levels in men and women aged 65 years and older showed that 32.4% of women and 23.3% of men had Hb levels lower than 13 g/dL, indicating that the higher overall prevalence of anaemia among older men just results from the genderspecific WHO definitions of anaemia2. This progressive increase of anaemia prevalence with age was also noted in a meta-analysis of 34 studies (85,409 elderly individuals); the overall prevalence was 17%, but fell to 6% when considering cases with a Hb of ≤11 g/dL, which indicates that anaemia was mild in the majority of cases3. Do these figures of anaemia prevalence in individuals living in the community apply to hospitalised patients? In a cohort investigation of adult patients (n=232,440) hospitalised for surgical or medical pathologies between January 2009 and August 2011, 19% presented with anaemia upon admission, whereas 60% of those who were not anaemic upon presentation developed hospital-acquired anaemia4. Another retrospective study of patients of any age (n=2,234) hospitalised in the departments of digestive diseases, internal medicine, cardiology or respiratory diseases between September and October 2010 found an anaemia prevalence of 50%5. In cancer patients, the European cancer anaemia survey found a prevalence of anaemia (Hb cut-off 12 g/dL) at recruitment which varied between 25% in patients with head and neck cancer and 53% in those with a haematological cancer5. In addition, among patients receiving treatment, the mean anaemia prevalence was 53%, ranging from 29% for those being treated with radiotherapy to 75% for those given cis-platinum based chemotherapy6. In 18 large observational studies encompassing over 650,000 surgical patients, the mean prevalence of pre-operative anaemia was around 35%, varying between 10.5% and 47.9%7-24. There were

Blood donation and blood transfusion in Spain (1997 – 2007): the effects of demographic changes and universal leucoreduction

BACKGROUND AND OBJECTIVE As epidemiological information is useful in planning the provision and assessing the efficiency of product use, we reviewed Spanish data on population, blood donation and blood component transfusion from 1997 to 2007, and the possible effect of universal leucoreduction. METHODS Data on the Spanish population were obtained from the National Institute of Statistics, whereas data on blood donation and blood component transfusion were acquired from the Spanish Ministry of Health. RESULTS During the study period, the Spanish population increased by 5.6 million persons (14.4%), and blood donation by 28.1%, although the amount of red blood cells (RBC) obtained increased by only 21.5% whereas RBC transfusions increased by 28.3%. The RBC transfusion rate was significantly higher after the implementation of universal leucoreduction (2002 - 2006) than during the pre-leucoreduction period (1997 - 2001) (difference = 2.54 units/1,000 population/year; 95%CI 1.81 - 3.27; P<0.001). We also observed statistical ly, but not clinically, significant differences for platelet and plasma transfusions. CONCLUSION The increase observed in the RBC transfusion index after implementation of universal leucoreduction may have been due to a reduction of the haemoglobin content in the RBC units. Our data on blood use do, therefore, seem to add to the case against universal leucoreduction, which has led to an incremental cost for unknown, but probably slight, benefits for patients.

Low vacuum re-infusion drains after total knee arthroplasty: is there a real benefit?

An international survey estimated that 1,300,000 total knee prostheses are implanted each year worldwide1. Total knee arthroplasty (TKA) is associated with a considerable amount of blood loss (20–40% of the circulating blood volume) which results in a significant post-operative decline in haemoglobin levels (−3–5 g/dL)2,3. As a result, 20% to 50% of TKA patients receive at least one allogeneic blood transfusion (ABT) to treat acute post-operative anaemia3–6. Evidence of the clinical and economic disadvantages of ABT in treating peri-operative anaemia has prompted recommendations for its restrictive use7–11 and a growing interest in multidisciplinary, multimodal, individualised strategies, collectively termed “patient blood management” (PBM), aimed at minimising ABT with the ultimate goal of improving patients’ outcomes12. In May 2010, the 63rd World Health Assembly adopted resolution WHA63.12 on “Availability, safety and quality of blood products” requesting the World Health Organisation to provide its member states with training and support on safe and rational use of blood products and on implementing PBM13. This new standard of care, which relies on detection and treatment of peri-operative anaemia (pillar 1) and reduction of surgical blood loss and peri-operative coagulopathy (pillar 2) to harness and optimise physiological tolerance of anaemia (pillar 3), thus allowing restrictive use of ABT, is now being established for elective orthopaedic surgery in several European countries12. The strategies of pillar 2 include identifying and planning the management of patients at high risk of bleeding (pre-operative), meticulous haemostasis and blood-sparing surgical techniques, use of pharmacological or haemostatic agents and cell salvage (intra-operative), and monitoring and management of post-operative bleeding, maintaining normothermia, and re-infusion of drained blood (post-operative)14. Post-operatively, the use of closed-suction drainage systems in TKA is common practice. The theoretical advantage of the use of such drains is a reduction in the occurrence of wound haematoma and compression of vital structures. Furthermore, the presence of postoperative haematoma is also related to increased postoperative pain and impaired wound healing and infection after surgery. Both effects result in impaired rehabilitation and prolonged hospital stay. However, there are at least three unanswered questions regarding the use of drains. The first question is whether they are efficacious in achieving their intended goal. In a recent meta-analysis of 36 studies involving 5,464 participants undergoing different types of orthopaedic surgery, the pooled results indicated no statistically significant difference in the incidence of wound infection, haematoma, dehiscence or reoperations, but a significantly greater need for ABT in patients managed with a post-operative drain (RR,1.25; 95% CI, 1.04–1.51)15. Although the use of drains after surgery is established and widespread, given the lack of sound evidence, this is an empirically based strategy. Nevertheless, if a post-operative drain is to be used, the second question is whether to use a low-vacuum or a high-vacuum drain. Again conflicting results have been published for lower limb arthroplasty surgery. Some studies reported no statistically significant differences between the two drainage systems with regards to blood loss, ABT rate and post-operative adverse events16,17, whereas in others the use of low vacuum drain within PBM was associated with reduced ABT requirements and cost-savings, without increasing post-operative complications18. Finally, it can be postulated that if post-operative drains are to be used, low-vacuum salvage/re-infusion drains may be beneficial to the patient in the event of high post-operative blood loss. Thus, the salvage and re-infusion of post-operative shed blood was introduced as a unique blood-saving concept to decrease peri-operative blood loss, to maintain higher post-operative haemoglobin levels and to decrease the use of ABT. In this procedure, blood from a post-operative drain is collected and then either returned with microaggregate filtering alone or washed, concentrated, and then returned19. In patients undergoing TKA, salvage and re-infusion of post-operative shed blood reduced the relative risk of receiving ABT by 60% when compared with the risk in a control group, but not the number of units transfused per patient (2 units/patient), the rate of post-operative febrile reactions and length of hospital stay11,20,21. It has also been suggested that post-operative cell salvage could have beneficial effects on the incidence of infection as well as deep venous thrombosis after arthroplasty surgery21,22. Interestingly, these beneficial effects were independent of whether washed or unwashed post-operative shed blood was re-infused, justifying its widespread use19–22, although some authors have questioned the quality and safety of unwashed PSB, suggesting that the blood should be washed prior to being returned to the patient23,24. Over the last 10 years the number of salvage/re-infusion devices sold in Europe has increased progressively, and at least one of them, Bellovac ABT, has surpassed the figure of 1,250,000 units (data provided by Wellspect HealthCare). The Spanish Consensus Statement on alternatives to ABT (Seville Document Update 2013) recommend the use of post-operative red cell salvage, with re-infusion of filtered and/or washed salvaged blood, to reduce the transfusion rate in TKA (grade 1B recommendation)11. However, no randomised studies comparing the use of a low-vacuum re-infusion drain with no drain had been performed to date. In this issue of Blood Transfusion, Horstmann et al.25 present the results of an open, randomised controlled study of 115 TKA patients, which was conducted to ascertain the superiority of either method in decreasing the drop in post-operative haemoglobin levels (primary end-point), and reducing peri-operative blood loss and ABT rate (secondary end-points). In the autotransfusion group, a mean of 515 mL of post-operative shed blood were re-infused within the first 6 hours after surgery (equivalent to 1 unit of packed red cells). Compared to the group in which drains were not used, the autotransfusion group had significantly higher haemoglobin levels during the first 3 days after surgery and lower total peri-operative net blood loss (−260 mL; P=0.03). In addition, there was a trend towards lower ABT rates (10.2% versus 19.6%; P=0.15), and no differences in pain scores, range of motion or adverse events during hospital stay and the first 3 months after surgery. Nevertheless, the study was not powered to detect significant differences in either ABT rate or incidence of post-operative complications and this is regarded as a limitation by the authors. These data add to the concept of the importance of visible and hidden blood loss in TKA, and to the efficacy of post-operative cell salvage at maintaining higher postoperative haemoglobin levels (+0.7 g/dL). Are these differences in haemoglobin levels clinically relevant? On the one hand, in a prospective, observational cohort study, Vuille-Lessard et al.26 found that moderate anaemia (haemoglobin 8–10 g/dL) was not associated with impaired functional recovery or quality of life in the immediate period after major arthroplasty in patients managed with a restrictive transfusion threshold (haemoglobin 7.5–8 g/dL). However, they recognised that “further studies will be required to determine the long-term consequences of a restrictive transfusion strategy in these patients”26. On the other hand, the use of low-vacuum reinfusion drains in TKA results in decreased post-operative blood loss, which in turn may be important to avoid reaching a predefined transfusion trigger, especially in patients with a low haemoglobin concentration on admission, thus reducingABT rates19–21. This target can also be achieved by peri-operative administration of tranexamic acid, although the safety of this antifibrinolytic drug in lower limb arthroplasty has not been convincingly demonstrated27. The results of several large studies strongly suggest that peri-operative ABT in elective orthopaedic surgery is associated with an increase in the risk of post-operative infection and/or prolonged length of hospital stay3,4,6,28. The main benefit of post-operative cell salvage is, therefore, its ability to reduce banked blood utilisation without compromising patients’ safety. This ability has been proven similar to that of the pre-donation of one unit of autologous blood29, a blood-saving strategy which is no longer recommended in TKA11,30. Re-infusion of unwashed post-operative shed blood has been shown to be cost-effective when compared to ABT6. Larger, sufficiently powered studies are necessary to definitely evaluate the blood-saving effect of postoperative cell salvage after joint arthroplasty, as well as the presumed reductions in both the incidence of infection and deep venous thrombosis and the length of hospital stay. Nevertheless, it must be borne in mind that, although this technique may be effective on its own, the aim of performing major surgical procedures without the use of ABT and without placing the patient at risk of complications may be better accomplished by combining several blood conservation strategies into a defined PBM algorithm11,12.

Could cost-effectiveness of postoperative shed blood salvage after elective knee arthroplasty be improved?

As shown by the Austrian benchmark study, unilateral primary total knee arthroplasty (TKA) results in a substantial blood loss (24%-47% of preoperative circulating red blood cell [RBC] volume), and more than 40% of patients receive allogeneic blood transfusion, with a large intercenter variability (12%-87%). However, although there may be substantial hidden blood loss due to bleeding into the tissues and residual blood in the joint after TKA, 50% of the true total loss occurs postoperatively and, consequently, salvage and return of washed or filtered shed blood from postoperative drainage may represent a safe and effective alternative to allogeneic transfusion in these patients. Moreover, in a retrospective review for a sample of 317 patients who underwent primary TKA, Rao and colleagues, using a detailed cost-analysis model, found that the mean unit costs for washed postoperatively salvaged blood (OrthoPAT, Haemonetics Corporation, Braintree, MA), unwashed salvaged blood (USB), and allogeneic banked blood were