A Simple Guideline Reduces the Need for Red Blood Cell Transfusions in Swiss Hospitals: A Prospective, Multicentre, Before-and-After Study in Elective Hip and Knee Replacement

INTRODUCTION Optimising the use of blood has become a core task of transfusion medicine. Because no general guidelines are available in Switzerland, we analysed the effects of the introduction of a guideline on red blood cell (RBC) transfusion for elective orthopaedic surgery. METHODS Prospective, multicentre, before-and-after study comparing the use of RBCs in adult elective hip or knee replacement before and after the implementation of a guideline in 10 Swiss hospitals, developed together with all participants. RESULTS We included 2,134 patients, 1,238 in 7 months before, 896 in 6 months after intervention. 57 (34 or 2.7% before, 23 or 2.6% after) were lost before follow-up visit. The mean number of transfused RBC units decreased from 0.5 to 0.4 per patient (0.1, 95% CI 0.08-0.2; p = 0.014), the proportion of transfused patients from 20.9% to 16.9% (4%, 95% C.I. 0.7-7.4%; p = 0.02), and the pre-transfusion haemoglobin from 82.6 to 78.2 g/l (4.4 g/l, 95% C. I. 2.15-6.62 g/l, p < 0.001). We did not observe any statistically significant changes in in-hospital mortality (0.4% vs. 0%) and morbidity (4.1% vs. 4.0%), median hospital length of stay (9 vs. 9 days), follow-up mortality (0.4% vs. 0.2%) and follow-up morbidity (6.9% vs. 6.0%). CONCLUSIONS The introduction of a simple transfusion guideline reduces and standardises the use of RBCs by decreasing the haemoglobin transfusion trigger, without negative effects on the patient outcome. Local support, training, and monitoring of the effects are requirements for programmes optimising the use of blood.

Implementation of a mandatory donor RHD screening in Switzerland

Starting in 2013, blood donors must be tested at least using: (1) one monoclonal anti-D and one anti-CDE (alternatively full RhCcEe phenotyping), and (2) all RhD negative donors must be tested for RHD exons 5 and 10 plus one further exonic, or intronic RHD specificity, according to the guidelines of the Blood Transfusion Service of the Swiss Red Cross (BTS SRC). In 2012 an adequate stock of RHD screened donors was built. Of all 25,370 RhD negative Swiss donors tested in 2012, 20,015 tested at BTS Berne and 5355 at BTS Zürich, showed 120 (0.47%) RHD positivity. Thirty-seven (0.15%) had to be redefined as RhD positive. Routine molecular RHD screening is reliable, rapid and cost-effective and provides safer RBC units in Switzerland.

New perioperative fluid and pharmacologic management protocol results in reduced blood loss, faster return of bowel function, and overall recovery.

Cystectomy and urinary diversion have high morbidity, and strategies to reduce complications are of utmost importance. Epidural analgesia and optimized fluid management are considered key factors contributing to successful enhanced recovery after surgery. In colorectal surgery, there is strong evidence that an intraoperative fluid management aiming for a postoperative zero fluid balance results in lower morbidity including a faster return of bowel function. Recently, a randomized clinical trial focusing on radical cystectomy demonstrated that a restrictive intraoperative hydration combined with a concomitant administration of norepinephrine reduced intraoperative blood loss, the need for blood transfusion and morbidity. The purpose of this review is to highlight specific anesthesiological aspects which have been shown to improve outcome after RC with urinary diversion.

Detection of haemorrhagic shock: Are vital signs obsolete? A commentary by Dr M. Luginbühl

The ATLS program by the American college of surgeons is probably the most important globally active training organization dedicated to improve trauma management. Detection of acute haemorrhagic shock belongs to the key issues in clinical practice and thus also in medical teaching. (In this issue of the journal William Schulz and Ian McConachrie critically review the ATLS shock classification Table 1), which has been criticized after several attempts of validation have failed [1]. The main problem is that distinct ranges of heart rate are related to ranges of uncompensated blood loss and that the heart rate decrease observed in severe haemorrhagic shock is ignored [2]. Table 1. Estimated blood loos based on patient's initial presentation (ATLS Students Course Manual, 9th Edition, American College of Surgeons 2012). Class I Class II Class III Class IV Blood loss ml Up to 750 750–1500 1500–2000 >2000 Blood loss (% blood volume) Up to 15% 15–30% 30–40% >40% Pulse rate (BPM) <100 100–120 120–140 >140 Systolic blood pressure Normal Normal Decreased Decreased Pulse pressure Normal or ↑ Decreased Decreased Decreased Respiratory rate 14–20 20–30 30–40 >35 Urine output (ml/h) >30 20–30 5–15 negligible CNS/mental status Slightly anxious Mildly anxious Anxious, confused Confused, lethargic Initial fluid replacement Crystalloid Crystalloid Crystalloid and blood Crystalloid and blood Table options In a retrospective evaluation of the Trauma Audit and Research Network (TARN) database blood loss was estimated according to the injuries in nearly 165,000 adult trauma patients and each patient was allocated to one of the four ATLS shock classes [3]. Although heart rate increased and systolic blood pressure decreased from class I to class IV, respiratory rate and GCS were similar. The median heart rate in class IV patients was substantially lower than the value of 140 min−1 postulated by ATLS. Moreover deterioration of the different parameters does not necessarily go parallel as suggested in the ATLS shock classification [4] and [5]. In all these studies injury severity score (ISS) and mortality increased with in increasing shock class [3] and with increasing heart rate and decreasing blood pressure [4] and [5]. This supports the general concept that the higher heart rate and the lower blood pressure, the sicker is the patient. A prospective study attempted to validate a shock classification derived from the ATLS shock classes [6]. The authors used a combination of heart rate, blood pressure, clinically estimated blood loss and response to fluid resuscitation to classify trauma patients (Table 2) [6]. In their initial assessment of 715 predominantly blunt trauma patients 78% were classified as normal (Class 0), 14% as Class I, 6% as Class II and only 1% as Class III and Class IV respectively. This corresponds to the results from the previous retrospective studies [4] and [5]. The main endpoint used in the prospective study was therefore presence or absence of significant haemorrhage, defined as chest tube drainage >500 ml, evidence of >500 ml of blood loss in peritoneum, retroperitoneum or pelvic cavity on CT scan or requirement of any blood transfusion >2000 ml of crystalloid. Because of the low prevalence of class II or higher grades statistical evaluation was limited to a comparison between Class 0 and Class I–IV combined. As in the retrospective studies, Lawton did not find a statistical difference of heart rate and blood pressure among the five groups either, although there was a tendency to a higher heart rate in Class II patients. Apparently classification during primary survey did not rely on vital signs but considered the rather soft criterion of “clinical estimation of blood loss” and requirement of fluid substitution. This suggests that allocation of an individual patient to a shock classification was probably more an intuitive decision than an objective calculation the shock classification. Nevertheless it was a significant predictor of ISS [6]. Table 2. Shock grade categories in prospective validation study (Lawton, 2014) [6]. Normal No haemorrhage Class I Mild Class II Moderate Class III Severe Class IV Moribund Vitals Normal Normal HR > 100 with SBP >90 mmHg SBP < 90 mmHg SBP < 90 mmHg or imminent arrest Response to fluid bolus (1000 ml) NA Yes, no further fluid required Yes, no further fluid required Requires repeated fluid boluses Declining SBP despite fluid boluses Estimated blood loss (ml) None Up to 750 750–1500 1500–2000 >2000 Table options What does this mean for clinical practice and medical teaching? All these studies illustrate the difficulty to validate a useful and accepted physiologic general concept of the response of the organism to fluid loss: Decrease of cardiac output, increase of heart rate, decrease of pulse pressure occurring first and hypotension and bradycardia occurring only later. Increasing heart rate, increasing diastolic blood pressure or decreasing systolic blood pressure should make any clinician consider hypovolaemia first, because it is treatable and deterioration of the patient is preventable. This is true for the patient on the ward, the sedated patient in the intensive care unit or the anesthetized patients in the OR. We will therefore continue to teach this typical pattern but will continue to mention the exceptions and pitfalls on a second stage. The shock classification of ATLS is primarily used to illustrate the typical pattern of acute haemorrhagic shock (tachycardia and hypotension) as opposed to the Cushing reflex (bradycardia and hypertension) in severe head injury and intracranial hypertension or to the neurogenic shock in acute tetraplegia or high paraplegia (relative bradycardia and hypotension). Schulz and McConachrie nicely summarize the various confounders and exceptions from the general pattern and explain why in clinical reality patients often do not present with the “typical” pictures of our textbooks [1]. ATLS refers to the pitfalls in the signs of acute haemorrhage as well: Advanced age, athletes, pregnancy, medications and pace makers and explicitly state that individual subjects may not follow the general pattern. Obviously the ATLS shock classification which is the basis for a number of questions in the written test of the ATLS students course and which has been used for decades probably needs modification and cannot be literally applied in clinical practice. The European Trauma Course, another important Trauma training program uses the same parameters to estimate blood loss together with clinical exam and laboratory findings (e.g. base deficit and lactate) but does not use a shock classification related to absolute values. In conclusion the typical physiologic response to haemorrhage as illustrated by the ATLS shock classes remains an important issue in clinical practice and in teaching. The estimation of the severity haemorrhage in the initial assessment trauma patients is (and was never) solely based on vital signs only but includes the pattern of injuries, the requirement of fluid substitution and potential confounders. Vital signs are not obsolete especially in the course of treatment but must be interpreted in view of the clinical context. Conflict of interest None declared. Member of Swiss national ATLS core faculty.

Early versus delayed application of Thomas splints in patients with isolated femur shaft fractures: The benefits quantified

AIMS To investigate and quantify the clinical benefits of early versus delayed application of Thomas splints in patients with isolated femur shaft fractures. MATERIALS AND METHODS Level IV retrospective clinical and radiological analysis of patients presenting from January to December 2012 at a Level 1 Trauma Unit. All skeletally mature patients with isolated femur shaft fractures independently of their mechanism of injury were included. Exclusion criteria were: ipsilateral fracture of the lower limb, neck and supracondylar femur fractures, periprosthetic and incomplete fractures. Their clinical records were analysed for blood transfusion requirements, pulmonary complications, surgery time, duration of hospital stay and analgesic requirements. RESULTS A total of 106 patients met our inclusion criteria. There were 74 males and 32 females. Fifty seven (54%) patients were in the 'early splinted' group and 49 patients (46%) were in the 'delayed splinted' group (P>0.05). The need for blood transfusion was significantly reduced in the 'early splinted' group (P=0.04). There was a significantly higher rate of pulmonary complications in the 'delayed splinted' group (P=0.008). All other parameters were similar between the two groups. CONCLUSION The early application of Thomas splints for isolated femur fractures in non-polytraumatised patients has a clinically and statistically significant benefit of reducing the need for blood transfusions and the incidence of pulmonary complications.

Thrombotic thrombocytopenic purpura during pregnancy versus imitator of preeclampsia.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organs due to a systemic endothelial cell injury secondary to a deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity. TTP is a rare complication of pregnancy with a poor prognosis and high fetal mortality, especially when it occurs during the first trimester. Recent data have supported that effective treatment of TTP is plasma therapy. Unfortunately a major problem remains in the delay in diagnosis due to confounding factors between other "imitators of preeclampsia." Rapid and readily available laboratory testing to quickly diagnose TTP is desperately needed to improve care and to save mother and future child life. CASE REPORT We describe a rare case of successful pregnancy after TTP manifestations occurring in the first trimester; most importantly, our experience represents the first case of atypical manifestation due to neurologic and kidney manifestations preceding laboratory assay alterations. RESULTS We treated a patient with plasma replacement of 30 mL/kg/day and daily plasmapheresis in combination with continuous infusion of fresh-frozen plasma 10 mL/kg/day. The response of clinical manifestation immediately improved. At 30 weeks, the patient had multiple episodes of high blood pressure and concomitant decrease of hemoglobin and platelet count, so a cesarean section was immediately performed. She delivered a healthy female baby. CONCLUSION Early diagnosis by ADAMTS13 activity, occasionally occurring before clinical manifestations, aided us in promptly administering commended and life-saving treatments.

Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy

BACKGROUND Multiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24- and 6-month dual antiplatelet therapy groups. METHODS AND RESULTS Bleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS-BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS-BLED. Major bleeding and transfusions were higher in the 24- versus 6-month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (Pint=0.05 and Pint=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24-month rather than 6-month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively. CONCLUSIONS Our analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all-comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long-term dual antiplatelet therapy regimen. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00611286.

Current insights into thrombotic microangiopathies: Thrombotic thrombocytopenic purpura and pregnancy.

The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with ThromboSpondin type 1 domains, no. 13). In several affected women disease onset during their first pregnancy leads to the diagnosis of hereditary TTP. Without plasma treatment mother and especially fetus are at high risk of dying. The relapse risk during a next pregnancy is almost 100% but regular plasma transfusion starting in early pregnancy will prevent acute TTP flare-up and may result in successful pregnancy outcome. Pregnancy may also constitute a mild risk factor for the onset of acute acquired TTP caused by autoantibody-mediated severe ADAMTS13 deficiency. Women having survived acute acquired TTP may not be at very high risk of TTP relapse during an ensuing next pregnancy but seem to have an elevated risk of preeclampsia. Monitoring of ADAMTS13 activity and inhibitor titre during pregnancy may help to guide management and to avoid disease recurrence. Finally, TTP needs to be distinguished from the much more frequent hypertensive pregnancy complications, preeclampsia and especially HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count) syndrome.

The European Hematology Association Roadmap for European Hematology Research: a consensus document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundation

Non-sexual household transmission of HCV infection: A cohort study

Objective. This study was designed to determine the prevalence and incidence of HCV infection among non-sexual household contacts of HCV-infected women and to describe the association between HCV infection and potential household risk factors in order to examine whether non-sexual household contact is a route of transmission for HCV infection. ^ Methods. A baseline prevalence survey included 409 non-sexual household contacts of 241 HCV-infected index women in the Houston area from 1994 to 1997. A total of 470 non-sexual household contacts with no evidence of HCV infection at baseline investigation were re-assessed approximately three years after baseline enrollment. Information on potential risk factors was collected through face to face interviews and blood samples were tested for anti-HCV with ELISA-2 and Matrix/RIBA-2. The relationships between HCV infection and potential risk factors were examined by using univariate and multivariate logistic regression analyses. ^ Results. The overall prevalence of anti-HCV positivity among 409 non-sexual household contacts was 4.4%. The highest prevalence of anti-HCV was found in parents (19.5%), followed by siblings (8.1%) and other relatives (5.6%); the children had the lowest prevalence of anti-HCV (1.2%). The univariate analysis showed that IDU, blood transfusion, tattoos, sexual contact with injecting drug users, more than 3 sexual partners in a lifetime, history of a STD, incarceration, previous hepatitis, and contact with hepatitis patients were significantly associated with HCV infection, however, sharing razors, nail clippers, toothbrushes, gum, food or beds with HCV-infected women, and history of dialysis, health care job, body piercing, and homosexual activities were not. Multivariate analysis found that IDU (OR = 221.7 with 95% CI of 22.8 to 2155.7) and history of a STD (OR = 11.7 with 95% CI of 1.2 to 113.1) were the only variables significantly associated with HCV infection. No such associations remained for other risk factors. The three-year cumulative incidence of anti-HCV among 352 non-sexual household contacts of HCV-infected women was zero. ^ Conclusion. This study has provided no evidence that non-sexual household contact is a likely route of transmission for HCV infection. The risk of sharing razors, nail clippers, toothbrushes, gum, food and/or beds with HCV-infected women is not evident and has not been shown to be the likely mode for HCV spread among family members. This study does suggest that IDU is the likely route of transmission for most HCV infection. Association also has been shown independently with a history of STD. The prevalence of anti-HCV among non-sexual household contacts was low. Exposure to common parenteral risk factors and sexual transmission between sexual partners may account for HCV spread among household members of HCV-infected persons. ^

Antigenic variation in surface proteins of Trypanosoma cruzi (Chagas' disease)

Chagas' disease, a devastating illness in the Western Hemisphere, is caused by the protozoan parasite Trypanosoma cruzi. Transmission is via bloodsucking insect vectors, congenitally, or through blood transfusion and/or organ transplantation. A significant percentage of heart-related illnesses and deaths each year are attributable to the number of persons with Chagas' disease. Currently, there is no FDA-approved routine screening of the U.S. blood supply being conducted by blood banks. The only current commercial assays available for detection of Trypanosoma cruzi are based on South American isolates, which may differ antigenically from those found in the US. In this study, the assay used intact parasites as antigen in an ELISA-type assay. Therefore, serological differences presumably reflected variations in surface antigens. The basis of differential antibody binding to these antigens is unknown. In this study, biochemical characterization and genetic polymorphism analysis will be performed on three defined surface proteins of T. cruzi epimastigotes.^

The epidemiology of Hepatitis B and Hepatitis C virus infection among college students who are not US/Canadian born in Houston

Introduction. A vast majority of studies conducted in both developed and developing nations have focused on the epidemiology of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) in high-risk populations; low-risk populations have been neglected. Recently Hwang et al conducted a unique large cross-sectional study in American university students that focused on cosmetic procedures and drug use for acquiring these infections among a low-risk young adult population In Houston. ^ Methods. This study is a secondary data analysis of the cross-sectional study conducted by Hwang et al. Data for this anonymous study were collected from 7,960 college students, among whom were the 2,561 non US/Canadian born students included in this study. All students completed a self-administered questionnaire and provided a blood sample. The epidemiology of HBV/HCV and risk factors for acquiring HBV/HCV infection was studied by comparing those with HBV/HCV infection versus those without. Both univariate and multivariate logistic regression was used to analyze the data. ^ Results. Overall prevalence of HBV and HCV infections were 22% and 0.8% respectively. By multivariable analysis, the factors that were independently associated with increased prevalence of HBV infection were increasing age per year (OR=1.06, 95% C.I=1.04-1.08), Black or Asian race (OR=6.21, 95% C.I=3.14-12.27), history of household contact with hepatitis (OR=1.87, 95% C.I=1.15-3.05), and having sexual partner with hepatitis (OR=5.20, 95% C.I=1.5-18.00). For HCV these factors included increasing age per year (OR= 1.08, 95% C.I=1.03-1.14), history of blood transfusion prior to 1991 (OR=25.45, 95% C.I=7.58-85.40), and Injection drug use. (OR=78.15, 95% C.I=12.19-500.85). Cosmetic procedures like tattooing were not significant risk factors for either HBV or HCV infection. ^ Conclusions. In a low-risk adult foreign born population, cosmetic procedures are not significant risk factors for HBV or HCV infection. The prevention strategies of these infections in this population should focus on safe sexual practices/abstinence and HBV vaccination should be provided to adolescents and sexually active adults. ^

Evidence of hepatitis C transmission in healthcare settings in Karachi, Pakistan

Transmission of Hepatitis C (HCV) in Pakistan is a continuing public health problem. Several cultural and behavioral practices promote HCV transmission through the use of unsafe needles and blood products. This study aimed to determine the prominent risk factors associated with HCV transmission in the Indus Hospital catchment population. A case-control study design was implemented to enroll 300 laboratory confirmed HCV+ participants from consulting clinics at Indus Hospital and 300 laboratory confirmed HCV− participants from both the consulting clinics and the surrounding community. Odds ratios and their 95% were calculated for each risk factor to create a two gender specific multivariable models and a combined multivariable model. Participants who received 12 or more injections in the past year, ever received a blood transfusion, or ever had dental work performed were all independently significant more likely to be HCV+ when compared to those who received 1–4 injections in the past year, never received a blood transfusion, or never had dental work performed. Female participants who received 12 or more injections in the past year, had a blood transfusion while pregnant, or ever had dental work performed were all significantly more likely to be HCV+ while males who received 12 or more injections in the past year were also significantly more likely to be HCV+. Participants who brought their own needles to their injections or infusions along with those who were born in the Sindh province were significantly less likely to be HCV+ when compared to those who did not bring their own needles or born in the Punjab province. ^ Clearly transmission in healthcare settings are implicated for HCV transmission. A population level preventative approach must be taken to educate both the population and healthcare practitioners to prevent further transmission in the Pakistani healthcare system. Participants should also be followed and re-interviewed to ask where they received their various treatments as well as assess their knowledge and attitudes towards injections, infusions, and other unsafe medical procedures.^