Severe sepsis kills an estimated 1,400 people worldwide every day. This often fatal infectious process accounts for an estimated 215,000 deaths in the United States (US) annually. The main goal of this project was to evaluate the impact of the Emergency Department Severe Sepsis Alert and Practice Protocol (EDSSAPP) post implementation, on time to first antibiotic administration, length of stay, and mortality in patients admitted via the ORMC ED with severe sepsis. This study evaluated the time to first antibiotic administration, total ED and hospital length of stay (LOS) and mortality of severe sepsis patients either with a severe sepsis alert (SSA) activated or no alert activated that were admitted to the hospital through the ED. A retrospective review of the electronic medical record (EMR) was conducted to gather the required data across three time cohorts: base line/time zero (T0), six months prior to the implementation of EDSSAPP; Time one (T1) the first six months following initial EDSSAPP implementation; and Time two (T2), six months following reinstatement of the corporate sepsis committee. The most significant finding of this study was the increased number of Severe Sepsis Alerts activated in time cohort T2 (n=113) compared to T1 (n=19). Another important finding was the decreased mortality in T2 (16.4%) compared to T0 (22.7%) and T1 (33%). Overall, the number of ED patients with severe sepsis who received antibiotics within the EDSSAPP required 60 minutes did not consistently improve across the three time cohorts, T0 (81.8%), T1 (71.7%) and T2 (80.6%). The hospital LOS of stay was increased by almost 1.5 days between those patients with a severe sepsis alert activated in T1 (9.00 days) compared to time T2 (10.48 days). There was no significant decrease in the ED LOS across time cohorts and between groups of patients who had a SSA activated versus no alert activated. However, there was a 1 hour and 28 minute decrease in ED LOS in patients who had a severe sepsis alert activated in T1 compared to T0. In addition, there was a 1 hour and 52 minutes decrease in ED LOS between patients who had a SSA activated compared to those who had no alert activated in T2. While EDSSAPP data does not demonstrate the statistically significant results that was expected, the challenges related to adherence by providers to EDSSAPP is as it is seen in the literature. Increased awareness via consistent communication of on-going audit results to ED personnel will heighten their awareness for severe sepsis and EDSSAPP. Improved collaborative efforts with the interdisciplinary team are needed to refocus everyone's efforts to increase early recognition that is followed by appropriate treatment interventions and documentation is essential. Lastly, the development of a formal process to follow up with individual providers as close to real time as possible following a SSA that includes accountability for care provided and related documentation would also contribute to both awareness and adherence.

Sepsis is an uncontrolled response to infection. Severe sepsis is associated with organ dysfunction, and has mortality rate of 30-50%. Identification of severity of sepsis and prediction on mortality is crucial in making clinical decisions. Recently, cell-free DNA (cfDNA) in blood was found to have high discriminative power in predicting ICU mortality in patients with severe sepsis. In an analysis of 80 severely septic patients, the mean cfDNA level in survivors (1.16±0.13μg/ml) was similar to that of healthy volunteers (0.93±0.76μg/ml), while that of non-survivors (4.65±0.48μg/ml) was notably higher. Therefore, rapid quantification of cfDNA concentration in blood will enable physicians to quickly predict mortality of sepsis and decide on treatment. Current methods for quantification of cfDNA involve multiple steps including centrifugation, DNA-extraction from plasma, and its quantification either through spectroscopic methods or quantitative PCR. The whole process is time consuming, thus is not suitable for immediate bedside assessment. To solve the problems, a microfluidic device is designed and fabricated in this thesis, which is potential for cfDNA quantification directly using blood in 5 minutes. The goal is to use this device for distinguishing survivors or healthy donors from non-survivors in patients with severe sepsis. The two-layer device consists of a sample channel (top) and an accumulation channel (bottom) that intersect each other. The accumulation channel is preloaded with 1% agarose gel, and the blood containing cfDNA and intercalating fluorescent dye is loaded in the sample channel. Fluorescently labeled DNA is able to be trapped and concentrated at the intersection using a DC electric field, and fluorescent intensity of the accumulated DNA is representative of its concentration in the blood. The simulated electric field in the sample channel reveals that both the magnitude and the gradient of electric field reach their maximum values at the intersection. Force analysis shows that DNA was driven into the gel by the dominate electrophoretic force, while red blood cells moved away from the gel due to a strong dielectrophoretic force. In this thesis, 4 types of samples have been used to characterize the performance of the device. It showed that DNA was efficiently accumulated at the intersection, and the fluorescent intensity could be measured using a fluorescent microscope. Samples from healthy donors were able to be distinguished from that of severely septic patients in 5 minutes. However, better resolution was needed for differentiating various cfDNA concentrations in patient samples. The discussion on the effect of applied voltage showed that 9V is an optimized setting compared with 3V and 15V. In addition, it has been proved that the fluorescent reagent could be immobilized in the device and the sample preparation could be absolutely eliminated. In summary, the device proposed in this thesis is capable of distinguishing severely septic patients from healthy donors using clinical plasma in 5 minutes, and is potential to be applied in clinical blood samples. It has low cost, and is ready to be developed into a fully functioned system. This tool can be a valuable addition to the ICU to rapidly assess the severity of sepsis for informed decision making. / Thesis / Master of Applied Science (MASc)

Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome. Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death. Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

Indiana University-Purdue University Indianapolis (IUPUI) / Hospital readmission is of growing importance in the healthcare industry because of associated patient and system costs, impact to the quality of patient care, and hospital Medicare payment penalties. The increasing interest in sepsis readmission prevention has highlighted the uniqueness of severe sepsis or septic shock survivors. The results of this study provide insight into the relationship between index hospital length of stay (LOS) and 30-day readmissions for older adults (> 65 years) who discharged home from an index hospital with a principle or secondary discharge diagnosis of severe sepsis or septic shock. The purpose of this study was to investigate the relationship between index hospital LOS and 30-day readmissions in older adults (> 65 years) whose expected primary payer was Medicare and who discharged home with a principle or secondary diagnosis of severe sepsis or septic shock. Data used to answer the proposed research questions consisted of older adult discharge records from the 2014 Nationwide Readmissions Database (NRD), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. Differences in 30-day readmissions between older adult age groups, gender, and older adult location were examined. The number of days to readmission since discharge was evaluated for the subset of older adults with a readmission. Approximately 15.6% of older adults were readmitted within 30 days of their discharge. Readmissions were statistically different based on the older adult’s age, gender, and LOS. Location did not have a significant effect on readmissions. Mean LOS among readmitted older adults was 10.1 days. Analysis indicates that an older adult’s LOS had a significant effect on readmissions, although models performed poorly. Findings suggest that there are certain factors that can predict older adults who are at risk for being readmitted after being discharged with a principle or secondary discharge diagnosis of severe sepsis or septic shock.

<strong>Background</strong>: The rate of maternal death from sepsis has increased in several European countries, most notably the UK, where sepsis is now the leading cause of direct maternal death. An increase in maternal mortality also implies an increase in the number of women with severe, life-threatening morbidity. Key information gaps in the understanding of severe maternal sepsis in the UK are: the incidence, main causative organisms, infection sources, and risk factors for severe maternal sepsis. <strong>Methods</strong>: Four population-based observational studies were conducted to address these evidence gaps. <strong>Results</strong>: The incidence of severe maternal morbidity from sepsis is increasing in the UK, a trend also evident in the USA. The most common sources are respiratory tract, genital tract and urinary tract infection. The predominant organisms causing infection are E. coli, group A streptococcus, and strong circumstantial evidence of Streptococcus pneumonia. Sepsis progresses very rapidly particularly with group A streptococcal infection. Approximately 20% of women with severe sepsis progress to septic shock and 2% of women die. Risk factors for severe maternal sepsis in the UK with a large effect size are: febrile illness or antibiotics in the 2 weeks prior to onset of severe sepsis (aOR=12.1, 95% CI 8.1-18.0), caesarean section after the onset of labour (aOR= 8.1, 95% CI 4.7-14.0), multiple pregnancy (aOR= 5.8, 95% CI 1.5-21.5), infection with group A streptococcus (aOR=4.8 for progression to septic shock, 95% CI 2.2-10.8), pre-labour caesarean section (aOR= 3.8, 95% CI 2.2-6.6), low socioeconomic status (aOR=2.6, 95% CI 1.03-6.7), and operative vaginal delivery (aOR=2.5, 95% CI 1.3-4.7). Risk factors are significantly cumulative. <strong>Conclusions</strong>: Infection prior to or after delivery, even if the woman appears to be well, should be a marker for close clinical monitoring. Suspicion of group A streptococcus should be regarded as an obstetric emergency and treated ahead of laboratory confirmation.

No paciente séptico, utiliza-se como tratamento inicial a reposição volêmica com o objetivo de restabelecer a pressão arterial e consequentemente a perfusão tecidual. Os pacientes não responsivos a expansão volêmica usualmente são tratados com medicações vasoativas. O emprego desses fármacos tais como noradrenalina, nessa situação, torna-se imprescindível, porém a hiporresponsividade do sistema adrenérgico é um obstáculo rotineiro em pacientes sépticos. A vasopressina aparece como uma alternativa, tanto como fármaco de primeira escolha como resgate quando o tratamento com vasoativos adrenérgicos falha. A avaliação da microcirculação é imprescindível visto a sua importância na patogênese da sepse, e no acompanhamento das diferentes terapias. Assim sendo, o presente projeto tem por objetivo avaliar o uso da vasopressina e da noradrenalina no tratamento da hipotensão de cães em sepse decorrente de piometra por meio imagem espectral obtida através da polarização ortogonal (OPS) e sobre variáveis hemodinâmicas, bem como sobre parâmetros de oxigenação e ventilação. Foram utilizados 13 cães em sepse grave apresentando no mínimo duas variáveis da resposta inflamatória sistêmica e no mínimo uma variável de disfunção orgânica na avaliação inicial. Em todos os animais foi realizada ressuscitação volêmica inicial com 15ml/kg em 15 minutos de solução de Ringer com lactato. Caso durante a anestesia a pressão arterial média não assumir valores superiores a 65 mmHg e a pressão venosa central não variasse 2mmHg ou apresentasse valores superiores a 8 mmHg, os animais foram distribuídos em dois grupos. O Grupo VASO recebeu inicialmente 0,0002UI/kg/min de vasopressina e o Grupo NORA 0,05 mcg/kg/min noradrenalina, podendo ter o incremento de 0,0002U/kg/min e 0,02 mcg/kg/min da dose inicial, respectivamente, com o objetivo até se atingir a PAM acima de 65mmHg. Foram confrontados os parâmetros de valores de densidade e fluxo encontrados com o OPS nos dois grupos, bem como dados hemodinâmicos e de ventilação. As imagens coletadas utilizando o OPS foram processadas e analisadas por software especifico. Nao houve diferenca estatistica entre os grupos estudados nos parametros, hemodinamicos, ventilatorios, de oxigenacao e da microcirculacao encontrados com o OPS. A frequência cardíaca foi menor no grupo VASO no momento TG quando comparada ao grupo NORA. Os parametros de densidade e fluxo capilar não diferiram do basal em nenhum dos grupos. Deste modo, conclui-se que tanto a vasopressina quanto a noradrenalina quando empregadas para o tratamento de hipotensao decorrente da sepse grave/choque septico, nao prejudicam a microcirculacao / In septic patients, volume replacement is used as initial treatment in order to restore blood pressure and consequently the tissue perfusion. Nonresponders patients to the increase in preload are usually treated with vasoactive medications. Those agents such as norepinephrine, in this situation, it is essential, but the hyporesponsiveness of the adrenergic system is a common obstacle in septic patients. Vasopressin is an alternative, both like the drug of choice as rescue when treatment of adrenergic hyporesponsiveness. The evaluation of microcirculation is essential for its importance in the pathogenesis of sepsis, and to guide the different therapies. The aim of this project is to evaluate the use of vasopressin and norepinephrine in the treatment of hypotension in sepsis in dogs due to pyometra through spectral image obtained by orthogonal polarization (OPS) and on hemodynamic variables, as well as oxygenation and ventilation parameters. Thirteen dogs in severe sepsis were used, presenting at least two variables of systemic inflammatory response and at least one organ dysfunction variable at baseline. In all animals was performed initial volume resuscitation with 15ml / kg in 15 minutes of Ringer\'s lactate solution. If during anesthesia mean arterial pressure not assume values greater than 65 mmHg and central venous pressure did not vary 2 mmHg or present values greater than 8 mmHg, the animals were divided into two groups. The Group VASO received 0,0002UI / kg / min of vasopressin and Group NORA 0.1 mcg / kg / min of noradrenaline, may have increment 0,0002U / kg / min and 0. 1mcg / kg / min initial dose, respectively, in order to achieve MAP above of 65 mmHg. The density values of parameters were compared and found flow with OPS in both groups, and hemodynamic data and ventilation. The images collected using OPS were processed and analyzed by specific software. There was no statistical difference between the groups studied in the parameters, hemodynamic, ventilation, oxygenation and microcirculation found with OPS. The heart rate was lower in group VASO in TG moment compared to NORA group. The density and capillary flow parameters from baseline were similar in all groups. Thus, it is concluded that both noradrenaline and vasopressin when used to treat hypertension caused by severe / sepsis, septic shock, do not impair the microcirculation

O avanço da terapia intensiva na medicina veterinária vem permitindo a realização de um melhor suporte e monitorização dos animais com sepse grave. Esta é uma síndrome clínica caracterizada por alterações inflamatórias sistêmicas (SIRS) associadas a disfunções orgânicas, como, por exemplo, lesão pulmonar aguda (LPA) e síndrome do desconforto respiratório agudo (SARA). No homem, esta síndrome resulta em uma significante taxa de mortalidade, porém, na medicina veterinária ainda faltam estudos sobre este assunto. Assim, o objetivo deste estudo foi avaliar a ocorrência de complicações respiratórias em animais com sepse grave submetidos à terapia intensiva. Neste estudo foram incluídos 14 animais com sepse grave secundária à piometra. Durante o período de tratamento intensivo os pacientes foram monitorados por meio de: freqüências cardíaca e respiratória, pressão arterial sistólica, débito urinário, pressão venosa central, lactato, saturação venosa central de oxigênio, hemogasometria arterial e radiografias torácicas. Todos os animias (100%) apresentaram alterações respiratórias, destes três cadelas vieram a óbito (21,42%) e 11 (78,57%) receberam alta do tratamento intensivo.Os animais submetidos à terapia intensiva devido ao desenvolvimento de sepse grave secundária à piometra, necessitam de um acompanhamento radiográfico torácico diário, a fim de se estabelecer medidas de suporte respiratório adequadas e, consequentemente, obter menores taxas de mortalidade. / The advances in intensive care has allowed to offer better support to animals with severe sepsis. This is a clinical syndrome characterized by systemic inflammatory response associated with organic dysfunction, such as acute pulmonary injury (ALI) and acute respiratory distress syndrome (ARDS). In humans, this syndrome results in significant mortality, but, in veterinary medicine there are not many studies about this. The aim of this study was to evaluate the development the pulmonary complications in animals submitted to intensive care. In this study were included 14 animals with severe sepsis secondary to pyometra. During the period of intensive care the animals were evaluated: heart and respiratory rates, systolic blood pression, urine output, central venous pression lactate, lactate, central venous saturation, arterial hemogasometric and thoracic x-ray. All animals (100%) had abnormal breathing, three of these dogs eventually died (21.42%) and 11 (78.57%) out of intensive care. Animals with severe sepse secondary to pyometra underwent intensive therapy, requiring a chest radiographic daily in order to establish adequate respiratory support, and thus achieve lower mortality rates.

Com o objetivo de analisar a evolução dos níveis de glicose e dos hormônios insulina, glucagon e cortisol de cadelas com piometra e sepse grave durante o tratamento intensivo, foram estudadas 13 cadelas que apresentaram duas alterações na resposta inflamatória sistêmica e no mínimo uma disfunção orgânica. Antes do procedimento cirúrgico foram colhidas amostras para realização de exames laboratoriais e avaliação dos níveis dos hormônios insulina, glucagon e cortisol. Durante o período de internação, os animais foram avaliados diariamente por meio da análise de perfis bioquímicos renal e hepático, hemograma, sódio, potássio, insulina, glucagon e cortisol. O nível de glicose foi avaliado antes do procedimento cirúrgico, a cada 3 h nas primeiras 6 h e a cada 6 h até a alta ou óbito dos pacientes. Após o procedimento cirúrgico, os animais obtiveram a inserção do aparelho de CGMS no subcutâneo, para avaliação da glicose subcutânea. Um grupo controle com nove animais foram submetidos às mesmas dosagens de glicose do grupo sepse. Para a análise estatística da comparação dos valores obtidos para o grupo controle foi utilizado o teste não paramétrico Wilcoxon. Para avaliação da glicose, glucagon, cortisol, insulina, sódio e potássio para o grupo sepse, utilizou-se abordagem de modelos mistos com medidas repetidas. Os animais do grupo sepse apresentaram 7,37±1,66 anos de idade e 23,88±8,5 kg de peso corpóreo. No primeiro dia de internação, 23 % dos animais apresentaram hiperglicemia e estes animais permaneceram maior período de internação quando comparado com os demais animais. Nenhum animal apresentou hipoglicemia; apenas a técnica utilizada com Medsense Optium® apresentou valores superiores quando comparado com os valores de referência. Os animais apresentaram valores elevados de glucagon no primeiro dia quando comparado com o último dia de internação; o mesmo comportamento foi apresentado pelo cortisol e insulina. Como conclusão do estudo os animais com sepse grave apresentaram hiperglicemia e elevação dos hormônios glucagon, cortisol e insulina que tenderam a normalização na alta. / Aiming the analysis of glucose, insulin, glucagon and cortisol hormones levels in female dogs with pyometra and severe sepsis during intensive treatment. It was studied 13 female dogs with pyometra diagnosis and severe sepsis, which, the animals presented two alterations on the systemic inflammation response and at least one organic dysfunction. Before surgical procedure, samples were collected to laboratory exams realization and evaluation of hormones levels (insulin, glucagon and cortisol). During the interning time, the animals were evaluated daily through the renal and hepatic biochemical profile analysis, hemogram, sodium, potassium, insulin, glucagon and cortisol. The level of glucose was evaluated before the surgical procedure, every 3 hours in the first 6 hours and every 6 hours until patient discharge or patient death. After the surgical procedure, the animals received the CGMS introduction in subcutaneous, for glucose subcutaneous evaluation. A control group of nine animals were submitted to the same dosages of glucose from sepsis group. For statistical analysis of values comparison obtained to the control group was utilized the non parametric testing of Wilcoxon. For glucose evaluation, glucagon, cortisol, insulin, sodium and potassium to the sepsis group, was utilized the mixed model approach with repeated measurements. The animals of sepsis group presented 7,37±1,66 years and 23,88±8,5 Kg of body weight. At the first interning day, 23% of animals presented hyperglycemia and these animals remained with a longer interning period when compared with other animals. None of animals presented hypoglycemia; there was a difference only related to the utilized technique (Medsense Optium® presented higher values when compared to the reference values). The animals presented high values if glucagon at the first day when compared to the last interning day; the same was noticed with cortisol and insulin. As conclusion to this study, the animals with severe sepsis presented hyperglycemia and increase of hormones levels of glucagon, cortisol and insulin, which tendered to normalization on their discharge.

Svår sepsis är ett allvarligt tillstånd med ett snabbt förlopp. Patientens tillstånd kräver tidig identi-fiering och behandling vilket minskar lidandet, morbiditeten och mortaliteten. Många patienter upptäcks och behandlas för sent både prehospitalt och hospitalt. Svår sepsis och septisk chock orsakar många dödsfall världen över, en av fyra avlider. I Sverige insjuknar cirka 19000 individer årligen. Patienten kan ha ett eller flera symtom som är allmänna och kan tolkas vara orsakade av andra sjukdomstillstånd. Symtomen på sepsis är feber, frossa, pettekier, hög eller låg andnings-frekvens, illamående, kräkningar, diarréer, svår smärta oftast i buken, muskelsvaghet och med-vetandepåverkan. Symtomen kommer ofta plötsligt men kan gå i regress för att bara något eller några dygn senare återkomma. Att tidigt kunna identifiera och behandla sjukdomstillståndet krä¬ver rätt kompetens av vårdaren och uppmärksamhet i vårdmötet. Som vårdare gäller det även att kunna ställa de rätta frågorna om insjuknande, tidigare sjukdomshistoria som infektioner och om en eventuell utlandsvistelse. Genom den här studien avser vi att förmedla kunskap om ambulanspersonalens bedömning av patienter med svår sepsis. Metoden som använts var kvalitativa forskningsintervjuer. Resultatet visade att utbildning är av stor vikt för att ambulanspersonalen tidigt ska kunna identifiera pati¬enter med sepsis. Feedback från mottagande enhet om den bedömning och behandling som gjorts prehospitalt har varit korrekt visade sig vara av betydelse för framtida korrekta bedömningar. / Program: Specialistsjuksköterskeutbildning med inriktning mot ambulanssjukvård

<p>The newly established Swedish Apheresis Registry makes it possible to do national inter-center comparisons. This study was undertaken to describe and analyze the use of therapeutic apheresis and the adverse effects in such therapy. The special case of plasma exchange as rescue therapy in multi-organ failure, including renal failure, was also studied. In Sweden, plasma for transfusion is prepared and stored to ensure rapid availability. Due to new EU legislation, validation of such plasma was performed. </p><p>The analysis indicated that the use of therapeutic apheresis was in line with recommendations of other international societies. The frequency and types of adverse effects were comparable to those reported in other studies from analogous time periods. Compared with other countries, it appears that more therapeutic resources are available in Sweden and that there is a lower frequency of adverse effects in specific procedures. No fatalities were reported. The unique comparison of differences between centers regarding plasma exchange identified areas for further improvement.</p><p>The study on plasma exchange as rescue therapy in severe sepsis or septic shock is the second largest reported. The result was promising, with a survival rate of 82%. The rapid availability of plasma for transfusion appears to be of clinical importance in patients with early coagulopathy and severe trauma but the present selection and storage procedures for plasma lead to a time-dependent increase of the number of units with cold-induced activation of the contact system and C1 inhibitor consumption before day 14. Improvements of plasma quality can be attained by using plasma from male donors only and by reducing the storage time from 14 to 7 days. </p><p>Further studies are needed to define the role of plasma exchange in severe sepsis/septic shock, to evaluate the outcome of each patient’s treatment and to establish the indications for the transfusion of plasma.</p>