Adrian Gerard Murphy, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.

• Assistant Professor of Oncology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/10003334/adrian-murphy

Legal representatives for the family medicine 031 dramamine 50mg generic, or the involvement of non-governmental organizations medications related to the female reproductive system order generic dramamine on-line, may be possible ways to ensure that important information is available medications with gluten buy dramamine without prescription. House-to-house inquiries should be conducted in the vicinity of important physical locations and (a) Obtain as much relevant information as the crime scene treatment centers discount dramamine 50 mg visa, if it has been identifed medicine 44390 cheap dramamine 50 mg online. House- possible symptoms quad strain purchase dramamine in united states online, through a systematic and fair to-house inquiries help the investigators to identify process, to assist the investigators in objectively witnesses who live or work in key areas, gather establishing the truth local information and intelligence, identify other (b) Identify possible suspects witnesses or suspects and raise awareness of the investigation, which may encourage people with (c) Allow individuals an opportunity to provide information to come forward. Interviews with family members and others to (d) Identify further witnesses collect ante-mortem data for body identifcation such as hair, blood, saliva samples, dental (e) Identify victims or chest X-rays, and information about possible (f) Establish the location of crime scenes and bone fractures and other injuries or diseases burial sites should be conducted by trained professionals (g) Establish background information and facts who are in a position to answer technical relevant to the alleged killing(s),94 and questions authoritatively and with at least a basic knowledge of the correct medical and (h) Identify leads in the investigation. Investigators conducting interviews should to take samples, and donors should complete approach all witnesses with an open mind and consent forms that state how the samples will be observe the highest ethical standards. A careful stored, who can access them, who manages the assessment of risk, strategies and adequate human genetic database and how the data is to be used. A media appeal may help to identify and locate Families in some circumstances could, with reason, people and material that could be useful to the fear for their safety. This could include setting up a be paid to the safety of the investigator, since a telephone hotline, an email address and/or a witness may be the perpetrator. A list of signifcant witnesses should be drawn up confdentially or even anonymously. These witnesses should also be given to offering a reward in return include those who saw or heard the crime being for relevant information. A specifc strategy should be developed, and people in the same organization or chain especially if a suspect is a state offcial, to ensure of command as the suspected perpetrator who that anyone coming forward will be assured that may be able to provide information linking the information they provide will be dealt with people other than the direct perpetrator to the confdentially, within the limits of the law. Where feasible and appropriately secure, investigators should consider recording 77. The assistance of law enforcement agencies in their interviews by audio or video means. During other States may help the investigation cover the investigation phase, witness lists are highly any gaps in the technical capacity of local sensitive and must be carefully safeguarded to investigators. International bodies such as ensure that witnesses are not exposed to undue Interpol, for example, might be able to support risk. Electronic documents that may identify a the investigation, and humanitarian organizations witness should be taken outside the investigation such as the International Committee of the Red offce only in encrypted form. Analysis should compare call-data numbers and data, cross-referencing the movements of all 78. Within the confnes of the applicable law, people of interest in the case, on pictorial charts mobile telephone data should be requested from using specialist software, if available. This information may help in establishing the identity, roles and relationships 8. Financial issues of persons of interest and their presence and participation in key activities (such as presence at 81. A fnancial profle of the victim should be key locations, attendance at meetings, the conduct developed where necessary and appropriate. In cases of investigation, investigators should familiarize missing persons, continued activity on an account themselves with the data-retention policies of the may help to determine if the suspected victim is still service providers. In all cases, a fnancial profle can reveal authorities to analyse the phone numbers that new leads for an investigation. Evidence mobile phone numbers with a particular customer?s of uncharacteristic fnancial payments or an name, address and other account information, extravagant lifestyle should be sought. Chronology of events and all prime suspects should be legally recovered and relevant data (e. A ?living? chronology of events should be received calls, text (sms) or other messages, developed as the investigation proceeds. This photographs, contacts and diary entries) should be sourced from any material obtained professionally downloaded. The phones can then during the investigation, including: be returned to the family of the deceased or to the suspect, as the case may be. Where a phone is (a) Witness statements recovered that appears to have been used by a (b) Known movements of the victim perpetrator, but the identity of the user or owner (c) Known movements of any suspects of the phone is not otherwise established, service provider or other information showing that the (d) Call and other communication data recovered phone has made or received calls or (e) Documents, including police reports logs and messages from family members of a prime suspect notebooks will make it easier to demonstrate, using phone (f) Mobile phone site data attribution analysis, that the phone belonged to or was used by a particular suspect. For all phones identifed as relevant it may also be useful to request subscriber details, method (i) Lifestyle data. International Mobile Station Equipment Numbers, which may identify the type, model and capability of the handsets used. Smart phones used by the victim or any suspects should be analysed for Wi-Fi locations activated and Internet sites visited for information which may provide leads in the investigation. Where possible, investigators should also obtain cell site coverage maps from service providers. An effective witness-protection programme is essential for some investigations, and should 84. Interviews form an integral part of almost any be in place before the investigation begins. If conducted well, they can obtain this includes reliable and durable protection accurate, reliable and complete information for witnesses at risk, including the secure from victims, witnesses, suspects and others. Detailed Guidelines on Interviews provide States should ensure that the authorities in charge more thorough guidance on how to conduct of witness protection should in no way be involved an interview effectively and appropriately, and in the alleged death. All formal and informal interviews should be that maximizes access to justice for affected recorded, regardless of where they take place, individuals and minimizes as much as possible right from the commencement of an investigator?s any negative impact the investigation may have contact with a prospective witness or suspect. Special care should be taken certain circumstances this may be subject to the when interviewing the bereaved or those who consent of the prospective witness or suspect. Interviews may be recorded in written form, audio, by trained individuals who apply the highest or video. Considerations as to the best method to professional and ethical standards in order to use may include the preference of the interviewee, obtain accurate information while respecting the interview setting, and concerns about privacy the rights and well-being of the interviewee. Risk assessments should be conducted before engaging with any witness to help ensure that the beneft of the engagement outweighs the risk. When necessary, and subject to the consent of the individual(s) concerned, investigators should take steps to protect an interviewee and others from ill-treatment or intimidation as a consequence of providing information. Possible measures include protecting the identity of the interviewee (within the parameters of the law and the rights of the defence guaranteed under international fair trial standards), physical protection, relocation and placement in an effective witness-protection programme. See also the Istanbul Protocol, which offers guidance on the conduct of interviews where torture is suspected. Labelling means assigning a unique reference most important evidence at a crime scene require number to each body or body part (as well as special attention and care, including respect for to each other piece of physical evidence). The the dignity of the deceased and compliance with labelling of human remains should be refected forensic best practices. Human remains are often in the crime scene notes, the photographs and recovered by police or other personnel without any sketches/diagrams/skeletal inventory forms education or training in human biology, and recorded at the scene. The same labelling needs thus there may be challenges in identifying body to be recorded on the packaging used to transport parts and/or skeletal elements. The recovery and store the remains and any associated of human remains should, preferably, be under evidence. The archaeology is also valuable in understanding labelling of human remains whether individual the taphonomic processes at the scene. Expertise bones, clusters of bones, body parts or complete in forensic anthropology and/or archaeology bodies should be unique and must be applied may assist in the recovery of burnt, fragmented or consistently throughout the documentation and buried remains. The labelling system should packaging, security (including chain-of-custody be agreed on prior to collection and packaging. When two or more parts of a body are found, unique designator codes, which can be based on it should not automatically be assumed that the the following criteria: separate body parts belong to the same body. All photographs should belonging to one unique individual; often include a reference number, a scale, and a this can be a single body part or skeletal direction indicator. Sketches the date on which the remains are discovered and diagrams should document the disposition should be refected in the code. The numbering of the remains and associated evidence at the system may be used for all evidence recovered scene. If it appears that there are multiple deceased, compass, a baseline, or any photogrammetric the exercise of recovering the human remains programme. If available, measurements and may follow that of a Disaster Victim Identifcation recordings can also be made electronically using procedure. The remains should be examined and any clothing, personal items and associated evidence photographed, with any observations recorded in the scene notes. Additionally, any visible trauma should be recorded in an anatomical diagram and, in the case of skeletal remains, also in a skeletal inventory form. Trace evidence that might be present on the hands and/or under the fngernails (such as fbres or 98. Plastic bags encourage moisture (c) Any visible defects/possible trauma condensation and mould growth if left in place too long, but for short periods of time (e. The inventory should be drawn up under the additional evidence that might be present. The body should be placed in a body bag body parts/skeletal elements and trauma should following chain-of-custody procedures. These not be taken as fnal until confrmed by analysis procedures include the correct labelling of the in the laboratory or mortuary. Any descriptions body and body bag, the completion of related and preliminary determinations noted in the feld documentation for security/chain of custody, and should be recorded in the crime-scene notes and the sealing and signing of the body bag. Once the body has been recovered, it should be labelling on the packaging needs to be consistent placed in refrigerated or cool storage to inhibit with the numbering in the inventory, on the further decomposition of the remains. Human remains are found in a wide variety are disarticulated and separated from each other of circumstances, each of which may affect to such a degree that any association between the recovery and handling of the remains. In these circumstances, where circumstances outlined below are for intact possible, a forensic anthropologist or forensic bodies, skeletal remains on the surface, and doctor should be present at the scene, allowing a buried bodies or skeletal remains. Intact bodies are human remains that are (b) Whether the remains represent one or more recognizable as one individual with most of individuals the soft tissue present. In some documentation, recovery and preparation of an cases such evidence might be contaminated inventory. The pattern of the scattering throughout (for example, by blood from the deceased), the scene should be documented in notes and displaced from its original location, or lost in sketches and through photography. This the clothing should be carefully removed, secured can indicate where a body or bodies frst came to in individual packaging and placed in the body rest prior to disassociating into individual parts. The rationale for this decision should be explained and recorded in the crime-scene notes and documented through photography. After assessing the pattern of scattering and movement of soil or differences in plant growth that recording the scene, the next task is to collect the might indicate the presence of a burial. Scattered skeletal elements need to be they are available, non-intrusive technologies packaged in paper bags and labelled, sealed such as satellite/aerial image analysis or and signed according to evidence-packaging hyperspectral image analysis, and geophysical procedures. Buried bodies/skeletal remains soil has been disturbed, consistent with the burial 110. Where appropriate, intrusive buried alone or of two or more persons buried archaeological excavation methods, such as metal either simultaneously or at different times. A primary grave is the one in which the deceased are present and to expose the physical size and is frst placed. Considerations in the recovery of buried remains is unchanged since the time of primary burial. Buried human remains can be encountered in A disturbed burial is one that has been altered various stages of decomposition, from complete after the time of primary burial, either by human bodies with soft tissues present to fully skeletonized intervention, or animal scavenging, or by remains. All secondary burials on whether disinterred remains are complete should be regarded as having been disturbed. In all instances, archaeological soil disturbances can be identifed through surveys methods should be used in the excavation of by experienced archaeologists. Such experts can any graves, as set out in the relevant Detailed identify modifcations in the landscape, vegetation, Guidelines. General principles recognition: for example, the appearance of the clothing or an item of jewellery such as a ring on 115. In not accept visual recognition as a form of positive any death investigation, the identifcation of the identifcation. Good-quality ante-mortem of recognition to help in its formal identifcation, and post-mortem data, properly compared, are this should be undertaken in controlled required for a valid identifcation. The process should be by family or friends is a form of ante-mortem supervised and witnessed by a forensic doctor, and post-mortem comparison. It is undertaken a trained mortuary technician, a grief counsellor universally, and is often reliable. The dead body should be professionally assessed Factors contributing to this possibility include as being capable of being recognized by visual facial congestion or lividity; lung oedema or inspection. The person being asked to make the stomach fuids issuing from mouth and/or nose; visual identifcation should always be informed the presence of facial fractures, other injuries, of the condition of the remains and asked if they or bleeding; or changes associated with wish to proceed. Family members may be anxious advanced state of decomposition; there should or distressed to the point where they may not be no signifcant injury affecting the central facial even look at the body or face of the deceased. A family member may rely on something other (This last requirement may not be compatible with than the facial appearance of the deceased for investigative priorities ?. Whatever methods of identifcation are employed, should be asked to look particularly at the body a methodical and holistic approach, involving the and face and engaged in discussion about what appropriate experts, with complete and detailed facial (or bodily) features he or she relied on in documentation, is always necessary. Visual recognition alone should not be relied In this way, any person witnessing the process can upon in cases of multiple deaths. Misidentifcation assess whether or not the conclusion of the person is more common in such circumstances owing viewing the dead body is likely to be reliable. The scientifc approach to identifcation bodies, or a number of dead bodies individually 120. In potentially unlawful death (and especially as one after the other, reduces the likelihood of a time passes and the body begins to show signs of reliable recognition. Additionally, personal effects decomposition, or the facial appearance is altered are not unique, and depending on the processes by the effects of injury or fre), any identifcation around the retrieval of the bodies they may have by visual recognition must be confrmed whenever been incorrectly put with the wrong body. These scientifcally reliable methods are sometimes n the scene, and the proper collection, recording, referred to as ?primary? methods of identifcation.

Treatment of central nervous system manifes- the establishment of more detailed guidelines for the tations in thyroid storm management of thyroid storm is needed in Japan and 5 everlast my medicine trusted 50 mg dramamine. Treatment of acute congestive heart failure in New diagnostic criteria for thyroid storm symptoms 5 weeks 3 days order generic dramamine from india, in addi- thyroid storm tion to those of Burch and Wartofsky [3 treatment 3rd degree burns buy 50 mg dramamine amex, 4 treatment 5th metacarpal fracture order dramamine 50mg visa, 9] treatment ingrown toenail generic 50mg dramamine visa, have 7 treatment venous stasis cheap dramamine 50mg with amex. The next obvious step is to iden- hepatic damage in thyroid storm tify therapeutic procedures that improve prognosis 8. Five areas are important in the treatment intensive care unit and therapeutic strategy of thyroid storm: 1) thyrotoxicosis (reduction of thy- for comorbidities roid hormone secretion and production); 2) systemic 9. Prognostic evaluation of thyroid storm symptoms and signs (including high fever, dehydra- 10. An algorithm for the diagnosis and manage- ato-gastrointestinal; 4) triggers; and 5) defnitive ment of thyroid storm therapy. Recent nation- lead to worse outcomes in patients with severe heart wide surveys in Japan have revealed that mortality failure [8]. Multiple organ failure was the ized by multiple organ failure, decompensation, and most common cause of death, followed by congestive highly variable clinical presentation, a clinical pic- Guidelines of thyroid storm management 1027 ture that requires comprehensive treatment. Thyroid strong and quality of evidence is high or moder- storm is an emergent disorder characterized by rapid ate, the clinical practice can be applicable to most deterioration in its clinical course. These recommendations and quality of evidence is high or moderate, the should 1) contain information on both the diagno- best course of action may differ depending on circum- sis and treatment of thyroid storm; 2) illustrate algo- stances and patient or social values. If the strength rithms; 3) consider the severity and pathophysiology of of recommendation is weak and quality of evidence thyroid storm; 4) be detailed, concrete, and useful for is low, the recommendation is very weak and other clinical practice; 5) be evidence-based; and 6) possibly alternatives may be equally reasonable. Based on the analysis evidence: insuffcient for grading means that there of data concerning the treatment of thyroid storm col- is insuffcient evidence to recommend for or against lected in nationwide surveys in Japan [8], the treatment routinely providing the service. We also describe how to evalu- Recommendations for Thyroid Storm ate the severity of thyroid storm from the viewpoint of prognosis. Diagnostic challenges for thyroid storm management of thyroid storm is illustrated in a sum- mary schema. The last section of this chapter refers Thyroid storm is an endocrine emergency that is to a prospective prognostic study using these recom- characterized by rapid deterioration within days or mendations. We hope to achieve successful outcomes hours of presentation and is associated with high mor- in the management of thyroid storm through effective tality [1-4]. Thyroid storm dation and quality of evidence were evaluated based can also be caused by medical precipitants such as thy- on the criteria shown in Table 1. In as follows: if the strength of recommendation is addition, several drugs that cause thyrotoxicosis as an Table 1 Strength of recommendation and quality of evidence Strength of recommendation Strong Benefts clearly outweigh risks and burdens, or risks and burdens clearly outweigh benefts Weak Benefts closely balanced with risks and burdens None Balance of benefts and risks cannot be determined Quality of evidence High Randomized controlled trials without important limitations, or overwhelming evidence from observational studies Moderate Randomized controlled trials with important limitations, or exceptionally strong evidence from observational studies Low Observation studies or case series Insuffcient for grading Evidence is conficting, of poor quality, or lacking See ref. Early awareness/suspicion, prompt Criteria Points diagnosis, and intensive treatment will improve sur- Thermoregulatory dysfunction Temperature (? Using fully evaluating the clinical condition of each patient both diagnostic systems to evaluate a patient?s condi- suspected of having thyroid storm. Comments suggest that the conversion of T4 to T3 could already When patients are diagnosed with thyroid storm be suppressed in severe thyroid storm. These fndings suggest that such as pruritus/rashes, agranulocytosis, and liver dys- inorganic iodide treatment may improve the outcome function. Since the amount of iodide in these solu- used as an essential treatment prior to thyroid surgery tions may differ between hospitals, the concentration in order to decrease intraoperative bleeding [38, 39]. Alternatively, ation of the reported doses in our nationwide surveys corticosteroids overdosing in some patients may [8]. The route of administration for inorganic iodide cause unfavorable hyperglycemia and worsening of (oral, sublingual, rectal, or via a nasogastric tube) may their general condition. Therefore, the type and dose be selected based on the patient?s clinical condition of corticosteroids needs to be determined carefully [42]. The dose of inorganic iodide may be increased on an individualized basis to improve the outcome of when administered rectally. Apart from inorganic iodide, lithium carbonate is also known to inhibit the release of thyroid hormone? Comments from the thyroid gland by an unknown mechanism [43, Corticosteroids should be given to ameliorate rel- 44]. The or iodide to reduce circulating thyroid hormone lev- recommended dose of hydrocortisone is 300 mg/day els, though serum lithium levels should be monitored (100 mg administered intravenously every 8 hours). There should be careful monitoring and prevention of potential side effects such C. Aggressive cooling with acetaminophen and laxis for relative adrenal insuffciency caused by the mechanical cooling with cooling blankets or ice packs hypermetabolic state in thyroid storm. Large doses of should be performed for thyroid storm patients with corticosteroids have been shown to inhibit both thy- high fever. Despite the predicted favorable effects Quality of evidence: low of corticosteroids mentioned above, detailed analysis 2. The focus of infection should be investigated in of nationwide surveys using multiple regression anal- patients with high fever and accompanying infection ysis showed that disease severity and mortality were should be treated. In Quality of evidence: moderate multiple regression analyses, both the use of cortico- steroids and their doses correlated with disease sever-? In a nationwide survey [4], exhibit no signs of infection, and treatment should be the body temperature of thyroid storm patients treated initiated as soon as possible. Use of therapeutic plasmapheresis to However, no signifcant differences were observed in treat thyroid storm disease severity and mortality between these patients [8]. Infection was shown to be Strength of recommendation: weak the second most common triggering factor for thyroid Quality of evidence: low storm (28%) in a nationwide survey [4]. Therefore, the control of infection ciently improves thyrotoxicosis by rapidly removing is important in order to improve prognosis in patients and exchanging the serum proteins to which approxi- with thyroid storm. However, based on many case antibiotic therapy needs to be started as soon as possi- reports from Japan and other countries in which thy- ble in patients exhibiting signs of infection [47]. These guidelines recommend that anti- viously been performed to remove excess serum thy- biotics with both Gram-positive and Gram-negative roid hormone in patients with thyroid storm. However, based on many case reports in which plications such as multiple organ failure. Six patients tion, citrate-related nausea and vomiting, vasovagal or died between days 6 and 37. Four cases were com- hypotensive reactions, respiratory distress, tetany, and plicated with multiple organ failure and 1 patient died convulsions. Thus, based on the literature and nation- commonly attributed to the underlying disease. Since thyrotoxicosis and dysfunction of multiple improved severe thyrotoxicosis in these patients, they organs such as the liver and kidney can affect pharmaco- died from a late-onset complication. However, the precise mechanisms First-line drugs for restlessness, delirium, and psy- responsible remain unknown. For patients who cannot tolerate is insuffcient evidence to support other specifc treat- oral medication, frst-generation antipsychotic drugs ments. In a small clinical study, mental symptoms such such as haloperidol and olanzapine [120] by intramus- as anxiety and depression in thyrotoxicosis were sig- cular or intravenous injection are the frst-line choices. Moreover, no associa- onset of thyroid storm [123], which can result in neu- tion was observed between the choice of medication to rotoxic effects [124]. Thyrotoxicosis can affect pharmacokinetics by Somnolence and coma can be caused by a variety of altering the absorption, distribution, metabolism, and conditions, such as hypoxemia due to heart failure or excretion of drugs [122]; these effects may change shock, liver failure, renal failure, severe infection, cere- dynamically during the treatment of thyroid storm. Thyroid storm is often complicated multiple organs such as the liver and kidney, which can by these conditions; therefore, a differential diagnosis also affect pharmacokinetics. Because the underlying cerebrovascular disease or should be individually determined. Early confrmed in the initial care of acute disturbances in initiation of rehabilitation is recommended to prevent consciousness. The administration of vitamin B1 prior disuse muscle atrophy, especially in patients receiving to or at the same time as glucose injection is recom- mechanical ventilation [125]. A differential netics diagnosis for cerebrovascular disease, meningitis, met- Thyrotoxicosis does not have a pronounced effect abolic disorders, or poisoning should be constructed on the pharmacokinetics of diazepam [126], phenytoin Guidelines of thyroid storm management 1037 Fig. It is given intravenously at an initial dose of in thyrotoxic patients the effect of propofol is decreased 0. Amiodarone fbrillation in thyroid storm may be considered for patients with impaired left ven- tricular systolic function. Other beta1-selective oral drugs are also rec- been used to evaluate the risk of stroke onset. Tachycardia should be treated aggressively because selected as the frst choice treatment. If the heart rate the results of our nationwide survey revealed that is <150 bpm, landiolol or esmolol can be changed to an tachycardia? The results of our nationwide survey showed that seconds, and its dosage should be controlled appropri- atrial fbrillation in the presence of thyroid storm ately while monitoring the heart rate (~150? Thyroid Furthermore, a patient with thyroid storm and bron- hormones have been shown to increase the density of chial asthma was successfully managed with esmolol beta-adrenergic receptors and cyclic adenosine mono- [144]. Since the 1970s, many stud- due to the pathophysiology of thyroid storm, which ies suggested the usefulness of propranolol. However, is characterized by peripheral vasodilation associated most of these studies proposed the usefulness of beta- with increased beta-adrenergic action. One is its short elimination half-life roid storm had atrial fbrillation and 130 did not have (t1/2) and duration of action. Atrial fbrillation status was unknown in 90 onset of action of intravenous propranolol and esmolol patients, of whom 13 died. The presence of atrial fbril- are similar, their t1/2 and duration of action are mark- lation in thyroid storm was associated with signif- edly different. The t1/2 alpha and beta for proprano- cantly increased mortality in our nationwide surveys lol are 10 minutes and 2. The the t1/2 alpha and beta for esmolol are 2 minutes and 9 reported incidence of atrial fbrillation in thyrotoxicosis minutes, respectively [140]. Atrial fbrillation demonstrated that the effects of beta-blockade com- further accelerates systemic hemodynamic disturbances pletely disappeared 18 minutes after the infusion of and increases mortality in thyroid storm; therefore, car- esmolol (300? Digitalis is recommended for tachy- ing these novel oral anticoagulants may be reevaluated cardia-induced heart failure due to atrial fbrillation in the future based on new information. Treatment of acute congestive heart fail- with caution because of the possibility of digitalis ure in thyroid storm intoxication, especially in patients with renal dysfunc- tion. Hemodynamic monitoring using a Swan-Ganz cath- be monitored and the dose adjusted appropriately as eter is recommended for patients with acute congestive the patient becomes euthyroid. Calcium channel blockers (intra- as the sum of the points for each risk factor (1 point venous) should be considered if hypertension is for each of the frst 4 factors and 2 points for history present. Guidelines of thyroid storm management 1041 ii) Drug therapy: Adrenergic agonists should be [153]. The short-acting beta1-selective adren- and isosorbide dinitrate) in 4 patients; carperitide in ergic antagonists landiolol or esmolol may be 6 patients; furosemide in 5 patients; and unknown or considered when heart rate is? None of these agents were used atrial fbrillation is present, digitalis should be in 229 patients. Although the use of these Strength of recommendation: high agents was associated with signifcantly increased Quality of evidence: low mortality in our nationwide surveys (p<0. An artifcial heart?lung machine should be used assessed with the Fisher?s exact test, this result was before the development of irreversible multiple organ attributed to these agents being used in patients in crit- failure when hemodynamic status has not improved ical condition with a high likelihood of death. The treatment of Quality of evidence: low acute congestive heart failure in patients with thyroid storm has not been examined in detail. Evidence supporting the recommendations use of vasoconstrictor agents with or without diuret- 1. Acute congestive heart failure in thyroid storm of cyclic adenosine monophosphate with overstimula- should be treated according to the Guidelines for the tion of beta-adrenergic receptors. Artifcial heart?lung machines were used in 9 on an individualized basis, with consideration of the patients in our nationwide surveys [4]: 2 patients with pathophysiology of thyroid storm. Our nationwide surveys revealed that 5 of 9 patients 2 patients with class 2 disease, and 1 patient with treated with an artifcial heart?lung machine sur- unknown status. An artifcial heart?lung machine should be class 4 disease, and 1 patient each with class 3 disease, used before the development of irreversible multiple class 2 disease, and unknown status. Hemodynamic monitoring with a Swan-Ganz cath- opment of irreversible multiple organ failure. Treatment of gastrointestinal disorders primarily by improving thyrotoxicosis with limited use and hepatic damage in thyroid storm of anti-emetics. Gastrointestinal symptoms, including diarrhea, nau- emergency room to prevent gastric ulcers and acute sea, and vomiting, are associated with thyrotoxicosis, gastric mucosal lesions. Patients under mechanical heart failure, neurological disorders, and gastrointesti- ventilation and those with coagulopathy are at the high- nal infection. Although proven to be highly effective in rais- ventilation may be risk factors for gastrointestinal hem- ing gastric pH, recent studies, including a meta-analy- orrhage and mortality. Guidelines antagonists (H2As) are recommended for patients in issued by the Agency for Healthcare Research and these instances. Furthermore, acid-suppressive drugs wide surveys showed that patient prognosis is worse can cause hypomagnesaemia, vitamin B12 defciency, when total bilirubin levels are? Differential upper respiratory tract infection, pneumonia, and clini- diagnosis for the origin of hepatic dysfunction and cal fractures of the hip, spine, and wrist. Gastrointestinal disorders contribute to poorer prognosis in patients with Diarrhea is the most common gastrointestinal symp- thyroid storm. Treating a reduction in serum thyroid hormone levels could congestive heart failure could contribute to the recov- stop diarrhea without the use of specifc antidiarrheals. Ursodeoxycholic acid, Antidiarrheals are not necessary for many cases of thy- which relieves liver dysfunction, and Stronger Neo- roid storm with coma. Thyroid storm causes muscle Minophagen C, a glycyrrhizin-containing liver pro- weakness in the diaphragm and esophagus, and gas- tector, can also be used; however, these drugs may tric wall motility dysfunction, which results in nau- induce further liver damage [160]. Severe liver failure induces reduced protein rial ketone body ratio (acetoacetate/3-hydoxybutyrate) synthesis, which results in coagulopathy, host defense <0. Three types of apheresis are used for acute disorders, and eventually multiple organ failure.

Purchase dramamine uk. Meet the Clines: Long QT Syndrome - Akron Children's Hospital video.

Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections symptoms 16 dpo generic 50 mg dramamine. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy symptoms diabetes type 2 order dramamine with a visa. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society-first revision symptoms zinc deficiency purchase dramamine with mastercard. Prescribing intravenous immunoglobulin: summary of Department of Health guidelines treatment yeast uti cheap dramamine 50 mg amex. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology treatment quadratus lumborum purchase cheap dramamine. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years medicine 7 day box order dramamine in united states online. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology. The use of immunoglobulin therapy for patients with primary immune deficiency: an evidence-based practice guideline. Produced in collaboration with the Ethiopia Public Health Training Initiative, the Carter Center, the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education. Important Guidelines for Printing and Photocopying Limited permission is granted free of charge to print or photocopy all pages of this publication for educational, not-for-profit use by health care workers, students or faculty. All copies must retain all author credits and copyright notices included in the original document. Under no circumstances is it permissible to sell or distribute on a commercial basis, or to claim authorship of, copies of material reproduced from this publication. Except as expressly provided above, no part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written permission of the author or authors. This material is intended for educational use only by practicing health care workers or students and faculty in a health care field. Hence, the authors hope that this lecture note would be immensely useful in solving this existing problem at significant level. The lecture note is intended for use by laboratory technologist both during their training and in their work places. There are twenty two chapters each beginning with specific learning objectives in which succeeding by a background of the topic in discussion. There are study questions at the end of each chapter for the reader to evaluate his understanding of the contents. In addition, important terms are defined in the glossary section at the end of the text. Special thanks are due to Mohammed Awole, Serkadis Debalke, Ibrahim Ali, Misganaw B/sellasie, Abiye Shume, Shewalem Shifa and Simon G/tsadik for their assistance in reviewing and critiquing this material. For her sustained devotion and extra effort, I express my deep gratitude and sincere appreciation to Zenaye Hailemariam, who has been most supportive with scrupulous attention and dedication in helping me throughout the preparation of this lecture note (Y. Included in its concerns are analyses of the concentration, structure, and function of cells in blood; their precursors in the bone marrow; chemical constituents of plasma or serum intimately linked with blood cell structure and function; and function of platelets and proteins involved in blood coagulation. Mankind probably has always been interested in the blood, since primitive man realized that loss of blood, if sufficiently great, was associated with death. And in Biblical references, ?to shed blood? was a term used in the sense of ?to kill?. Before the days of microscopy only the gross appearance of the blood could be studied. Clotted blood, when viewed in a glass vessel, was seen to form distinct layers and these layers were perceived to constitute the substance of the human body. Health and disease were thought to be the result of proper mixture or imbalance respectively of these layers. Microscopic examination of the blood by Leeuwenhoek and others in the seventeenth century and subsequent improvements in their rudimentary apparatus provided the means whereby theory and dogma would gradually be replaced by scientific understanding. Currently, with the advancement of technology in the field, there are automated and molecular biological techniques enable electronic manipulation of cells and detection of genetic mutations underlying the altered structure and function of cells and proteins that result in hematologic disease. It is composed of different kinds of cells (occasionally called corpuscles); these formed elements of the blood constitute about 45% of whole blood. Blood is about 7% of the human body weight, so the average adult has a blood volume of about 5 liters, of which 2. Blood plasma When the formed elements are removed from blood, a straw-colored liquid called plasma is left. Some of the proteins in plasma are also found elsewhere in the body, but those confined to blood are called plasma proteins. These proteins play a role in maintaining proper blood osmotic pressure, which is important in total body fluid balance. Most plasma proteins are synthesized by the liver, 2 Hematology including the albumins (54% of plasma proteins), globulins (38%), and fibrinogen (7%). Other solutes in plasma include waste products, such as urea, uric acid, creatinine, ammonia, and bilirubin; nutrients; vitamins; regulatory substances such as enzymes and hormones; gasses; and electrolytes. Formed elements the formed elements of the blood are broadly classified as red blood cells (erythrocytes), white blood cells (leucocytes) and platelets (thrombocytes) and their numbers remain remarkably constant for each individual in health. In adults, they are formed in the in the marrow of the bones that form the axial skeleton. Mature red cells are non- nucleated and are shaped like flattened, bilaterally indented spheres, a shape often referred to as ?biconcave disc? with a diameter 7. In stained smears, only the flattened surfaces are observed; hence the appearance is circular with an area of central pallor corresponding to 3 Hematology the indented regions. The red cells contain the pigment hemoglobin which has the ability to combine reversibly with 02. In the lungs, the hemoglobin in the red cell combines with 02 and releases it to the tissues of the body (where oxygen tension is low) during its circulation. Carbondioxide, a waste product of metabolism, is then absorbed from the tissues by the red cells and is transported to the lungs to be exhaled. The red cell normally survives in the blood stream for approximately 120 days after which time it is removed by the phagocytic cells of the reticuloendothelial system, broken down and some of its constituents re utilized for the formation of new cells. White Blood Cells They are a heterogeneous group of nucleated cells that are responsible for the body?s defenses and are transported by the blood to the various tissues where they exert their physiologic role. Their production is in the bone marrow and lymphoid tissues (lymph nodes, lymph nodules and spleen). Polymorphonuclear leucocytes/granulocytes o Neutrophils o Eosinophils o Basophiles. Eosinophils Eosinophils have the same size as neutrophils or may be a bit larger (12-14?m). Increase in their number (eosinophilia) is associated with allergic reactions and helminthiasis. Basophiles have a kidney shaped nucleus frequently obscured by a mass of large deep purple/blue staining granules. Their cytoplasmic granules contain heparin and histamine that are released at the site of inflammation. Small lymphocytes have round, deep-purple staining nucleus which occupies most of the cell. They have more plentiful cytoplasm that stains pale blue and may contain a few reddish granules. They have a centrally placed, large and ?horseshoe? shaped nucleus that stains pale violet. Their cytoplasm stains pale grayish blue and contains reddish blue dust-like granules and a few clear vacuoles. They are capable of ingesting bacteria and particulate matter and act as "scavenger cells" at the site of infection. Platelets these are small, non nucleated, round/oval cells/cell fragments that stain pale blue and contain many pink granules. They 8 Hematology are produced in the bone marrow by fragmentation of cells called megakaryocytes which are large and multinucleated cells. When blood vessels are injured, platelets rapidly adhere to the damaged vessel and with one another to form a platelet plug. During this process, the soluble blood coagulation factors are activated to produce a mesh of insoluble fibrin around the clumped platelets. This assists and strengthens the platelet plug and produces a blood clot which prevents further blood loss. It also carries nutrients from the gastrointestinal tract to the cells, heat and waste products away from cells and hormones form endocrine glands to other body cells. It also adjusts body temperature through the heat-absorbing and coolant properties of its water content and its variable rate of flow through the skin, where excess heat can be lost to the environment. Blood osmotic pressure also influences the water content of cells, principally through dissolved ions and proteins. In postnatal life in humans, erythrocytes, granulocytes, monocytes, and platelets are normally produced only in the bone marrow. Lymphocytes are produced in the secondary lymphoid organs, as well as in the bone marrow and thymus gland. Although many questions 10 Hematology remain unanswered, a hypothetical scheme of hemopoiesis based on a monophyletic theory is accepted by many hematologists. According to this theory, the main blood cell groups including the red blood cells, white blood cells and platelets are derived from a pluripotent stem cell. This stem cell is the first in a sequence of regular and orderly steps of cell growth and maturation. The pluripotent stem cells may mature along morphologically and functionally diverse lines depending on the conditioning stimuli and mediators (colony-stimulating factors, erythropoietin, interleukin, etc. During fetal life, hemopoiesis is first established in the yolk sac mesenchyme and later transfers to the liver and spleen. The splenic and hepatic contribution is gradually 11 Hematology taken over by the bone marrow which begins at four months and replaces the liver at term. From infancy to adulthood there is progressive change of productive marrow to occupy the central skeleton, especially the sternum, the ribs, vertebrae, sacrum, pelvic bones and the proximal portions of the long bones (humeri and femurs). Hemopoiesis occurs in a microenvironment in the bone marrow in the presence of fat cells, fibroblasts and macrophages on a bed of endothelial cells. An extracellular matrix of fibronectin, collagen and laminin combine with these cells to provide a setting in which stem cells can grow and divide. In the bone marrow, hemopoiesis occurs in the extravascular part of the red marrow which consists of a fine supporting reticulin framework interspersed with vascular channels and developing marrow cells. A single layer of endothelial cells separates the extravascular marrow compartment from the intravascular compartment. When the hemopoietic marrow cells are mature and ready to circulate in the peripheral blood, the cells leave the marrow parenchyma by passing through fine "windows" in the endothelial cells and emerge into the venous sinuses joining the peripheral circulation. Increased demands for cells as a consequence of disease or physiologic 14 Hematology change are met by increased cell production. Several hematopoietic growth factors stimulate differentiation along particular paths and proliferation of certain progenitor cells. In addition, there are several different cytokines that regulate hematopoiesis of different blood cell types. Cytokines are small glycoproteins produce by red bone marrow cells, leucocytes, macrophages, and fibroblasts. They act locally as autocrines or paracrines that maintain normal cell functions and stimulate proliferation. The classes of hematopoietic growth factors and their functions are described in Table 1. Also fatty marrow that starts to replace red marrow during childhood and which consists of 50% of fatty space of marrow of the central skeleton and proximal ends of the long bones in adults can revert to hemopoiesis as the need arises. Formation of apparently normal blood cells outside the confines of the bone marrow mainly in the liver and spleen in post fetal life is known as Extramedullary Hemopoiesis. Formation of Red blood cells (Erythropoiesis) 17 Hematology Erythropoiesis is the formation of erythrocytes from committed progenitor cells through a process of mitotic growth and maturation. The first recognizable erythyroid cell in the bone marrow is the proerythroblast or pronormoblast, which on Wright or Giemsa stain is a large cell with basophilic cytoplasm and an immature nuclear chromatin pattern. Subsequent cell divisions give rise to basophilic, polychromatophilic, and finally orthochromatophilic normoblasts, which are no longer capable of mitosis. At the same time the nuclear chromatin pattern becomes more compact tan clumped until, at the level of the orthochromatophilic normoblast, there remains only a small dense nucleus, which is finally ejected from the cell. Under normal conditions the transit time from the pronormoblast to the reticulocyte entering the peripheral blood is about 5 days. Pronormoblast (Rubriblast) Pronormoblast is the earliest morphologically recognizable red cell precursor. The chromatin forms delicate clumps so that its pattern appears to be denser and coarser than that seen in the pronormoblast. Cytoplasm: slightly wider ring of deep blue cytoplasm than in the pronormoblast and there is a perinuclear halo. Polychromatophilic Normoblast Size: 12-14?m in diameter Nucleus: smaller than in the previous cell, has a thick membrane, and contains coarse chromatin masses. Nucleus: small and central or eccentric with condensed homogeneous structure less chromatin. Reticulocyte After the expulsion of the nucleus a large somewhat basophilic anuclear cell remains which when stained with new methylene blue, is seen to contain a network of bluish granules. This network is responsible for the name of the cell and consists of precipitated ribosomes.

Other considerations Recently medications j tube cheap dramamine 50 mg with visa, a number of studies have been published that show that pre-operative anaemia is a risk factor for post-operative mortality medicine hat college generic dramamine 50 mg with visa. The following recommendations are not evidence-based symptoms urinary tract infection cheap dramamine 50mg amex, but are based on expert opinion (opinion of the working group) and international guidelines symptoms brain tumor order dramamine 50mg visa. The only indication for a therapeutic erythrocyte transfusion in the case of chronic anaemia is a symptomatic anaemia* medicine allergies order dramamine toronto. Prophylactic erythrocyte transfusions can be indicated for asymptomatic chronic anaemia in a patient without cardio-pulmonary limitations and an Hb < 4 mmol/L medications over the counter dramamine 50 mg low cost. Prophylactic erythrocyte transfusions can be indicated in the case of limited cardio- pulmonary compensation abilities or risk factors in accordance with table 5. If there are no obvious limited cardio-pulmonary compensation abilities or risk factors, the following Hb triggers can be maintained for prophylactic erythrocyte transfusions for chronic anaemia: Age (years) Hb trigger (mmol/L) < 25 3. In the Netherlands, iron deficiency in childhood occurs primarily in ex-premature children, children of foreign parents who drink a lot of cow?s milk, asylum seekers and teenagers with a limited diet that is deficient in nutrients. A prospective study of 100 elderly orthopaedic patients revealed that 18% had pre- operative iron-deficiency anaemia (Hb < 7. After four weeks of iron substitution, the Hb concentration had improved significantly with an average of 0. The patients without anaemia were randomised between four weeks of iron medication (pre-operative and post-operative) and no medication. The group treated with iron (Fe) had a significantly higher (> 0,5 mmol/L) Hb during the first post-operative week than the group that did not receive Fe, without a significant difference in the need for transfusion during the surgery (Andrews 1997). A comparable randomised study of asymptomatic patients with colorectal cancer also showed a higher initial Hb concentration in the group with iron supplementation, but also a significant decrease in the number of transfused units (average 2 to 0) (Liddler 2007). Munoz showed that intravenous administration of iron to patients who had pre-operative anaemia resulted in an increase in Hb level of 2. Another study examined the effect of post-operative administration of oral iron for 3 weeks after total knee arthroplasty; there was no clear difference in the level of Hb and recovery after surgery (Mundy 2005). A recent study showed no correlation between the pre-operative iron status and the need for peri-operative or post-operative transfusion. However, the pre-operative Hb level did appear to have a predictive value for the peri-operative and/or post-operative need for transfusion (Fotland 2009). Nutritional megaloblastic anaemia can be caused by: - Folic acid deficiency caused by nutritional deficiency and/or alcoholism, increased use such as in haemolysis and pregnancy, medication (trimethoprim and methotrexate) and malabsorption. The blood can also be macrocytic in the case of myelodysplasia and auto-immune haemolytic anaemia. Megaloblastic anaemias only become symptomatic at very low Hb levels (< 3 4 mmol/L) due to the slow development and associated compensation of oxygen transport. If megaloblastic anaemia is suspected, treatment consists of the administration of vitamin B12 and folic acid, with blood being collected first for diagnosis. A transfusion indication only occurs in patients who cannot compensate for anaemia such as severe heart failure or instable angina. Administration of vitamin B12 for such severe anaemia will not guarantee fast correction, meaning that a transfusion could be indicated. Level 4 D Expert opinion the pre-operative Hb level influences the peri-operative need for transfusion. Pre-operative screening and substitution of iron-deficiency Level 2 anaemia can improve the post-operative Hb. In patients undergoing elective, major surgical procedures it is recommended to treat any iron-deficiency anaemia for a minimum of four weeks prior to surgery. In addition, these patients often have a deep thrombocytopenia, meaning that a higher Hb is desirable for good haemostasis. Solid tumours Anaemia in non-haematological malignancies is usually the result of a chronic disease and not the suppression of haematopoiesis by bone marrow metastases. Chemotherapy, radiotherapy, haemolysis (micro-angiopathy), coagulopathy and bleeding can contribute to the occurrence of anaemia. With solid tumours there is also a (relative) shortage of erythropoietin (Miller 1990). Anaemia is more common during platinum-based chemotherapy (Wood 1995, Skilling 1993). There are no randomised studies about the relationship between the level of Ht and the effect of chemotherapy and/or radiotherapy on the disease. Patients with cancer often receive transfusions at an Hb < 6 mmol/L, particularly if they have an active lifestyle, but this limit is not based on research. Blood Transfusion Guideline, 2011 111 111 Other considerations A separate point of discussion is whether or not allogeneic transfusions can inhibit the patient?s immunity against tumours and thereby promote relapse of the cancer after surgical treatment that should be curative (see Chapter 7. If anaemia is the result of bone marrow suppression, it will improve upon response to treatment. Transfusion risks (see also Chapters 2 and 7) For irradiation of erythrocytes: see Chapter 2. There are also data that point to a decreased immune response to allo- antigens (due to the nature of the treatment or not) (Schonewille 1999, Fluit 1990). Therefore, the risk of the occurrence of irregular erythrocyte antibodies in patients with lympho-proliferative conditions is small. Myeloid conditions In general, patients with acute myeloid leukaemia receive multiple erythrocyte and platelet transfusions; in the case of chronic myeloid leukaemia transfusions are necessary following transplantation or in the (pre)terminal stages of the disease. Patients with myelofibrosis who often have splenomegaly benefit less from erythrocyte transfusions. There is also no evidence for a specific transfusion policy of red blood cells for acute myeloid leukaemia (Milligan 2006). Patients with myelodysplasia are usually older (on average 68 years) at the time of diagnosis. More than 90% require erythrocyte transfusions (20 30 units / year), often without treatment alternatives. Anaemia is not such a big problem with the use of the new generation of protease inhibitors. The Hb concentration can drop to < 5 mmol/L, but because the patients are often young and do not have any symptoms of hypoxaemia, transfusions are generally not indicated. Older observational studies show that blood transfusions administered during bowel surgery for Crohn?s disease have a favourable immune-modulating effect and extend the interval until the next exacerbation. However, a meta-analysis of 4 of the 7 historical studies found insufficient evidence for this (Hollaar 1995). Anaemia with chronic illness rarely results in a transfusion indication at an Hb > 5. Within the gynaecological setting, transfusions are mostly given peri-operatively; the indications are identical to those applied in general surgery. The chronic anaemia caused by menstrual abnormalities also does not differ from other situations of chronic iron-deficiency anaemia (see paragraph 4. The aim of iron supplementation in pregnancy is to achieve a ferritin level of > 80? Little is currently known about the treatment of anaemia with erythropoietin during pregnancy. Approximately 30 35% of Dutch pregnant women are of foreign descent and have a higher incidence of haemoglobinopathy (refer to transfusion problems in pregnancy for patients with sickle cell anaemia, paragraph 4. Component choice During pregnancy, transmission of certain viruses via donor blood (in particular Parvo-B19) should be avoided in order to prevent foetal morbidity and mortality (Health Council: see paragraph 2. There are no data concerning transmission of Parvo-B19 via blood transfusions to pregnant women. It is known that Parvo-B19 infection during the first term of pregnancy causes approximately 10% intra-uterine death due to hydrops (Tolfvenstam 2001). The Health Council advised in 2002 that sero-negative pregnant women should receive Parvo-B19 safe transfusions in the first and second term of pregnancy (Health Council report 2002). Level 3 C Tolfvenstam 2001 During the first and second terms of pregnancy it is advisable to select Parvo-B19 safe components for transfusion to sero-negative pregnant Level 4 women in order to prevent transmission of Parvo-B19. D Health Council 2002 the aim of iron suppletion during pregnancy is to achieve a ferritin level > 80? Level 3 C Elion-Gerritzen 2001 Other considerations There are many similarities in the guideline for transfusion to pregnant women, but there is very little scientific evidence to support it. The need for a transfusion during pregnancy should be considered per individual patient, depending on underlying disease and the health of the foetus. Parvo-B19 safe transfusions are recommended for sero-negative pregnant women (see Chapter 2. Particularly in bone marrow, there is a large quantity (> 700 mL, approximately 40% of the bone marrow volume) of erythrocytes present. There are various options to prevent/reduce transfusion reactions caused by haemolysis due to bood group incompability (Klumpp 1995). In adults the only measure is usually to reduce the erythrocyte volume of the bone marrow / stem cell component to < 15 mL if the patient has an IgG and/or IgM titre greater than 16 in combination with slow administration and good hydration of the patient. The administration speed must be adjusted according to the anti-A and/or anti-B titre of the patient (the higher the titre, the slower the administration). Further reduction of the erythrocyte volume to < 10 Blood Transfusion Guideline, 2011 115 115 mL is recommended in children (Rowley 2000). The height of the IgG/IgM titre has not been standardised between the various centres. In addition to delayed haemolytic reactions, complications include prolonged aplasia and ?pure red cell aplasia? (Fitzgerald 1999, Salmon 1999, Lyding 1999, Laurencet 1997, Oziel- Taleb 1997, Bornhauser 1997, Moog 1997, Toren 1996, Greeno 1996, Lopez 1994, Sniecinski 1988, Hows 1986, Warkentin 1983). The consensus by Societe Francaise de Greffe de Moelle even recommends washing of the transplant at a titre > 32. A good compromise is plasma reduction at a titre > 32 (Rowley 2000, Lapierre 2000). Anti-A/anti-B antibodies from the donor can also be stimulated by (tissue) expression of blood group A and/or B in the patient. Multiple specificities such as D, c, Cw, e, E, Jka and Le have been found (Lapierre 2001, Bornhauser 1997, Godder 1997, Lopez 1994). The identification of the specificity is easier if the pre-transplant erythrocyte typing of donor and recipient is known. As a rule, the autoantibody formation is self-limiting if immunological recovery is achieved, although the condition is fatal in 50% of patients due to haemolysis, multi-organ failure or refractory thrombocytopenia (Horn 1999, Chen 1997, Drobyski 1996, Lord 1996). The consensus by Societe Francaise de Level 3 Greffe de Moelle even recommends washing of the transplant at a titre > 32. C Labar 2000 Other considerations the working group members are of the opinion that it is important to have access to complete pre-transplantation data if possible, also in the case of a non-related donor due to post-transplantation haemolysis. In order to prevent antibody-mediated haemolysis of erythrocytes it is recommended to transfuse with either O erythrocytes or erythrocytes that are compatible with donor and recipient in case of minor and major blood group antagonism. Blood Transfusion Guideline, 2011 117 117 In France, national protocols are maintained and evaluated for the transfusion policy after transplantation. Blood components for stem cell transplant patients should be irradiated (see also table in Chapter 2. National agreement on the guidelines mentioned under recommendation 4 is desirable. A review of the studies on the effect of recombinant erythropoietin in children treated with chemotherapy for cancer was recently published. A lower requirement for blood transfusion (up to 20% compared to control individuals) is reported in 29 studies of chemotherapy, with four studies being randomised and double-blind. The quality of life was examined in 35 studies, of which three were randomised and double-blind. No randomised, double-blind study of the transfusion requirements and quality of life has been performed for patients receiving radiotherapy. A randomised study is necessary to be able to make definitive conclusions about the quality of life, blood conservation and cost efficacy by erythropoietin, with a similar Hb as a target value in both arms of the study group. Chemotherapy- treated cancer patients with anaemia had an increased risk of mortality of Level 1 10%, and a decreased long-term survival. Only 6% of the patients who previously required transfusions became independent of transfusions. The limitations of this study compared to the study by Zeng are that the Shao study was smaller in size and measured response rate instead of survival. C Bessho 1997, Shao 1998, Zeng 2006 124 Blood Transfusion Guideline, 2011 Recommendation 4. Due to the limited number of prospective studies for the indication for blood transfusion in sickle cell disease, some of the recommendations have been formulated based on expert opinion (evidence level 4). The indications for blood transfusion will be discussed consecutively in acute situations (4. Blood transfusions for anaemia are only indicated in the case of symptomatic anaemia (see also paragraph 4. An acute deterioration of the anaemia in sickle cell disease can be due to a number of factors other than blood loss: acute aplastic crisis, acute sequestration in the liver and/or the spleen, or due to a haemolytic crisis. Threatened anaemia due to aplastic crisis An aplastic crisis is usually caused by a Parvo virus B19 infection. The parvo virus inhibits haematopoiesis, which due to the short circulation time of erythrocytes in patients with sickle cell disease, results in a threatened anaemia with noticeable reticulopaenia. A large Blood Transfusion Guideline, 2011 125 125 observational study revealed that more than 75% of children with sickle cell disease and a Parvo B19 infection require a transfusion (Smith-Whitley 2004). Threatened anaemia due to acute liver and/or spleen sequestration Acute liver and/or spleen sequestration usually occurs in early childhood and is a rapidly developing and potentially fatal complication. In these cases the blood is withdrawn from the circulation, which results in acute severe anaemia, hypovolaemia and rapid progressive splenomegaly. Transfusions are recommended in symptomatic cases of acute sequestration and it should be taken into consideration that a portion of the erythrocytes will return to the circulation after sequestration, which can cause a rapid increase in Hb with associated hyperviscosity (Ohene-Frempong 2001, Josephson 2007, Wahl 2009).