Haematological evaluation of bruising and bleeding in children undergoing child protection investigation for possible physical maltreatment: A British Society for Haematology Good Practice Paper

Abstract

This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process available at: https://b-s-h.org.uk/media/16732/bsh-guidance-development-process-dec-5-18.pdf. The BSH produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. Due to the paucity of high-quality evidence, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature (http://www.gradeworkinggroup.org) was not used to assess the strength of the recommendations. A literature search was performed on 26 January 2021 and included searches of MEDLINE (using PubMed), EMBASE (using Ovid) and the Cochrane library databases. Details of the search can be found in Appendix S1. References known by the authors were also included and references from relevant publications were searched. Due to the paucity of published data all types of publication, including editorials, case reports and conference abstracts, were included. Those relating to non-human studies, adult studies and published in non-English journals were excluded. The writing group produced the draft guideline. Review of the manuscript was performed by the BSH Haemostasis and Thrombosis Task Force, the BSH Guidelines Committee and the BSH sounding board. It has been supported by The Royal College of Paediatrics and Child Health (RCPCH) Child Protection Standing Committee. It has also been reviewed by the United Kingdom Haemophilia Centre Doctor's Organisation, Family Justice Council and the National Network of Designated Healthcare Professionals for Safeguarding Children; these organisations do not necessarily approve or endorse the contents. The aim of this Good Practice Paper is to advise on haematological evaluation of bruising and bleeding in children undergoing child protection investigation for possible physical maltreatment; to consider which children should undergo investigations, which tests are indicated, the interpretation and reporting of abnormal results, multi-disciplinary working, and the contribution of healthcare professionals to statutory child protection proceedings and to court proceedings. The guidance has been written to assist haematologists, paediatric haematologists, paediatricians, and laboratory scientists to achieve an informed and consistent approach that supports accurate diagnosis and exclusion of bleeding disorders, reduces unnecessary testing and supports safety planning for this group of children and young people. Inadequate evaluation has the potential to miss a significant bleeding disorder diagnosis or overlook a diagnosis of physical abuse, whilst extensive testing, sometimes on the advice of court appointed medical experts and not always clinically indicated, can result in unnecessary venepuncture, false positive results, and potentially erroneous diagnoses. Pre-analytical problems and physiological variation is frequent, particularly in younger children, and can lead to difficulties in the accurate interpretation of test results. Inaccurate diagnosis and inconsistent clinical management can pose difficulties for safe decision-making in court proceedings. Many children presenting with soft tissue injury do not require blood investigations. The decision to investigate is a matter of clinical judgement and is a decision for the treating clinician.1 Table 1 describes examples of clinical presentations where haematological investigations are not likely to be required although this is not exhaustive. The purpose of haematological investigation when physical maltreatment is suspected in a child presenting with bruising or bleeding, is to identify or exclude the presence of an inherited or acquired bleeding disorder that may have influenced the propensity to bruising/bleeding. Competent assessment of a child aims to differentiate injuries suggestive of physical maltreatment from findings that may be normal for the developmental stage of the child and from bruising/bleeding associated with an underlying bleeding disorder. In the context of children presenting with bleeding at a critical site, particularly intracranial haemorrhage (ICH), haematology expertise is relied on to distinguish a contributory/causal underlying bleeding disorder from a secondary coagulopathy occurring as a consequence of the haemorrhage. An important caveat is that physical maltreatment and bleeding disorders can co-exist in the same child. In addition, no single panel of tests definitively rules out a bleeding disorder diagnosis. Evaluation of the need for haematological investigation involves assessment of the personal and family history of bleeding, the age and developmental stage of the child, any accounts provided of accidental trauma, and the examination findings. A bleeding history is important to identify those who may have an inherited bleeding disorder (IBD). A structured bleeding history should explore mucocutaneous bleeding symptoms (e.g., epistaxis, gum bleeding, prolonged bleeding from minor wounds, menorrhagia, gastrointestinal tract bleeding), bleeding in relation to previous haemostatic challenges (e.g., surgery, dental extractions, trauma) and, in the case of younger children, bleeding during the neonatal period (e.g., cephalohaematoma, prolonged umbilical stump bleeding, bleeding from Guthrie heel prick or immunisation sites) and bruising with minor trauma from an early age. A standardised bleeding assessment tool, e.g., the International Society for Haemostasis and Thrombosis Bleeding Assessment Tool (ISTH-BAT), can be used to quantitate bleeding symptoms in order to generate a bleeding score. The presence of multiple bleeding symptoms and/or severe bleeding symptom(s) contribute to a higher score and therefore a greater chance of a bleeding disorder diagnosis. The ISTH-BAT has been shown to improve pre-test probability in the investigation type 1 of von Willebrand disease in adults but has not been validated in the setting of child protection investigations.2 Family history of significant bleeding symptoms and/or an IBD diagnosis may be relevant, along with a history of parental consanguinity as rare IBDs are often recessively inherited. The limitations of a positive family history should however be noted and even in boys with severe haemophilia A only 50% of new diagnoses have a positive family history. An acquired bleeding disorder usually presents with a recent onset of unexplained haemorrhagic symptoms. Thrombocytopenia, due to immune thrombocytopenia (ITP) or a bone marrow disorder may present with widespread petechiae, bruising and mucosal bleeding. The possibility of medication-related coagulopathy is elicited from the medication history, which should also identify the neonatal administration of vitamin K; deficiency of the latter can present as vitamin K deficiency bleeding (VKDB), which occurs in babies aged from birth to 3 months and can cause bruising and significant gastrointestinal or ICH.3 Clinical examination should include a detailed assessment and documentation of bruising along with examination for any current or recent mucosal or concealed bleeding. As the frequency and nature of normal bruising, along with the likelihood of sustaining injury, varies with the degree of mobility, the developmental stage of the child should be assessed. In relation to non-haematological causes of increased propensity to bruising such as Ehlers Danlos syndrome and osteogenesis imperfecta, clinical examination findings of collagen disorders should be sought, including blue sclerae, abnormal dentition, short stature, dysmorphic facies, increased skin and joint laxity and atrophic scars.4 Further consideration of these conditions lies out with the scope of this document. Several studies have sought to identify features that can help to differentiate abusive bruising from accidental bruising in normal children and children with IBDs.5-9 Specific anatomical sites that are more likely to be associated with abuse include bruising to the buttocks, cheeks, ears, neck, and the front of the trunk or thighs. This contrasts with bruising over bony prominences, particularly the lower legs and a T-shaped facial distribution, which is commonly seen in accidental injury in mobile children, including those with IBDs.8, 10 Petechiae and linear bruising patterns and bruising in pre-mobile children are also more likely to be features of physical maltreatment.6, 11 While children with IBDs have more and larger bruises than usual at all developmental stages, bruises affecting the ears, neck, cheeks, eyes and genitalia remain uncommon.7, 12 The possibility of a bleeding disorder should be considered in all children presenting with unexplained bleeding at a critical site in the setting of suspected physical maltreatment, particularly ICH but also gastrointestinal bleeding, retinal bleeding,13 intraspinal bleeding and haemarthrosis. Intracranial haemorrhage, particularly subdural bleeding, presenting in infancy beyond the neonatal period is most often due to abusive head trauma.14 However, this time period overlaps with the age group most likely to present with ICH secondary to an IBD and is also the age at which VKDB may present. While IBDs are rare in the general population failure to make a prompt diagnosis may result in a significant treatment delay and poorer outcome. Spontaneous ICH in IBDs is uncommon and usually, but not exclusively, occurs in children with a severe bleeding disorder, the most common being severe haemophilia A.15, 16 Factor XIII deficiency is a rare IBD but is associated with a high risk of ICH, which is estimated to occur in around one-third of cases in the absence of preventative treatment. Bleeding that is out of proportion to a reported account of head trauma, or bleeding at a critical site can be the first presentation of an IBD. Consider laboratory investigations when: Figure 1 shows a proposed pathway to guide the haematological investigations in cases of suspected physical maltreatment. When indicated, it is important that testing is timely to avoid delay in appropriate action if a bleeding disorder is or is not identified. When haematological evaluation is required, first-line tests should be requested. These tests are a full blood count, blood film, and a coagulation screen that includes prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen level. These tests are primarily to identify or exclude an acquired condition. It is important to note that many IBDs will not be ruled out by normal first-line investigations, although some inherited disorders will be identified following coagulation screening, e.g., isolated prolonged APTT in severe haemophilia. It has been standard practice in many centres, including some district general hospitals (DGHs), to include von Willebrand disease (VWD) screen in first-line investigations. This is not advised. VWD screen results are frequently erroneous due to problems with sample preparation, sample transport, and analysis by laboratories with limited experience: this can result in repeated testing and may distort or delay medical opinion provided to the child protection investigation. In addition, if an IBD is suspected, second-line tests should be undertaken to investigate for all IBDs and not only VWD. If the presentation might indicate an IBD then the child should undergo second-line tests (at the same visit as first-line tests where practical). In the case of unexplained bleeding at a critical site, second-line tests should always be performed. If the first-line tests are normal and the clinician is confident that the child has no personal or family history to suggest an IBD, then no further tests are required. The decision-making process in relation to the need for second-line testing, which tests to perform, and where to do the testing should involve discussion between the paediatrician and haematologist according to the locally agreed referral pathway (refer to ‘Developing a regional approach’ below). Second-line testing includes factor (II, V, VII, 1-stage and chromogenic VIII, IX, X, XI and XIII) assays, VWD testing and tests to assess platelet function (platelet aggregometry, flow cytometry and platelet nucleotide studies). Additional tests for rarer IBDs may be appropriate in selected cases with an extensive bleeding history. Historically, platelet aggregometry has been the preferred option for the assessment of platelet function. A minimum volume of 12–20 ml whole blood is required to provide sufficient platelet-rich plasma by centrifugation for a full panel of agonists.17 Where flow cytometry is available the typically more severe platelet function disorders, Bernard Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT), can be detected by reduction in glycoprotein Ib and IIb/IIIa expression, respectively, using a much smaller volume of blood (5–6 ml). However, flow cytometry does not exclude other platelet function disorders. Screening using the Platelet Function Analyser (PFA) has significant limitations and is not recommended for routine use in this setting. It has low sensitivity for mild disorders18 and there are other factors that can affect the result, e.g., some drugs, mode of sample collection and sample transport. Use of the PFA should be limited to situations where there is no access to standard laboratory tests of platelet function and the diagnosis of a severe platelet function disorder would alter management and potentially outcome. Undertaking genetic or genomic testing in addition to phenotypic haematological investigations does not increase the diagnostic yield in this patient group and is not indicated. Abnormalities that are not sufficient to result in phenotypic laboratory abnormalities are unlikely to account for the clinical presentation. However, it may be appropriate to consider storing a blood sample for directed genetic testing from a moribund child when other testing is unavailable. some cases there may be a to a considered approach to second-line testing, of clinical of IBD, age and e.g., it may be to factor and VWD testing only tests to assess platelet function if those are However, this approach should be the of the of a child and the of who have to a to have blood in a Platelet aggregometry is not recommended in children the age of 12 months and may be in children the age of 3 due to the volume of blood required for In these flow cytometry can be used for assessment of platelet to the more severe platelet function disorders, and If flow cytometry is not available then a limited aggregometry panel a smaller volume of ml whole may be e.g., a single of the collagen and and high and low of Many children haematological investigations will be for or in a setting. between and the to locally agreed testing and referral is to and consistent first-line haematological testing and some second-line coagulation testing may be possible in the with help in interpretation of results from the adult haematology may have limited of paediatric interpretation of results in relation to paediatric and of child further are to test locally and for help with the interpretation of results from the paediatric haematology or to the of the child to a paediatric for second-line In this latter it is important that the lead for the child protection investigations is identified. If the lead is not to remain the there should be to discussion to identify an appropriate lead paediatric to provide advice and opinion in the may be some in which a child is to be or is in a moribund condition. that the results may be by and in these blood may need to be at the and to the for is important to A blood sample should be paediatric and to the appropriate by a minimum and may erroneous results and should not be The blood should be to The sample should be to the laboratory at which may be most if early in the that are out of may be of the to test platelet and plasma at or for should not be from that have been with as frequently occurs of for platelet function testing may need to be in children who have been to to alter platelet with a high such as children with underlying may require the volume of to be The presence of and may also with children may require repeated testing, which can be for the child and It is good practice to avoid more than to at blood on a due to in coagulation due to The clinical for blood testing be the to child and and the clinician may that further should be should be by an or that the clinical e.g., protection to that are in a timely plasma should be in case further tests are the laboratory and haematologist in of the may help to the testing and The limitations of the routine tests need to be as laboratory have to factor found in first-line investigations should be to the International for laboratory testing for all tests that are second-line testing the use of a which is for the whole results would be reported with paediatric normal However, due to the difficulties in normal all age in significant published paediatric are usually Further may on the coagulation and need not only for age but also for the interpretation of laboratory results is as a bleeding disorder diagnosis will be of clinical for the child and court proceedings require accurate medical to make safe are challenges in the interpretation of coagulation test results in children, particularly those who are may as a result of developmental of some tests and the need to the findings in the context of the clinical presentation. This of may interpretation by a haematologist who may in require advice from a haematologist with expertise in paediatric The frequency of clinically significant or abnormal result in a laboratory test undertaken as of an investigation of suspected physical maltreatment has been reported as and an acquired bleeding disorder or IBD in although there is variation between studies in of the for testing, the nature of the testing performed and the interpretation of abnormal laboratory tests in of clinical The results of coagulation tests in smaller children, particularly can be by may result in sample or sample This is particularly relevant to the testing of platelet function using aggregometry due to the volume of blood required. not to of coagulation factors due to prolonged of to a laboratory may provide It is recommended that are of blood Several coagulation factor with age and in the age by which have the same normal as is also a in coagulation factor between and factor be with to normal In this most commonly to low of factors and XI in young factor and von Willebrand factor are and are seen in to trauma, surgery, or This may be sufficient to mild haemophilia A or type 1 VWD if blood is during the in this setting may not exclude the diagnosis of a mild bleeding In a of for or has been reported to exclude VWD on a single test with a of but at lower testing may be of the has been as a consequence of injury, to A in of suspected injury high of prolonged and APTT of and respectively, at In the is prolonged and of the vitamin factors (II, VII, and are sometimes by a prolonged by administration of or vitamin with or results in of the is a consequence of during It can result in an isolated prolonged which to normal using a APTT but does not on a with normal It does not result in a bleeding it is associated with acquired prothrombin evidence of a beyond 3 months in 50% of The of testing should be according to clinical e.g., in the absence of haemorrhagic symptoms or the need for an testing of suspected physiological reduction in coagulation should be are usually at months of This may require the to provide the court with of the available results in the a suspected acquired the for testing will on the usual for of the In the case of an that is likely to be clinically referral to a paediatric haematologist is recommended for testing and management It is appropriate for normal results to be reported by a paediatrician or haematologist with limited in paediatric However, reporting of abnormalities that are identified on haemostatic testing should be performed by a haematologist with sufficient expertise in laboratory should be in the interpretation of an that would be to cause only minor haemorrhagic symptoms as the diagnosis of a mild bleeding disorder may not be sufficient to the presenting It may not be the of the reporting haematologist to the clinical presentation was by the bleeding disorder diagnosis but it is important to the clinical of the disorder of that has been identified. the interpretation of minor abnormalities that are likely to be due to such as minor in platelet in children, expertise in the limitations of laboratory Appendix some cases that many of the in this Good Practice Healthcare professionals have a to in child protection possible child physical maltreatment may be as a to written and evidence in family proceedings and in proceedings. This is usually the but a haematologist may be to on the results of laboratory This is from being as an which lies the scope of this although it is that an paediatrician or haematologist would the same good practice guidance on the of is provided by the Council and by the can access from for are of and are to provide interpretation of the (e.g., investigation and an of diagnosis and In family this usually involves a written by to written from on of the of the can be if it is required by or directed by a should use and that who are not will and medical or other should be If the is that are being a of should not to this in which are clinically should be undertaken the and, where in a that supports the court for the If the court that an which is not on clinical to be undertaken to assist in this will be directed and by the The of the clinician may be sought to the investigation. Additional of the BSH Haemostasis and Thrombosis at the time of writing and The authors would to the BSH sounding and the BSH for in this good practice The BSH the during the writing of this good practice authors have a of to the BSH and Task that may be on The following authors have undertaken and for for and for and for and and have no of to of the writing group will the writing group if any new evidence available that would alter the strength of the in this or it The will be and from the BSH current if it If new are an will be published on the BSH While the advice and in this guidance is to be and accurate at the time of to the the BSH the any for the of this Additional may be found in the at the of the Appendix S1. Appendix case is not to this as no new data were or Appendix Appendix The is not for the or of any by the than should be directed to the for the

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