Guidelines for Shared Care Centres and Community Staff
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1 Reference: CG1410 Written by: Dr Jeanette Payne Peer reviewer Dr Jenny Welch Approved: February 2016 Approved by D&TC: 8th January 2016 Review Due: February 2019 Intended Audience This document contains information and clinical guidelines for management of children attending the Sheffield Children s Hospital Haematology department or designated shared care centres. It is to be used by staff within the Trust, the Shared Care Trust or the community whenever they are caring for these children either in hospital or at home. Table of contents 1. Introduction 2. Bleeding Disorders Haemophilia A and B von Willebrand s Disease 3. Immune Thrombocytopenic Purpura (ITP) 4. Thrombosis and Thrombophilia SC(NHS)FT 2016 Page 1 of 6
2 1. Introduction The following is not intended to be a comprehensive reference for haemostatic and thrombotic problems in childhood. For the most part children with congenital bleeding disorders or with a clinically significant thrombosis should be managed either wholly or with considerable liaison with the haematology department at Sheffield Children s Hospital. 2. Bleeding Disorders A neonate or child suspected of having a bleeding disorder should as baseline investigations have a blood count and clotting screen (including PT, APTT and fibrinogen) performed. They are currently the best available tests to screen for severe disorders of clotting and to narrow the focus of further investigations. If the blood count and clotting screen are normal then a significant disorder of haemostasis is much less likely. However, these tests will sometimes be normal in some bleeding disorders e.g. in mild forms of von Willebrand s disease, mild haemophilia A and B. They will not detect some of the very rare disorders e.g. Glanzmann s thrombasthenia, Factor XIII deficiency. The results of baseline investigations should be used to direct further testing. If thrombocytopenia is found a blood film should be requested to look at the morphology of the platelets and for any associated abnormalities. Abnormal clotting screens may be discussed with a local haematologist but in neonates or children suspected of having a bleeding disorder we would recommend prompt discussion with a paediatric haematologist at our centre so that arrangements for further investigations can be made. Since normal baseline investigations do not exclude a significant bleeding disorder if there is sufficient clinical concern i.e. personal and/or family history of excessive bleeding we would suggest referral to our centre for further investigations. Clinical Presentation Haemophilia A or B. Family history is absent in the 30% of sporadic haemophilia cases arising from a new mutation in maternal or grandparental germ line. This means that even in the absence of a family history a diagnosis of haemophilia must be considered in a male child presenting with a bleeding/bruising problem. Possible clinical presentations: Severe haemophilia. Usually presents <2yrs. Can present at any age including neonatal period with abnormal bleeding/bruising after surgery, intramuscular injections or venepuncture. Needs to be considered in differential diagnosis of a male neonate with intracranial haemorrhage. Most common presentation is with abnormal bruising and with spontaneous joint and muscle bleeds once infant is mobile. Spontaneous bleeding in CNS, GI tract and mucosal membranes or prolonged bleeding following injury are less common presentations. Moderate haemophilia. Bleeding following haemostatic challenge e.g. trauma, surgery and dental extractions. Occasionally spontaneous bleeding. Mild haemophilia. Bleeding following haemostatic challenge. May not present until adolescent or even adulthood. SC(NHS)FT Page 2 of 6
3 Laboratory findings Haemophilia is due to either a deficiency of factor VIII (haemophilia A) or IX (haemophilia B). A clotting screen will show an isolated prolongation of the activated partial thromboplastin time (APTT). The diagnosis is then made by specific factor assays that assess the activity of factor VIII or IX. In mild haemophilia the APTT may not be abnormal even with a reduction in factor activity and specific assays would be required to exclude the diagnosis. Any neonate or child who is bleeding and is found to have an isolated significantly prolonged APTT should be discussed even prior to receiving the results of factor assays. Urgent factor assays can be then arranged and if necessary transfer of the patient to our unit for ongoing investigation and management. von Willebrand s Disease von Willebrand s disease (vwd) is the commonest congenital disorder of haemostasis, affecting up to 1% of the population. It often presents with easy bruising as the sole symptom, although mucosal bleeding is also common. Post-pubertal females may have menorrhagia. Family history is frequently positive, but may be silent and only uncovered on parental testing. The diagnosis is made by a combination of clinical history, family history and results of laboratory tests. Laboratory testing includes assays for factor VIII, and quantitative and qualitative tests of von Willebrand factor (vwf antigen and Ristocetin Co factor assays are most commonly performed). The majority of cases are mild with concentrations just below the normal range. This may cause diagnostic difficulty, as the venepuncture ordeal can stimulate release of factor VIII and vwf from endothelial stores, often pushing marginally sub-normal concentrations to within the normal range. Where suspicion is strong, and concentrations borderline normal, repeat tests may be justified. Another significant variable affecting the levels of vwf is the patient s blood group and borderline or mildly reduced levels need to be interpreted with this in mind. Due to the complexity of establishing this diagnosis UK recommendations are that the care of these children is overseen by haemophilia comprehensive care centres, which will also facilitate the correct treatment approach if/when treatment is required. Management All children with congenital bleeding disorders in this geographical region should be registered at the Sheffield Children s Hospital Haemophilia Comprehensive Care Centre. All children have 24 hour/day open access to the centre and to our ward M3. Parents are told to contact the haematology consultant on-call if requiring out of hours treatment or advice. Dental care is provided by The Charles Clifford Dental Hospital to enable us to manage haemostatic cover for dental work. Although parents are advised to come directly to Sheffield Children s Hospital, if a child with a congenital bleeding disorder does attend a local hospital it is important that their management is discussed with a haematology consultant from our centre. This is essential for all injuries and bleeds or if any surgical intervention may be required for an unrelated problem. Surgery on children with bleeding disorders should take place at Sheffield Children s Hospital where we can manage haemostatic aspects of medical care on site. SC(NHS)FT Page 3 of 6
4 3. Immune Thrombocytopenic Purpura (ITP) Childhood Immune Thrombocytopenic Purpura (ITP) usually presents between the ages of 2 and 10yrs but can occur at any age and may follow a viral infection or immunisation. Presentation is with a short history of often impressive bruising, petechiae and sometimes mucosal bleeding. Patients are otherwise well. The diagnosis of childhood ITP is by exclusion made on the basis of an otherwise well patient, without significant lymphadenopathy or organomegaly, with isolated thrombocytopenia and a normal blood film. Coagulation screening is only necessary if there is a possibility of meningococcal infection, features to suggest an inherited bleeding disorder in addition, or a suspicion of NAI. The platelet count is usually less than Children with higher platelet counts rarely show any symptoms. A bone marrow test is not required to make a diagnosis of ITP. The history of bruising and purpura is sometimes more chronic, with symptoms developing more slowly over weeks or months. In these children caution should be exercised and particular attention paid to the possibility of a congenital disorder. ITP is usually a benign disorder that requires no active management other than careful explanation and counselling. This is because serious bleeding is rare, and about 80% of children with ITP will recover spontaneously within 6months. Concern over the possibility of CNS bleeding or significant GI bleeding has in the past led to unnecessary treatment of children with ITP. Pronounced skin purpura and bruising, however extensive do not indicate a serious bleeding risk on their own. Children and their parents may benefit from the contacts and literature available from ITP support groups such as The ITP Support Association ( Most children can be managed well at home, and do not require hospital admission, which should be reserved for children with clinically important bleeding (severe epistaxis, i.e. lasting more than 30 min with heavy bleeding, GI bleeding, intracranial bleeding, history of significant trauma etc.). Patients with mucosal bleeding can be given tranexamic acid orally 15-25mg/kg (maximum 1.5g) three times a day. For uncontrolled bleeding an ENT/dental opinion is advised. Children with serious or troublesome bleeding should be discussed with a consultant paediatric haematologist from our centre. Since specific treatment is only rarely required, treatment with steroids or immunoglobulin should not be used without consultation with a specialist paediatric haematologist. Patients and parents should be counselled on the need to: Avoid intramuscular injections Avoid non-steroidal pain killers (including ibuprofen and aspirin) Report all head injuries, and any serious bleeding Avoid contact sports or activities with high risk of trauma or head injury until advised otherwise Other activities can be continued as normal, and the child should be encouraged to continue schooling (but inform school staff) on the basis that ITP is a disorder that may last several weeks or months. SC(NHS)FT Page 4 of 6
5 Parents should be advised to watch for other signs of bleeding and be given a contact name and 24-hour telephone number e.g. local paediatric ward/paediatric registrar on-call. Most children with mild or moderate symptoms only (the majority) can be safely managed as outpatients with initially weekly then less frequent visits. A repeat FBC should be performed within the first 7 10 days to check that there is no evidence of a serious marrow disorder emerging, particularly aplasia. When the thrombocytopenia persists but the child remains well, the intervals between visits can be stretched out in order to minimise interference with schooling. Children who require essential surgery or dental work whilst thrombocytopenic may require treatment to boost the platelet count. If the child is having a general anaesthetic it may be appropriate to do a bone marrow aspirate whilst the child is asleep. Any need for surgery should be discussed with a consultant paediatric haematologist. Children who continue to be severely thrombocytopenic with significant bleeding symptoms are very rare, and should be referred to a specialist paediatric centre for management Chronic ITP in childhood Most children with ITP will remit within 6 months. The management of children with continuing thrombocytopenia is essentially the same as for acute ITP. Many children settle with an adequate platelet count and have no symptoms unless injured. If thrombocytopenia persists beyond 6 months management will depend on the presence and severity of bleeding symptoms. Children who do not have active bleeding problems may be continued to be managed expectantly. Spontaneous remissions from ITP continue to occur beyond 6 months. However, referral for assessment by a paediatric haematologist should be considered to re-evaluate the diagnosis and consider any need for treatment. It is recommended by the BCSH that all children with chronic severe ITP should be referred to a paediatric haematologist for management and long term follow-up. 4. Thrombosis and Haemophilia Symptomatic venous thromboses are rare in childhood. The incidence is around 5: children according to registry data. The highest risk period is the neonatal period but events are almost always in association with central lines and/or in sick neonates. Most thromboses in children are secondary events occurring in association with at least one risk factor. Central venous lines are the single most important risk factor for thromboses in children. The optimum treatment of venous thrombotic events is not well defined but the principles of treatment with anticoagulation are derived from the limited data in children and from adult practice. Guidance on investigation and management of thrombotic events will depend on local facilities and expertise. Involvement of a local consultant haematologist is advised. Specialist advice is available from the contacts below if required. SC(NHS)FT Page 5 of 6
6 Thrombophilia Venous thromboembolic events (VTEs) in children are usually associated with underlying clinical conditions such as central venous lines, cancer and cardiac diseases. Idiopathic events are rare in childhood. A number of inherited conditions that can increase the risk of a thrombosis have been described. The well-established characterised and accepted inherited thrombophilias are deficiencies of antithrombin, protein C and protein S, activated protein C resistance/factor V Leiden mutation and prothrombin G20210A mutation. Given the low prevalence of thromboses in childhood even in if a child carries a mutation for one of these conditions in the absence of other risk factors they are very unlikely to have a VTE Testing of children for thrombophilic defects is discouraged since management is rarely affected by the knowledge of a defect. The initial management of VTE in those with thrombophilia is no different from the management of VTE in any other patient. Interpretation of results is difficult in the presence of an acute thrombosis and by heparin and warfarin so testing should be avoided in these circumstances. It is generally not helpful to screen asymptomatic children who have family history of VTE even if a thrombophilic defect is found in a relative. Homozygous protein C, protein S, antithrombin deficiency usually present in newborns with severe clinical manifestations, such as purpura fulminans or idiopathic extensive large vessel thrombosis. Testing is justifiable in these limited situations. Neonatal purpura fulminans is treated with replacement therapy with fresh frozen plasma or plasma-derived factor concentrate, if available, as well as symptomatic anticoagulant therapy. When laboratory investigation for heritable thrombophilia is pursued, it is essential that facilities are in place for the provision of informed and detailed advice based on a clear appreciation of the limitations of the laboratory tests and the major uncertainties regarding the clinical usefulness of the results obtained. There is little if any clinical value in testing for heritable thrombophilia if the appropriate mechanisms for tracing, careful informed counselling and testing of at risk relatives are not in place, as there is a risk of engendering confusion, misinformation, false reassurance and unnecessary anxiety. If you have any concerns, before embarking on investigation, please do consult with the Paediatric Haematologist SC(NHS)FT Page 6 of 6
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