Immune Thrombocytopaenia (ITP)

Disclaimer

These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline. 

Read the full PCH Emergency Department disclaimer.

Aim 

To guide PCH medical staff with the assessment and management of immune thrombocytopenia (ITP). 

Definition1-3

ITP is an uncommon disorder, affecting 1- 3 in every 10,000 children. The platelet count is < 100 x 109/L, and may be as low as < 20 x 109/L. Children present with petechiae, purpura (bruising), and sometimes mucosal bleeding. Rarely there may be rectal bleeding or haematuria. The risk of intracranial haemorrhage (ICH) is < 1%. 

Risk

Failure to follow this guideline will potentially result in unnecessary investigations, incorrect management and follow-up of patients with ITP.

Background1-5

  • ITP is the most common cause of thrombocytopenia in childhood.
  • It is the result of immune mediated destruction of platelets, often precipitated by viral infections, and there are no other coagulation problems.
  • Children present between the ages of 2 - 10 years, with peak incidence in the preschool years. 
  • ITP can be divided into two clinical syndromes:
    • Acute ITP - 90% of children. These patients present acutely with spontaneous bruising, and the ITP resolves within weeks to months of diagnosis.
    • Chronic ITP - 10% of children. This lasts more than 6 months, and often beyond 12 months. The presentation may be more insidious.

ITP flowchart

Assessment

  • Well children presenting with petechiae and purpura; mucosal bleeding is uncommon.
  • The clinical assessment is aimed at excluding other causes of petechiae / purpura and thrombocytopenia e.g. malignancies.
  • The severity of the disease is determined by the clinical picture, not the platelet count, which may be < 20 x 109/L
  • Intracerebral haemorrhage is rare, but should be considered in any patient with ITP presenting with neurological symptoms or signs

History

  • Petechiae and purpura – type, severity, duration.
  • Mucosal bleeding - epistaxis, haematuria, rectal bleeding, severity and duration.
  • Previous haemostasis problems with procedures.
  • Systemic symptoms - especially any recent viral infections in the last 6 weeks.
  • ICH should be considered if there are CNS symptoms or signs such as lethargy, headache, vomiting, reduced level of consciousness
  • Possible systemic lupus erythematosus (SLE) - photosensitive rash, arthritis, myalgia, oral ulcers, hair loss, dry eyes or mouth, fatigue, weight loss, fever. Consider in older children,  high risk ethnic background (e.g. Aboriginal, Asian, African, Maori) 
  • Possible malignancy: chronic pain, fevers, weight loss, pallor
  • Recurrent infections: suggestive of immunodeficiency.
  • Recent live virus vaccination (e.g. MMR).
  • Medications: quinine, penicillin, digoxin, anti-epileptics, salicylates, heparin, warfarin.
  • Family history: SLE, thrombocytopenia or other haematological or immunological disorders.
  • Co-morbid conditions that may increase the risk of bleeding.
  • Lifestyle factors that may pose a risk for trauma and bleeding.

Examination

  • Usually a well looking child with normal observations
  • Bleeding signs: document location and size of purpura, areas of petechiae. Look for mucosal bleeding, check for retinal haemorrhages.
  • There should be NO pallor, lymphadenopathy or hepatosplenomegaly.  These findings are NOT consistent with ITP
  • No evidence of infection
  • Full, documented CNS examination
  • Dysmorphic features: suggestive of a congenital syndrome e.g. Fanconi Syndrome, Thrombocytopenic-Absent Radius (TAR) syndrome.

Investigations

  • Urinalysis: tranexamic acid is contraindicated  if patient has haematuria 
  • Full Blood Picture (FBP): shows thrombocytopenia (may be < 20 x 109/L), normal haemoglobin, normal white cell count, and normal blood film aside from large (left shifted-megakaryocytic) platelets and occasionally some atypical lymphocytes.
  • The blood film must be reviewed by a Laboratory Haematologist to confirm the film features are in keeping with the clinical diagnosis of ITP.
  • Urgent cerebral imaging should be considered in patients with CNS symptoms and signs
  • No INR, APTT or clotting tests are required unless significant haemorrhage or non-accidental injury (NAI) is suspected.
  • A bone marrow aspirate is rarely required, and is only considered when the diagnosis is uncertain and a haematological malignancy needs to be excluded.

Differential diagnoses

A broad differential diagnosis should be considered, especially for older children.
  • Systemic Lupus Erythematosus (e.g. SLE).
  • Haematological malignancies (e.g. leukaemia).
  • Aplastic anaemia.
  • Infections - viruses, meningococcal disease.
  • Drug induced thrombocytopenia.
  • Haemolytic uraemic syndrome.
  • Other coagulation disorders e.g. disseminated intravascular coagulation (DIC).

Management

  • ITP will spontaneously remit without any treatment within 6 months in most paediatric patients.
  • Treatment decisions should be based on bleeding rather than platelet count.
  • The table below has been used in trials of paediatric patients with ITP to guide therapy decisions.

Table 1: Severity scoring of bleeding in patients with IPT4,5

 Bleeding grade Bleeding risk Description Recommended treatment
 0  None  No new haemorrhage of any kind
 No treatment usually required
 1  Minor  Few petechiae (≤ 100 total) and / or ≤5 small bruises (≤3cm diameter), no mucosal bleeding
 No treatment usually required
 2  Mild  Many petechiae (>100 total) and / or large bruises (>3cm diameter)
 No treatment usually required
 3A  Low risk moderate  Blood crusting in nares, painless oral purpura, oral/palatal petechiae, buccal purpura along molars only, mild epistaxis ≤5 min
 No treatment usually required
 3B  High risk moderate  Epistaxis > 5min, haematuria, haematochezia, painful oral purpura, significant menorrhagia
 Treatment usually indicated
 4  Severe  Mucosal bleeding or suspected internal haemorrhage (brain, lung, muscle, joint etc.) that requires immediate medical attention or intervention 
 Treatment usually indicated
 5  Life threatening/fatal  Documented intracranial haemorrhage or life-threatening or fatal haemorrhage at any site 
 Treatment usually indicated

Management of patients with no to low / moderate risk of severe bleeding (Grade 0 to 3A)

These patients:
  • Have skin manifestations of ITP, or a history of mucosal bleeding which has stopped at the time of clinical assessment.
  • Can usually be managed conservatively without treatment, with outpatient follow-up.
  • May be considered for treatment in exceptional circumstances such as imminent overseas travel, adolescent with self-image issues, or a high risk of trauma

Management of patients with high-moderate risk (Grade 3B)

These patients:
  • have epistaxis >5mins, haematuria, rectal bleeding, painful oral purpura, or significant menorrhagia 
  • usually require treatment

Treatment

  • Does not influence the natural history of ITP but can acutely raise the platelet count. 
  • Should be decided by the General Paediatric Team
  • Options include:
    • Tranexamic acid: 25mg/kg (up to 1.5 g maximum) orally, three times daily for 3 to 5 days with medical review at day 5.4,6 
      • Oral tranexamic acid is available in 500mg tablets.  The tablets are scored and can be cut in half. For doses not in increments of 250mg, an aliquot can be performed by dispersing the tablets in 10-20mL of water and administering a portion of the resulting liquid.
      • If the tablets are unavailable, tranexamic acid injection can be diluted with water and given orally.
    • Prednisolone: 4mg/kg/day (max 200mg) orally in 2-4 divided doses for 4 days 4,7
  • Oral prednisolone is available in 1mg, 5mg and 25mg tablets as well as a 5mg/mL liquid.
and / or, 
    • Intravenous immunoglobulin (IVIg): See dose below. 
      • All requests for IVIg should be directed to the National Blood Authority (NBA).  Requests that do not meet the NBA criteria require an Individual Patient Application (IPA) to the CAHS Drug & Therapeutics Committee (DTC).

Management of severe bleeding

  • Severe bleeding needing immediate intervention includes:
    • Epistaxis for more than 1 hour
    • Profuse oral or rectal bleeding
    • Severe menorrhagia
    •  Any internal haemorrhage (including intracranial haemorrhage)
  • Discuss the management of these patients immediately with the on call General Paediatric Consultant and Paediatric Clinical Haematologist (and the General Surgical Team, Neurosurgical Team, ENT Surgical Team if required).
    • Manage Airway, Breathing, Circulation 
    • Establish IV access (large bore cannula if possible)
    • Obtain urgent Group and Hold +/- cross matched cells 
    • Consider blood transfusion to achieve homeostasis
    • Seek surgical assistance to manage bleeding 
    • Discuss treatment with on–call clinical haematologist 


In the presence of severe bleeding causing clinical instability, consider intravenous immunoglobulin (IVIg) 0.8g / kg as a single dose as it can raise the platelet count rapidly.

Platelet transfusions should only be given for intra-cranial haemorrhage or other life-threatening bleeding.

A short course of high dose intravenous methylprednisolone (15-30mg/kg/day, up to 1g maximum) may be given for intracranial haemorrhage after IVIg and platelets, with treatment titrated against the platelet count and with rapid tapering. Dose and frequency to be advised by a paediatric haematologist. 
Refer also to the methylprednisolone (WA Health only) monograph autoimmune / inflammatory disorders section for guidance.4,9

Consider tranexamic acid 10 mg/kg (up to1g maximum) intravenously as a single dose.4,6

Admission criteria

  • Severe bleeding, irrespective of the platelet count.
    • Epistaxis > 1 hou
    • Hematemesis
    • Haemoptysis
    • Intracranial haemorrhage (ICH)
  • If unsure after hours, discuss with the on-call Emergency Consultant; consider admission to the ED Short Stay Unit. 

Discharge criteria

Patients can be sent home from the Emergency Department when:
  • The diagnosis is definite and there is no active bleeding.
  • The child is well and the social situation is such that there is good parental supervision and safety in the home (with respect to the risk of trauma).
  • There is the opportunity to reassure and educate the parents in the Emergency Department.
  • There is appropriate follow up arranged with the general paediatric team within the next 1-2 weeks.

Referrals and follow-up

  • Patients discharged with ITP require review by a senior doctor (Registrar or Consultant) to reassure parents and discuss outpatient management.  If discharged from ED by a Registrar this should be discussed with the Consultant General Paediatrician on-call.
  • Refer to General Paediatrics Outpatients.
  • Referral to the Paediatric Haematology Outpatient clinic can be done by the general paediatric team if the diagnosis remains uncertain, the white cell count is abnormal, the blood film is atypical, there is failure to respond to treatment or platelets have not resolved in 6 months (Chronic ITP).
  • Rheumatology referral if history or examination suggestive of SLE.
  • The platelet count should be monitored no more frequently than weekly.

Additional considerations:

  • Avoid IM immunisations until resolution, although in chronic cases this may need to be on a risk-benefit assessment.
  • Stop / do not prescribe non-steroidal anti-inflammatory drugs (NSAIDs). 
  • Avoid contact sports until resolution.

Rural Patients

  • Discuss the diagnosis and management with the nearest local Paediatrician.
  • If unavailable, discuss with the on-call general paediatrician at PCH.
  • Most patients can be managed locally, without the need to transfer to PCH.
  • See the links below for the GP letter and Health Fact Sheet for parents.

Health information (for carers)

  • The patient should avoid trauma – specifically no bicycles or trampolines.
  • The patient should not take any non-steroidal anti-inflammatory medications e.g. ibuprofen.
  • Provide ITP Health Fact Sheet.

Management paperwork

  • Referral done to the General Paediatric Team Outpatient Clinic.
  • The ITP GP Letter should be printed out and faxed / posted to the GP.
  • The ITP Health Fact Sheet should be given to the family.
  • A FBP request form should be given to the family to arrange prior to their outpatient appointment (should be done within 2 weeks of the appointment).

References

  1. Cole C. Rapid update on childhood immune thrombocytopenic purpure. J Paediatrics & Child Health. 2012;48 pp378-9
  2. Provan D SR, Newland A C, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2) pp168-86
  3. Schoettler ML, Graham D, Tao W, Stack M, Shu E, Kerr L, et al. Increasing observation rates in low-risk pediatric immune thrombocytopenia using a standardized clinical assessment and management plan (SCAMP(R)). Pediatric blood & cancer. 2017;64(5).
  4. Children’s Health Queensland Hospital and Health Service. Newly Diagnosed Immune Thrombocytopenia (ND-ITP) in Children. Clinical Guideline.  June 2019.
  5. Grainger J D. Suspected or known Immune Thrombocytopenia Management Plan (Children). Central Manchester University Hospitals, NHS Foundation Trust. 2015. http://www.uk-itp.org/docs/ITP/suspected_or_known_immune_thrombocytopenia_management_plan__children_.pdf
  6. Australian Medicines Handbook, Children’s Dosing Companion. Tranexamic Acid. Last updated July 2019.
  7. Cooper N. A review of the management of childhood immune thrombocytopenia: how can we provide an evidence-based approach? British Journal of Haematology. 2014;165(6):756-67
  8. Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Jr., Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-207
  9. Beck CE, Nathan PC, Parkin PC, Blanchette VS, Macarthur C. Corticosteroids versus intravenous immune globulin for the treatment of acute immune thrombocytopenic purpura in children: a systematic review and meta-analysis of randomized controlled trials. J Pediatr. 2005 Oct;147(4):521-7. PubMed PMID: 16227040. Epub 2005/10/18. Eng .


Endorsed by:  Director, Emergency Department   Date:  Dec 2019


 Review date:   Dec 2022


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