Inherited bleeding and or platelet disorders


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Inclusion criteria

  • Diagnosis of a bleeding and/or platelet disorder* of unknown cause before the age of 50 and following haematological consultation, AND
  • family history or consanguineous parents,
  • OR syndromic features (incl. neurodevelopmental, immunological, nephrology, skeletal, hearing, etc.),
  • OR early onset severe childhood case of unknown cause
  • OR deficiency of coagulation factor without causal coding variants in the corresponding gene

*Platelet disorder is defined as one or more of the following:

  • Platelet count greater than 400x10e9/L or less than 100x10e9/L
  • Mean Platelet Volume (MPV) greater than 13 fL and /or macrothrombocytopenia, or MPV less than 7fL
  • Abnormal platelet morphology, ideally confirmed by high resolution microscopy
  • Abnormal platelet function test, replicated on an independent sample

Exclusion criteria

  1. Acquired bleeding and /or platelet disorders
  2. Cases with platelet counts greater than 400x10e9/L and age less than 30 must be tested and found to be negative for somatic mutations in JAK2 and CALR
  3. Use of prescription or over-the-counter drugs known to be associated with abnormal platelet (function) phenotypes and/or bleeding disorders, including:
    • anticoagulant medications
    • aspirin, clopidogrel, dipyridamole, etc.
    • nonsteroidal anti-inflammatory drugs (incl. COX-2 selective anti-inflammatory drugs)
  4. Patients with evidence of an autoimmune or other systemic condition known to affect haemostasis and platelet homeostasis, including
    • Autoimmune thrombocytopenia (ITP)
    • Other autoimmune disorders, e.g. SLE
  5. Other medical conditions known to be associated with abnormal platelet count and volume and / or abnormal platelet function
    • Acute viral infection
    • Bone marrow aplasia
    • DIC (Disseminated intravascular coagulation)
    • Hepatic failure
    • HIV positivity and/or AIDS
    • HUS (Haemolytic-uraemic syndrome)
    • Malignancies, particularly those compromising haematopoiesis
    • Splenomegaly
    • TTP (Thrombotic thrombocytopenia purpura)
    • Uraemia

Prior genetic testing guidance

– Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.

– Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Prior genetic testing genes

Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:

Closing statement

These requirements will be kept under continual review during the main programme and may be subject to change.

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