Haematology: ITP Flashcards
Describe the presentation of ITP in children [+]
Cutaneous rash
* ITP most frequently manifests as the sudden appearance of a petechial rash (small, purpuric lesions up to 2mm diameter), however larger purpura or bruising can also be present
* This cutaneous rash is present in approximately 86% of children with diagnosed ITP
* In greater than 50% of children with ITP, a cutaneous rash is the only clinical symptom
Mucocutaneous bleeding
* Bleeding from mucosal surfaces occurs in approximately 40% of children with ITP
* The location of the bleeding can vary:
* Epistaxis (20%)
* Oral bleeding, for example buccal and gingival surfaces (20%)
* Very infrequently, bleeding can occur from the gastrointestinal, menstrual or urinary tract (< 5%)
Severe haemorrhage
* A very rare clinical symptom of ITP is severe haemorrhage (< 3%)
* Intracranial haemorrhage (< 1%) may present with signs and symptoms such as:
* Headache
* Persistent vomiting
* Altered mental state e.g. confusion, drowsiness
* Seizures
NB: TOM TIP: Petechiae are pin-prick spots (around 1mm) of bleeding under the skin. Purpura are larger (3 – 10mm) spots of bleeding under the skin. When a large area of blood is collected (more than 10 mm), this is called ecchymoses. These are all non-blanching lesions.
Describe the pathophysiology of ITP [3]
ITP is caused by a type II hypersensitivity reaction. It is caused by the production of antibodies that target and destroy platelets. This can happen spontaneously, or it can be triggered by something, such as a viral infection.
TOM TIP: ITP is worth remembering as it is a key differential diagnosis of a [1]
TOM TIP: ITP is worth remembering as it is a key differential diagnosis of a non-blanching rash.
Ix for ITP? [3]
Full blood count
- Platelets: An isolated thrombocytopenia with a platelet count of < 100x109/L is usually the only blood abnormality
- White blood cells - Should be within normal limits
Haemoglobin - Usually within normal limits
Peripheral blood smear:
- Platelets will appear reduced in number
Red and white blood cells will be of normal count and morphology
Bone marrow biopsy
- BMJ recommend performing this test only if there is an atypical blood film. Should appear normal
As stated prior, in ITP, there should be an isolated thrombocytopenia.
What would the following suggest as a ddx? [4]
Premature white cells e.g. blasts
Predominant giant platelets, or very small platelets
Reticulocytosis
Schistocytosis
Premature white cells e.g. blasts (consider possible lymphoma or leukaemia)
Predominant giant platelets, or very small platelets (consider inherited thrombocytopaenia syndromes)
Reticulocytosis (consider haemolytic anaemia)
Schistocytosis (consider microangiopathic haemolytic anaemia)
What are they key ddx for ITP? [5]
Henoch Schonlein purpura
Haematological malignancy
Meningococcal disease
Disseminated intravascular coagulation (DIC)
Congenital thrombocytopenic syndromes
How would you differentiate ITP to HSP? [3]
Similarities
* Both can have petechiae
* Both more common in children than adults
* Both tend to have a viral prodrome
Differences
* HSP tends to be characterised by palpable purpura
* Arthritis/arthralgia present
* Rash tends to be present in lower limbs and buttock area
How would you differentiate ITP to haem. malignancy ? [2]
In malignancy, patients may have concurrent signs of concern including enlarged lymph nodes, splenomegaly, bone pain, joint pain and/or unexpected weight loss
Bloods may show abnormalities such as neutropenia, atypical or immature cells, marked anaemia and/or leukocytosis
How would you differentiate ITP to meningococcal disease
? [2]
ITP - children are normally otherwise well unlike meningococcal.
Differences
* Children will be unwell (e.g. irritability, lethargy)
* Usually will have abnormal vital signs (e.g. tachycardia, tachypnoea, widened pulse pressure, febrile)
* Bloods may show raised white cell count and CRP
How would you differentiate ITP to DIC ? [3]
Usually patients are very unwell
Can present with sepsis (e.g. hypotension, tachypnoea, fever)
Bloods may show elevated prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer
The management of ITP is different in children compared to adults.
How is it managed? non severe [+]
Conservative management
* ITP in children will resolve spontaneously within 3 weeks in 30-70% of children, according to BMJ
Active management
- This is restricted to children with major bleeding symptoms (e.g. ongoing epistaxis, mucosal bleeding) or a severely low platelet count
- Prednisolone 1-2mg/kg/day orally, with tapering as soon as symptoms begin to clear
- IVIg and anti-D immunoglobulin - - Reserved for if corticosteroids are contraindicated or ineffective
- chronic ITP: medications such as mycophenolate, rituximab and thrombopoietin receptor agonists can be considered (with specialist input)
Tx for severe life-threatening ITP ? [+]
The first line management is with: IVIg, corticosteroids, plus platelet transfusions
- IVIg 1g/kg intravenously as a single dose
- Prednisolone 1-2mg/kg/day orally
- Alternatively, UptoDate suggest methylprednisolone 30 mg/kg per day (up to 1 g) intravenously for 3-4 days
Platelet transfusions
- UptoDate recommend platelet transfusions of a bolus dose of 10-30 mL/kg, then followed by a continuous infusion
- The role of these platelet transfusions is to ensure that the child maintains a haemostatic platelet count and to guide further treatment
Describe the chronic complications of ITP [3]
Severe bleeding
Those at higher risk of severe bleeding include:
* Those with platelet count < 10,000/microL
* Traumatic event, e.g. head injury, falls
* Concurrent use of blood thinning medications e.g. aspirin, NSAIDs, warfarin, heparin (rare in children)
Intracranial haemorrhage
Chronic ITP
- Chronic ITP is defined as ITP which persists for >12 months since presentation
The types of leukaemia that affect children from most to least common are:
Acute lymphoblastic leukaemia (ALL) is the most common in children
Acute myeloid leukaemia (AML) is the next most common
Chronic myeloid leukaemia (CML) is rare
ALL peaks aged [] – [] years
AML peaks aged under [] years
ALL peaks aged 2 – 3 years
AML peaks aged under 2 years
There are several conditions that predispose to a higher risk of developing leukaemia.
What are they? [4]
Down’s syndrome
Kleinfelter syndrome
Noonan syndrome
Fanconi’s anaemia
Describe the pathophysiology of G6PD deficiency [2]
G6PD deficiency is a condition where there is a defect in the G6PD enzyme normally found in all cells in the body.
- It is inherited in an X linked recessive pattern, meaning it usually affects males, as they have only a single copy of the gene on their single X chromosome. It causes crises that are triggered by infections, medications or fava beans (broad beans).
- The G6PD enzyme is responsible for helping protect cells from damage by reactive oxygen species (ROS)
- A deficiency in G6PD makes cells more vulnerable to ROS, leading to haemolysis in red blood cells. Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia.
G6PD defiency:
- TOM TIP The key piece of knowledge for G6PD deficiency relates to triggers. In your exam look out for a patient that becomes [2] after eating [1], developing an [1] or being treated with [1] medications.
TOM TIP The key piece of knowledge for G6PD deficiency relates to triggers. In your exam look out for a patient that becomes jaundice and anaemic after eating broad beans, developing an infection or being treated with antimalarial medications. The underlying diagnosis might be G6PD deficiency.
Describe the presentation of G6PD deficiency [+]
Dx? [1]
G6PD often presents with neonatal jaundice.
Other features of the condition are:
* Anaemia
* Intermittent jaundice, particularly in response to triggers
* Gallstones
* Splenomegaly
* Heinz bodies may be seen on a on blood film. Heinz bodies are blobs of denatured haemoglobin (“inclusions”) seen within the red blood cells.
Diagnosis can be made by doing a G6PD enzyme assay.
Describe the pathophysiology of Langerhans cell histiocytosis [2]
Langerhans cell histiocytosis (LCH) is a rare idiopathic infiltrative condition characterised by the excessive proliferation of Langerhans cells of bone marrow and their subsequent deposition in organs.
- Langerhans cells are myeloid dendritic cells.
Describe the clinical features of Langerhans cell histiocytosis [+]
Bone (75%):
- Most commonly a solitary lytic lesion of the cranial vault found incidentally
- Long bones are the second most common location which often presents as pain or a pathological fracture - femur in children, ribs in adults
Skin (40%).
* Can present as vesicles and bullae (most common in infancy) or as dermatitis, nodules or petechiae
Lymph nodes (20%).
* Cervical lymphadenopathy.
Liver/Spleen (15%).
* Jaundice in liver involvement.
* Cystic lesions.
* Organomegaly (NB denotes worse prognosis).
Lung (10%).
* Pneumothorax.
* Cysts and cavitating nodules.
Central nervous system (5%).
* Diabetes insipidus - 5 times more likely to develop in multi-system disease. Higher risk if solitary bone lesion present within skull.
Ix for Langerhans cell histiocytosis? [3]
Plain film radiographs are an appropriate initial imaging request.
- If a lytic lesion is found on a skeletal radiograph it may be appropriate to request a full skeletal surgery and chest radiograph.
- Likewise if a pulmonary nodule is discovered on a chest radiograph it may be appropriate to request a skeletal survey.
- High resolution CT scan is of benefit when pulmonary involvement is suspected and will show interstitial infiltrate in the mid and lower zones with costophrenic angle sparing. Mature disease may present with a honeycomb appearance in the same distribution.
FBC:
- Typical finding are anaemia and hypercalcaemia (due to skeletal involvement)
- Deranged liver enzymes, direct hyperbilirubinemia and hypoalbuminaemia may be evident if there is hepatic involvement.
Biopsy
- is the gold standard investigation for diagnosis of Langerhans cell histiocytosis (LCH) with bone or skin biopsy preferred.
- Langerhans cells have distinctive morphological features however to be diagnostic they must be identified via immunohistochemical staining of CD1a or CD207 surface receptors.
- Alternatively, identification of ‘Birbeck granules’ by electron microscopy enables LCH to be differentiated from other proliferative disorders. However his method is less cost-effective and more time consuming than staining.
Describe the tx for LCH for:
* Bone disease [2]
* Skin disease [2]
* LNs [3]
* Multisystem [43232233wq]
Bone:
* Surgical curettage the mainstay of treatment for a solitary lesion.
* Radiotherapy, bisphosphonates and chemotherapy can be considered if the site of the solitary lesion is inaccesable or multiple lesions are present.
Skin:
* Topical steroids.
* PUVA therapy.
Lymph nodes:
* Surgical excision of a single node.
* Systemic steroids for multiple nodes.
* Chemotherapy for nodes resistant to treatment.
Multi-system disease:
* A combination of cytotoxic medications and systemic steroids are used in multi-system disease and refractory single organ disease.
* Children: prednisolone and vinblastine with 6-mercaptopurine added after the first six weeks for a total duration of 6-12 months.
* Adults: cladribine or cytarabine is recommended for 6-12 months.
