Immune Thrombocytopenic Purpura; A case of a child presenting with purpura and easy bruising

Case scenario ;

Master Z, A 5 years old previously healthy boy presented with purpura and a petechial rash mostly over the lower limbs which developed over 24 hours. There were no other bleeding manifestations like gum bleeding ,hematuria. He has had a sore throat a week ago. On examination he appeared well but with purpuric rash over the trunk and legs. There was no Pallor, lymphadenopathy or hepatosplenomegaly. Fundus examination was normal.

Full blood count showed reduced platelet counts ( 17 × 10*9/L) with normal hemoglobin and white cell counts. There were large platelets on the blood picture.

Before going in to the differentials of the above case, let’s first understand what is a purpura/ petechiae/ ecchymosis ?

Petechiae are small, usually non blanching, rounded red or purple spots that are approximately 1-2 mm in size. They are caused by intradermal capillary bleedings. Purpura are larger( but less than 1 cm), typically raised lesions resulting from bleeding within the skin. Ecchymosis is described as hemorrhagic spots that measure over 1 cm in size.

Differential diagnosis for Easy bruising

Low platelets is not the only cause for Easy bruising. Following table will show the causes and how to differentiate from one another.

Immune Thrombocytopenic Purpura ( ITP)

ITP is an acute immune-mediated condition of platelet destruction most commonly affecting young children. It is the most common cause of thrombocytopenia in childhood. The incidence is approximately 4/100,000 children per year. 80-85% remit spontaneously within a few months; 15-20% run a chronic course of >6 months duration.

Pathophysiology

It is usually caused by destruction of circulating platelets by antiplatelet IgG autoantibodies. The reduced platelet count may be accompanied by a compensatory increase of megakaryocytes in the bone marrow

Diagnosis

ITP is a diagnosis of exclusion, so careful attention must be paid to the history, clinical features, and blood film to ensure that another more sinister diagnosis is not missed.

History

Typically a child with newly diagnosed ITP:

Examination

Typical features:

Investigations

Full blood count– isolated thrombocytopenia (platelet count usually <20×10*9/L) with an increased mean platelet volume (MPV) and an otherwise normal red cell and white cell counts

Blood picture– large platelets

Other investigations,

Place of bone marrow biopsy ,

Usually not indicated, Unless there is high index of suspicion when either the clinical picture or FBC + film are atypical or particularly if steroid treatment is contemplated.

Atypical features in blood film are

Management

Management depends on the level of severity of ITP.

Grading of Disease Severity

Degree of severityIncidenceClinical picture
Mild77% of childrenFew petechiae and small (<5cm) bruises. Epistaxis, stopped by applied pressure within 20 minutes
Moderate20% of childrenNumerous petechiae and large (>5cm) bruises. Epistaxis longer than 20 minutes. Intermittent bleeding from gums, lips, buccal, oropharynx or gastrointestinal tract. Menorrhagia, hematemesis, hematuria, melena – without hypotension and falling Hb<20g/l
Severe3% of childrenEpistaxis requiring nasal packing or cautery. Continuous bleeding from gums, buccal, oropharynx. Suspected internal hemorrhage (lung, muscle, joint). Menorrhagia, hematemesis, hematuria, melena – leading to hypotension and falling Hb>20g/l
Life-threateningRare, 0.1%-0.9% of childrenIntracranial hemorrhage or continuous or high volume bleeding resulting in hypotension or prolonged capillary refill and requiring fluid resuscitation or blood transfusion


The goal of all treatment strategies is to achieve a platelet count that is associated with adequate hemostasis rather than a “normal” platelet count. Treatment can be divided into the following:


Mild to moderate disease

Careful Observation is the mainstay. Patient can be managed as inpatient or outpatient.

Parents and Children should be advised on,

  1. to exert caution regarding activities associated with trauma e.g. ski-ing, avoid any contact sport e.g. rugby, boxing. Helmets should be worn if cycling and if swimming, no diving is recommended in shallow end. It is sensible to avoid sports where there is a risk of head injury whilst the platelet count is below 50 x10*9/l
  2. to avoid the use of NSAIDs during disease course (no aspirin, ibuprofen/Nurofen/Calprofen). Parents can be reassured that paracetamol is safe to take
  3. Avoid herbal remedies that can increase the risk of bruising or bleeding
  4. Avoid intramuscular injections when platelets<100
  5. Alert dentist if due to have any dental procedure
  6. Monitor disease course with regular follow-up in outpatients

Severe disease

Child should be admitted. Attention to Airways, Breathing and Circulation as with any other emergency should be given.

Pharmacological treatment is the mainstay along with observation for life threatening bleeds. First line agents are Corticosteroids/ Intravenous immunoglobulin / anti D immunoglobulin.

In children with newly diagnosed ITP who have non-life-threatening mucosal bleeding and/or diminished health-related quality of life it is recommended Corticosteroids rather than intravenous immunoglobulin or anti-D immunoglobulin as first line.

For patients where corticosteroids are contra-indicated or otherwise not preferred, either intravenous immunoglobulin or anti-D immunoglobulin can be used.

Life threatening disease

Child should be admitted. Attention to Airways, Breathing and Circulation as with any other emergency should be given.

Platelet transfusion is the first line concurrently with intravenous immunoglobulin and IV methylprednisolone. Careful monitoring is required to prevent progression into intracranial hemorrhages.

Treatment modalities

Corticosteroids ( via oral route)

It is recommended short courses of steroid treatment ( 7 days or shorter) with prednisone (2 – 4 mg/kg/day; maximum, 120 mg daily, for 5-7 days) rather than a dose of 1-2mg/kg for 2 weeks, and then weaning off for non life threatening disease.

Methyl Prednisolone only to be administered in life threatening or severe hemorrhage, with IVIG. (Dose: 30mg/kg/day for 3 days p/o, followed by 20mg/kg/day for 4 days )

For patients receiving corticosteroids, the treating physician should ensure the patient is adequately monitored for potential side effects regardless of the duration or type of corticosteroid selected. Those include;

Hypertension, hyperglycemia, sleep and mood disturbances, gastric irritation or ulcer formation, glaucoma, myopathy and osteoporosis.

Intravenous Immunoglobulin (IVIg)

Used when a rapid increment of platelets is needed( in life threatening disease). Standard Dose: 1gram/kg per dose as a single dose by intravenous infusion. Repeat dose on Day 2 if no improvement. (The second dose may be omitted if symptoms have remitted and the platelet count is >20×10*9/L on the second day)

Ensure a full blood count is checked post treatment and at 1 week to document response.

When administering IVIg the physician should keep in mind of potential side effects,

Treatment with Blood Products

Platelet transfusions should only be used for life-threatening hemorrhages following consultation with a Consultant Pediatrician and/or Hematologist. Best practice suggests giving platelet transfusion – 1 complete unit(if child>15 kg) and re-check the count at 10 minutes post transfusion. Platelets are consumed extremely quickly in ITP; therefore, it is necessary to administer IV immunoglobulin concurrently.

Second line therapy

In children with ITP lasting ≥3 months who have non-life-threatening mucosal bleeding and/or diminished health-related quality of life and do not respond to first-line treatment, following options for second-line therapies presented in the order they should be pursued :

  1. Thrombopoietin receptor agonist (eltrombopag or romiplostim)
  2. Rituximab ( monoclonal antibody )
  3. Splenectomy

Follow up

Patients who are not admitted to the hospital should receive education and expedited follow-up with a hematologist within 24-72 hours

Patients receiving treatment, should have daily FBC for the first 2-3 days(usually still an inpatient) and thereafter at the direction of the Consultant (usually regular FBC until recovery of platelet count >50×10*9/L). They should be discharged when clinical symptoms have remitted, Hb levels are stable and platelet count is rising. FBC should be done at 1 week post treatment to check for response.

Upon discharge the parents should be advised to return urgently in the presence of any of the following:

In about 80% of children, the disease is acute, benign, and self-limiting, usually remitting spontaneously within 6 weeks to 8 weeks.

Chronic ITP

In 20% of children, the platelet count remains low 6 months after diagnosis; this is known as chronic ITP. In the majority of children, treatment is mainly supportive; drug treatment is only offered to children with chronic persistent bleeding that affects daily activities or impairs quality of life. Children with significant bleeding are rare and require specialist care. A variety of treatment modalities are available, including, Rituximab, Newer agents such as thrombopoietic growth factors(used in children with severe nonresponsive disease) or Splenectomy(mainly reserved for children who fail drug therapy as it significantly increases the risk of infection and patients require lifelong antibiotic prophylaxis).

If ITP in a child becomes chronic, regular screening for SLE should be performed, as the thrombocytopenia may predate the development of autoantibodies.

In Summary,

Immune Thrombocytopenic Purpura is one of the commonest causes of childhood thrombocytopenia. In spite of it’s impressive cutaneous manifestations and extremely low platelet count, the outlook is good and most will remit quickly without any intervention. However when treating a child with easy bruising, the sinister causes like leukemia and also child abuse should be kept in mind and need to be excluded first.

References