Thrombocytopenia and immune thrombocytopenia: SAQ

This boy has the classic presentation of newly diagnosed immune thrombocytopenia. He is a well preschool child, one to two weeks after a viral illness, with sudden bruising and petechiae, an isolated thrombocytopenia, a normal haemoglobin and white cell count, large platelets and no blasts on the film, and no organomegaly. The diagnosis is made on these features, and the management rests on the ASH 2019 observation-first principle. [1][4]

Question 1 (10 marks)

Outline the diagnosis, the immediate management, and the safety-netting for this boy, justifying each step with the relevant evidence. [1]

A full-mark answer addresses the clinical diagnosis, the observation decision, the safety-netting, and the timing of the next review. [4]

Diagnosis and the diagnostic criteria (3 marks). This is immune thrombocytopenia, defined by the Rodeghiero standard as an isolated thrombocytopenia with a platelet count under 100 times ten to the nine per litre, in an otherwise well child, with a normal blood film showing large platelets and no blasts, and no hepatosplenomegaly or lymphadenopathy. The term immune has replaced the older idiopathic, and the term purpura has been dropped. The diagnosis is clinical and is made by exclusion, and a bone marrow aspirate is not indicated for this typical presentation, because the ASH 2019 guideline recommends against the routine marrow aspirate in the child with isolated thrombocytopenia and a normal film. The marrow is reserved for the atypical case with other cytopenias, blasts, or organomegaly. [1][4]

The observation decision (4 marks). The ASH 2019 guideline recommends, as a strong recommendation based on moderate-quality evidence, observation over treatment for the child with newly diagnosed ITP and no bleeding or only mild skin bleeding, regardless of the platelet count. This boy has mild skin-only bleeding, the bruising and the petechiae, and so he is managed by observation even though his platelet count is only 12 times ten to the nine per litre. The rationale is threefold: the bleeding risk in the child with no or mild bleeding is low, the treatments carry their own harms such as the IVIG infusion reactions and the corticosteroid side effects, and the natural history is toward remission in about 70 to 80 percent within six months. The platelet count is monitored, but it is not the trigger for treatment, because the bleeding severity drives the decision. [1]

Safety-netting and follow-up (3 marks). The family is given the written safety-net advice, because the observation is active, not passive. The family is taught that the bruising and the petechiae are expected, that the child should avoid the contact sports and the platelet-interfering medications such as the non-steroidal anti-inflammatories, and that any severe headache, persistent bleeding, or altered consciousness is an emergency that demands the immediate assessment, because it may signal the intracranial haemorrhage. The child is reviewed in the haematology clinic within a week to ten days, and the count is monitored until it rises. [1]

Question 2 (10 marks)

Explain how the management changes if the bleeding worsens, and critically appraise the first-line and second-line therapy and the trial evidence. [1]

A full-mark answer reproduces the first-line doses, the second-line strategy, and the trial evidence for each. [10]

First-line therapy (4 marks). If the bleeding worsens to the moderate or the severe grade, the boy moves from observation to first-line treatment. The ASH 2019 guideline offers three first-line agents. IVIG is given as a single dose of 0.8 to 1 g per kg, and it is chosen when a rapid rise in the platelet count is wanted, because it works within twenty-four to forty-eight hours. A short course of corticosteroids is given as oral prednisolone at 1 to 2 mg per kg per day for a short course that is then tapered and stopped, and it is chosen when the oral route and the cost favour it. Anti-D is given as 50 to 75 micrograms per kg for the Rh-D positive child with a negative direct antiglobulin test and an intact spleen, and the Blanchette trial of 1994, a randomised comparison of IVIG, anti-D, and oral prednisone, established these agents. The anti-D carries the risk of the clinically significant intravascular haemolysis, which has led to its withdrawal or restriction in several countries. [1]

Severe and life-threatening bleeding (2 marks). The severe bleed, such as the intracranial haemorrhage, demands the immediate combined administration of IVIG and high-dose corticosteroids together with a platelet transfusion, alongside the urgent imaging and the neurosurgical and critical-care referral. The aim is to raise the platelet count as fast as possible, because the IVIG works within twenty-four to forty-eight hours and the platelet transfusion provides a temporary bridge. The severe bleed is rare, with an incidence estimated below one percent, but it is the killer of ITP, and the fellow does not wait for the response to one agent before adding the others. [1]

Second-line therapy and the chronic phase (4 marks). If the thrombocytopenia persists beyond twelve months, the boy moves into the chronic phase, and about 20 to 25 percent of children reach this phase, per the ICIS twelve-month follow-up registry. The second-line therapy is led by the thrombopoietin-receptor agonists, which work by stimulating the megakaryocyte to produce more platelets, addressing the impaired-production half of the mechanism. Eltrombopag, the oral thrombopoietin-receptor agonist, was evaluated in the PETIT trial reported by Bussel in 2015, a randomised placebo-controlled study in children with persistent and chronic ITP, at a dose of 25 to 75 mg once daily for the six-and-over and 12.5 to 50 mg for the under-six, and it showed a durable platelet response. Rituximab, the anti-CD20 monoclonal antibody, is the second second-line option, and the splenectomy, once the second-line treatment of choice, is now rare, because the thrombopoietin-receptor agonists have taken over, and because the splenectomy carries the lifelong risk of the overwhelming post-splenectomy infection. [6][10]