Thrombocytopenia and immune thrombocytopenia: Viva

This is the classic presentation of newly diagnosed immune thrombocytopenia in a well preschool child. The structured oral runs from the diagnostic criteria through the observation decision, the first-line therapy if the bleeding worsened, the second-line strategy, and the trial evidence. [1][4]

Opening: make the diagnosis

Examiner. The platelet count is 12 times ten to the nine per litre. What is the diagnosis, and how do you confirm it? [4]

Candidate. This is immune thrombocytopenia, ITP, 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 diagnosis is clinical and is made by exclusion. The normal haemoglobin and white cell count, the large platelets and the absence of blasts on the film, the well child, and the absence of organomegaly all fit. A bone marrow aspirate is not indicated, because the ASH 2019 guideline recommends against the routine marrow aspirate in the typical presentation. [1][4]

Examiner (probe). What would make you doubt the diagnosis? [3]

Candidate. The features that exclude ITP are the other cytopenias, the anaemia or the neutropenia, the blast cells on the film, the hepatosplenomegaly or the significant lymphadenopathy, and the fever or the bone pain. Any of these points to the acute leukaemia or another infiltrative disorder, and I would order the bone marrow aspirate. The small platelets would point to the Wiskott-Aldrich syndrome, and the schistocytes would point to the haemolytic uraemic syndrome. [3]

Branch 1: observation or treatment

Examiner. The platelet count is only 12 times ten to the nine per litre. Do you treat? [1]

Candidate. I observe, not treat. The ASH 2019 guideline recommends, as a strong recommendation, 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 observed even though the count is 12 times ten to the nine per litre. The rationale is that the bleeding risk in the mild case is low, that the treatments carry their own harms, and that about 70 to 80 percent remit within six months. The platelet count is monitored, but it is the bleeding severity, not the count, that drives the decision to treat. [1]

Examiner (probe). What safety-netting do you give the family? [1]

Candidate. I give the written safety-net advice. 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 clinic within a week to ten days, and the count is monitored until it rises. [1]

Branch 2: first-line therapy

Examiner. The boy develops a severe epistaxis that does not stop. What do you give? [8]

Candidate. He has moved to the moderate bleed, and I start the first-line therapy. The ASH 2019 guideline offers three agents, and I choose IVIG at a single dose of 0.8 to 1 g per kg, because he needs a rapid rise in the platelet count and the IVIG works within twenty-four to forty-eight hours. The alternatives are a short course of oral prednisolone at 1 to 2 mg per kg per day, chosen when the oral route and the cost favour it, and the anti-D at 50 to 75 micrograms per kg, chosen only for the Rh-D positive child with a negative direct antiglobulin test and an intact spleen. The Blanchette trial of 1994, a randomised comparison of the three, established these first-line agents. [1][8]

Examiner (probe). Tell me about the anti-D. [8]

Candidate. The anti-D works by coating the Rh-D positive red cells, which are then cleared in the spleen alongside the antibody-coated platelets, so the platelet count rises because the competing red-cell clearance spares the platelets. It must not be given to the Rh-D negative child, the child with a positive direct antiglobulin test, or the child without a spleen, and it carries the risk of the clinically significant intravascular haemolysis, which has caused the severe anaemia and the acute kidney injury. This is why the anti-D has been withdrawn or restricted in several countries. [8]

Branch 3: severe bleeding

Examiner. A child with ITP develops a sudden severe headache and vomiting. What do you do? [1]

Candidate. This is the intracranial haemorrhage until proven otherwise, and it is the killer of ITP. I give the immediate combined IVIG and the high-dose corticosteroids together with the platelet transfusion, because the IVIG works within twenty-four to forty-eight hours and the platelet transfusion provides the temporary bridge. I do not wait for the response to one agent before adding the others. I arrange the urgent imaging, and I involve the neurosurgery and the critical care. The severe bleed is rare, with an incidence estimated below one percent, but it is the one presentation that demands the urgent combined therapy. [1]

Branch 4: the chronic phase and the second-line

Examiner. A year later the boy is still thrombocytopenic. What now? [10]

Candidate. He has reached the chronic phase, defined by persistence beyond twelve months, and about 20 to 25 percent of children reach this phase, per the ICIS twelve-month follow-up registry. I begin the second-line therapy, led by the thrombopoietin-receptor agonists. Eltrombopag, the oral thrombopoietin-receptor agonist, was evaluated in the PETIT trial of Bussel in 2015, a randomised placebo-controlled study in children with persistent and chronic ITP, and it showed a durable platelet response 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. It works by stimulating the megakaryocyte to produce more platelets, addressing the impaired-production half of the mechanism. Rituximab, the anti-CD20 monoclonal antibody, is the second option, and the splenectomy, once the second-line treatment of choice, is now rare. [10]

Examiner (probe). Why is the splenectomy now rare? [10]

Candidate. Two reasons. The thrombopoietin-receptor agonists have taken over the second-line space, because they are effective and they do not require the surgery. And the splenectomy carries the lifelong risk of the overwhelming post-splenectomy infection, which is the price of removing the organ. When a splenectomy is still considered, for the refractory case, the child is vaccinated against the pneumococcus, the meningococcus, and Haemophilus influenzae type b at least two weeks beforehand, and the lifelong penicillin prophylaxis is begun. [10]

Closing: the prognosis

Examiner. Sum up the outlook for this boy. [1]

Candidate. The outlook is overwhelmingly favourable. About 70 to 80 percent of children remit within six months, and the intracranial haemorrhage is rare, with an incidence estimated below one percent. With the observation-first principle, the first-line therapy for the bleeding child, the second-line thrombopoietin-receptor agonist for the chronic phase, and the safety-net advice, this boy can expect a childhood free of the catastrophic bleed, and the small minority who reach the chronic phase are supported by the multidisciplinary team. [1]