Idiopathic thrombocytopenic purpura (ITP)

ITP is an immune-mediated disease in which autoantibodies are formed against platelets.

The autoantibodies are most often directed against glycoprotein IIb/IIIa on platelet membrane.

These antibodies sensitize the platelets, resulting in their premature removal from the circulation by
reticulo-endothelial system cells.

ITP can either occur in isolation or sometimes it may be associated with an underlying immune
dysregulation caused by conditions such as connective tissue diseases, HIV infection, B-cell malignancies,
pregnancy and certain drug therapies.

However, whatever is the cause of ITP, the clinical presentation and pathogenesis are similar.

Clinical features

In children it usually occurs acutely & occurs 2 weeks after infection. In them, it is with sudden self-
limiting purpura.

In adults, ITP more commonly affects females and may have an insidious onset.

Moreover, in adults the disease runs usually a chronic remitting and relapsing course.

Unlike ITP in children, where there is a preceding history of viral infection, in adults, there is usually no
viral infection before the development of ITP.

The presentation of ITP depends on the degree of thrombocytopenia.

Many cases with counts of more than 50×109 /L are discovered by chance on investigations done for
some other reason like annual health checkup for example.

Spontaneous mucosal bleeding typically occurs only when the platelet count is below 20 × 109 /L.

At higher counts than this, the patient may complain of easy bruising, sometimes epistaxis, or a female
patient may present with menorrhagia.

Symptoms or signs of a connective tissue disease may be apparent at presentation or emerge several
years later.

There is no splenomegaly in ITP.

Investigations:

CBC will show thrombocytopenia.

The peripheral blood film is normal, apart from a greatly reduced platelet number.

Antiplatelet autoantibodies, if tested, are often present.

Bone marrow biopsy: The bone marrow biopsy is usually not necessary for the diagnosis but if done, it
reveals an obvious increase in megakaryocytes.
Patients aged over 65 years should, however, be considered for a bone marrow examination to look for
an accompanying B-cell malignancy

Appropriate autoantibody testing performed if a diagnosis of connective tissue disease is likely.

HIV testing should be considered because a positive result will have major implications for appropriate
therapy.

Management

Many patients with stable compensated ITP and a platelet count of more than 30×109 /L do not require
treatment to raise the platelet count, except at times of increased bleeding risk, such as surgery and
biopsy.

Glucocorticoids: For patients with spontaneous bleeding or if platelets <20 x 109/L, first-line therapy is
with high doses of glucocorticoids, either prednisolone (1 mg/kg daily) or dexamethasone (40 mg daily
for 4 days).

Pulsed Methylprednisolone may also be used in severe cases.

This suppresses antibody production and inhibit phagocytosis of sensitised platelets by reticulo-
endothelial cells.

Aim is to keep platelets > 30 x 109/L.

Reduce the dose of steroids after remission.

IVIG: Intravenous immunoglobulin raise the platelet count by blocking antibody receptors on reticulo-
endothelial cells and thus raise platelet count by inhibiting their clearance by the reticuloendothelial
cells.

IVIG is combined with glucocorticoid therapy if there is evidence of significant mucosal bleeding or if
there is a slow response to glucocorticoids alone.

Platelet transfusions are not used except during life threatening hemorrhage or during splenectomy,
because they are quickly destroyed by autoantibodies.

As mentioned before, ITP may become chronic in adults, with remissions and relapses.

Relapses should be treated by re-introducing glucocorticoids.

Second Line Therapies:

Indications: If a patient has two relapses or primary refractory disease, second-line therapies are
considered.

The options for second-line therapy include immunosuppression, splenectomy and thrombopoietin
receptor agonists (TPO-RA).

The order in which therapies should be used is not entirely clear.

Low-dose glucocorticoid therapy, and immunosuppressants such as rituximab, ciclosporin,

mycophenolate and tacrolimus may produce remissions and reduce relapses.
Splenectomy produces complete remission in about 70% of patients. Improvement in the disease also
occurs in 20–25% favourable cases.

Where splenectomy is considered, the precautions need to be in place. We will come to these
precautions in a while.

Next are the thrombopoietin receptor agonists. These are reserved for refractory cases of ITP. These
include Eltrombopag which is an oral thrombopoietin-receptor agonist and Romiplostim – which is an
injectable thrombopoietin analogue. They induce response in around 75% of cases, usually within 10–14
days.

Now coming n to precautions which need to be in place for patients undergoing splenectomy. One by
one these are:

 Vaccinate with pneumococcal, Haemophilus influenzae type B, meningococcal group C

and influenza vaccines at least 2–3 weeks before elective splenectomy. Vaccination
should be given after emergency surgery but may be less effective
 Pneumococcal re-immunisation should be given at least 5-yearly and influenza annually.
Vaccination status must be documented
 Life-long prophylactic penicillin V (500 mg twice daily) is recommended. In penicillin-
allergic patients, consider a macrolide
 Patients should be educated regarding the risks of infection and methods of prophylaxis
 A card or bracelet should be carried to alert health professionals to the risk of
overwhelming sepsis
 In sepsis, patients should be resuscitated and given IV antibiotics to cover
pneumococcus, Haemophilus and meningococcus, according to local resistance patterns
 The risk of cerebral malaria is increased in the event of infection
 Animal bites should be promptly treated with local disinfection and antibiotics, to
prevent serious soft tissue infection and sepsis