Idiopathic thrombocytopenic purpura medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

Mechanism Based Approach to Treatment

• Inhibit phagocyte-mediated clearance of antibody-coated platelets; Steroids; Splenectomy; Anti-D; IV-IgG
• Decreased autoantibody production; Rituximab , Steroids; Azathioprine & other immunosuppressants (eg cytoxan, cyclosporine, etc).
• Impair T & B cell interactions; Steroids; Rituximab
• Enhance platelet production; Thrombopoietic agents; IL-11.

Observation

Most children with ITP will recover even without specific treatment. Among adults ITP is typically a chronic disease. It is insidious in onset and, in some patients, refractory to treatment. 90% of childhood ITP cases are an acute, self-limited disease, developing several weeks after a viral illness, lasting for 4-6 weeks, then spontaneously remitting. The bleeding risk is low and treatment is reserved only for the most severely affected patients. Because spontaneous recovery is expected in children wit ITP some pediatric hematologists recommend supportive care only, no drugs. In less than 20% of children thrombocytopenia may persist for >6-12 months and even many of these kids can experience a spontaneous remission.

Steroids/IVIgG

Platelet count below 20,000 is an indication for treatment; the patients with 20,000-50,000 platelets/μL are considered on a case by case basis, and there is generally no need to treat the patients with above 50,000 platelets/μL. Hospitalization is recommended in the cases of significant internal or mucocutaneous bleeding. The treatment begins with intravenous steroids (methylprednisolone or prednisone), intravenous immunoglobulin (IVIg) or their combination and sometimes platelet infusions in order to raise the count quickly. After the platelet count stabilized and in the less severe cases oral prednisone (1-2 mg/kg) is used. Most cases respond during the first week of treatment (RR ~70%). After several weeks of prednisone therapy, the dose is gradually reduced. However, 60-90% of patients relapse after the dose decreased below 0.25 mg/kg and stopped. Pulsed high-dose dexamethasone shows (in untreated patients) a high RR of ~90% with a long-term RR of ~80% when several cycles of treatment are given. However long term high dose steroids have a myriad of toxicities and should be avoided if possible.

Anti-D

A relatively new strategy is treatment with anti-D, an agent also used in mothers who have been sensitized to rhesus antigen by a Rh+ baby, but the patient must be Rh+. IV anti-D (WinRhoSD) can also increase the platelet count especially at a higher dose of 75 mcg / kg. IV anti-D is effective in patients who are Rh-positive and non-splenectomized with a RR equal to 70%. Its toxicities include mild hemolysis, fever, chills, headache, nausea and vomiting.

Steroid Sparing Agents

Immunosuppresants like mycophenolate mofetil and azathioprine are becoming more popular for their effectiveness. Rituximab has also been used successfully for some patients. Rituximab is used in refractory ITP with success; circulating B-cells become undetectable after a single dose of Rituximab but recover after 3-6 months. Rituximab can be detected in the serum of patients 3-6 months after treatment. The duration of Rituximab correlates with the stability of the platelet response. However, although the short-term CR = 46% the long-term CR is only 18%. The typical schedule is 375 mg / m2 qwk x4 wks. Rituximab (375 mg / m2 d7, 14, 21, 28) / Dexamethasone was compared to Dexamethasone alone (40 mg QD, d1 through 4, given in monthly cycles. Initial and sustained response rates were better with the combination therapy (reference; Zaja R et al ASH 2008).

Extreme cases (very rare, especially rare in children) may require vincristine, a chemotherapy agent, to stop the immune system from destroying platelets. For the most part this and other agents such as cytoxan, cyclosporine and danazol have fallen into disuse.

Intravenous immunoglobulin, while sometimes effective, is expensive and the improvement is temporary (generally lasting less than a month). However, in the case of a pre-splenectomy ITP patient with dangerously low platelet counts, and a poor response to other treatments, IVIgG treatment can increase platelet counts, making the splenectomy operation less dangerous. It is also commonly used as a long-term (though monthly) treatment. The administration of IV-IgG is safe for maternal and fetal platelet counts during pregnancy, delivery and in the neonatal period. IV-IgG is administered at 400-1000 mg/kg/day over 1 to 5 days and gives a better RR than prednisone. The duration of action is only 2 to 4 weeks. Its toxicities are nausea, headache, chills and occasional vascular events (eg MI, CVA) in older patients. The possible mechanism of action is a transient impairment of the reticuloendothelial clearance or macrophage blockade, inhibition of complement binding to platelets and interference of immune complexes binding to platelets. IV-IgG and WinRho essentially are the same type of treatment.

Platelet Transfusion

Platelet transfusion is not normally recommended and is usually unsuccessful in raising a patient's platelet count. This is because the underlying autoimmune mechanism that destroyed the patient's platelets to begin with will also destroy donor platelets. An exception to this rule is when a patient is bleeding profusely, when transfusion of platelets can quickly form a platelet plug to stop bleeding, a life-threatening hemorrhage. Intravenous immunoglobulin administration, with the platelet transfusion, may improve their survival.

The ITP in AIDS has a thrombocytopenia that is multifactorial involving both TPO and platelet problems. Mechanisms may involve portal hypertension that leads to splenomegaly causing platelet sequestration. Hepatits C (HCV) causes decreased TPO production leading to decreased platelet production. Steroids may be helpful but, with their taper, the count usually decreases again. Intravenous immunoglobulin's effect is transient. For ITP-HIV the primary treatment should be directed at HIV suppression with HAART. HIV patients whose platelet count fails to increase to > 50,000 with HAART can be treated with steroids.

Pregnant patients with ITP and platelet counts < 30,000 can be treated with intravenous immunoglobulin (IV-IgG) or steroids at the lowest dose possible to avoid hypertension, eclampsia and adrenal suppression of the fetus. ~10-30% of pregnant females with ITP have an infant with platelets <50,000, however, intracranial hemorrhage is rare. For these females administer prednisone during the last month of pregnancy to decrease the likelihood of thrombocytopenia in the fetus. Mothers with ITP who have previously given birth to infants without thrombocytopenia tend not to be thrombocytopenic. The maternal platelet count doesn't correlate with fetal and females with a prior history of ITP with ITP in remission (eg after splenectomy) may still deliver severely thrombocytopenic infants. This likely occurs because asplenic patients in clinical remission may not necessarily be in immunologic remission and circulating platelet-reactive IgG may still be present in their plasma.

Contraindicated medications

Idiopathic thrombocytopenic purpura is considered an absolute contraindication to the use of the following medications:

• Triamcinolone
• Sulfamethoxazole/Trimethoprim