Page 21 - Haematologica Vol. 107 - September 2022

REVIEW ARTICLE - ITP: diagnosis and second-line treatment J.B. Bussel and C.A. Garcia
of thyroid function and this finding may be more frequent in women with ITP. The question remains of whether these conditions should be tested for in all patients or only if there are suggestive findings. If the patient is fatigued that would necessarily instigate an evaluation of underlying causes that would include hypothyroidism. Fatigue and depression are relatively common but poorly understood in ITP,17 thus requiring comprehensive evaluation.
What if the immune thrombocytopenia is secondary to a subclinical viral infection?
Multiple viruses have been associated with ITP. In children, ITP is often thought to be a post-infectious sequela. There may also be an underlying viral disease which is asymp- tomatic and thus eludes detection. It remains unclear whether all patients with ITP should be screened for hepatitis C and human immunodeficiency virus; with the coronavirus pandemic, it might be appropriate to screen for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).18 Treatment of these three viral infections would alter ITP management. The primary treatment for both hepatitis C and human immunodeficiency virus would likely increase the platelet count. However, if hepa- titis C has progressed to cirrhosis, the platelet effects of antiviral treatment may be limited. Another viral infection that could be subclinical is cytomegalovirus which might be revealed only by atypical lymphocytes and/or mildly elevated liver tests. Cytomegalovirus can worsen ITP in patients receiving immunosuppressive treatments be- cause these agents will activate the cytomegalovirus and thus worsen the ITP making it more resistant to treatment.19,20 Helicobacter pylori may “cause” ITP, but only in certain places, e.g., Japan and Italy, is searching for it at diagnosis of ITP routine and is its eradication a uni- formly effective approach to ITP.21
What if the patient has an inherited thrombocytopenia?
Our patient’s bleeding resolved in parallel with the im- provement of her platelet count, which suggests that she does not have platelet dysfunction, as seen in Bernard- Soulier or Wiskott-Aldrich syndrome. Furthermore, she does not have any syndromic features consistent with an inherited thrombocytopenia. Review of her prior records revealed that she has had at least one prior normal pla- telet count.
The stability of her blood counts after initial treatment ex- cludes cyclic thrombocytopenia which is an often-for- gotten form of inherited thrombocytopenia.22 There are very many forms of inherited thrombocytopenia and new ones seem to be discovered regularly. Certain features should suggest an inherited thrombocytopenia:23,24 (i) other family members with thrombocytopenia; (ii) no past normal platelet count; (iii) too many too large platelets on a blood smear (not all inherited thrombocytopenias have
macrothrombocytes but most do); (iv) features of a syn- drome such as thrombocytopenia-absent radius syn- drome; (v) failure to respond to treatment for ITP, such as IVIG and steroids: (vi) bleeding out of proportion to the platelet count e.g., Bernard-Soulier syndrome, Wiskott-Al- drich syndrome, RUNX-1 mutations; and (vii) a relatively stable platelet count. In the absence of an apparent spe- cific syndrome, whole exome screening may be helpful, although this approach is effective in less than half of such cases.25 Ideally this possibility would be explored in conjunction with an experienced geneticist. The impor- tance of making a precise diagnosis is not limited to the management of the platelet count per se, but extends to the associated medical problems including a possible pro- pensity to autoimmune conditions, malignancy, or bone marrow aplasia.
What if the immune thrombocytopenia is secondary to other blood disorders?
While chronic lymphocytic leukemia and myelodysplastic syndrome would be very unlikely in our patient given her young age, other clinical conditions could be present, such as autoimmune lymphoproliferative syndrome and sys- temic lupus erythematosus. It has not yet been decided which tests should be performed to search for specific conditions, particularly if there are not specific symptoms or conditions suggesting a particular entity. We assay im- munoglobulin levels and do thyroid tests in our patients, as we certainly did in this young woman. Ideally in the fu- ture there would be an established panel of tests for pa- tients with putative ITP which would explore inherited thrombocytopenias, bone marrow failure, secondary ITP, other diagnoses that could resemble ITP such as myelo- dysplastic syndrome, markers of the future course of the ITP, the degree of bleeding, and to which treatments the patient would respond best.
What is the optimal second-line treatment for a young female with immune thrombocytopenia?
There are numerous options that can be considered in this non-pregnant premenopausal female (Table 1)
Rituximab
Rituximab and other (generic) anti-CD20 monoclonal anti- bodies exert immunosuppressive effects by depleting B lymphocytes. This occurs uniformly in the blood and bone marrow but what happens to B cells in lymph nodes is not well-defined. Women under the age of 40 years with a less than 2-year history of ITP usually respond to rituximab, with the response rate and especially the “cure” rate being high.26 If our patient and her hematologist opt for rituxi- mab, she would receive four infusions of 375 mg/m2 weekly for 4 weeks. If she has a good response, close monitoring may not be needed. While studies have not de-
Haematologica | 107 September 2022
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