Page 30 - Haematologica Vol. 107 - September 2022

REVIEW ARTICLE - ITP: diagnosis and second-line treatment J.B. Bussel and C.A. Garcia
combinant human thrombopoietin (rhTPO, available in China) and evaluated 33 pregnancies in 31 women with ITP in pregnancy who did not respond to or relapsed after an initial response to prednisone.72 Seventy percent of the women responded to rhTPO with an increase in the maternal platelet count and no overt maternal toxicity. Importantly, the babies, followed until 1 year of age, did not have any identified side effects of rhTPO treatment. A follow-up compilation of ITP cases explored 13 preg- nancies in 12 women, including one who delivered a pair of twins, in whom a TPO-RA was used.73 Usage of TPO- RA was divided equally between eltrombopag and romi- plostim and both agents appeared effective and safe. Third, a safety surveillance program report of use of romiplostim in 186 women with ITP who received romi- plostim during pregnancy indicated that in over 50 preg- nancies with known pregnancy outcomes and in over 50 pregnancies with known birth outcomes, romiplostim appeared safe.74 There were 12 births with thrombo- cytopenia requiring treatment, consistent with the ma- ternal ITP; all were discharged home with eight having their thrombocytopenia resolved pre-discharge. Al- though limited by incomplete information, 75 women were exposed to romiplostim in the first trimester be- cause of having been treated with romiplostim at the time they became pregnant. From the over 150 preg- nancies for which any data were available, five infants had some kind of adverse finding: one had cytomega- lovirus infection, one had unilateral inguinal hernia, one had a single umbilical artery with no other findings re- ported, one child was normal at birth but at the age of 2 was identified as autistic and one infant, whose mother received only one dose of romiplostim in the third trimester, had trisomy 8.
In summary, according to three reports of the use of three different thrombopoietin agents in pregnancy, these drugs appear to be safe as a class with no informa- tion available for avatrombopag, very limited information for eltrombopag, and considerable safety but little effi- cacy information for romiplostim. While efficacy is likely to be preserved in the mother, it is not known whether transplacental passage of these agents increases the neonatal platelet count. Our conclusion is that a throm- bopoietin agent should only be used when the benefit outweighs the risk. However, if a thrombopoietin agent is considered in the third trimester, the available data strongly suggest that romiplostim is safe for the fetus (Figure 1, Table 2).
After scheduled vaginal delivery, our patient does well as does her baby. She breastfeeds but her newborn has persistent thrombocytopenia with platelet counts down to 30 x 109/L. She is prompted to stop breast feeding and, upon doing so, the infant’s platelet count rapidly in- creases to normal. The mother’s platelet count also re-
turn to its pre-pregnancy level and all treatment can be stopped.
Section III: Second-line treatment of immune thrombocytopenia in an older male patient
What if instead of a young woman in her early 20s, our patient is a 63-year-old male?
This patient is generally healthy but slightly overweight and had his gall bladder removed without incident 6 years ago. He has taken daily losartan, atorvastatin, and a baby aspirin for several years. Upon presentation with bruises, petechiae and profuse bleeding from his gums when he brushes his teeth, he is told to stop his aspirin. He is given dexameth- asone 40 mg/day for 4 days and a single dose of IVIG 1 g/m2/kg because of the aspirin. His platelet count increases dramatically within 2 days.
What diagnostic considerations are important here? First, as with the young woman, ITP must be distinguished from other thrombocytopenias; these are common in the elderly but different from those in a young woman. Autoimmune diseases such as systemic lupus erythematosus are much less likely, as are inherited thrombocytopenias. CVID is possible at any age but in addition to assaying serum im- munoglobulins, serum protein electrophoresis to look for monoclonal proteins is appropriate. Other congenital im- munodeficiency diseases are less likely, but lymphoprolif- erative diseases are more common. Chronic lymphocytic leukemia and non-Hodgkin lymphoma are both B-cell dis- eases associated with ITP. A blood smear may show too many small mature-looking lymphocytes; if T- and B-cell studies are performed, they would reveal too many B cells. Clonal hematopoiesis of indeterminate potential might occur but it is not clear what this condition would portend assuming the clonal cells do not reflect an overt malig- nancy. Preliminary information suggests that clonal T-cell populations may mediate refractoriness.75 Ultrasound and/or computed tomography scans to look for malignancy may be indicated.
An important cause of thrombocytopenia in elderly patients is myelodysplastic syndrome. A bone marrow examination is necessary to diagnose this condition. Typically, marrow will be hyperplastic, but marrow cells will be undergoing apoptosis and not producing mature blood cells and reveal dyspoiesis. Diagnostics have improved remarkably as has clinical discrimination of different subtypes of myelodys- plastic syndrome. Nonetheless. cases of myelodysplastic syndrome early in their evolution may be difficult to distin- guish from “difficult” ITP.76
Drug-induced thrombocytopenia is a possibility since older patients may be taking more medications. Limited labora- tory testing is available to demonstrate that thrombo-
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