Page 20 - Haematologica Vol. 107 - September 2022

REVIEW ARTICLE - ITP: diagnosis and second-line treatment J.B. Bussel and C.A. Garcia
Section I. A young female patient with immune thrombocytopenia: second-line treatment options
The patient’s history
A 20-year-old female returns home from college. She notesheavierperiodsandeasybruising.Herinternistsees that she is pale and has visible petechiae on her arms. Complete blood counts show mild anemia (hemoglobin 10.2 g/dL) and thrombocytopenia with a platelet count of 5x109/L The internist sends her urgently to the emergency room concerned that she might possibly have leukemia. There is no hepatosplenomegaly or lymphadenopathy or other abnormal findings on physical examination.
Review of a peripheral blood smear reveals no blasts or abnormalities of other cell lines although her mean cor- puscular volume is low (72 fL) and several of her very few platelets are large. She is diagnosed with ITP and given prednisone 1 mg/kg. Over the next few days, she has typi- cal steroid-related side effects: feeling “a little crazy”, in- somnia and abdominal pain. Her bruises and petechiae disappear, and her period ends. Her hematologist pre- scribes oral iron supplements and changes her prednisone to dexamethasone 40 mg daily for 4 days. Her steroid-re- lated side effects worsen during the 4 days on dexameth- asone 40 mg; however, she soon feels better with no further petechiae, bruising, or menstrual bleeding noted. Her platelet count normalizes to 147x109/L and her hemo- globin improves to 11.2 g/dL. She begins checking her blood counts monthly. The improved complete blood count with a nearly normal mean corpuscular volume ex- cludes bone marrow failure, and also thalassemia trait or microangiopathic hemolytic anemia. Similarly, the normal hemoglobin and neutrophil count do not suggest Evans syndrome. Her platelet counts remain in the normal range and her hemoglobin improves to the normal range. At her next visit, her platelet count has decreased to 80x109/L. One month later, her platelet count is 28x109/L with con- tinued normal hemoglobin and infrequent small bruises. With her platelets trending downward, second-line treat- ment for her ITP is considered.
There is less urgency to consider secondary ITP or a missed diagnosis since she is doing well but at any change of management, it is good practice to re-evaluate. Below we consider some of the “what if” clinical scenarios for this young female.
What if the patient is persistently anemic despite iron supplementation?
If the mean corpuscular volume is low, consider workup for underlying thalassemia trait or iron deficiency with the latter being common in the setting of heavy menses. Iron replacement is not always straightforward; using oral re-
placement every other day may be equally effective as daily administration.7 Resorting to IV iron may be important es- pecially if oral replacement does not correct iron status and/or there are signs of a chronic inflammatory disease. If the mean corpuscular volume is high, bone marrow failure must be considered. There could also be pernicious anemia secondary to vitamin B12 deficiency or an autoimmune hemolytic anemia, such as Evans syndrome. Another possibility is microangiopathic anemia with thrombo- cytopenia, whether in the form of thrombotic thrombocyto- penic purpura or hemolytic uremic syndrome. In these cases, there would likely be increased reticulocytosis. While individually each of these conditions is rare, having one of many rare conditions would not be as surprising.
If heavy menstrual bleeding persists, a progesterone-based approach is superior to an estrogen-based approach in women with ITP as the former raises the platelet count.8 While estrogen-based therapies are more commonly used in general practice for heavy menstrual bleeding, they might worsen ITP.9 In contrast, progestational agents have pre- viously been tried as treatment in ITP with good effect. Pro- gesterone may be administered orally at a dose of 5-10 mg daily or medroxyprogresterone acetate (Depo-Provera) can be given intramuscularly once every 3 months but the latter may result in intermittent vaginal bleeding.
What if the immune thrombocytopenia is part of a larger spectrum of autoimmune disease?
Our patient’s immunoglobulins were normal, so she does not have common variable immunodeficiency (CVID) or IgA deficiency. Neither the diagnosis of CVID nor that of IgA deficiency requires a history of infections; in fact, there may be a history of autoimmunity, especially in a patient presenting with ITP, or allergy. Furthermore, the diagnosis of CVID is often not made until after the age of 30.10 The IgG level does not have to be very low in cases of CVID presenting as ITP, which may account for the lack of in- fectious history in many of these patients. In cases of CVID, and possibly systemic lupus erythematosus with ITP, there may have been an episode of ITP years before treated with steroids, with the patient having gone into remission for years without any medication (Charlotte Cunningham-Rundles, personal communication). Other immunodeficiency states are also associated with ITP, not all of which will include hypogammaglobulinemia.11
Given our patient’s age and gender, it would not be sur- prising if she was positive for antinuclear antibodies and was developing systemic lupus erythematosus. A study from France suggests that hydroxychloroquine may be considered in an ITP patient positive for antinuclear anti- bodies.12 Nor would it be surprising if her thyroid tests were abnormal, as thyroid disorders in young women with ITP are usually autoimmune.13-16 In a young woman, there is a relatively high rate (as high as 5-10%) of abnormalities
Haematologica | 107 September 2022
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