Page 29 - Haematologica Vol. 107 - September 2022

REVIEW ARTICLE - ITP: diagnosis and second-line treatment J.B. Bussel and C.A. Garcia
production.61 While requiring confirmation, this hypoth- esis fits with both platelet counts falling and cases of ITP in pregnancy becoming progressively more difficult to treat with steroids and IVIG. Fortunately, there is rarely clinically significant bleeding in pregnant women with ITP unless the platelet counts become very low; one excep- tion may be subchorionic hematomas.
Tranexamic acid can be used after delivery to reduce blood loss in this period and thus reduce blood trans- fusion requirements. The risk of postpartum thrombosis seems very low, although pulmonary emboli have been reported in two cases.62
Steroids in pregnancy
The standard treatments for ITP during pregnancy are steroids and IVIG (Table 3) which are the most widely used and felt to be the safest. The prednis(ol)one rec- ommendation for ITP in pregnancy, because of the li- mited duration of anticipated treatment, is relatively low-dose prednisone (e.g., 10-20 mg daily) based on tar- geting a platelet threshold of 20-30x109/L. Prednis(ol)one often exacerbates physiological changes of pregnancy e.g., hyperglycemia, hypertension, and fluid retention; dexamethasone is to be avoided because of its fetal ef- fects. If this lower dose of prednisone is successful, it avoids the risks of long-term high-dose steroids for the mother. Little to no prednisone enters the fetus because of placental b-11-hydroxylase.63
WIntravenous immunoglobulin in pregnancy
IVIG is effective; however, it must be given often e.g., bi- weekly so steroids are the recommended treatment. One study suggests that both steroids and IVIG are slightly less effective in pregnant women.64 Overall, whether the efficacy of IVIG and prednis(ol)one in pregnancy is main- tained becomes more important later in pregnancy. Pa- tients who are difficult to treat require higher and higher doses of prednisone and more and more frequent IVIG dosing as pregnancy progresses.
The treatment of fetal and neonatal alloimmune throm- bocytopenia has provided safety information that may be extrapolated to ITP. ‘Aggressive intrapartum treatment’ exceeds that of the treatment of ITP by including IVIG 1- 2 g/kg/week and prednisone 0.5 mg/kg/day for many weeks. The apparent safety of these very high doses helps to assuage concerns regarding their use in ITP.65 Even with less severe ITP, preparing for safe delivery often involves intervention to undergo epidural anes- thesia, for which the platelet count is often “required” to be greater than 80x109/L. The requirements for spinal anesthesia may not be as strict and are more variable than they are for epidural anesthesia. Even in a patient who responds well to IVIG and prednis(ol)one combina- tion treatment, a platelet count of 80x109/L or higher is
often achieved for only 2-5 days. If these treatments are relied upon, scheduling elective delivery is crucial so that administration of IVIG can be timed to achieve its optimal effect. The patient could either undergo a Caesarian sec- tion or have her membranes ruptured so she enters labor at the desired time. An amniocentesis may be required to assess fetal lung maturity.
Rituximab in pregnancy
In one study of 231 pregnancies with maternal exposure to rituximab for treatment of autoimmune cytopenias and other autoimmune disease, few neonatal infections were seen among the exposed neonates.66 Hypogamma- globulinemia will not be present at birth if the mother does not herself have low IgG levels; however, it may manifest at 2 to 4 months of age if there is a persistent absence of infant B cells. Women are encouraged to avoid pregnancy for more than 4-6 months after rituxi- mab exposure to prevent transmission of the rituximab to the fetus.66 As shown in Figure 1, we believe that ri- tuximab can be used in patients who do not respond well to steroids and IVIG.
Intravenous anti-D, azathioprine, cyclosporine, and splenectomy in pregnancy
Eight patients were treated with IV anti-D (WinRho) with reasonable efficacy and fetal safety;67 no cases of neo- natal anemia or hyperbilirubinemia were seen. Azathio- prine has been extensively used in women who have undergone renal transplantation and become pregnant.68 The registry of these patients suggested that azathio- prine is relatively safe during pregnancy, but azathioprine takes 1-3 months to increase the platelet count. Infants of mothers taking azathioprine are noted to have an in- creased prematurity rate, lower birth weight, and intra- uterine growth restriction; no malformations were seen. Immune impairment was reported in some exposed in- fants.69 The effects of cyclosporine in pregnant women with ITP appear to be like those of azathioprine: reason- ably effective, slow in onset, and with limited fetal risk. Experience of cyclosporine use in pregnant women has also been gained in the post-transplantation setting.70 Mycophenolate is contraindicated in pregnancy.71 If sple- nectomy is required, it is recommended that it be per- formed in the second trimester because the risk to the fetus is less than in the first trimester and the size of the uterus will be less obstructive than in the third trimester. Experience consists of isolated case reports.
Thrombopoietin receptor agonists in pregnancy
A major recent development affecting ITP in pregnancy is the use of thrombopoietin agents. Three sets of evi- dence for the use of thrombopoietin agents in pregnancy exist beyond scattered case reports. One study used re-
Haematologica | 107 September 2022
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