Safety and efficacy of danazol in immune thrombocytopenia: a systematic review.

Background: The treatment landscape for relapsed or refractory immune thrombocytopenia (ITP) after corticosteroids is complex. Objectives: We aimed to assess the efficacy of danazol in treating ITP and evaluate the safety and adverse events following its administration. Methods: We searched the databases PubMed, EMBASE, and ClinicalTrials.gov for all published studies assessing danazol's efficacy and safety in treating ITP. The retrieved studies were screened by title and abstract, followed by full-text screening based on the eligibility requirements. The quality assessment was performed using a set of questionnaires. The data were extracted on the descriptive characteristics of the studies and participants, drug dosage, efficacy measures, and adverse effects, and the data were synthesized. Results: A total of 17 studies consisting of 901 participants were included. The overall response rate is around 61% in this analysis. Among the participants, 315 (34.9%) were men. The age of participants ranged from 16 to 86 years. Danazol combined with other pharmacologic interventions, including all-trans-retinoic acid or glucocorticoids, generated better results. The most common side effects appear to be liver injury and elevation of liver enzymes, weight gain, oligomenorrhea, amenorrhea, and myalgia. Conclusion: Danazol at low-to-medium doses was well tolerated and succeeded in improving ITP. Danazol therapy may be helpful in the treatment of chronic ITP that is corticosteroid refractory and when corticosteroids or splenectomy (or both) is contraindicated. Danazol can be considered for further research and development in treating primary immune thrombocytopenia.

Red blood cell distribution width is a useful biomarker to predict bleeding and thrombosis risks in patients with immune thrombocytopenic purpura.

Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks before ITP treatment to optimize therapy and appropriately manage these complications. We performed a retrospective cohort study of 120 patients with primary ITP to identify a biomarker to predict bleeding and thrombosis. We compared blood test results at diagnosis between patients with and without bleeding or thrombosis episodes. The standard deviation of red blood cell distribution width (RDW-SD) differed significantly between those with and without bleeding and between those with and without thrombosis, leading us to identify it as a variable representative of risk. RDW-SD was significantly associated with patient age and with histories of several vascular diseases. Multivariate regression analyses showed that RDW integrated several variables associated with vascular risks. RDW-SD was significantly associated with difficulty with corticosteroid discontinuation (hazard ratio [HR], 2.22, p = 0.01), incidence of bleeding (HR, 2.75, p< 0.01), incidence of thrombosis (HR, 2.67, p< 0.01) and incidence of infection (HR, 1.78, p = 0.04). The RDW-SD value at the time of ITP diagnosis is a useful biomarker to predict the risks of bleeding, thrombosis, and other complications.

COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.

Key Clinical Message: Vincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID-19 vaccination. Our case report highlights the need for further research to establish standard management guidelines for COVID-19-vaccine-associated ITP. Abstract: Adult immune thrombocytopenia (ITP) can occur as a rare complication following several viral infections or a rare adverse event or complication of vaccination. In this paper, we report a case of a 39-year-old male patient with severe refractory ITP that began 4-weeks after receiving his third (booster) dose of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech). He was given oral dexamethasone 40 mg daily for 4 days followed by prednisone at 1 mg/kg (85 mg daily) for 10 days. In the following weeks, we attempted several other lines of therapy to treat his ITP, including anti-RhD immunoglobulin, which, unfortunately, caused moderate hemolysis requiring packed red blood cell transfusion, intravenous immunoglobulin (given at a subtherapeutic dose of 0.4 g/kg for only 1 day since it was not available), rituximab, and eltrombopag. The patient, unfortunately, showed no response to any of these treatments. This was an indicator to initiate salvage therapy with vincristine 2 mg weekly for 3 weeks. The patient's platelet count started to increase remarkably during the third week of vincristine and normalized after 4 weeks. We review the findings, clinical characteristics, and management approaches that were reported in the literature regarding COVID-19-vaccine-induced ITP. More in-depth research is needed to delineate standard guidelines for the management of such cases. This report underscores the importance of resorting to vincristine and eltrombopag as great options for severe and refractory ITP related to the COVID-19 vaccine.

Cerebral venous sinus thrombosis in patient of immune thrombocytopenic purpura managed with mechanical thrombectomy: An anecdotal endovascular experience from lower middle income country.

Cerebral venous sinus thrombosis in itself is rarely encountered clinical entity and its association with immune thrombocytopenic purpura (ITP) makes it more unusual presentation. No any as such standard guidelines exist that guides the prompt evidence based management in such concurrent cases but neuroendovascular modality can play a pivotal role.

Neuromyelitis Optica and Immune Thrombocytopenic Purpura Treated With Rituximab in a Patient With Combined Neurologic and Hematologic Disorder: A Case Report.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory demyelinating disease of the central nervous system affecting the optic nerves and spinal cord. Immune thrombocytopenia (ITP), on the other hand, is an autoimmune disorder characterized by a platelet count of <100 in the absence of any known condition that could be associated with thrombocytopenia. This case report focuses on a 56-year-old female presenting with the unique coexistence of NMOSD and ITP. A 56-year-old woman of Russian descent had a sudden onset of right eye blindness at the age of 24 and was diagnosed with multiple sclerosis. She developed petechial rashes on both lower extremities two weeks before consultation with no associated findings. Cranial MRI revealed multiple nodular and patchy areas of hyperintense signals on T2-weighted/fluid-attenuated inversion recovery without restricted diffusion. A thoracolumbar MRI revealed long segment foci of intramedullary cord non-enhancing abnormal hyperintense signal from T2 to T11. Cerebrospinal fluid aquaporin 4 IgG was negative. A complete blood count revealed platelets of 4 × 109/L, leading to the management of ITP. She was started on methylprednisolone 1 g/day for five days. Her platelet count improved eventually and rashes resolved. Rituximab treatment was initiated at a dose of 1 g on day 1 and day 15. On the 18th day of admission, the Expanded Disability Status Scale and functional score improved to 6.0 from 7.0 upon admission.

Hemostatic mechanism of Jianpi Yiqi Shexue decoction in treatment of immune thrombocytopenia.

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), ß-endorphin (ß-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, ß-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and ß-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and ß-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The ß-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the ß-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of ß-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.

Immune Thrombocytopenic Purpura (ITP) and Chorioretinopathy in Chronic Granulomatous Disease: A Case Report.

BACKGROUND: Chronic Granulomatous Disease (CGD) is a rare immunodeficiency disorder characterized by impaired phagocytic function, leading to recurrent infections and granuloma formation. Genetic mutations in NADPH oxidase complex components, such as CYBB, NCF1, NCF2, and CYBA genes, contribute to the pathogenesis. This case report explores the possible ocular and hematologic complications associated with CGD. CASE PRESENTATION: A 6-year-old girl with a history of vitrectomy, membranotomy, and laser therapy due to congenital blindness (diagnosed with chorioretinopathy) was referred to the hospital with generalized ecchymosis and thrombocytopenia. Diagnostic workup initially suggested chronic immune thrombocytopenic purpura (ITP). Subsequent admissions revealed necrotic wounds, urinary tract infections, and recurrent thrombocytopenia. Suspecting immunodeficiency, tests for CGD, Nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) were performed. She had a low DHR (6.7), and her NBT test was negative (0.0%). Her whole exome sequencing results confirmed autosomal recessive CGD with a homozygous NCF1 mutation. CONCLUSION: This case underscores the diverse clinical manifestations of CGD, including recurrent thrombocytopenia and possible early-onset ocular involvement. The diagnostic challenges highlight the importance of a multidisciplinary approach involving hematologists, immunologists, and ophthalmologists for accurate diagnosis and management. The rare coexistence of ITP in CGD emphasizes the intricate link between immunodeficiency and autoimmunity, requiring tailored therapeutic strategies.

Intracerebral Hemorrhage in a Patient With Newly Diagnosed Immune Thrombocytopenic Purpura Precipitated by a Viral Illness.

Intracerebral hemorrhage (ICH) is a rare and severe complication of immune thrombocytopenic purpura (ITP) that can be spontaneous. Viral illnesses, other infections, autoimmune disorders, and medications can cause ITP. ITP causes a significant decrease in platelet levels, increasing bleeding risk. ITP can be treated by steroids, intravenous immunoglobulin, plasmapheresis, platelet transfusion, biological agents, and splenectomy. ICH treatment involves the treatment of underlying ITP, as well as any neuro-interventional procedures needed. In this case report, we look at the presenting symptoms and treatment course of an interesting case of ICH in a patient who developed ITP after a viral upper respiratory infection.

Chronic Myelomonocytic Leukemia-Associated Immune Thrombocytopenic Purpura: A Report of a Rare Case and a Review of Literature.

Chronic myelomonocytic leukemia (CMML) presents as a complex hematologic malignancy with myelodysplastic and myeloproliferative features. Our case report explores the rare coexistence of CMML with immune thrombocytopenic purpura (ITP) in a 63-year-old female patient. CMML diagnosis followed World Health Organization criteria, and the patient was classified as having high-risk myelodysplastic syndrome (MDS)-CMML stage 2. Initial treatment with subcutaneous azacytidine for CMML proved partially effective, highlighting persistent severe thrombocytopenia. Subsequent investigations revealed secondary ITP associated with Crohn's disease. Conventional ITP therapies, including high-dose steroids and intravenous immunoglobulin, showed limited efficacy. Eltrombopag, a thrombopoietin receptor agonist, was initiated, resulting in the normalization of platelet counts within six weeks. Our case emphasizes the diagnostic challenges and intricate treatment landscape of CMML-associated ITP, suggesting eltrombopag as a potential therapeutic option in refractory cases. The study contributes to the evolving understanding of the complex interplay between myeloid disorders and immune-mediated hematological conditions, calling for personalized and multidisciplinary approaches to enhance patient outcomes.

Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients.

Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives.

Immune Thrombocytopenic Purpura and Intracranial Stenting.

Patients with immune thrombocytopenic purpura (ITP) presenting with indications for dual antiplatelet therapy (DAPT) can be difficult to manage due to the precarious balance of managing the need for increased platelet counts as well as inhibition of platelet activity. This case represents a 65 year old woman with ITP who presented with a bilateral subarachnoid hemorrhage secondary to a left ophthalmic aneurysm that required placement of a pipeline embolization device (PED) necessitating DAPT. After treatment of her ITP with pulse dexamethasone for four days, she was safely discharged on one month of DAPT with aspirin and ticagrelor then switched to aspirin monotherapy without any immediate complications. During her period of DAPT, she did not receive additional medical treatment for her ITP. This case successfully presents a high-risk ITP patient requiring DAPT for a neurosurgical procedure and illustrates that these patients can be safely and successfully treated with DAPT once their ITP is stabilized.

Evaluation of the hematological inflammatory parameters in the patients with immune thrombocytopenic purpura: A case-control study.

Background and Aims: Inflammation is one of the immune thrombocytopenic purpura (ITP)'s aggravating elements due to inflammatory cells' function. This study aims to identify and evaluate hematological inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin-to-platelet ratio (HPR), in patients with ITP compared to the control group. Methods: We retrospectively analyzed the profile of 190 ITP patients from August 2019 to January 2021 at Imam Reza Hospital of Mashhad, Iran, along with 100 healthy individuals who had no ITP-related clinical or laboratory symptoms. Immune cell counts, NLR, PLR, and HPR were calculated using the complete blood count at the time of diagnosis and after the treatment. The results were analyzed through MedCalc, SPSS software, and the receiver operating characteristic curve. Results: The result showed that white blood cell (WBC) and neutrophil counts were higher in ITP patients (WBC: p: 0.001, neutrophil: p: 0.001), and conversely, platelet and lymphocyte counts were higher in the control group compared to ITP patients (platelets: p: 0.001, lymphocytes: p: 0.001). The indices analysis between the two groups revealed that NLR was significantly increased in ITP patients (p: 0.001), but PLR was significantly reduced in ITP patients (with the mean platelet count of 23.44 ± 35.26 × 109/L) compared to the control group (with the mean platelet count of 234.04 ± 55.88 × 109/L). The HPR index also significantly increased in ITP patients (p: 0.001). Conclusion: An increase in NLR, PLR, and a decrease in HPR can be considered a valuable diagnostic algorithm in patients with ITP.

Conspicuous Peripheral Retinal Hemorrhages with a Relatively Preserved Posterior Pole in Immune Thrombocytopenic Purpura.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a rare auto-antibody mediated disease of isolated thrombocytopenia (<100,000/µL) with normal haemoglobin levels and leukocyte counts. Only a small number of ITP cases have been reported with accompanying ophthalmological findings. Herein, we report an ITP case with demonstrative retinal haemorrhages. CASE PRESENTATION: A fifty-five-year-old woman with a known history of type 2 diabetes mellitus was referred to our clinic with blurred vision. After detailed anamnesis and clinical assessment, she was diagnosed as primary ITP in haematology department, and systemic steroid (1.5mg/kg) therapy was initiated. During her follow-up, a concomitant peripheral facial paralysis (PFP) emerged. In the course of follow-up, her platelet counts increased gradually, the retinal haemorrhages regressed partially, and the PFP recovered completely. CONCLUSION: ITP is a rare haematologic disease that sometimes manifests with additional systemic involvements, and this disease should be remembered in the differential diagnosis of unusual retinal haemorrhages, which might be the only presenting feature.

Total abdominal hysterectomy in a patient with immune thrombocytopenic Purpura: A case report.

INTRODUCTION: Immune Thrombocytopenic Purpura poses unique challenges in surgical settings due to an increased risk of bleeding. This report details the perioperative management of a patient with Immune Thrombocytopenic Purpura undergoing Total Abdominal Hysterectomy, emphasizing the importance of tailored approaches for such cases. CASE PRESENTATION: A 41-year-old female with Immune Thrombocytopenic Purpura and symptomatic uterine fibroids, despite medical management, opted for Total Abdominal Hysterectomy. Prednisolone therapy and platelet transfusion were used preoperatively to optimize platelet counts. DISCUSSION: Effective management was achieved through meticulous surgery, continued prednisolone therapy, and vigilant postoperative monitoring. This case highlights the value of a multidisciplinary approach in ensuring positive surgical outcomes for Immune Thrombocytopenic Purpura patients. CONCLUSION AND RECOMMENDATION: This case underscores the significance of individualized perioperative care for Immune Thrombocytopenic Purpura patients undergoing major surgery. By optimizing medical therapy and maintaining close monitoring, favorable results can be achieved, enhancing the quality of life for such patients. It is recommended that such comprehensive approaches are considered in similar cases.

Efficacy and safety of mycophenolate mofetil in patients with immune thrombocytopenic purpura: a systematic review and meta-analysis.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP. METHODS: We systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design. RESULTS: Nine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly. CONCLUSION: This systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/.

Idiopathic Thrombocytopenic Purpura: Current Limitations and Management.

Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenia, is a blood disorder characterized by a reduction in the number of platelets. A reduction in the number of platelets beyond the normal levels leads to several consequences. A severe reduction in blood platelet levels leads to a rash of purple spots on the skin, joints, etc. due to leakage in the small blood vessels, easy bruising, bleeding gums, intestinal bleeding, and hemorrhage. Suppose a case of ITP resolves in fewer than six months. In that case, it is an acute case of ITP. Still, if a case settles in more than six months, it is a case of ITP. The cause of a reduced platelet count can be increased peripheral destruction or impaired production; this is termed an autoimmune condition in which the body's immune system attacks platelets thinking it to be a foreign antigen. ITP in children occurs commonly following a previous viral attack. Even though evaluating patients' reports is useful for understanding and guiding the treatment, these estimates might not be regularly evaluated in clinical settings. First-line drugs in the treatment of ITP are corticosteroids, and long-term use of these drugs has several side effects, such as excessive increase in weight, mental health disturbances, and sleep disturbances; additional therapies to treat hemorrhage are usually momentary. As a result, it is essential to recognize the flaws in current procedures and adopt innovative measures for the management and minimization of difficulties.

Impact of Helicobacter pylori Infection upon the Evolution and Outcome of Pediatric Immune Thrombocytopenic Purpura: A Comprehensive Review.

In adults with immune thrombocytopenic purpura (ITP), the identification of H. pylori infection and its subsequent eradication proved to aid platelet recovery. Similar findings, at a smaller scale, were allegedly reported by some pediatric studies. This review's objective was to establish the influence of H. pylori infection and its eradication upon platelet count and recovery in pediatric ITP. Three databases, namely Pubmed, Scopus and Web of Science, were searched for pediatric studies which investigated a link between H. pylori infection and thrombocytopenia. The search results retrieved a number of 21 articles which complied to the inclusion and exclusion criteria. Some studies report lower platelet values among children with ITP and documented H. pylori infection, as well as an improve in platelet numbers after H. pylori treatment. However, results are controversial, as multiple authors failed to identify a higher prevalence of H. pylori among children with ITP or a lack of significant change in therapeutic outcome with the addition of an eradication regimen to standard treatment. The main limitations of current pediatric studies remain the small study samples and the short follow-up periods of the included subjects. Hence, the long-term impact of H. pylori in children with ITP is still uncertain.

Treatment of immune thrombocytopenia during pregnancy with thrombopoietin receptor agonists.

The introduction of thrombopoietin receptor agonists (TPO-RAs) led to a paradigm shift in the management of immune thrombocytopenia (ITP). However, TPO-RAs are not approved for use during pregnancy due to the absence of evidence and concerns for possible effects on the fetus due to their expected transplacental transfer. This comprehensive review examines the safety and efficacy of TPO-RA in 45 pregnancies of women with ITP (romiplostim n = 22; eltrombopag n = 21; both in the same pregnancy n = 2). Mothers experienced failure of the median of three treatment lines during pregnancy prior to TPO-RA administration. A platelet response (>30 × 109 /L) was seen in 86.7% of cases (including a complete response >100 × 109 /L in 66.7%) and was similar between eltrombopag and romiplostim (87.0% and 83.3%, p = 0.99). The maternal safety profile was favourable, with no thromboembolic events encountered. Neonatal thrombocytopenia was noted in one third of cases, with one case of ICH grade 3, and neonatal thrombocytosis was observed in three cases. No other neonatal adverse events attributable to TPO-RAs were seen. This review suggests that the use of TPO-RA during pregnancy is associated with a high response rate and appears safe. Nevertheless, TPO-RA should not be routinely used in pregnancy and should be avoided in the first trimester until further evidence is accumulated.