Sarcoidosis-Associated Immune Thrombocytopenic Purpura and Focal Segmental Glomerulosclerosis

Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.

Graves' disease-induced immune thrombocytopenic purpura in an African female: a case report.

BACKGROUND: Immune thrombocytopenic purpura is a condition associated with an unusual, unexplained, and sometimes very severe reduction in the level of platelets in the blood. Though documented, its association with Graves' disease is not very common and can easily be missed or misdiagnosed, leading to excessive bleeding and mortality. Treatment with steroids and antithyroid medications has been shown to be beneficial in correcting thrombocytopenia in these patients, although the response is varied. We report on a patient with Graves' disease who presents with immune thrombocytopenic purpura. CASE PRESENTATION: A 37-year-old Ghanaian female presented to our hospital's emergency department with a complaint of palpitations, difficulty breathing, easy fatigue, and headaches. She had been referred from a peripheral hospital as a case of thrombocytopenia, severe anemia, and anterior neck swelling. She was diagnosed with Graves' disease 2 years ago, became euthyroid during treatment, but defaulted. On further examination and investigation, she was diagnosed with immune thrombocytopenic purpura and was also found to have elevated free T3 and T4, and suppressed thyroid stimulating hormone. She also had high thyroid autoantibodies. She was initially started on oral prednisolone but there was no stabilization of platelets until methimazole was introduced, which improved and normalized her platelet count. CONCLUSION: The association of Graves' disease with immune thrombocytopenic purpura, though documented, is uncommon, and very few cases have been reported thus far. There have not been any reported cases in Ghana or Sub-Saharan Africa and hence, clinicians should be aware of this association when investigating immune thrombocytopenic purpura and should consider Graves' disease as a possible cause. From this study, we observed that there was no improvement in platelet count following the use of corticosteroid therapy until methimazole was started.

Management of Hepato- biliary-pancreatic Surgery during the COVID-19 Pandemic

Purpose: We examined the effect of COVID-19 on diseases treated with hepato- biliary- pancreatic surgery from the experience of nosocomial infection at our hospital. Method(s): We examined the treatment of 106 patients admitted by the Division of Hepato- Biliary- Pancreatic Surgery to The Jikei University Hospital for elective surgery from January through May 2020. Result(s): Of the 106 operations, 90 (85%) were performed as scheduled and did not include COVID-19-positive patients. Operations for 16 patients (15%) were postponed, but 5 (31%) of these operations were urgent or quasiurgent and were performed during the study period. Of 95 patients who underwent surgery, 50 (53%) had a malignant tumor, 3 (3%) had a borderline malignant tumor, and 42 (44%) had a benign lesion, of which 41 were gallstones or gallbladder polyps and 1 was an intraductal papillary mucinous neoplasm that caused pancreatitis. Surgery for the latter tumor was postponed while conservative treatment improved conditions, but pancreatitis recurred 2 weeks after discharge, leading to a quasiurgent surgery. Conclusion(s): Owing to COVID-19, 15% of the scheduled elective hepato- biliary- pancreatic operations were postponed. Even lesions considered benign or not requiring emergency surgery should be treated promptly. Thus, the timing of treatment should be determined so that the risks of exacerbation and COVID-19 can be balanced.Copyright © 2022 Jikei University School of Medicine. All rights reserved.

A Pregnant 19-Year-Old Patient with Refractory Immune Thrombocytopenia and Concomitant SARS-CoV-2 Infection: Case Report

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder in which platelet destruction occurs through autoantibodies. Several new therapies have been approved in recent years for the treatment of ITP, including thrombopoietin receptor agonists. However, the data describing the use of these drugs during pregnancy are limited. DISCUSSION: We present the case of a 19-year-old woman who was admitted to the hospital with a platelet count of <2 × 109/L. As part of her initial therapy, she was prescribed steroids and intravenous immunoglobulin. Shortly after, she had respiratory symptoms, which led to the diagnosis of SARS-CoV-2 (COVID-19), for which she received remdesivir. Because of her persistent thrombocytopenia, the patient was prescribed rituximab, followed by treatment with romiplostim. Her thrombocytopenia did not improve, and she underwent a splenectomy in her second trimester. She eventually delivered her baby at 37 weeks, without any maternal or fetal complications. CONCLUSION: This case highlights the use of several treatment modalities, including remdesivir, rituximab, romiplostim, and splenectomy, in a pregnant woman who was diagnosed with ITP and COVID-19 and had no obvious fetal complications from these treatments. This case adds to the current nascent data regarding the use of these drugs during pregnancy. [ABSTRACT FROM AUTHOR] Copyright of Journal of Hematology Oncology Pharmacy is the property of Green Hill Healthcare Communications, LLC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Immune thrombocytopenic purpura secondary to COVID-19 vaccination: A systematic review.

INTRODUCTION: This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID-19 immunization to determine their epidemiological characteristics, clinical course, therapeutic strategies, and outcome. MATERIALS AND METHODS: We conducted the review using four major databases, comprising PubMed, Scopus, Web of Science, and the Cochrane library, until April 2022. A systematic search was performed in duplicate to access eligible articles in English. Furthermore, a manual search was applied to the chosen papers' references to enhance the search sensitivity. Data were extracted and analyzed with the SPSS 20.1 software. RESULTS: A total of 77 patients with de novo COVID-19 vaccine-associated ITP were identified from 41 studies, including 31 case reports and 10 case series. The median age of patients who developed COVID-19 vaccine-associated ITP was 54 years (IQR 36-72 years). The mRNA-based COVID-19 vaccines, including BNT16B2b2 and mRNA-1273, were most implicated (75.4%). Those were followed by the adenovirus vector-based vaccines, inclusive of ChAdOx1 nCoV-19 and vAd26.COV2.S. No report was found relating ITP to other COVID-19 vaccines. Most cases (79.2%) developed ITP after the first dose of COVID-19 vaccination. 75% of the patients developed ITP within 12 days of vaccination, indicating a shorter lag time compared to ITP after routine childhood vaccinations. Sixty-seven patients (87%) patients were hospitalized. The management pattern was similar to primary ITP, and systemic glucocorticoids, IVIg, or both were the basis of the treatment in most patients. Most patients achieved therapeutic goals; only two individuals required a secondary admission, and one patient who presented with intracranial hemorrhage died of the complication. CONCLUSIONS: De novo ITP is a rare complication of COVID-19 vaccination, and corresponding reports belong to mRNA-based and adenovirus vector-based vaccines, in order of frequency. This frequency pattern may be related to the scale of administration of individual vaccines and their potency in inducing autoimmunity. The more the COVID-19 vaccine is potent to induce antigenic challenge, the shorter the lag time would be. Most patients had a benign course and responded to typical treatments of primary ITP.

SEVERE THROMBOCYTOPENIA DUE TO ELECTRON-BEAM POLYSULFONE DIALYZER MEMBRANE REACTION MASQUERADING AS CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA

SESSION TITLE: Critical Thinking SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: We describe a case of severe thrombocytopenia due to reaction with an electron-beam sterilized polysulfone (PS) membrane in a patient with a previous diagnosis of reported chronic immune thrombocytopenic purpura (ITP). This phenomenon has been previously described but is rarely reported. Electron-beam (e-beam) sterilized PS membranes are classically more biocompatible than cellulose-based membranes but adverse reactions may occur as demonstrated in our case. CASE PRESENTATION: An 84-year-old woman with ESRD on hemodialysis (HD) and reported chronic ITP refractory to glucocorticoids with severe thrombocytopenia at baseline presented for evaluation of chest pain. She was incidentally found to have severe thrombocytopenia and treated with high dose glucocorticoids with minimal improvement in her thrombocytopenia and transitioned to chronic glucocorticoid taper. She had a severe chronic thrombocytopenia despite glucocorticoids which was suspected to be chronic ITP and diagnosed after initiation of outpatient HD. HD was held the first few days of her admission. She was found to have multifocal pneumonia due to SARS-CoV-2 infection. She developed progressive hypoxemic respiratory failure requiring intubation with sepsis treated with vancomycin & piperacillin-tazobactam. BAL revealed ESBL Escherichia coli & transitioned to ertapenem. She developed recurrent thrombocytopenia following HD and her PLT would improve between HD sessions. Evaluation of usual culprits of thrombocytopenia was unrevealing. Reaction to the PS membrane was suspected and a cellulose-based dialyzer membrane was used instead for subsequent sessions of HD with recovery of the platelet counts to normal. The remainder of her course was significant for tracheostomy with ventilator dependence and surrogate pursued compassionate care. DISCUSSION: We describe an interesting case of severe thrombocytopenia due to PS membrane reaction which was previously labeled as chronic ITP. Usual culprits such as pseudothrombocytopenia, HIT, HIV, HCV, hypersplenism, alcohol use, nutritional deficiencies, and rheumatologic disease were excluded. Synthetic membranes like PS-membranes are traditionally regarded as more biocompatible but filter reactions are described [1]. It is hypothesized that e-beam radiation may affect dialyzer membrane integrity or structure, or produce intermediary products which may cause platelet activation, aggregation, and adsorption, and therefore thrombocytopenia [2]. There is a high prevalence of thrombocytopenia among critically ill patients undergoing HD [3]. CONCLUSIONS: Thrombocytopenia due to PS dialyzer membrane is a rarely reported phenomenon and may be underrecognized in critically ill patients. This entity should be considered in the differential diagnosis of patients undergoing HD who develop thrombocytopenia. Early recognition may reduce incidence of bleeding and need for blood products in these patients. Reference #1: Golli-Bennour EE, Kouidhi B, Dey M et al. Cytotoxic effects exerted by polyarylsulfone dialyser membranes depend on different sterilization processes. Int Urol Nephrol 2011;43: 483–490. Reference #2: Batalini F, Aleixo GF, Maoz A, Sarosiek S. Haemodialysis-associated thrombocytopenia: interactions among the immune system, membranes and sterilisation methods. BMJ Case Rep. 2019 Sep 4;12(9):e229594. doi: 10.1136/bcr-2019-229594. PMID: 31488440;PMCID: PMC6731774. Reference #3: Griffin BR, Jovanovich A, You Z, Palevsky P, Faubel S, Jalal D. Effects of Baseline Thrombocytopenia and Platelet Decrease Following Renal Replacement Therapy Initiation in Patients With Severe Acute Kidney Injury. Crit Care Med. 2019;47(4):e325-e331. doi:10.1097/CCM.0000000000003598 DISCLOSURES: No relevant relationships by Adefemi Adeyemo No relevant relationships by Zachary Chandler No relevant relationships by Bijal Patel No relevant relationships by Vandana Seeram

A CASE OF REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA INDUCED IMMUNE THROMBOCYTOPENIC PURPURA SUCCESSFULLY TREATED WITH VENETOCLAX

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. Approximately 2% of patients with CLL develop immune thrombocytopenic purpura (ITP) during the course of the disease. When resistant to steroids, this constitutes as indication for treatment of the CLL. Here we report a patient with refractory ITP secondary to CLL successfully treated with venetoclax. Aims: To present an interesting case with CLL related refractory ITP treated successfully with novel agent venetoclax. Methods: Patient data was taken from the patient herself and Hospital records. Informed consent to publish the case is obtained from patient. Permission for off-label venetoclax and eltrombopag was obtained from Ministry of Health of Turkey. Results: 46-year-old female patient presented with lumps on her neck that were present for the last 9 months in November 2020. She has a history of frequent pneumonia and otitis but no constitutional symptoms. Her physical examination reveals multiple 2cm lymphadenopathies on her neck and no organomegaly or other pathological features. Blood work shows mild lymphocytosis (6800/mm3) with no serious cytopenias. Peripheral blood smear, flow cytometry and bone marrow biopsy were all compatible with CLL. She was classified as Binet A CLL and was followed up with no treatment after appropriate vaccinations against capsulated pathogens. In July and August 2021 she received two doses of mRNA vaccination against COVID-19. On 1st November 2021 she experienced excessive menstrual bleeding and blood work showed platelet count of 23000/mm3, she was started on steroids (1 mg/kg/day) and after 4 days platelet count has risen to 55000/mm3, she discontinued steroids on her own against medical advice. On 13th of November she presented with extensive petechiae and purpura and was again started on steroids and was given the courses of intravenous immunoglobulins (IVIG) without any sustained response. She was refractory to platelet transfusions too. She was transferred to our clinic. She was found to have del11q and del13q. She refused bone marrow examination. She was treated with rituximab, steroids, vincristine, IVIG and eltrombopag for ITP without success (Fig. 1). She had a minimal response to IVIG only. She received two courses of bendamustine (90 mg/kg for two days) also without success. Three courses of plasmapheresis yielded no response either. After mild success with immunadsorbtion apharesis she was started on venetoclax plus rituximab with ramp-up. Sustained response was achieved within the first week of venetoclax therapy. (Figure Presented ) Summary/Conclusion: Gordon et al. reported 2 CLL cases one with ITP and other with Evans syndrome successfully treated with venetoclax. We think, this treatment should be considered in patients with refractory immune cytopenias secondary to CLL and assessed with prospective clinical trials.

CLINICAL EFFICACY AND TOLERABILITY OF VENETOCLAX PLUS RITUXIMAB IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA - REAL WORLD ANALYSIS OF POLISH ADULT LEUKEMIA STUDY GROUP

Background: The introduction of venetoclax into clinical practice has improved the outcome of patients with relapsed/refractory chronic lymphocytic leukemia (RR-CLL). The results of the MURANO trial published in March 2018 showed significantly longer progression-free survival (PFS) and overall survival (OS) in RR-CLL patients treated with venetoclax and rituximab (VEN-R) comparing to bendamustine and rituximab (BR) and resulted in the approval of VEN-R in the therapy of RR-CLL in the European Union and the United States. It should be noted that the results of registration studies often do not correspond with the data from real-life observations. Aims: To study the clinical efficacy and safety profile of VEN-R treatment in RR-CLL patients outside clinical trials. Methods: We performed retrospective analysis of RR-CLL patients treated with VEN-R in hematology centers of the Polish Adult Leukemia Study Group (PALG) from 2019 to 2021. Results: Clinical data of 117 RR-CLL patients treated with VEN-R were collected. Median patient age upon initiation of VEN-R therapy was 67 years (range 33 - 84 years). Seventy-two patients (61.5%) were men. Median Cumulative Illness Rating Scale (CIRS) was 6 (range 2 -16). Patients were treated with a median of 2 (range 1-9) previous lines of therapy, whereas 32 patients (27.4%) had relapsed following the first line of treatment. Overall, 25 patients (21.4%) had 17p deletion, whereas TP53 mutation was identified in 13 patients (11.1%). The median follow-up was 9.96 months (range 0.27 -29.13). The overall response rate (ORR) was 95.2%. Seventeen patients (14.5%) achieved complete remission (CR), 83 (70.9%) partial remission (PR), while in 5 patients (4.3%) disease progression was noted. In the patients with 17p deletion (n=22) or TP53 mutation (n=11), CR and PR were observed in 4 (12.1%) and 29 (87.9%) patients, respectively. The median PFS in the whole cohort was 20.8 (95% CI 18.43 -not reached) months and the median OS was not reached. In our study none of the analyzed clinico-pathological factors had significant impact on ORR, PFS and OS. During the follow-up time four (3.4%) cases of Richter transformation were diagnosed. There were 18 deaths recorded during the course of observation;3 (16.7%) due to disease progression and 7 (38.9%) due to COVID-19 infection. The others were due to infections other than SARS-CoV-2 (n=3, 16.7%) and the cause of death could not be specified in five cases (27.8%). Eighty-three patients (70.9%) remain on treatment, while treatment was discontinued in thirty-four cases (29.1%). Reasons for therapy discontinuation included patient's death (52.9%), treatment-related cytopenias (17.6%), disease progression (14.7%), Richter's transformation (11.8%), autoimmune hemolytic anemia (5.9%), diarrhea (2.9%) and infections (8.8%). In one case treatment discontinuation was due to consent withdrawal and one patient was lost to follow-up. The following adverse events of VEN-R treatment were reported during the study: all grade neutropenia (71.8% with grade 3/4 in 55.6%), anemia (51.3%), thrombocytopenia (47%), pneumonia (9.4%), neutropenic fever (6.8%), autoimmune hemolytic anemia (4.3%), immune thrombocytopenic purpura (1.7%), diarrhea (4.3%) and in one case exacerbation of heart failure was observed. Summary/Conclusion: In this retrospective analysis the outcomes of treatment with the VEN-R regimen in real-life setting were worse than those reported in the MURANO trial.

PROSPECTIVE OBSERVATIONAL STUDY IN PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) TREATED WITH TPO-R AGONISTS (TPO-RA): ELTROMBOPAG (EPAG) AND ROMIPLOSTIM (ROMI) - THE PEPITE STUDY

Background: Initially, the marketing authorization (MA) of EPAG and ROMI was to adult patients (p.) with ITP ≥12 months (m.) and refractory to other treatments (t.), splenectomized or contraindicated to splenectomy. The MA was extended for EPAG in 2019 to p. aged ≥1 year with ITP ≥6 m., refractory to other t. (corticoids (CS), IgIV). In 2017, French national guidelines suggested the use of TPO-RA as an option of t. in 2nd line (L). Aims: The PEPITE study, still ongoing, aims to assess the modalities of use, effectiveness and safety of TPO-RAs in reallife. Methods: Prospective, observational, multicenter study including adult p. who initiated TPO-RA with persistent (pITP) or chronic (cITP) ITP. Inclusions occurred between 12/21/2018 and 07/17/2020. Here's the interim analysis, cut-off date: 03/22/2021. Characteristics at baseline were presented in 114 p. (analyzed pop). Efficacy analysis of TPO-RA was assessed in p. with a platelet count (PLAT) <100 G/L at TPO-RA initiation (efficacy pop 113 p.). Responses were defined as: response (R) = PLAT ≥30 G/L, complete response (CR) = PLAT ≥100 G/L and non-response (NR) = PLAT <30 G/L. Results: 123 p. included through 40 centers by 25 hematologists and 15 internists, and 77 p. were still on TPO-RA at 6 m. At baseline, mean age 62.7 ± 20.1 years, 55% men, 29% with at least 1 cardiovascular risk factor. At diagnosis: median PLAT = 26 G/L [0 to 134 G/L], 31% of p. with bleedings. 97% of p. received at least one L of t. before TPO-RA: CS 96%, IVIG 56%, rituximab 47%, dapsone 18%, hydroxychloroquine 11%, danazol 6% and 7% of p. were splenectomized. Median number L of t. = 2 and 8% of p. had more than 4 L. Median time between diagnosis and TPO-RA initiation was 2.6 years [0.3 to 49.3 years], 33% of p. with pITP (n=21 with ITP 3 -<6 months, n=16 with ITP 6 - <12 months) and 67% with cITP. At TPO-RA initiation: 9% of p. were on CS and 48% p. had PLAT <30 G/L (median PLAT = 30 G/L), 95 p. (83%) received EPAG and 19 p. (17%) ROMI. For the 77 p. still on TPO-RA at 6 m., R rate = 97% and CR = 60%. Within 6 m., 10 p. had permanently (perm.) discontinued TPO-RA, main causes were therapeutic effect deemed sufficient (TEDS) for 6 p. and NR for 2 p. For the 27 p. still treated with TPO-RA at 18 m., R rate = 93% and CR = 48%. Within 18 m., 12 p. had perm. stopped TPO-RA, including 7 p. for TEDS and 1 p. NR. P. initiated TPO-RA with ITP 3 -<6 months (N = 21), 9 (43%) p. were still on TPO-RA at 6 months, 5 (56%) in CR. Over the entire follow-up, 24p. (21%) perm. discontinued TPO-RA, main causes were TEDS for 9 p., adverse event (AE) for 5 p. and absence of R for 4 p. Of the 105 p. treated with EPAG at least once, 62 (59%) experienced at least one AE, and 26 SAE occurred in 17 p. The most common AEs were respectively 6% for headache and 3% for SARS-CoV-2 infections, diarrhea, asthenia, insomnia, arthralgia and alopecia. Of the 40 p. treated with ROMI at least once, 19 (48%) experienced at least one AE and 17 SAEs occurred in 10 p. The most common AEs: SARS-CoV-2 infections (5%) and arthralgias (5%). No deaths related to TPO-RA was reported. Summary/Conclusion: Preliminary data from the PEPITE study show that TPO-RA are prescribed in early ITP, including 33% with pITP (18% with ITP 3-<6 m.) and are used in 7% of cases after splenectomy. At 6 m. R on t. was 97% and CR on t. was 60%. Within 6 m., 6 p. had perm. stopped TPO-RA due to TEDS. The real-life effectiveness and safety data for EPAG and ROMI are consistent with data reported in extension studies, with the specificity of occurrence of SARS-CoV-2. The final analysis is scheduled after 24 m.

MANAGEMENT OF AUTOIMMUNE HAEMOLYTIC ANAEMIA DURING PREGNANCY OR POST-PARTUM: AN INTERNATIONAL MULTI-CENTRE EXPERIENCE

Background: Autoimmune haemolytic anaemia (AIHA) during pregnancy is a rare finding, and few is known about maternal and foetal outcomes. AIHA may either develop or relapse during gestation and postpartum or be an issue in a patient on active therapy who becomes pregnant. AIHA management during pregnancy and lactation is not standardized and drug use is often limited by safety concerns. Aims: We studied AIHA impact on pregnancy focusing on disease severity, treatment need and maternal/foetal outcome. Methods: Through a multicentric retrospective cohort study, we identified 38 pregnancies occurred in 28 women from 1997 to 2021 in 10 European centres in Italy, Denmark, France, the Netherlands, USA, and Spain. All included patients had a previous AIHA history or developed/exacerbated AIHA during gestation or postpartum. AIHA was classified according to the direct antiglobulin test. Results: We registered 18 warm AIHA (10 IgG;8 IgG+C3d), 2 cold agglutinin disease, 3 mixed and 5 atypical forms (Table 1). Evans syndrome (i.e., association of AIHA and immune thrombocytopenia or neutropenia) was present in 4. Mean age at AIHA diagnosis was 27 (3-39) and at pregnancy 32 (21-41) years. AIHA diagnosis predated pregnancy in 15 women and had required at least 1 therapy line in all of them, and >2 lines in 12 (rituximab, N=7;cytotoxic immunosuppressants, N=6;splenectomy, N=5). Among these 15 patients, 6 had a relapse during pregnancy, 3 during postpartum and 9 were on active treatment at the time of pregnancy (steroids, N=8;cyclosporine, N=1;azathioprine, N=1;the latter stopped after positive pregnancy test). A patient with a previous AIHA, relapsed as immune thrombocytopenic purpura during pregnancy. Further 8 patients had an AIHA onset during gestation and 2 postpartum. A patient had AIHA onset during the postpartum of the 1st pregnancy and relapsed during the 2nd one. In the 20 women experiencing AIHA during pregnancy/postpartum, median Hb and LDH levels were 6,4 g/dL (3,1 - 8,7) and 588 UI/L (269-1631), respectively. Management consisted in blood transfusions (N=10) and prompt establishment of steroid therapy+/-IVIG (N=20), all with response (complete N=13, partial N=7). After delivery, rituximab was necessary in 4 patients and cyclosporine was added in one. Anti-thrombotic prophylaxis was given in 7 patients. Overall, we registered 10 obstetric complications (10/38, 26%), including 4 early miscarriages, a premature rupture of membranes, a placental detachment, 2 preeclampsia, a postpartum infection and a biliary colic. Apart from the case of biliary colic and one of the two cases of preeclampsia, 8/10 complications occurred during active haemolysis and treatment for AIHA. Nine foetal adverse events (9/38, 24%) were reported: a transitory respiratory distress of the new-born in a mother with active AIHA, 3 cases of foetal growth restriction, a preterm birth, an infant reporting neurologic sequelae, a case of AIHA of the new-born requiring intravenous immunoglobulins, blood transfusions and plasma exchange, and 2 perinatal deaths. The latter both occurred in women on active AIHA therapy and were secondary to a massive placental detachment and a symptomatic SARS-CoV-2 infection. (Figure Presented ) Summary/Conclusion: AIHA developing/reactivating during pregnancy or postpartum is rare (about 5%) but mainly severe requiring steroid therapy and transfusions. Importantly, severe maternal and foetal complications may occur in up to 26% of cases mostly associated with active disease, pinpointing the importance of maintaining a high level of awareness. Passive maternal autoantibodies transfer to the foetus seems a rare event.

A Systematic Review of Reported Cases of Immune Thrombocytopenia after COVID-19 Vaccination.

With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization.

Immune thrombocytopenic purpura: an early cutaneous manifestation of a dangerous and not yet fully understood complication of COVID-19 infection

COVID-19 has created a series of clinical conundrums since its emergence. We report a case of severe immune thrombocytopenic purpura (ITP) in a 67-year-old gentleman in April 2020. He presented to hospital with a rapidly evolving rash, 3 weeks following infection with COVID-19. Clinically he had a widespread non palpable petechial rash, haemorrhagic blisters across his oral mucosa and severe epistaxis. His platelet count was 2 × 109 L-1 (150-450 × 109 L-1). Full blood count and clotting studies were otherwise normal. With ITP not yet well reported as a complication of COVID-19, there was a treatment dilemma. ITP is an acquired autoimmune-mediated disorder (often with a viral or vaccine precipitant) and first-line treatment is immunosuppression. However, due to concurrent infection with the novel COVID-19 virus, a thrombopoietin receptor agonist (TPO-RA) (eltrombopag 50 mg once daily) was instead commenced. Persistent epistaxis, oral bleeding and a platelet count < × 109 L-1 required intravenous immunoglobulin (1 g kg-1) to be administered on day 7 of TPO-RA treatment. By day 12 of TPO-RA treatment the platelet count had successfully normalized. The patient remains in remission 18 months on. Since this case, ITP has become a recognized phenomenon of both COVID-19 infection and COVID-19 vaccination (Pishko AM, Bussel JB, Cines DB. COVID-19 vaccination and immune thrombocytopenia. Nat Med 2021;27: 1145-6). Moreover, corticosteroid therapy has become the first evidence-based therapy for severe COVID-19 infection (Horby P, Lim WS, Emberson J et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384: 693-704), although their use in COVID-19- related ITP remains unclear. This case demonstrates an important cutaneous manifestation of the COVID-19-provoked disrupted haemostasis pathways, which results in significant morbidity and mortality. Additionally, this case describes practical real-life multidisciplinary team decision-making to emerging complications of a uniquely studied virus.

Untangling a rare case of hypoxia

Introduction: Hypoxia is a very common symptom during this COVID-19 pandemic. Detailed history, clinical examination and relevant investigations are important in distinguishing rare causes from commonest. Case Report: 52-year-old lady presented to emergency room with sudden onset breathlessness. She was recently diagnosed with Idiopathic Thrombocytopenic Purpura (ITP). She was found to be hypoxic with a room air saturation of 82% in pulse oximeter. She was started on high flow oxygen. But her saturation didn't improve. Chest X-ray showed normal lung fields and bedside echocardiography revealed normal cardiac status. Point of care blood gas analysis (ABG) revealed a normal partial pressure of oxygen (Pao2-100). The discrepancy between oxygen saturation recorded in pulse oximetry and PaO2 in blood gas analysis tempted us to relook the ABG. It was found that the methaemoglobin level in ABG was 10.7%. When we analysed her drug history, we found that there was dapsone intake for the treatment of ITP which strongly supported us to reach the diagnosis of methemoglobinemia. She was then treated with intravenous methylene blue in the emergency room. She responded well and her repeated ABG revealed normalized level of methaemoglobin. Her hypoxia also resolved. Dapsone was later removed from her regular medications. Conclusion: Methemoglobinemia is an extremely rare cause for hypoxia. Though rare its potentially life threatening if not identified on time. Refractory hypoxia with a discrepancy in spo2 and PaO2 should raise the suspicion of methemoglobinemia. IV methylene blue is the recommended treatment for methemoglobinemia.

Thrombocytopenia with and without Thrombosis Following COVID-19 Vaccination

Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia]. Methods: The study population included adults >18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes. Results: Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR. Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT);and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to >44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment. Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67;D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients. Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. [Formula presented] Disclosures: Carrier: Sanofi: Honoraria;Pfizer: Honoraria, Research Funding;Servier: Honoraria;Bayer: Honoraria;Leo Pharma: Honoraria, Research Funding;BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria;Aspen: Honoraria;Bayer: Honoraria;LEO Pharma: Honoraria;Pfizer: Honoraria;Sanofi: Honoraria. Castellucci: BMS: Honoraria;Pfizer: Honoraria;Amag Pharmaceuticals: Honoraria;The Academy: Honoraria.

A Case of Idiopathic Thrombocytopenic Purpura After Booster Dose of BNT162b2 (Pfizer-Biontech) COVID-19 Vaccine.

Vaccination is now considered the best measure in minimizing the morbidity and mortality from the Covid-19 pandemic. Almost all the vaccines are considered safe except for minor and occasional side effects. Some of the commonly reported complications from the COVID-19 vaccines are vaccine-induced thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome/vaccine-induced pro-thrombotic immune thrombocytopenia syndrome. In this case report, we present a case of a 75-year-old female who had an uncomplicated first and second vaccine dose but developed VITT after the booster dose of the vaccine. The patient was treated with dexamethasone and platelet transfusions. So far no such cases have been reported after the third (booster) dose of the Pfizer-Biontech vaccine. With this case report, we present the case of the patient and discuss the literature related to vaccine-induced thrombocytopenia.

Idiopathic thrombocytopenic purpura as a hematologic manifestation of COVID-19 infection: A case report.

The hematologic system is one of the vulnerable parts of the human body in coronavirus disease-2019 (COVID-19) infection. Lymphopenia and disseminated intravascular coagulation (DIC) are among the most frequent consequences of COVID-19. Idiopathic thrombocytopenic purpura is one of the common causes of thrombocytopenia in adults. It is defined by thrombocytopenia when platelet counts <105/µl in the absence of anemia and leukopenia. Traditionally, infections, typically viral, have been known as the main culprits of low platelet counts before the involvement of ITP. According to the literature, C virus (HCV), HIV, varicella-zoster virus (VZV), and cytomegalovirus (CMV) are considered secondary causative agents for the development of ITP. In this study, we reported a case that was afflicted with concurrent severe thrombocytopenia diagnosed as ITP and COVID-19 infection.