Immune thrombocytopenia during the COVID-19 pandemic.

Abstract

British Journal of HaematologyVolume 193, Issue 6 p. 1093-1095 CorrespondenceFree Access Immune thrombocytopenia during the COVID-19 pandemic Eun-Ju Lee, Corresponding Author Eun-Ju Lee eul7001@med.cornell.edu orcid.org/0000-0002-8340-6027 Division of Hematology, New York Presbyterian Hospital — Weill Cornell, New York, NY, USASearch for more papers by this authorXinguang Liu, Xinguang Liu orcid.org/0000-0002-1808-4498 Department of Hematology, Shandong University, Jinan, ChinaSearch for more papers by this authorMing Hou, Ming Hou Department of Hematology, Shandong University, Jinan, ChinaSearch for more papers by this authorJames B. Bussel, James B. Bussel orcid.org/0000-0002-2884-9247 Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital — Weill Cornell, New York, NY, USASearch for more papers by this author Eun-Ju Lee, Corresponding Author Eun-Ju Lee eul7001@med.cornell.edu orcid.org/0000-0002-8340-6027 Division of Hematology, New York Presbyterian Hospital — Weill Cornell, New York, NY, USASearch for more papers by this authorXinguang Liu, Xinguang Liu orcid.org/0000-0002-1808-4498 Department of Hematology, Shandong University, Jinan, ChinaSearch for more papers by this authorMing Hou, Ming Hou Department of Hematology, Shandong University, Jinan, ChinaSearch for more papers by this authorJames B. Bussel, James B. Bussel orcid.org/0000-0002-2884-9247 Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital — Weill Cornell, New York, NY, USASearch for more papers by this author First published: 14 April 2021 https://doi.org/10.1111/bjh.17457Citations: 2AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Given past experience with widespread viral infections, for example influenza, we expected that SARS-CoV-2 would create a large number of de novo cases of immune thrombocytopenia (ITP). Perhaps a silver lining on the cloud of SARS-CoV-2 is that for patients with ITP, the virus is not having a major effect, as evidenced by few reports of ITP in conjunction with SARS-CoV-2 infection. We performed a retrospective review of patients ≥18 years diagnosed with COVID-19 and ITP seen at New York Presbyterian–Weill Cornell Medicine (NYP-WCM) or Shandong Provincial Chest Hospital–Shandong University (SPCH-SDU) from February to August 2020. Ten patients from NYP-WCM and two from SPCH-SDU were identified (Table I). The study was approved by the Institutional Review Board of NYP-WCM and the Medical Ethical Committee of SPCH-SDU. There were 10 patients with pre-existing ITP and two with presumed new SARS-CoV-2-associated ITP (Table I). Patient 8 was diagnosed with ITP during hospitalization for COVID-19 and Patient 10 developed isolated ITP six weeks following SARS-CoV-2 infection; neither had a prior history of thrombocytopenia. For those with pre-existing ITP, SARS-CoV-2 infections were managed as outpatients (n = 3), ER visits (n = 2), and hospitalizations (n = 5). During active COVID-19, five patients required ITP treatment for platelet nadirs of 8–33 × 109/l. Patient 7 received platelet transfusion, steroids and intravenous immunoglobulin (IVIg). Patients 1 and 9 received IVIg alone. Patient 1 had been on weekly romiplostim, twice daily mycophenolate mofetil (MMF) and IVIg as needed since 2017. She had fevers, fatigue, body aches and was ITP-Bleeding Assessment Tool: Skin 1 (petechiae), Mucosae 1 (epistaxis).1 Due to morbid obesity, limited mobility, and advanced age, she received weekly home infusions of IVIg 80 g for counts <10–20 × 109/l. Patient 9, on prednisone 15 mg daily for platelets 20–30 × 109/l, was hospitalized at SPCH-SDU. He received IVIg 10 g daily for two days with platelet improvement from 18 to 28 × 109/l. Patient 8 received inpatient IVIg 15 g daily for three days, methylprednisolone 80 mg BID, and convalescent plasma for SARS-CoV-2-associated ITP with platelets increasing from 33 to 83 × 109/l. Several weeks following SARS-Cov-2 diagnosis, Patient 10 received IVIg with steroids for de novo ITP with platelet improvement from 6 to 82 × 109/l. Patient 7 had chronic ITP with platelets of 8 × 109/l requiring platelet transfusions. In the setting of multiorgan failure, he declined additional treatment and passed away. Two patients received steroids alone for exacerbations of known ITP during infection with SARS-CoV-2. Patient 11’s platelets dropped from 60–70 to 23 × 109/l two weeks after diagnosis. His platelets improved to 180 × 109/l on prednisone 20 mg daily. Patient 4’s platelets dropped from a baseline of 60–70 to 26 × 109/l. She received dexamethasone 40 mg for four days with platelets rising to 105 × 109/l. Five patients (Patients 2, 3, 5, 6, 12) did not modify their ITP treatment despite COVID-19. Three (Patients 2, 3, 6) were on treatment (eltrombopag, steroids, rituximab, respectively). Patient 5 was discharged from the ER with haematology follow-up for platelets 26 × 109/l and Patient 12 was diagnosed with SARS-Cov-2 on routine screening for caesarean section with platelets 94 × 109/l. Patients 3, 4, 6, 8 were hospitalized and received prophylactic anticoagulation with enoxaparin 40 mg SC daily (NYP-WCM) or nadroparin 3 800 U SC daily (SPCH-SDU) without bleeding events. Patient 6 developed deep vein thrombosis (DVT) and pulmonary embolus (PE) despite prophylactic enoxaparin. He received therapeutic heparin and was discharged on apixaban. Patient 2 presented with a new headache due to cerebral venous sinus thrombosis and was discharged on apixaban. Treatments of ITP, ongoing or newly initiated, can impact the course and outcome of SARS-CoV-2. Thrombosis is a major concern in patients with SARS-CoV-2 infection2, 3 and immunosuppression could worsen infection. The American Society of Hematology offers recommendations limited by data to expert opinion4 for ITP management in SARS-CoV-2 infection. IVIg is not immunosuppressive, rapidly increases platelets, and has anti-inflammatory effects. To avoid prolonged visits and SARS-CoV-2 exposures, home administration (like Patient 1) is useful. Steroids may risk increasing viral susceptibility early in infection; however, published reports and our own experience suggest steroid use does not often lead to worse outcomes in COVID-19.5-7 No consensus exists regarding increased severity of COVID-19 infection in patients who have received rituximab or are on other chronic immunosuppressants.8-10 Anti-CD20 agents impair humoral responses to de novo infections and vaccines for at least 4–6 months. We agree with avoiding immunosuppressives or rituximab during the COVID-19 pandemic pending reasonable alternatives.11 We also caution use of splenectomy due to increased thrombotic risk and risk of overwhelming sepsis. The risk of thrombotic events with SARS-CoV-2 is well documented2, 3 and prophylactic anticoagulation is recommended in hospitalized patients including those with ITP.4, 12, 13 Cases of thrombosis in COVID19-infected ITP patients have been reported, including two patients included in this report.5, 7, 14 Patient 6 developed DVT/PE despite prophylactic anticoagulation. Although an advantage of thrombopoietin receptor agonists (TPO-Ras) would be absence of immunosuppression, caution is recommended during the COVID19 pandemic in patients with additional thrombotic risk factors such as post-splenectomy and platelet counts >100 × 109/l (Patient 2). Follow-up information through February 2021 is available for seven patients (Patients 1, 2, 3, 6, 8, 9, 10). None required hospitalization for recurrent ITP flares. Both patients with presumed new SARS-CoV-2-associated ITP (Patients 8, 10) maintain normal platelet counts without platelet-specific treatment. Patient 8 did not require treatment beyond IVIg and steroids received during hospitalization. Patient 10 was successfully tapered off steroids in October 2020. The starting platelet counts in our 12 patients were somewhat higher than in the 14-patient French series6 which had a high percentage of de novo cases whereas 10 of our 12 involved pre-existing ITP. As with ITP in the absence of SARS-CoV-2 infection, treatment needs to be individualized. Steroids, IVIg, rituximab, immunosuppressives, splenectomy and TPO-RAs are discussed above and considerations based on experience applicable to SARS-CoV-2 infection emphasized. Ongoing experience continues to be gathered to better inform care to SARS-CoV-2 infected ITP patients. Acknowledgements EL, XL, MH, JB performed the research and analyzed the data, EL and JB wrote the paper, XL and MH revised the paper. All authors approved the final manuscript. Conflicts of interest EL, XL and MH have no disclosures. JBB has served on advisory boards and/or consulted for Amgen, Novartis, Dova, Rigel, UCB, Argenx, Momenta, Regeneron, RallyBio, and CSL-Behring. Table I. Patient characteristics. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Patient 11 Patient 12 Age (years) 89 53 38 54 20 61 88 65 50 73 72 38 Gender (M/F) F F F F F M M M M M M F Body mass index (kg2/m) 42·3 24·5 32·8 64·5 23·4 23·8 22·4 24·6 22·4 26·2 28·3 25·3 Comorbidities Multiple sclerosis, hypertension, hyperlipidaemia, hyperthyroidism Hypothyroidism None Asthma McCune–Albright syndrome Warm autoimmune haemolytic anaemia, hypertension Low-grade B-cell lymphoma None None Celiac disease, hypertension, hyperlipidaemia Ankylosing spondylitis, hypertension, hyperlipidaemia Autoimmune gastritis, Hashimoto's thyroiditis ITP (de novo/existing) Existing Existing Existing, pregnancy-associated Existing Existing Existing Existing De novo Existing De novo Existing Existing Distant ITP treatments Azathioprine, steroids, rituximab, eltrombopag Rituximab, steroids, splenectomy Steroids, IVIg during pregnancies Steroids IVIg, steroids Steroids, IVIg, romiplostim, rituximab None None Steroids, IVIg, recombinant thrombopoietin None Steroids None ITP treatment prior to COVID19 hospitalization Romiplostim, mycophenolate mofetil, IVIg PRN Eltrombopag Prednisone 30 mg None None Rituximab None None Prednisone 15 mg None None None COVID19 hospitalization type Outpatient ER Floor, non-ICU Floor, non-ICU ER Floor, non-ICU Floor, non-ICU Floor, non-ICU Floor, non-ICU Outpatient¶ ¶ No hospitalization for COVID-19, hospitalized two months after COVID-19 diagnosis for de novo ITP. Outpatient Labour & delivery**** Diagnosed with COVID19 on screening prior to admission to Labour & Delivery for planned caesarean section. Hospitalization length (days) N/A** No hospitalization for COVID-19 or ITP, treated at home. 2 3 4 <1 7 4 26† † Per institutional policy, discharge pending negative nucleic acid testing. 21† † Per institutional policy, discharge pending negative nucleic acid testing. N/A N/A N/A Oxygen requirement N/A None Nasal cannula Nasal cannula None Nasal cannula Nasal cannula High flow nasal cannula Nasal cannula N/A N/A None Thrombosis? No Cerebral venous sinus thrombosis No No No Pulmonary embolus, deep vein thrombosis None None None None None None Platelet nadir (×109/l) 8 158 112 26 26 137 8 33 18 6 23 94 ITP rescue treatment IVIg None None Dexamethasone 40 mg × 4 days None None Platelet transfusion Methylprednisolone 80 mg BID with taper, IVIg IVIg IVIg, solumedrol Prednisone 20 mg None Platelets (×109/l) on discharge or after outpatient treatment N/A 158 236 105 26 346 13‡ ‡ Deceased without escalation of care per patient's wishes. 83 28 82 180 N/A Prophylactic anticoagulation No No Yes Yes§ § Anticoagulation started when platelets were >50 × 109/l. 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