Posted on Authorea 8 Mar 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161522874.41200611/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. aai Elkayam Natalie Exchange After Plasma Improved Angiopathy Thrombotic Associated COVID19 h eia nesv aeui o aaeeto etcsokadauersiaoyfiuescnayto to secondary admitted failure was respiratory Patient acute and range. and shock septic normal g/dL activated of in 11.7 (INR), management all of presentation for ratio were (Hgb) unit on normalized fibrinogen care (CBC) hemoglobin international intensive and count cells/L, including medical (aPTT) was 13.4 the profile time complete (CRP) (WBC) Coagulation Her thromboplastin protein cell 243k/uL. partial C-reactive ng/ml. blood of 297.9 count white reactive. be platelet levels following: to was bilirubin the found PCR with was demonstrated (COVID19) IU/L ferritin studies Coronavirus-2019 tests 79/63 and laboratory function (ALT) 38.6mg/dL liver Initial limits. transaminase and (AST)/alanine normal 2334IU/L failure. was to transaminase within (LDH) respiratory declined aspartate dehydrogenase acute lactate were saturation of endotracheally mg/dL, oxygen (LFT) was 1.0 account via she her of oxygen (122 supplementation, on which creatinine oxygen of tachycardic ventilated demonstrated to on L mmHg, refractory mechanically mask hypoxia 6 132/87 and and on non-rebreather of dyspnea intubated 80% progressive a pressure was to to blood Due saturation escalation a 75%. oxygen with requiring Her (36.4) cannula arrival breaths/minute). Upon afebrile nasal (25 symptoms. was tachypneic progressively similar for she with had and home which department room, beats/minute) at cough emergency sick dry emergency also the a was the husband and to Her chills to presented fevers, week. reported preceding history patient the medical The during worsened known breath. of no shortness with of evaluation woman Chinese 44-year-old A presentation: ([email protected]) Case MD Raju, Gagan author: Corresponding 2 1 M.D. Jay, Exchange M.D. Plasma Elkayam, After Natalie thrombotic Improved COVID19 Angiopathy for Thrombotic exchange Associated COVID19 plasma of normalized; benefit Platelets possible initiated. exchange indicating plasma 50.7%, ADAMTS13. empiric CVVHD. normal resulted and despite requiring suspected level bilirubin, was ADAMTS13 rising TTP and improved; platelets, failure and she renal hemoglobin intubation, dropping requiring to failure Due respiratory COVID-19 for admitted Woman Abstract 2021 8, March 2 1 Peeke eateto ahlg,Mioie eia etr roln Y USA NY, Brooklyn, Center, USA Medical NY, Maimonides Brooklyn, Pathology, Center, of Medical Department Maimonides Oncology, and Hematology of Department amndsMdclCenter Medical Maimonides Center Cancer Maimonides 2 1 ek,Sehn M.D. Stephen, Peeke, ; 1 aa Raju Gagan , 1 aa au M.D. Raju, Gagan ; 1 1 atnBluth Martin , 1 lt,Mri,MD Ph.D. M.D. Martin, Bluth, ; 1 2 iuHuang Yiwu , 2 a Lipshitz Jay , 2 un,Yw,M.D. Yiwu, Huang, ; 2 n Stephen and , 1 Lipshitz, ; Posted on Authorea 8 Mar 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161522874.41200611/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. infiatipoeeti e lnclsau,bohmcly ylbrtr ausadwt significant with and values laboratory by experienced biochemically, patient status, The clinical results. ADAMTS13 for her suspicion pending in laboratory with and improvement initiated clinical significant was high a FFP a with to with presentation Due patient’s initial exchange infection. despite peripheral plasma the COVID19 (TTP), on TTP, concurrent purpura schistocytes of and of thrombocytopenic count addition, account number thrombotic platelet for significant In on normal for a concern concern considered of the infection. the presence raised also onset underlying raised The smear was rapid her infection changes. The inflammatory TTP to COVID19 and severe due without coagulopathic mentation. of angiopathy process normal context consumptive thrombotic with the by COVID19-induced and in induced count failure thrombocytopenia platelet renal possible normal and with thrombocytopenia presented of initially patient The Diagnosis Differential 1. Figure thrombotic-angiopathy-improved-after-plasma-exchange discontinued. image1.emf was exchange plasma therapy. file (drawn subsequently replacement level Hosted 50.7%, renal ADAMTS13 required at the longer resulted exchanges, consistent no plasma exchange) was patient consecutive field. plasma exchange The five power plasma of after high with However initiation per concurrent TTP. on schistocytes before improvement of smear in clinical diagnosis Peripheral decrease rapid the exchange. significant the with plasma a that improvement of demonstrated there- required was day clinical exchange subsequently presumption normalize third plasma and significant The eventually the of exchange showed exchange, on day and plasma volume also pressure fourth of increase blood the plasma patient day elevated to second initial The to continued the the due after and antihypertensives After levels exchange. requirement 68k bilirubin vasopressor plasma exchange. Total declining to daily plasma with initiation. 18k with of exchange from concurrent day plasma increased one of after, count day within one platelet 2.9 improvement: within her to significant 945 4.0 demonstrated to values from 3802 laboratory improved from patient’s improved with days. the level exchange consecutive exchange, five plasma LDH plasma underwent for of empiric patient (FFP) initiation commence plasma The After to frozen level. made fresh ADAMTS13 was of of decision volume receipt a blood angiopathy, of one thrombotic advance for in suspicion exchange clinical plasma high of ADAMTS13 account identified. On were lymphocytes Polymorphonuclear activated large 30-50k. some sent. around and was estimated cells count band testing many platelet granules, though manual toxic identified and were with observed clumps cells of with platelet were stippling No assessment platelets basophilic large field). occasional for power some red RBCs, 5-6/high obtained nucleated normochromic (approximately numerous identified was demonstrated polychromasia, schistocytes evaluation many some smear with Peripheral hematology (RBC) (TTP). values, cells purpura blood platelet thrombocytopenic and thrombotic hemoglobin possible dropping to negative. day Due was one antibody within admission. count (HIT) platelet her 65k/ thrombocytopenia Her throughout to induced demand transfusion. 243 stable Heparin to PRBC from remained received attributed dropped she count was and admission which WBC g/dL of ng/mL, Her 6.8 1.41 to to process. decreased hemoglobin up hemodiafiltration infectious to venovenous Her trended underlying up continuous troponin underwent to bilirubin Her patient due total The failure. worsening renal admission. and acute her worsening mg/dL), for of severe demonstrated days (CVVHD) 45/2.2 of 3 findings (BUN)/creatinine management within laboratory nitrogen for mL/dL her 4.0 urea care hospitalization, of her (blood standard of function the day renal one in Within indicated changes. as infection. infection pulmonary therapy COVID19 COVID19 no dexamethasone with received demonstrated consistent patient which opacities chest, The glass the ground of predominantly angiography bilateral, CT and underwent She infection. COVID19 acute eihrlserwt ueosshsoye seen. schistocytes numerous with smear Peripheral vial at available https://authorea.com/users/400277/articles/512609-covid19-associated- μ n ute erae o23k/ to decreased further and L 2 μ .Pl omsts a negative. was test Coombs Poly L. Posted on Authorea 8 Mar 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161522874.41200611/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. iie cl,priual o ainswt OI-9mconipty a ersn sfltreatment useful a COVID-19. References: represent of may manifestation microangiopathy, devastating sig- COVID-19 on particularly with pose used patients to a ex- exchange sure for for Plasma plasma is particularly consideration. immune COVID-19 that scale, scientific of for limited conceivable further reinstitution modality warrants a is evidence and therapeutic with emerging It a plasma improvement the as the challenges, reporting exchange in nificant [6][7]. literature plasma mediators infection employing of inflammatory While COVID19 of body removal homeostasis. with growing cytokine response patients a for dramatic ill to accounts a severely change adds exhibited in report that current exchange The microangiopathy plasma the thrombotic exchange. of COVID-19-associated plasma most a to in COVID19 level in had in ADAMTS13 impairment patient infection ADAMTS13 in Our suggesting COVID19 decrease study first with mild the was a patients This found documentation [5]. admitted 40–55). had also infection CI patients 50 They 95% of with on 2-4% smears. (47% about study subjects peripheral that COVID19 retrospective found on following They schistocytes a diagnosed values. of was out laboratory which various carried evaluated TTP they al of which al. case et [3]. a et. Albiol Covid-19 of by Martinelli of report diagnosis al. a the et also following Hindilerden is TTP [4]. by There autoimmune infection reported infection. acquired is COVID19 with case to diagnosed Another due woman [2]. TTP 57-year-old death secondary a of of of likelihood reports high case and are levels infection factor There severe Willebrand von indicate elevated to and schistocytes likely of more presence patients were LDH, that elevated found levels, patients [1]. ADAMTS13 ADAMTS13 COVID19-infected microangiopathy low in with with microangiopathy thrombotic along thrombotic activated secondary events viral evaluating mediated study of mi- A that complex triggers the suggested and immune underlying in been activation as and has trigger implicated storm it endothelial a are unclear; cytokine as to unique inhibitors remains by role a this related injury important of and endothelial mechanism be an infection The play direct COVID19 may viruses angiopathies. with coagulopathy thrombotic that association of this evidence complications, known pathogenesis is and that a There symptoms is postulated of /hemolysis. There array crovascular is 2020. wide It a in exhibit literature coagulopathy. to the found in been published have as infection COVID19 with Patients with consistent not intervention. exchange was plasma Discussion COVID19-induced profile to with diagnosed briskly coagulation was responded patient patient’s laboratory which our clear microangiopathy, angiopathy, The yet thrombotic thrombotic levels, a ADAMTS13 of normal field. evidence of pathologic power account and On high (DIC). coagulation intravascular per disseminated schistocyte in decrease SiH,Zo . eP ucsflteteto lsaecag olwdb nrvnu immunoglobin intravenous by followed exchange plasma A of treatment (2020). Successful P. al. He C., et Zhou Luca H., G., Shi Forni, 6. G., Salvagno, S., Friso, F., Pizzolo, purpura: M., thrombocytopenic Montagnana, thrombotic N., autoimmune Martinelli, associated 5. “Covid-19 al. associated et (TTP) Fehmi purpura Hindilerden, thrombocytopenic thrombotic 4. Autoimmune R. Martino Cell R., secondary Awol Stem for N., Evidence Albiol MR. 3. Gil Oncol. S, Rahman JD, Gonzalez-Lugo Hematol. GJ, Krause microangiopathies. M, Barouqa thrombotic JM, Sweeney Viral-associated 2. R. Silva da Lopes 1. naciial l ain ih21 oe ooaiu neto.ItJAtmco gns 2020:105974. Agents. Antimicrob J Int infection. coronavirus novel 2019 with patient ill 19. critically COVID 170–172 a in in 193: microangiopathy Sep; secondary 2020 a . of 193. presence Research. the doi:10.1016/j.thromres.2020.07.005 Thrombosis supports 136-138. deficiency (2020): ADAMTS13 195 relative vol. research Thrombosis case.” 10.1007/s00277-020-04097-0. a of doi: Report 28:1–2. May 2020 Hematol. Ann. COVID-19. with doi:10.1101/2020.10.20.20215608 23. Oct Preprint. 2020 COVID-19. in microangiopathy thrombotic 10.5144/1658-3876.2011.51. doi: 2011;4(2):51–59. Ther. 3 medRxiv 0022.02.0168 Published 2020;2020.10.20.20215608. . Posted on Authorea 8 Mar 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161522874.41200611/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ZagL,Za . aS,Ce . a .Ecc fteaetcpam xhnei eeeCOVID-19 severe in exchange plasma therapeutic of Efficacy Y. Gao J., Chen S., Ma H., Zhai L., Zhang 7. ains rJHeao.22 o:10.1111/bjh.16890 doi: 2020 Haematol. J Br patients. 10.1016/j.ijantimicag.2020.105974. doi: 4