Posted on Authorea 2 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161737224.42943852/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. akPepin Mark Stroke Cardioembolic Recurrent as Manifesting Purpura Thrombotic Thrombocytopenic Immune-mediated “Smoldering” of Case A akE Pepin E. Mark Stroke Manifest- Cardioembolic Purpura Recurrent Thrombocytopenic as Thrombotic ing Immune-mediated “Smoldering” of Case longstanding A as educational manifesting offer iTTP. We man of variants years. 62-year-old chronic 3 a atypical, of in of period (iTTP) identification a TTP over the immune-mediated thrombogenesis regarding valvular of insights and case strokes, a cardioembolic recurrent describe we thrombocytopenia, report, current the In Abstract 2021 2, April 1 1 reesbemnfsain fti aeadqikyftlhmtlgcdsre.UtetdTPi yial a typically is TTP Untreated disorder. hematologic the prevent fatal to quickly critical and is rare (TTP) this purpura of thrombocytopenic manifestations thrombotic irreversible of treatment and recognition Prompt Abstract [email protected] E-mail: 35294-0015 AL Birmingham, 2503 NP 2 1720 Hematology/Oncology of Division Medicine, of Department Birmingham at Alabama of University M.D. May, Jori *Correspondence: References: Figures: Count: Word USA 35294, Title: AL Running Birmingham, Birmingham, at Alabama of University eto imdclEngineering, Biomedical of Dept h nvriyo lbm tBirmingham at Alabama of University The nd vneSouth Avenue 2 1 9 1 ydSaca Eyad , ydSaca Eyad , 1,697 mleigimn-eitdTTP immune-mediated Smoldering 2 o .Kwon Y. Soo , 1 o on Kwon Young Soo , 2 eto Neurology, of Dept 2 n oiMay Jori and , 1 n oiMay Jori and , 1 3 eto eiie iiino Hematology/Oncology; of Division Medicine, of Dept 3 * 1 Posted on Authorea 2 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161737224.42943852/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. rae hn6shsoye e ihpwrfil.AAT1 ciiywsotie tti ie measuring time, this at obtained was activity ( ADAMTS13 performed field. was power smear high blood per peripheral schistocytes a 6 than thrombocytopenia, greater his of thrombocytopenia causes his evaluate To Meanwhile, unrevealing. 30,900/mm altogether bioprosthetic to was the decreasing days worsened, ensuing of had the side in atrial workup the trans-esophageal infectious follow-up to tensive a attached valve; mass mitral ( multilobed bioprosthetic leaflet his 1.3x0.7cm also of MRI a leaflet The demonstrated territory. mitral ma- echocardiogram ACA anterior left the and to the occlusion, adjacent in (ACA) material stroke ( artery ischemic infarcts acute cerebral prior an multiple anterior confirmed showed left (MRI) a imaging resonance revealed evaluation gnetic angiogram Laboratory (CT) murmur. tomography 58,200/mm diastolic Computed of apical count disease). left kidney platelet chronic harsh 9.4g/dL, known a with of with man and hemoglobin alert an aphasia, a revealed receptive revealed examination Physical and stable. expressive hemodynamically and severe afebrile was he admission, stroke. history On (Humira initial a adalimumab revealed his also given to Records was presentation. prior he current year his which one of for time psoriasis, the MCA until plaque right this valve twoof the take (Eliquis mitral to in as continued apixaban ischemia bioprosthetic he with well (multifocal and requiring stroke stroke stroke, treatment as prior identified, second first began two was his his stroke, Following he vegetation of had ischemic distribution), endocarditis. valve time He acute for the mitral concern At for large member. for (TIAs). presentation replacement a family attacks altered occlusion), a to ischemic acutely transient MCA by prior with suspected (right down years for department found two visits emergency was department our the emergency he to within after presented admissions weakness who man right-sided hospital 62-year-old and a status of mental case the report and up We fever, in fatal injury, rapidly kidney is Presentation acute iTTP Case exchange, anemia, [5]. plasma patients hemolytic via of treatment microan- thrombocytopenia, 90% prompt thrombotic to factor of Without in Willebrand pentad [4]. results von member sequelae TTP classic resultant neuropsychiatric of in motif, and a cleavage activity platelets 1 ADAMTS13 with proteolytic of decreased type aggregation the giopathy Thus, spontaneous for thrombospondin the [3]. responsible mitigating a thrombosis in- fragments, microvascular is with multimeric an ADAMTS13 inactive rarely metalloproteinase into more 2]. and (vWf) or [1, disintegrin (iTTP), (ADAMTS13) immune-mediated a 13 an of be deficiency can herited (TTP) purpura 13. thrombocytopenic member Thrombotic motif, 1 type artery; thrombospondin cerebral a middle Introduction with MCA, metalloproteinase artery; and cerebral disintegrin anterior a ACA, ADAMTS13, purpura; thrombocytopenic thrombotic TTP, adalimumab Abbreviations stroke, thromboembolic microangiopathy, purpura, thrombocytopenic of Thrombotic form “smoldering” under-recognized of an identification TNF represents Keywords the a likely regarding adalimumab, insights case of educational this contribution several since potential iTTP. offer iTTP, the We of support iTTP. presentations to of atypical development evidence as the correlative manifesting In period provide to man a 62-year-old We inhibitor, treatment. over a thrombogenesis appropriate years. in valvular (iTTP) of 3 and TTP absence strokes, of immune-mediated cardioembolic the of recurrent case in thrombocytopenia, a days longstanding describe within we 90% report, current exceeding the mortality with disease rapid-onset i.1B Fig. .Gvncnenfrbceiledcrii,eprcatboiswr tre.Hwvr ex- However, started. were antibiotics empiric endocarditis, bacterial for concern Given ). i.1A) Fig. 3 w-iesoa rn-hrccehcriga hwdechogenic showed echocardiogram trans-thoracic Two-dimensional . ytetidiptetday. inpatient third the by 2 ® wn ocnenfrrcretcardioembolic recurrent for concern to owing ) ® 3 n raiieo .m/L(consistent 1.7mg/dL of creatinine and , o h attreyas approximately years, three last the for ) i.1C Fig. ,revealing ), α Posted on Authorea 2 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161737224.42943852/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. fiT.Lsl,tecretcs nesoe h motneo ytmtcciia praht obtain to approach clinical systematic presentations. atypical a for of even Statement importance iTTP, Ethics of the treatment underscores and re- iTTP- case recognition and with prompt current resolved TNF thrombocytopenia both the that support chronic Lastly, thrombogenesis to iTTP. as valvular evidence recurrent manifested of correlative provide of which We setting iTTP therapy. the directed “smoldering” in apparent strokes of cardioembolic current case a report We concern of TNF out to diagnosis iTTP relapse. due Conclusion a following deficiency trigger suspended to ADAMTS13 was potential adalimumab acquired a patient’s as that our decline aware count Nevertheless, contributed have platelet not may reported. his are medication of this timing we suggests the however, psoriasis verified, plaque be of cannot treatment ( iTTP for patient’s initiation this adalimumab for additional and trigger of avoidance precise the the and While diagnosis iTTP eval- earlier smear iTTP in peripheral during of resulted with events. unrecognized have identification, cases thromboembolic could largely prompt previous schistocytes, was whether identify rare, of thrombocytopenia recurrent to question Although of patient’s the uation had The raising absence therapy. patient events, iTTP-directed [6]. stroke the the previous of reported in two thromboem- that initiation been of iTTP have fact since resolution endocarditis to year the experienced with one related by has for was supported and events and anticoagulation, is bolic appropriate thrombus possibility despite valve ( this stroke prior mitral diagnosis, thromboembolic PEX years the at of the that initiation testing in prove with present ADAMTS13 throm- normalized was definitively of count iTTP cannot period platelet of multi-year we his form preceding that “smoldering” patient’s fact a the the suggests stroke, during checked thromboembolic not a and was report bocytopenia level we thrombo- ADAMTS13 Herein, progressive an chronic, Although treatment. with and stroke. presenting recognition thromboembolic recurrent iTTP prompt and of without cytopenia variant disease “smoldering” fatal under-recognized, rapidly iTTP. potentially a for treatment classically of is his initiation after iTTP the year since one events approximately thromboembolic composition, further manuscript Discussion no of had time splenec- has the ultimately He at and vincristine, remission diagnosis. ADAMTS13 caplacizumab, in undetectable iTTP was had with of patient treatment recurrence disease again the and receiving His was count year, titer, tomy. PEX subsequent platelet inhibitor values. in the elevated decline undetectable In an by to with remission. confirmed ADAMTS13 achieved iTTP of patient of return the relapses cessation, and and multiple PEX LDH, rituximab, after in with shortly rise along relapsed count, initiated, patient platelet the in Unfortunately, drop baseline. with pre-admission to returning status ( daily to nisone recovered count ( bacterial focal platelet count a platelet The with his than thrombus in thrombus decline fibrin aseptic 3-year a an gradual, replacement. of a described revealed descriptive report also more records The < finding his reviewed. a of was tissue, Review evaluation vegetation. valve vegetation pathologic pathology, mitral valve valvular fibrotic recurrent mitral patient’s underlying original the of his testing explanations additional of repeat for equivocal, search initially of the was titer In it a although with measured; iTTP also for was diagnostic titer was inhibitor ADAMTS13 The TTP. < iue2A Figure % hrfr,teaetcpam xhneteay(E)wspopl ntae o h ramn of treatment the for initiated promptly was (PEX) therapy exchange plasma therapeutic Therefore, 1%. .0)( 0.001) i.2A Fig. i.2B Fig. .Aaiua a enrpre ocuetrmoyoei i te ehnss[7-9]; mechanisms other via thrombocytopenia cause to reported been has Adalimumab ). ,aptenitrutdol ytemlil rnfsosrcie uigmta valve mitral during received transfusions multiple the by only interrupted pattern a ), .Teptetbgnsoigeiec fsmtmtcipoeet ihhsmental his with improvement, symptomatic of evidence showing began patient The ). > 150,000/mm > . niio units. inhibitor 8.0 3 fe al ramnswt E ln ih8m pred- 80mg with along PEX with treatments daily 3 after 3 α niiina e-neonzdtrigger yet-unrecognized a as inhibition Figure2A α .Frhroe although Furthermore, ). niiinhsytbeen yet has inhibition ρ 052 P -0.592, = Posted on Authorea 2 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161737224.42943852/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. inifrto n utpepirinfarctions. prior multiple and infarction tion A. 1. Figure 1 Figure Figures 2012. Colitis, al., Crohns et M.J., Casanova, 9. al., et ustekinumab. and T., secukinumab Nakahara, 8. al., et disease. A., Salar, 7. 2018. Adv, J.N., George, 6. Group. Study Apheresis Canadian al., purpura. et thrombocytopenic G.A., Rock, 5. Literature. Ultmann, J.E. of and E.L. Amorosi, 4. purpura. thrombocytopenic thrombotic al., in et involved X., Zheng, 3. recipient. allograft renal a in al., et P.T., Pham, 2. al., activity. protease et factor-cleaving K., Willebrand Kokame, 1. References disclose. to nothing have authors The fellowship postdoctoral statement and Disclosure (HL137240) Foundation. grant Humboldt F30 von NRSA NIH Alexander a the by M.E.P. through case. to provided his was of support publication Training acknowledgements the for and consent funding values, provided Owing of laboratory next-of-kin confidentiality. Sources patient’s all his the condition, 1996, preserves that of poor manner patient’s Act a Accountability the in presented to and are Portability information Insurance patient and Health images, the with accordance In u,2007. Gut, 2 1) .1510-1516. p. (12): eiie 1966. Medicine, xa 2FARmgei eoac mgn eosrtn h ct etAAdistribu- ACA left acute the demonstrating imaging resonance magnetic FLAIR T2 Axial h eakbedvriyo hobtctrmoyoei upr:aperspective. a purpura: thrombocytopenic thrombotic of diversity remarkable The 56 niia n dlmmbidcdtrmoyoei nawmnwt ooi Crohn’s colonic with woman a in thrombocytopenia adalimumab-induced and Infliximab tutr fvnWlern atrcevn rtae(DMS3,ametalloprotease a (ADAMTS13), protease factor-cleaving Willebrand von of Structure niioso DMS3 oeta atri h as ftrmoi microangiopathy thrombotic of cause the in factor potential a ADAMTS13: of Inhibitors 6 oprsno lsaecag ihpam nuini h ramn fthrombotic of treatment the in infusion plasma with exchange plasma of Comparison 8:p 1169-70. p. (8): 1) .1034-7. p. (10): uain n omnplmrhssi DMS3gn epnil o von for responsible gene ADAMTS13 in polymorphisms common and Mutations eeeaaiua-nue hobctpnai ain ihConsdisease. Crohn’s with patient a in thrombocytopenia adalimumab-induced Severe hobctpnai srai ain eunilytetdwt adalimumab, with treated sequentially patient psoriatic a in Thrombocytopenia rnpatto,2002. Transplantation, 45 emtl 2019. Dermatol, J 2:p 139-+. p. (2): hobtcTrmoyoei upr eoto 6CssadReview and Cases 16 of Report - Purpura Thrombocytopenic Thrombotic rcNt cdSiUSA 2002. A, S U Sci Acad Natl Proc B. ilCe,2001. Chem, Biol J 46 w-iesoa rn-spaelehcrigah of echocardiography trans-esophageal Two-dimensional 4 74 5:p e157-e158. p. (5): 8:p 1077-80. p. (8): nlJMd 1991. Med, J Engl N 276 4) .41059-63. p. (44): 99 1) .11902-7. p. (18): 325 6:p 393-7. p. (6): Blood J Posted on Authorea 2 Apr 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161737224.42943852/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. PX.Frbt rps h oe ii fnra LN ltltlvl r shown. are levels platelet (LLN) exchange normal plasma of therapeutic limit of intervals lower three linear the and graphs, Simple (Dx) both (MVR). iTTP For with performed. replacement (PEX). were diagnosis valve shading) noting (gray mitral interval admission, thromboembolic confidence throughout prosthetic 95% and and with line) (CVA) decline (black accidents regression platelet cerebrovascular between 3 noting correlation A. negative Longstanding complications. 2: Figure cardioembolic-stroke smoldering-immune-mediated-thrombotic-thrombocytopenic-purpura-manifesting-as-recurrent- image2.emf of file initiation Hosted to prior smear 2 blood Peripheral Figure C. vegetation. therapy. 1.5cm exchange a plasma demonstrating valve mitral prosthetic vial at available he-ertedo eraigpaee eessneiiito faaiua (adal.), adalimumab of initiation since levels platelet decreasing of trend Three-year https://authorea.com/users/405474/articles/516437-a-case-of- 5 B. ltltlvl plotted levels Platelet