Posted on Authorea 11 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161305496.61936521/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. e od:ftladnoaa lomuetrmoyoei;alimn entlnurpna HLA; 0 Figures: neutropenia; neonatal alloimmune 1 thrombocytopenia; Tables: alloimmune neonatal neonatal ; and hemolytic fetal drug-related words: FNAIT caused Key HLA title: running Brief 131; count: word Abstract 1615; count word Text Jiangsu Email: of 15253201708, 16 Tel.: No ,China, University, Province Qingdao [email protected] Shandong of Qingdao, Hospital of Affiliated District The Southern Neonatology, Road, of Department Sun, Mengya * 1 Sun Mengya and anemia antibodies hemolytic drug-induced leucocyte human maternal with associated neutropenia and thrombocytopenia alloimmune Neonatal entlalimn hobctpnaadnurpnaascae ihmtra human maternal anemia with Sun hemolytic Mengya associated drug-induced and neutropenia antibodies and antigen leucocyte thrombocytopenia alloimmune might donation Neonatal oocyte to due manifestations. clinical twin the HLA-incompatible transfusion cell of complete severity the red the that thrombocytopenia required markedly to hypothesize that severe developed contributed We (DIHA) provoked mother anemia have report twin. that hemolytic We the drug-induced this antibodies where ANN. addition, in anti-neutrophil In oocytes and detected donated or FNAIT twins. was by the anti- of of vitro of combination one in in the absence produced neutropenia antigen alone the and pregnancy leukocyte let in twin ANN, first Human antibodies a or HLA of FNAIT elevated antibodies. case in anti-neutrophil unusual result very by to a , caused reported here platelet frequently rarely against are is antibodies antibodies (ANN) with (HLA) associated neutropenia commonly neonatal is alloimmune (FNAIT) and thrombocytopenia alloimmune neonatal and Fetal Abstract 2021 11, February 1 h ffiitdHsia fQndoUniversity Qingdao of Hospital Affiliated The eateto entlg,TeAlae optlo iga nvriy China University, Qingdao to: of Correspondence Hospital Affiliated The Neonatology, of Department 1* 1 a Liu Yan , a Liu Yan , NI ea n entlalimn thrombocytopenia alloimmune neonatal and fetal Abbreviations FNAIT Abbreviations 1 ioQin Miao , 1 ioQin Miao , 1 igLi Ting , 1 igLi Ting , 1 ogJiang Hong , 1 1 n ogJiang Hong and , 1 1 Posted on Authorea 11 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161305496.61936521/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. tepe aia eiey eaenscinwspromdudreiua nshsa n iebr male refusing live-born members 2 family and and fetus anesthesia, pregnancy right epidural twin the the of under to pregnancy, and weeks due performed weeks, During was gestation, 26 2-3 section of positive. by at min, weeks cesarean differed Rh examination delivery, 5 37 twins vaginal and Ultrasound At the min, attempted type of fluid. hospitals. 1 O values amniotic other measurement was excessive for was and main had from type type points hospital the section blood blood that our fertilization-embryo 10 mother’s cesarean father’s revealed in vitro was The gestation the a check-ups in failure. score and regular by through ovarian Apgar (OD) had positive, to delivered donation due mother the Rh was donators) oocyte and He and different received type from g, infant weeks. were B the 2060 oocytes 37 of two was of mother (the weight September age transfer The on birth gestational min. delivered The a 10 was and infant with pregnancy. The G1P2 delivery. twin was after a He shortly bruising 2020. diffuse with 4, presented infant male anemia. A had tazobactam also and neonate sodium report The a anti-piperacillin Case by report HPAs. antigen-A2, we caused or ANN, HNAs leucocyte anemia rarely, to human antibodies. hemolytic more sodium antibodies by drug-induced and, detectable confirmed caused NAIT without we neutropenia for Finally, antibodies and etiology A68 Although thrombocytopenia an and ANN[5]. alloimmune as A24 and neonatal FNAIT reported neutrophils, cause and of been to neutrophils case seldom of and have platelets surface on antibodies the act on HLA can distributed antigens antibodies act are I neutrophil antigens anti-HLA-class that human I and inherited (HLA)-class antibodies paternally antigen produce leukocyte neonatal Human to or fetus mechanism neutropenia[4]. the similar in of a resulting antigens is (HNAs), uses surface complication neutrophil also utero[3]. severe serious the in (ANN) to on most occurs severe neutropenia (ICH) The moderately hemorrhage neonatal with intracranial observed. Alloimmune neonates of be In 80% may approximately Se- platelet 1a. and bleeding FNAIT. causing (HPA) hemorrhage[2], antigens, in and antigen intracranial involved surface platelet bruising, are platelet by petechiae, antibodies neonatal caused thrombocytopenia, or corresponding mostly fetal their is immunoglob- on and FNAIT produces acts antigens vere mother that platelet The Numerous pregnancy. the during destruction[1]. through antigens surface (IgG) incompat- platelet G the maternal by ulin caused and disease fetal alloimmune an of is ibility (FNAIT) thrombocytopenia alloimmune HLA; neonatal and Fetal neutropenia; neonatal alloimmune thrombocytopenia; Introduction manifestations. alloimmune clinical neonatal neonatal the anemia; of twin and hemolytic severity HLA-incompatible fetal drug-related the complete to red the contributed words: required that have that hypothesize Key might We (DIHA) donation anemia twin. oocyte hemolytic this twin to drug-induced thrombocytopenia in first due addition, severe detected a pregnancy provoked In was anti- of that twins. transfusion HLA case antibodies the elevated cell unusual anti-neutrophil markedly of blood very one developed or a in mother anti-platelet here neutropenia the of FNAIT report and where absence We in oocytes the ANN. result donated in and to by bodies FNAIT reported vitro of in rarely anti- combination by produced are the caused pregnancy anti- antibodies alone frequently (HLA) with let is antigen ANN, associated (ANN) leukocyte or neutropenia commonly Human neonatal is alloimmune antibodies. (FNAIT) and neutrophil antigens, thrombocytopenia platelet alloimmune against human neonatal bodies maternal and Fetal anemia with hemolytic Abstract: associated drug-induced and neutropenia antibodies and antigen leucocyte thrombocytopenia alloimmune Neonatal P ltltantigen platelet anemia hemolytic drug-induced antigen leukocyte human neutropenia neonatal alloimmune HPA DIHA HLA ANN 2 Posted on Authorea 11 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161305496.61936521/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. pcfiiyTp yeType Type 5886.43 5887.53 9218.72 Type Other B51(B*51:01) B51(B*51:02) A69(A*69:01) 11093.89 11560.24 11804.51 Specificity infant the B 12596.31 in and antigens A 13308.81 HLA I Class 13345.24 A24(A*24:02) 14004.46 A2(A*02:06) A2(A*02:01) A24(A*24:03) A2(A*02:03) A68(A*68:01) A68(A*68:02) Type) (Specificity/Gene Positive infant. Strong the of mother’s typing the B in and antibodies A HLA HLA I and Class mother the in present we antibodies , I anti-HLA class the HLA of children. cause the the positivity. of strong is 1 antigen showed Table incompatibility I and antigen class children HLA I and HLA-A24 mother the class Anti-HLAA2, the tested anti-HLA of further positive. that sera were prove were the antibodies in further I antibodies detected To class anti-HNA birth. were anti-HLA and after antibodies but day HLA-A68 children, antibodies and 10th and anti-HPA transfused, mother the determinants, were the on antigenic in (WRBCs) g/L negative glycoprotein 100 cells of of blood level detection red a For Washed drug-induced reached microcolumn confirmed hemoglobin (MGT-AGTs). with and we tests antibodies given, and antibodies sodium globulin was irregular phototherapy considered, tazobactam antihuman and and was and positive, sodium tests antibodies RhD anti-piperacillin and gel acquired by O by caused group anemia were caused reached infants hemolytic hemoglobin during the days, given positive, three was negative. was for factor test were sodium Coombs stimulating tazobactam The and colony g/L. sodium 68 10 piperacillin no received with x and treatment then 0.41 immunoglobulin, After He NICU. after was level temporarily count platelet significantly. The rise lowest rise can mother. the not infant’s and did the leukocyte-depleted 10 continuously, with count with x decreased matched transfused 120 platelet and was than the he irradiated more the to were first, but month, increased At that first each), platelets each). the with ml/kg A g/kg treatments (1 During vitamin (10 two IVIG fibrinogen. received times of hemorrhage. supplement He doses three intracranial to 10 platelets negative. no twice of total was showed transfusion sodium a culture birth received piperacillin bacterial infant after and with examination bleeding blood treated ultrasound stop the was He head to and (NICU). days, sulphenamide unit four and care analysis for K1 intensive gas sodium neonatal the Blood tazobactam to and negative. admitted was was 2 (TORCH) normal. for Infant generally pathogens thrombin (IgG) were other sec, G examination of Immunoglobulin 85.2 and biochemical count g/L. was virus blood (WBC) 1.13 time simplex and cell was thromboplastin herpes fibrinogen blood partial virus, and activated white cytomegalic presented sec, sec, a infant 19.40 19.20 revealed 43 was The was count time rate time blood g. prothrombin breathing complete 2060 infant The beats/min, weight The 123 and skin. rate kPa), the mmHg=0.133 heart 3.29x10 on (1 36.0, bruising mmHg diffuse temperature 54/26 with physical follows: pressure were on as membrane blood found was were fetal beats/min, abnormality and results obvious placenta no examination and the The g, and 3240 fluid, was 1 amniotic infant clear of weight had examination. birth them The of intact. Both delivered delivered. were infants 9 L bouenurpi on f1.38x10 of count neutrophil absolute /L, niesi h infant the B in and antigens A HLA I Class Positive MFI serum mother’s the in antibodies HLA I Class 9 Ladfial oapoiaey7-7x10 72-97 approximately to finally and /L 9 L eolbno 6 /,adpaee on f3 10 x 32 of count platelet and g/L, 164 of hemoglobin /L, 3 niesi h infant the B in and antigens A HLA I Class Type) (Specificity/Gene serum mother’s the in antibodies HLA I Class 9 Lo h 5hdyatrbrh Neutrophils birth. after day 25th the on /L a 9 Lbfr icag.Neutrophils discharge. before /L Toxoplasma niesi h infant the B in and antigens A HLA I Class MFI serum mother’s the in antibodies HLA I Class uel virus, rubella , 9 /L. Posted on Authorea 11 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161305496.61936521/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. rqetcue fDH ae narve fcs eot rm21–06 hsrve loexamined sequence, chronological also review account: This into taken 2010–2016. be from must reports elements case core are of several cephalosporins review and and penicillins a DIHA, but on of million/year, based per probability is reported 1 DIHA (DAT) the D[15] only Renard of test approximately antiglobulin nonimmune[14]. causes is or direct DIHA for frequent immune of The as sodium incidence destruction (DIHA). the RBC the tazobactam (DAT) anemia of of that hemolysis hemolytic and test cause and the drug-induced antiglobulin sodium classifying detected, be direct for were piperacillin invaluable to antibodies The with sodium confirmed tazobactam HLAs. treatment by was and characterized present infant after birth sodium are not Anti-piperacillin the occurred NAIT do days. However, and/or anemia erythrocytes three ANN (LBWI). and mature antibody-induced infant positive, as HLA weight NICU. was anemia, birth difference. the of low the in absence explain a 2 the may infant is results in which These occurred g, g. Anemia 2060 3240 was was neonates. 1 thrombocytopenic 2 infant among infant a of weight was had weight of placental antibodies and antibodies weight I weight class I birth birth anti-HLA class maternal with The of anti-HLA associated level inversely with increasing and An mothers linearly controls. to than weight born birth neonates was lower wassignificantly culture considered. thrombocytopenic bacterial counts.G-CSF not that blood was neutrophil showed and increased, infection and Dahl[13] not FNAIT of platelets platelet were for possibility of increasing indicators reason the inflammatory surfaces in the and infant’s effective The be negative, anti-HLA- The may is also NICU. anti-HLA-A2, antibodies 2. the transfusion anti-HLA found in infant IVIG the given we and that not infants. However, serum believe in We mother’s and ANN HLA. 2. anti-HPA the same and infant no the both in have found in do investigation or antibodies neutrophils immunohematological serum anti-HLA-68 The mother’s and the the enough. A24 confirm, in to strong and difficult antibodies is HLA and case anti-HNA exclusion for of the test diagnosis in to a 1 refused correlation is 1 members infant FNAIT/ANN infant antibody-mediated family why and anti-HLA the is mother Although However, which between 2. HLA different, 1. infant the completely infant between that in be that hypothesize antibodies may In We than B55 genotype compatible B51 A68 . thrombocytopenia. HLA more HLA A2 OD of is the that uncomplicated symptoms carrying suggesting and show successful not oocytes expected, the match- of two did HLA than for development of the pregnancies relevant the degree case, OD be for higher our uncomplicated significantly beneficial could a in be recipients observed children might and they compatibility and donors and mothers pregnancy, between between OD antigens. compatibility in HLA ing HLA allografts I from high fetal class that were of the for found first survival to homozygous oocytes al.[12] a were contributed two have which of et the might antibodies, case Lashley donation; donation mother’s unusual the semen oocyte very macrophages of B55 to and a intensity B51 due fetal oocyte here fluorescence pregnancy A68 to by median report twin A2 alloantibodies fertilization we HLA-incompatible However, vitro of donors. in two binding destruction. produced platelet or contro- pregnancy fetal cells, placental still twin of differential neonatal is as inhibition FNAIT/ANN on such in discrepancy, of expression this resulting cause address HLA the to reduced considered postulated cause women be been absorption, rarely pregnant have can antibodies of theories[8-11] anti-HLA antibodies 18-30% Several While anti-HLA In versial. whether detected[7]. method[6]. women ANN, be Luminex pregnant preg- or can sensitive of of FNAIT antibodies more 49.3% 7%-39% anti-HLA the technology, pregnancies, Approximately with of multiple B55 detected development women. with B51 be the pregnant can With of antibodies A68 serum antibodies. with A2 the anti-HLA develop in women common nant very are antibodies Anti-HLA Discussion B62. and B37 B67, B42, B56, a B A te:ohrseicte ihatbde ihMFhge hn10:B8 3,B3 1,B2 5,B76, B55, B72, B18, B53, B35, B78, 1000: than higher MIF with antibodies with specificities other Other: 4 Posted on Authorea 11 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161305496.61936521/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. Table.pdf file Hosted interest. of conflict no is there that declare authors The effective are INTEREST IVIG OF and CONFLICT Corticosteroids diagnosis. differential anemia. and treating in evidence, objective data, epidemiological Rnr ,Rsee .Du-nue eoyi nma hraooia set.Tasu lnBiol. Clin Transfus aspects. the Pharmacological in anemia: step hemolytic critical Drug-induced a A. test: Rosselet antiglobulin D, direct Renard The 15. CS. Cohn Jr, DR Tharp anti-HLA SA, Maternal Koepsell H. ND, Tiller Zantek B, Straume 14. B, Skogen TB, Stuge K, Flo in G, matching Acharya A, HLA Husebekk of J, advantage Dahl Selective 13. FH. Claas M, meaningful? Spruyt-Gerritse or GW, myth Haasnoot 2000 thrombocytopenia: LE, alloimmune Lashley Rev. fetomaternal Med 12. Transfus and IgG. antibodies maternal HLA of E. transfer Taaning the 11. and receptors Fc Placental EK. Kristoffersen 10. Kn E a J ryP,CslaJ,BaeoeK alnN,KneyS,KclrT.The TS. Kickler SD, Kennedy NA, Callan K, Blakemore JF, H. Casella Yamada PF, I, Bray Morioka KJ, M, Kao Hashimoto KE, Y, King Ebina 9. M, Deguchi K, Tanimura M, Morizane M, significance and Uenaka appearance of 8. time incidence, the of study Platform. prospective Luminex A DP. Using Hill PR, Antibodies Braude Anti-HLA L, Regan Pregnancy-Induced of 7. Analysis A. Nieto M, Vilches 6. hu- against antibodies of Implication S. Chabra H, Ji P, Warner M, Gallagher G, Teramura Hiraoka I, Gimferrer S, Saito 5. T, Kamijo Y, Kurokawa Y, Nakazawa T, Ishida K, Sakashita K, Koike R, Ranasinghe WH, Hagimoto Ouwehand 4. LM, Williamson D, Allen and GA, Smith review J, Walton literature K, Campbell a C, Ghevaert thrombocytopenia: 3. alloimmune Feto-maternal RF. Clin Burrows Res JA, Pract Best Spencer 2. thrombocytopenia. alloimmune neonatal and Foetal D. Oepkes D, Winkelhorst 1. 07Sp2()1014 o:1.06jtal.070.1.Eu 07Jn2.PI:28648734. PMID: 23. Jun 2012 2017 Epub Epub 10.1016/j.tracli.2017.05.013. 10.1002/ajh.23218. doi: doi: Sep;24(3):110-114. 2017 Jul;87(7):707-9. 2012 22566278. Hematol. PMID: J 6. Reprod Am 26547815. May J PMID: hemolysis. 29. neonates. of Oct thrombocytopenic evaluation 2015 in Epub weight 10.1016/j.jri.2015.10.003. birth doi: reduced Feb;113:27-34. with 2016 associated Immunol. are antibodies doi: I class Nov;112:29-33. 26232147. 2015 PMID: Immunol. 23. Reprod Jun 2015 J Epub pregnancies. 10.1016/j.jri.2015.05.006. donation oocyte 10914422. uncomplicated PMID: successful 10.1053/tm.2000.7397. doi: Jul;14(3):275-80. 2000 Rev. Med Transfus 1996 10914418. Antigens. PMID: Tissue 10.1053/tm.2000.7393. doi: study. Mar Jul;14(3):234-43. prospective a 2019 8740770. PMID: thrombocytopenia: Sci. neonatal 10.1111/j.1399-0039.1996.tb02542.x. Med in doi: J antibodies Mar;47(3):206-11. Kobe HLA of role Cases. Four of PMC6668651. PMCID: Report 31327862; A PMID: 5;64(6):E197-E199. Thrombocytopenia: Alloimmune Feb;6(2):294-8.Neonatal 1991 Reprod. Hum 2056027. PMID: pregnancy. human 10.1093/oxfordjournals.humrep.a137325. in doi: antibodies lymphocytotoxic anti-paternal 26680049. of PMID: 10.1016/j.transproceed.2015.09.032. doi: Nov;47(9):2608-10. 2015 Proc. Transplant 10.1016/j.transci.2018.09.018. 30318177. doi: PMID: Dec;57(6):773-776. 29. 2018 thrombocytope- Sep alloimmune Sci. 2018 neonatal Apher Epub and Transfus fetal neutropenia. of and presentation alloimmune nia simultaneous of in antigen case leukocyte a man in antibody HLA maternal 10.1046/j.1537-2995.2001.41050615.x. for doi: 11346696. role May;41(5):615-20. PMID: possible 2001 Transfusion. A A. neutropenia. neonatal Komiyama M, 10.1111/j.1479- Kobayashi A, doi: Transfusion. 17465957. PMID: thrombocytopenia. alloimmune Feb;41(1):45-55. 10.1111/j.1537-2995.2007.01208.x. fetomaternal doi: of 2001 cases May;47(5):901-10. 200 2007 of outcome Gynaecol. and Management Obstet E. J Z N 11284646. PMID: Aust 828x.2001.tb01293.x. PMID: analysis. 6. Feb statistical 2019 Epub 10.1016/j.bpobgyn.2019.01.017. doi: Jul;58:15-27. 30827816. 2019 Gynaecol. Obstet vial at available https://authorea.com/users/395130/articles/508457-neonatal-alloimmune- 5 Posted on Authorea 11 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161305496.61936521/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. antibodies-and-drug-induced-hemolytic-anemia thrombocytopenia-and-neutropenia-associated-with-maternal-human-leucocyte-antigen- 6