Pregnancy-Induced Haemolytic Anaemia: a Case Report from Ile-Ife, Nigeria

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Oluwaseun, Adepiti C. Akinfolarin, Asafa M. Abiola, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4770119/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Haemolytic anaemia, though uncommon, may occur in pregnancy. A rarer variant, Idiopathic haemolytic anaemia or Coomb-negative haemolytic anaemia has been described. This causes haemolysis during pregnancy and spontaneously resolves after delivery, only to recur during subsequent pregnancies, with the woman being entirely symptom-free during her non gravid state. We encountered a clinical scenario that typifies this rare clinical presentation in a 31-year-old unbooked G5P3+1 (2A) +1 perinatal mortality referred from a private hospital at an estimated gestational age of 32 weeks +4 days. Her clinical history and investigations were suggestive of idiopathic haemolytic anaemia of pregnancy. She was managed with haematinics, had 4 units of blood transfused, and was commenced on glucocorticoids. She was then counseled for and had a scheduled caesarean section at EGA of 34 weeks +0D on account of concomitant fetal malpresentation and was delivered of a live male neonate with no signs of jaundice. The patient recovered with dramatic resolution of the yellowness of the eyes postpartum and was discharged on postoperative day 5 with normal indices and was discharged alongside her baby in stable condition. The rare incidence of this clinical presentation and a favourable fetal and maternal outcome, in this case, merits its presentation. Hemolytic anemia Coomb’s negative Pregnancy Blood transfusion Perinatal Morbidity Introduction Anaemia in pregnancy is a common problem in pregnant women worldwide, affecting nearly 50% of pregnancies globally. 1 2 Aetiologic factors of anaemia in pregnancy such as iron and folate deficiency are common and related to nutritional deficiency and/or intestinal helminthic infections while other forms such as hemolytic anaemias are infrequent causes of anaemia in pregnancy 3 Regardless of the aetiology, anaemia in pregnancy is associated with increased maternal morbidity, impairment quality of life in women, need for blood transfusions, post-partum haemorrhage, as well as maternal mortality while intrauterine growth restriction, low birth weight, preterm delivery, and perinatal death are adverse fetal outcomes that could result in pregnant women with background anaemia 1 4 5 6 A rare form of hemolytic anemia known as “pregnancy-induced hemolytic anemia”, a condition in which moderate to severe hemolytic anaemia occurs only in pregnancy, resolves spontaneously after delivery and recurs in subsequent pregnancies has been reported. 7 Most of the reported patients are young women who present with hemolysis usually during the 3rd trimester, although in some, mild to moderate hemolysis can be detected earlier during the 1st or 2nd trimester. 7 We encountered a 31 year old unbooked G5P3 + 1 (2A) + 1 perinatal mortality with the only clearly identified association with recurring hemolytic anaemia being a gravid state who presented with jaundice and severe anaemia in her third trimester with spontaneous resolution of her symptoms following delivery. Case Report A 31-year-old seamstress at 32 weeks + 4 days gestation was referred to our facility on account of complaints of yellowness of the eyes and progressive body weakness of a month duration, with associated easy fatigability and pallor. There was no history of bleeding per vaginum or rupture of membranes, and she perceived fetal movements adequately. She had been receiving pregnancy care at a maternity home and had no complaints prior to onset of the symptoms. She had initially presented after 2 weeks of onset of symptoms to a private hospital where she was noted to have a packed cell volume of 10% and had 5 units of blood transfused. She was subsequently referred to our facility with a post transfusion packed cell volume of 22% for further evaluation and multidisciplinary care She had no antecedent febrile illness, cough or urinary symptoms and had only been on routine iron supplements and folic acid. She had no family or personal history suggestive of a bleeding disorder. Her haemoglobin genotype was AA. She had similar history of yellowness of her eyes in her previous pregnancies with mild degrees of body weakness and complete resolution of symptoms following vaginal delivery at term in her first and second confinement Her last (third) confinement however resulted in an adverse perinatal outcome (stillbirth). She had presented on referral from a private hospital on account of jaundice, severe anaemia and intrauterine fetal death at estimated gestational age of 31 weeks + 3 days. She had cervical ripening and induction of labour following optimization with a total of 6 units of blood and subsequently delivered a macerated male fetus. She however requested to be discharged against medical advice on account of financial constraints and defaulted from postpartum follow up She also gave a history of a spontaneous first trimester miscarriage after her first childbirth, the cause of which was not established At presentation in our facility, she was examined and found to be pale and icteric. Her body temperature was 36.9 degrees Celsius, pulse rate of 112 beats/min and she had a blood pressure of 120/60 mm Hg. There was a loud apical systolic ejection murmur on cardiac auscultation. There was hepatomegaly with the liver palpable at about 6 cm below the right costal margin and the spleen was 4 cm below the left subcostal region The symphysiofundal height corresponded to 31 weeks of gestation. Fetal heart rate was 136 beats/min. Laboratory investigations revealed a packed cell volume of 22%, a reticulocyte count of 4%, and a negative direct Coombs test. Her White blood cell count (WBC) and platelet counts were within normal limits. She had no malaria parasite seen on blood film appearance. Her retroviral screening was negative. Screening test for G6PD deficiency and osmotic fragility test were normal. Liver function test revealed elevated serum aspartate aminotransferase of 70 IU and alanine aminotransferase of 44 IU. She also had hyperbilirubinemia with a total bilirubin of 145 µmol/L and conjugated bilirubin of 107 µmol/L. Stool microscopy was negative for ova of parasites and occult blood. Her blood group was “AB” positive. On further workup, lactate dehydrogenase was observed to be raised to 502 mU/mL. She had normal values for other biochemical investigations such as serum electrolytes, urea and creatinine, blood sugar. Urine dipstick was negative for leucocytes, red blood cells and schistosoma ova She had an obstetric ultrasound done which revealed a singleton live fetus in longitudinal lie and breech presentation with an adequate liqour volume, anterior placentation and biometry in keeping with a gestational age of 33 weeks. Cardiotocography was normal Financial constraints limited other investigations Patient was placed on double dose haematinics and had 3 units of packed red blood cells transfused and was also started on oral prednisolone. She had a post transfusion packed cell volume a week after admission which came out to be 28% which did not reflect the expected rise in haematocrit following transfusion of 3 units of blood. The yellowness of the eyes also persisted. A decision to transfuse with one more unit of blood, administer antenatal corticosteroids to aid fetal lung maturation and counsel for a scheduled caesarean section at 34 weeks was made. She had also expressed a desire to have a bilateral tubal ligation at presentation and this was incorporated into her management plan She subsequently had a scheduled caesarean section with bilateral tubal ligation at estimated gestational age of 34 weeks and was delivered of a live male neonate with a birth weight of 2.5 kg and APGAR score of 9 at 1st minute and 10 at 5th minute. Baby had no signs of jaundice, was admitted for observation on account of prematurity, evaluated and was discharged in a stable condition after 4 days from the neonatal unit. Patient was monitored postoperatively and a progressive clearance of jaundice in the postoperative period was observed. On reevaluation on post operative day 4. She had no complaints, the jaundice had subsided and repeat packed cell volume was 32% She was discharged in a stable clinical condition on post operative day 5 after counselling on exclusive breast feeding, immunization, and cord care and given an appointment to be seen at 2 weeks and 6 weeks postpartum. At her 6th week postpartum visit, she had no jaundice or any other evidence of hemolysis and her repeat packed cell volume was 34%. Discussion Antepartum anemia affects over one third of pregnant women worldwide and is associated with maternal and perinatal morbidity, such as need for blood transfusions, maternal infections ,low birth weight, preterm birth, and increased risk of fetal neurodevelopmental disorders following delivery, with extreme of cases resulting in maternity or perinatal mortality 8 Pregnancy-induced hemolytic anemia, a rare maternal complication in which hemolytic anaemia occurs during pregnancy and resolves soon after delivery has been described in literature 9 10 Though the exact pathophysiologic mechanisms underlying this clinical condition is yet to be fully comprehended, a suspicion of immune-related mechanisms as well as the possible existence of a fetus -derived factor inducing maternal red blood cell hemolytic processes has been documented 11 Coombs negative hemolytic anaemia have also been linked to the possibility of natural killer cell induced haemolysis, low affinity autoantibodies, IgM autoantibodies and IgA autoantibodies 12 Variation in clinical presentation and response to steroids have also been documented to characterise the few reported cases of idiopathic hemolytic anaemia in pregnancy 7 Corticosteroid administration which were reported to be of therapaeutic benefit in some cases, did not result in any clinical response in our case, as was also observed in one of the reported cases 13 . Splenomegaly, which has also been postulated to contribute to red cell destruction 7 , was also observed in our patient Pivotal to the diagnosis of idiopathic hemolytic anaemia was the negative Coombs test identified in our patient. It is however worth noting that there has been documented instances of immune hemolytic anemia in a few patients where the concentration of antibody attached to the red cell is below the threshold for detection by the usual antiglobulin test. 14 Most of the reported cases of idiopathic hemolytic anaemia presented in the third trimester and improved with delivery, with recurrence typically observed in subsequent pregnancies. However, there appeared to be a progression in severity with each of the pregnancy in our patient, culminating in a fetal demise in her third confinement The anemia is usually severe, as was seen in this patient, with life threatening effects on the mother and fetus 7 . Differential diagnosis of anemia in pregnancy such as infections and infestations, exposure to chemicals, haemoglobinopathies, immunosuppression were ruled out with elaborate investigations . Cases of pregnant women with idiopathic, Coomb negative hemolytic anaemia are few and far between, and the management of such patient is still controversial and challenging as there is limited literature on this topic 15 , 7 . Multiple blood transfusions, iron supplements and steroid therapy plays a vital role in the management of these patients 16 12 . In our case the patient had these management modalties instituted, though evidence of continued hemolysis was observed. There was however dramatic improvement following the delivery of the baby. Iatrogenic preterm delivery via a scheduled caesarean section following administration of dexamethasone for enhancement of fetal lung maturation was carried out in this patient. She was discharged in a stable clinical condition with her baby Conclusion Coomb’s negative hemolytic anemia of pregnancy, though a rare entity, may be life-threatening. Prompt diagnosis and timely institution of multidisciplinary management modalties, including blood transfusion and appropriate timing of delivery is essential to ensure a favourable fetomaternal outcome. Declarations Consent for publication: Patient gave consent for the publication of this case report and accompanying images Ethics approval Being a case report, ethics approval was waived Author Contribution ContributorsDr A.S drafted the paper and performed the literature search and review.Dr. A.I provided hematology expertise and contributed to revision of the paper.Dr . A.M provided a joint hematology expertise and contributed to the revision of the paper Dr A.C was the consultant who supervised the patient management and also contributed to revision of the paper Dr O.A provided specialist perinatologist input to patient management and contributed to revision of paper Prof A.K was co-consultant who also contributed to revision of paperProf F.O provided overall professorial supervision of the paper The authors declare that they have no conflict of interest regarding the publication of this case report.FundingNo funding from an external source supported the publication of this case report.Patient consentObtained. References Shand AW, Kidson-Gerber GL. Anaemia in pregnancy: a major global health problem. Lancet. 2023;401(10388):1550–1. Ugwu NI, Uneke CJ. Iron deficiency anemia in pregnancy in Nigeria-A systematic review. Niger J Clin Pract. 2020;23(7):889–96. Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-related maternal mortality. J Nutr. 2001;131(2S-2):604S-614S; discussion 614S. Abdallah F, John SE, Hancy A, Paulo HA, Sanga A, Noor R, et al. Prevalence and factors associated with anaemia among pregnant women attending reproductive and child health clinics in Mbeya region, Tanzania. PLOS Glob Public Health. 2022;2(10):e0000280. Karami M, Chaleshgar M, Salari N, Akbari H, Mohammadi M. Global Prevalence of Anemia in Pregnant Women: A Comprehensive Systematic Review and Meta-Analysis. Matern Child Health J. 2022;26(7):1473–87. Kua PL, Omunakwe HE, Okafor AC, Williams GM. Anaemia in labour: A prospective assessment of women in rivers state university teaching hospital, nigeria. Blood. 2019;134(Supplement1):4804–4804. Gupta M, Kala M, Kumar S, Singh G, Chhabra S, Sen R. Idiopathic hemolytic anemia of pregnancy: A diagnostic dilemma. J Hematol. 2014;3(4):118–20. Butwick AJ, McDonnell N. Antepartum and postpartum anemia: a narrative review. Int J Obstet Anesth. 2021;47:102985. Katsuragi S, Sameshima H, Omine M, Ikenoue T. Pregnancy-induced hemolytic anemia with a possible immune-related mechanism. Obstet Gynecol. 2008;111(2 Pt 2):528–9. Laužikienė D, Ramašauskaitė D, Lūža T, Lenkutienė R. Pregnancy induced autoimmune warm antibodies hemolytic anemia: A case report. Geburtshilfe Frauenheilkd. 2015;75(11):1167–71. Agarwal AM, Rets A. Laboratory approach to investigation of anemia in pregnancy. Int J Lab Hematol. 2021;43(Suppl 1):65–70. Venkatachala RP, Sheela CN, Anandram S, Ross CR. Autoimmune hemolytic anaemias in pregnancy: experience in a tertiary care hospital in south india. J Obstet Gynaecol India. 2021;71(4):379–85. Kumar R, Advani AR, Sharan J, Basharutallah MS, Al-Lumai AS. Pregnancy induced hemolytic anemia: an unexplained entity. Ann Hematol. 2001;80(10):623–6. Gilliland BC. Coombs–negative immune hemolytic anemia. Semin Hematol. 1976;13(4):267–75. Starksen NF, Bell WR, Kickler TS. Unexplained hemolytic anemia associated with pregnancy. Am J Obstet Gynecol. 1983;146(6):617–22. Dominico SA. Coombs negative hemolytic anemia of unknown origin in pregnancy. J Blood Lymph. 2012;02(02). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Jul, 2024 Editor assigned by journal 23 Jul, 2024 Submission checks completed at journal 23 Jul, 2024 First submitted to journal 19 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4770119","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":330727214,"identity":"53c91c2b-f887-4aef-bb09-e4d8cb2cff78","order_by":0,"name":"Ayodele S. 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Benjamin","email":"","orcid":"","institution":"Obafemi Awolowo University Teaching Hospitals Complex","correspondingAuthor":false,"prefix":"","firstName":"Fasubaa","middleName":"O.","lastName":"Benjamin","suffix":""}],"badges":[],"createdAt":"2024-07-19 21:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4770119/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4770119/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62766247,"identity":"851d2c5b-3ab4-428b-90fd-a86f00644c69","added_by":"auto","created_at":"2024-08-19 08:34:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":222066,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4770119/v1/19dff4cc-adbd-42d0-a319-f34071a7acb8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePregnancy-Induced Haemolytic Anaemia: a Case Report from Ile-Ife, Nigeria \u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnaemia in pregnancy is a common problem in pregnant women worldwide, affecting nearly 50% of pregnancies globally. \u003csup\u003e1 2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAetiologic factors of anaemia in pregnancy such as iron and folate deficiency are common and related to nutritional deficiency and/or intestinal helminthic infections while other forms such as hemolytic anaemias are infrequent causes of anaemia in pregnancy \u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRegardless of the aetiology, anaemia in pregnancy is associated with increased maternal morbidity, impairment quality of life in women, need for blood transfusions, post-partum haemorrhage, as well as maternal mortality while intrauterine growth restriction, low birth weight, preterm delivery, and perinatal death are adverse fetal outcomes that could result in pregnant women with background anaemia \u003csup\u003e1 4 5 6\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA rare form of hemolytic anemia known as \u0026ldquo;pregnancy-induced hemolytic anemia\u0026rdquo;, a condition in which moderate to severe hemolytic anaemia occurs only in pregnancy, resolves spontaneously after delivery and recurs in subsequent pregnancies has been reported.\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMost of the reported patients are young women who present with hemolysis usually during the 3rd trimester, although in some, mild to moderate hemolysis can be detected earlier during the 1st or 2nd trimester. \u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe encountered a 31\u0026nbsp;year old unbooked G5P3\u0026thinsp;+\u0026thinsp;1 (2A)\u0026thinsp;+\u0026thinsp;1 perinatal mortality with the only clearly identified association with recurring hemolytic anaemia being a gravid state who presented with jaundice and severe anaemia in her third trimester with spontaneous resolution of her symptoms following delivery.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 31-year-old seamstress at 32 weeks\u0026thinsp;+\u0026thinsp;4 days gestation was referred to our facility on account of complaints of yellowness of the eyes and progressive body weakness of a month duration, with associated easy fatigability and pallor. There was no history of bleeding per vaginum or rupture of membranes, and she perceived fetal movements adequately. She had been receiving pregnancy care at a maternity home and had no complaints prior to onset of the symptoms.\u003c/p\u003e \u003cp\u003eShe had initially presented after 2 weeks of onset of symptoms to a private hospital where she was noted to have a packed cell volume of 10% and had 5 units of blood transfused. She was subsequently referred to our facility with a post transfusion packed cell volume of 22% for further evaluation and multidisciplinary care\u003c/p\u003e \u003cp\u003eShe had no antecedent febrile illness, cough or urinary symptoms and had only been on routine iron supplements and folic acid. She had no family or personal history suggestive of a bleeding disorder. Her haemoglobin genotype was AA.\u003c/p\u003e \u003cp\u003eShe had similar history of yellowness of her eyes in her previous pregnancies with mild degrees of body weakness and complete resolution of symptoms following vaginal delivery at term in her first and second confinement\u003c/p\u003e \u003cp\u003eHer last (third) confinement however resulted in an adverse perinatal outcome (stillbirth). She had presented on referral from a private hospital on account of jaundice, severe anaemia and intrauterine fetal death at estimated gestational age of 31 weeks\u0026thinsp;+\u0026thinsp;3 days. She had cervical ripening and induction of labour following optimization with a total of 6 units of blood and subsequently delivered a macerated male fetus. She however requested to be discharged against medical advice on account of financial constraints and defaulted from postpartum follow up\u003c/p\u003e \u003cp\u003eShe also gave a history of a spontaneous first trimester miscarriage after her first childbirth, the cause of which was not established\u003c/p\u003e \u003cp\u003eAt presentation in our facility, she was examined and found to be pale and icteric. Her body temperature was 36.9 degrees Celsius, pulse rate of 112 beats/min and she had a blood pressure of 120/60 mm Hg. There was a loud apical systolic ejection murmur on cardiac auscultation. There was hepatomegaly with the liver palpable at about 6 cm below the right costal margin and the spleen was 4 cm below the left subcostal region\u003c/p\u003e \u003cp\u003eThe symphysiofundal height corresponded to 31 weeks of gestation. Fetal heart rate was 136 beats/min.\u003c/p\u003e \u003cp\u003eLaboratory investigations revealed a packed cell volume of 22%, a reticulocyte count of 4%, and a negative direct Coombs test. Her White blood cell count (WBC) and platelet counts were within normal limits. She had no malaria parasite seen on blood film appearance. Her retroviral screening was negative.\u003c/p\u003e \u003cp\u003eScreening test for G6PD deficiency and osmotic fragility test were normal.\u003c/p\u003e \u003cp\u003eLiver function test revealed elevated serum aspartate aminotransferase of 70 IU and alanine aminotransferase of 44 IU.\u003c/p\u003e \u003cp\u003eShe also had hyperbilirubinemia with a total bilirubin of 145 \u0026micro;mol/L and conjugated bilirubin of 107 \u0026micro;mol/L. Stool microscopy was negative for ova of parasites and occult blood. Her blood group was \u0026ldquo;AB\u0026rdquo; positive.\u003c/p\u003e \u003cp\u003eOn further workup, lactate dehydrogenase was observed to be raised to 502 mU/mL. She had normal values for other biochemical investigations such as serum electrolytes, urea and creatinine, blood sugar.\u003c/p\u003e \u003cp\u003eUrine dipstick was negative for leucocytes, red blood cells and schistosoma ova\u003c/p\u003e \u003cp\u003eShe had an obstetric ultrasound done which revealed a singleton live fetus in longitudinal lie and breech presentation with an adequate liqour volume, anterior placentation and biometry in keeping with a gestational age of 33 weeks. Cardiotocography was normal\u003c/p\u003e \u003cp\u003eFinancial constraints limited other investigations\u003c/p\u003e \u003cp\u003ePatient was placed on double dose haematinics and had 3 units of packed red blood cells transfused and was also started on oral prednisolone. She had a post transfusion packed cell volume a week after admission which came out to be 28% which did not reflect the expected rise in haematocrit following transfusion of 3 units of blood. The yellowness of the eyes also persisted.\u003c/p\u003e \u003cp\u003eA decision to transfuse with one more unit of blood, administer antenatal corticosteroids to aid fetal lung maturation and counsel for a scheduled caesarean section at 34 weeks was made. She had also expressed a desire to have a bilateral tubal ligation at presentation and this was incorporated into her management plan\u003c/p\u003e \u003cp\u003eShe subsequently had a scheduled caesarean section with bilateral tubal ligation at estimated gestational age of 34 weeks and was delivered of a live male neonate with a birth weight of 2.5 kg and APGAR score of 9 at 1st minute and 10 at 5th minute. Baby had no signs of jaundice, was admitted for observation on account of prematurity, evaluated and was discharged in a stable condition after 4 days from the neonatal unit.\u003c/p\u003e \u003cp\u003ePatient was monitored postoperatively and a progressive clearance of jaundice in the postoperative period was observed. On reevaluation on post operative day 4. She had no complaints, the jaundice had subsided and repeat packed cell volume was 32%\u003c/p\u003e \u003cp\u003eShe was discharged in a stable clinical condition on post operative day 5 after counselling on exclusive breast feeding, immunization, and cord care and given an appointment to be seen at 2 weeks and 6 weeks postpartum.\u003c/p\u003e \u003cp\u003eAt her 6th week postpartum visit, she had no jaundice or any other evidence of hemolysis and her repeat packed cell volume was 34%.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAntepartum anemia affects over one third of pregnant women worldwide and is associated with maternal and perinatal morbidity, such as need for blood transfusions, maternal infections ,low birth weight, preterm birth, and increased risk of fetal neurodevelopmental disorders following delivery, with extreme of cases resulting in maternity or perinatal mortality \u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePregnancy-induced hemolytic anemia, a rare maternal complication in which hemolytic anaemia occurs during pregnancy and resolves soon after delivery has been described in literature \u003csup\u003e9 10\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThough the exact pathophysiologic mechanisms underlying this clinical condition is yet to be fully comprehended, a suspicion of immune-related mechanisms as well as the possible existence of a fetus -derived factor inducing maternal red blood cell hemolytic processes has been documented \u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCoombs negative hemolytic anaemia have also been linked to the possibility of natural killer cell induced haemolysis, low affinity autoantibodies, IgM autoantibodies and IgA autoantibodies \u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eVariation in clinical presentation and response to steroids have also been documented to characterise the few reported cases of idiopathic hemolytic anaemia in pregnancy \u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCorticosteroid administration which were reported to be of therapaeutic benefit in some cases, did not result in any clinical response in our case, as was also observed in one of the reported cases \u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSplenomegaly, which has also been postulated to contribute to red cell destruction \u003csup\u003e7\u003c/sup\u003e, was also observed in our patient\u003c/p\u003e \u003cp\u003ePivotal to the diagnosis of idiopathic hemolytic anaemia was the negative Coombs test identified in our patient. It is however worth noting that there has been documented instances of immune hemolytic anemia in a few patients where the concentration of antibody attached to the red cell is below the threshold for detection by the usual antiglobulin test. \u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMost of the reported cases of idiopathic hemolytic anaemia presented in the third trimester and improved with delivery, with recurrence typically observed in subsequent pregnancies. However, there appeared to be a progression in severity with each of the pregnancy in our patient, culminating in a fetal demise in her third confinement\u003c/p\u003e \u003cp\u003eThe anemia is usually severe, as was seen in this patient, with life threatening effects on the mother and fetus \u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDifferential diagnosis of anemia in pregnancy such as infections and infestations, exposure to chemicals, haemoglobinopathies, immunosuppression were ruled out with elaborate investigations .\u003c/p\u003e \u003cp\u003eCases of pregnant women with idiopathic, Coomb negative hemolytic anaemia are few and far between, and the management of such patient is still controversial and challenging as there is limited literature on this topic \u003csup\u003e15\u003c/sup\u003e, \u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMultiple blood transfusions, iron supplements and steroid therapy plays a vital role in the management of these patients \u003csup\u003e16 12\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our case the patient had these management modalties instituted, though evidence of continued hemolysis was observed. There was however dramatic improvement following the delivery of the baby. Iatrogenic preterm delivery via a scheduled caesarean section following administration of dexamethasone for enhancement of fetal lung maturation was carried out in this patient.\u003c/p\u003e \u003cp\u003eShe was discharged in a stable clinical condition with her baby\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCoomb\u0026rsquo;s negative hemolytic anemia of pregnancy, though a rare entity, may be life-threatening. Prompt diagnosis and timely institution of multidisciplinary management modalties, including blood transfusion and appropriate timing of delivery is essential to ensure a favourable fetomaternal outcome.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003e Patient gave consent for the publication of this case report and accompanying images\u003c/p\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003eBeing a case report, ethics approval was waived\u003c/p\u003e \u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eContributorsDr A.S drafted the paper and performed the literature search and review.Dr. A.I provided hematology expertise and contributed to revision of the paper.Dr . A.M provided a joint hematology expertise and contributed to the revision of the paper Dr A.C was the consultant who supervised the patient management and also contributed to revision of the paper Dr O.A provided specialist perinatologist input to patient management and contributed to revision of paper Prof A.K was co-consultant who also contributed to revision of paperProf F.O provided overall professorial supervision of the paper The authors declare that they have no conflict of interest regarding the publication of this case report.FundingNo funding from an external source supported the publication of this case report.Patient consentObtained.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShand AW, Kidson-Gerber GL. Anaemia in pregnancy: a major global health problem. Lancet. 2023;401(10388):1550\u0026ndash;1.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUgwu NI, Uneke CJ. Iron deficiency anemia in pregnancy in Nigeria-A systematic review. Niger J Clin Pract. 2020;23(7):889\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-related maternal mortality. J Nutr. 2001;131(2S-2):604S-614S; discussion 614S.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbdallah F, John SE, Hancy A, Paulo HA, Sanga A, Noor R, et al. Prevalence and factors associated with anaemia among pregnant women attending reproductive and child health clinics in Mbeya region, Tanzania. PLOS Glob Public Health. 2022;2(10):e0000280.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKarami M, Chaleshgar M, Salari N, Akbari H, Mohammadi M. Global Prevalence of Anemia in Pregnant Women: A Comprehensive Systematic Review and Meta-Analysis. Matern Child Health J. 2022;26(7):1473\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKua PL, Omunakwe HE, Okafor AC, Williams GM. Anaemia in labour: A prospective assessment of women in rivers state university teaching hospital, nigeria. Blood. 2019;134(Supplement1):4804\u0026ndash;4804.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGupta M, Kala M, Kumar S, Singh G, Chhabra S, Sen R. Idiopathic hemolytic anemia of pregnancy: A diagnostic dilemma. J Hematol. 2014;3(4):118\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eButwick AJ, McDonnell N. Antepartum and postpartum anemia: a narrative review. Int J Obstet Anesth. 2021;47:102985.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKatsuragi S, Sameshima H, Omine M, Ikenoue T. Pregnancy-induced hemolytic anemia with a possible immune-related mechanism. Obstet Gynecol. 2008;111(2 Pt 2):528\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLaužikienė D, Ramašauskaitė D, Lūža T, Lenkutienė R. Pregnancy induced autoimmune warm antibodies hemolytic anemia: A case report. Geburtshilfe Frauenheilkd. 2015;75(11):1167\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAgarwal AM, Rets A. Laboratory approach to investigation of anemia in pregnancy. Int J Lab Hematol. 2021;43(Suppl 1):65\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVenkatachala RP, Sheela CN, Anandram S, Ross CR. Autoimmune hemolytic anaemias in pregnancy: experience in a tertiary care hospital in south india. J Obstet Gynaecol India. 2021;71(4):379\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKumar R, Advani AR, Sharan J, Basharutallah MS, Al-Lumai AS. Pregnancy induced hemolytic anemia: an unexplained entity. Ann Hematol. 2001;80(10):623\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGilliland BC. Coombs\u0026ndash;negative immune hemolytic anemia. Semin Hematol. 1976;13(4):267\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStarksen NF, Bell WR, Kickler TS. Unexplained hemolytic anemia associated with pregnancy. Am J Obstet Gynecol. 1983;146(6):617\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDominico SA. Coombs negative hemolytic anemia of unknown origin in pregnancy. J Blood Lymph. 2012;02(02).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hemolytic anemia, Coomb’s negative, Pregnancy, Blood transfusion, Perinatal Morbidity","lastPublishedDoi":"10.21203/rs.3.rs-4770119/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4770119/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHaemolytic anaemia, though uncommon, may occur in pregnancy. A rarer variant, Idiopathic haemolytic anaemia or Coomb-negative haemolytic anaemia has been described. This causes haemolysis during pregnancy and spontaneously resolves after delivery, only to recur during subsequent pregnancies, with the woman being entirely symptom-free during her non gravid state.\u003c/p\u003e\n\u003cp\u003eWe encountered a clinical scenario that typifies this rare clinical presentation in a 31-year-old unbooked G5P3+1 (2A) +1 perinatal mortality referred from a private hospital at an estimated gestational age of 32 weeks +4 days.\u003c/p\u003e\n\u003cp\u003eHer clinical history and investigations were suggestive of idiopathic haemolytic anaemia of pregnancy.\u003c/p\u003e\n\u003cp\u003eShe was managed with haematinics, had 4 units of blood transfused, and was commenced on glucocorticoids. She was then counseled for and had a scheduled caesarean section at EGA of 34 weeks +0D on account of concomitant fetal malpresentation and was delivered of a live male neonate with no signs of jaundice. The patient recovered with dramatic resolution of the yellowness of the eyes postpartum and was discharged on postoperative day 5 with normal indices and was discharged alongside her baby in stable condition.\u003c/p\u003e\n\u003cp\u003eThe rare incidence of this clinical presentation and a favourable fetal and maternal outcome, in this case, merits its presentation.\u003c/p\u003e","manuscriptTitle":"Pregnancy-Induced Haemolytic Anaemia: a Case Report from Ile-Ife, Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-19 08:26:43","doi":"10.21203/rs.3.rs-4770119/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-23T12:39:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-23T08:55:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-23T08:54:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2024-07-19T21:06:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c82ff501-680e-460a-a868-9613a98f3a8b","owner":[],"postedDate":"August 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-29T13:39:43+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-19 08:26:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4770119","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4770119","identity":"rs-4770119","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}