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Table 1.  

All patients AIHA in pregnancy AIHA in puerperium Controls
Mean age at pregnancy (y) (range) 32 (21–41) 32 (21–39) 29.5 (24–41) 32 (20–40)
Number of observed pregnancies 45 18 6 56
AIHA type*

Warm

14 7 2

Warm IgG+C

9 6 3

Atypical

5 3 1

Mixed

3

Cold

2 2
Associated conditions, n (%) 8 6 2
Week of gestation, median (range) 20.5 (5–32)
Week from delivery, median (range) 6 (4–6)
AIHA therapies

Steroids

23 17 6

Blood transfusions

14 10 4

Immunoglobulins injection

7 6 1

Rituximab (postpartum)

4 4

Cyclosporin (postpartum)

1 1
Antithrombotic prophylaxis

Heparin

4 3 1

ASA

2 1 1

LMWH+ASA

2 2
Total, n (%) 8 (33) 6 (33) 2 (33)
Maternal complications

Risk of preterm birth

2

Preeclampsia

2 1 1

Placental detachment

1 1 1

PPROM

1 1 1

Biliary colic

1

Cholestasis of pregnancy

1

Infective complication

2 2 1

Venous thrombosis

1

Gestational diabetes

1

Decrease in Hb level

1
Total, n (%) 7 (15) 5 (28) 10 (18)
Miscarriages, n (%) 6 (13)† 1 (5)

Fetal complications

Fetal growth restriction

3 2 1 3

Death

2 2

AIHA of the newborn

1 1

Preterm birth

2 2

Epilepsy

1 1

Perinatal respiratory distress

1 1
Total n (%) 10 (22) 9 (50) 1 (16) 3 (5)

Table 1. Clinical features of autoimmune hemolytic anemia (AIHA) develop during pregnancy or postpartum/
puerperium in age-matched healthy women

ASA, acetylsalicylic acid; C, complement; LMWH, low molecular weight heparin; PPROM, preterm premature rupture of membranes.
*Five patients had Evans syndrome (ie, the association of AIHA with immune thrombocytopenia and/or neutropenia); atypical AIHA included 1 IgA-mediated and 4 DAT-negative forms. In the latter case, the diagnosis was established after excluding all other potential causes of hemolysis and was based on the steroid response.
†Five out of 6 miscarriages occurred in a woman with refractory AIHA, who never achieved a complete response, even without frank relapses during pregnancy.

CME

Autoimmune Hemolytic Anemia During Pregnancy and Puerperium: An International Multicenter Experience

  • Authors: Bruno Fattizzo, MD; Marta Bortolotti, MD; Norma N. Fantini, MD; Andreas Glenthøj, MD, PhD; Marc Michel, MD; Mariasanta Napolitano,  MD; Simona Raso, MD; Frederick Chen, FRCP, FRCPath, PhD; Vickie McDonald, MD; Irina Murakhovskaya, MD; Josephine Mathilde Iris Vos, MD, PhD; Andrea Patriarca, MD; Maria Eva Mingot-Castellano, MD, PhD; Giulio Giordano, MD; Margherita Scarrone, MD; Tomàs José Gonzaléz-Lopez, MD, PhD; Laura Trespidi, MD; Daniele Prati, MD; Wilma Barcellini, MD
  • CME Released: 4/20/2023
  • Valid for credit through: 4/20/2024, 11:59 PM EST
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    You Are Eligible For

    • Letter of Completion

Target Audience and Goal Statement

This activity is intended for hematologists, immunologists, obstetricians, neonatologists, and other physicians caring for women with autoimmune hemolytic anemia (AIHA) during pregnancy and their offspring.

The goal of this activity is for learners to be better able to describe AIHA severity, treatment need, and impact on maternal and fetal outcomes during pregnancy/puerperium, according to the results of the first multicenter international cohort study evaluating AIHA, which reported on 45 pregnancies in 33 women followed at 12 centers from 1997 to 2022.

Upon completion of this activity, participants will:

  • Describe autoimmune hemolytic anemia (AIHA) severity and treatment during pregnancy and puerperium, according to the results of the first multicenter international cohort study evaluating AIHA, which reported on 45 pregnancies in 33 women followed at 12 centers from 1997 to 2022
  • Determine the impact of AIHA on maternal and fetal outcomes during pregnancy and puerperium, according to the results of the first multicenter international cohort study evaluating AIHA
  • Identify clinical implications of AIHA severity, treatment need, and impact on maternal and fetal outcomes during pregnancy and puerperium, according to the results of the first multicenter international cohort study evaluating AIHA


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


Faculty

  • Bruno Fattizzo, MD

    Hematology Unit
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Department of Oncology and Oncohematology
    University of Milan
    Milan, Italy

  • Marta Bortolotti, MD

    Hematology Unit
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Department of Oncology and Oncohematology
    University of Milan
    Milan, Italy

  • Norma N. Fantini, MD

    Department of Transfusion Medicine and Hematology
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Milan, Italy

  • Andreas Glenthøj, MD, PhD

    Department of Hematology
    Copenhagen University Hospital - Rigshospitalet
    Copenhagen, Denmark

  • Marc Michel, MD

    Centre de Référence Maladies Rares sur les Cytopénies Auto-Immunes de l'Adulte
    Centre Hospitalier Universitaire Henri Mondor
    Assistance Publique-Hôpitaux de Paris
    Créteil, France
    Université Paris-Est Créteil
    Paris, France

  • Mariasanta Napolitano, MD

    Hematology Unit
    Thrombosis and Hemostasis Reference Regional Center
    University of Palermo
    Palermo, Italy

  • Simona Raso, MD

    Department of Hematology and Rare Diseases
    Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
    Palermo, Italy

  • Frederick Chen, FRCP, FRCPath, PhD

    Clinical Hematology
    Barts Health National Health Service Trust
    Queen Mary University
    London, United Kingdom

  • Vickie McDonald, MD

    Clinical Hematology
    Barts Health National Health Service Trust
    Queen Mary University
    London, United Kingdom

  • Irina Murakhovskaya, MD

    Department of Hematology and Oncology
    Albert Einstein College of Medicine/Montefiore Medical Center
    Bronx, New York

  • Josephine Mathilde Iris Vos, MD, PhD

    Department of Hematology
    Amsterdam University Medical Center
    University of Amsterdam
    Amsterdam, The Netherlands
    Sanquin
    Amsterdam, The Netherlands

  • Andrea Patriarca, MD

    Department of Translational Medicine
    Azienda Ospedaliera-Universitaria "Maggiore della Carità"
    University of Eastern Piedmont
    Novara, Italy

  • Maria Eva Mingot-Castellano, MD, PhD

    Servicio de Hematología
    Hospital Universitario Virgen del Rocio
    Seville, Spain

  • Giulio Giordano, MD

    UOC Medicina
    Servizio e Ambulatorio di Ematologia
    Ospedale di Riferimento Regionale "Antonio Cardarelli"
    Campobasso, Italy

  • Margherita Scarrone, MD

    Department of Obstetrics and Gynecology
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Milan, Italy

  • Tomàs José Gonzaléz-Lopez, MD, PhD

    Servicio de Hematología
    Hospital Universitario de Burgos
    Burgos, Spain

  • Laura Trespidi, MD

    Department of Obstetrics and Gynecology
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Milan, Italy

  • Daniele Prati, MD

    Department of Transfusion Medicine and Hematology
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Milan, Italy

  • Wilma Barcellini, MD

    Hematology Unit
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Milan, Italy

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has no relevant financial relationships.

Editor

  • Nancy Berliner, MD

    Editor-in-Chief, Blood

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.


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From Blood
CME

Autoimmune Hemolytic Anemia During Pregnancy and Puerperium: An International Multicenter Experience

Authors: Bruno Fattizzo, MD; Marta Bortolotti, MD; Norma N. Fantini, MD; Andreas Glenthøj, MD, PhD; Marc Michel, MD; Mariasanta Napolitano,  MD; Simona Raso, MD; Frederick Chen, FRCP, FRCPath, PhD; Vickie McDonald, MD; Irina Murakhovskaya, MD; Josephine Mathilde Iris Vos, MD, PhD; Andrea Patriarca, MD; Maria Eva Mingot-Castellano, MD, PhD; Giulio Giordano, MD; Margherita Scarrone, MD; Tomàs José Gonzaléz-Lopez, MD, PhD; Laura Trespidi, MD; Daniele Prati, MD; Wilma Barcellini, MDFaculty and Disclosures

CME Released: 4/20/2023

Valid for credit through: 4/20/2024, 11:59 PM EST

processing....

Abstract and Introduction

Abstract

Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1–8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.

Introduction

It has long been known that pregnancy is associated with perturbations of the immune system homeostasis, including autoimmune phenomena. It has been estimated that 1 in 50 000 pregnancies may develop antierythrocyte autoantibodies with different phenotypic expressions. However, not all patients with antierythrocyte autoantibodies develop overt autoimmune hemolytic anemia (AIHA).[1] The latter is a rare disease with an estimated incidence of 0.8 to 3 out of 100 000 individuals per year and is predominant in females.[2] De novo or relapsing AIHA during pregnancy or puerperium is even rarer, with mainly case reports, mostly of warm immunoglobulin G (IgG) type.[3] Very little is known about disease characteristics, management, maternal-fetal outcomes, and safety concerns limit treatment. Here, we report the results of the first multicenter international cohort study evaluating AIHA in the setting of pregnancy/puerperium. We aimed to delineate AIHA severity, treatment need, and the impact on maternal and fetal outcomes.