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Sickle Cell Disease In Pregnancy

Author Information

Parihar AS*, Warke HS**, Mali K***.

(* Second Year Resident, ** Associate Professor, ***Assistant Professor. Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)

Abstract

Sickle cell is the most common inherited condition worldwide. Pregnancy exacerbates the complications associated with sickle cell disease while sickle cell disease in pregnancy is associated with increased risk of obstetric complications. We present a case of successful pregnancy in a case of sickle cell disease.

Introduction

Sickle cell disease is a group of inherited disorders, caused by mutation in the ‘sickle’ gene, inherited in an autosomal recessive manner, resulting in abnormal structure of haemoglobin.
Sickle cell disease includes sickle cell anemia (HbSS) and the heterozygous conditions of hemoglobin S and other clinically abnormal hemoglobins including hemoglobin C, D, E, O,  Arab as well as combination with beta thalassemia. The abnormal hemoglobin undergoes polymerization under hypoxic conditions leading to abnormal rigid and fragile sickle shaped red cells causing haemolytic anemia and occlusion of small vessels thereby leading to painful crisis.

Sickle cell disease is associated with increased maternal and fetal complications.[1] There is an increased risk of spontaneous abortions, infection, thromboembolic events, antepartum hemorrhage, premature labor, antenatal hospitalizations, increased need for operative intervention and acute painful crisis during pregnancy. Some studies have also shown increased risk of pre-eclampsia and pregnancy induced hypertension [2, 3] while some studies have shown no association.[4, 5] Sickle cell disease is associated with fetal complications such as intra-uterine fetal growth restriction, premature births, abnormal fetal heart rate and increased incidence of perinatal mortality.[6]

A multidisciplinary approach, high vigilance of the health care providers and compliance of the patient is required to effectively manage the pregnancy in a case of sickle cell disease.

Case Report

A 26 year old, G4P2L1MTP1 with 32 weeks of gestation came to emergency department with complaints of gastroenteritis and fever with chills. She was a known case of sickle cell disease diagnosed in 2006 (HbSS 76.3%) with history of previous two lower segment cesarean sections. First cesarean section was done at term for meconium stained liquor. Baby was diagnosed with microcephaly at birth. Baby died of unknown cause at 7 years of age and was not investigated for hemoglobinopathy. Second cesarean section was done at term for fetal distress in a baby with intrauterine growth retardation. Baby was later diagnosed to have sickle cell trait. She had required multiple exchange transfusions in previous two pregnancies.
  
She was antenatally registered at 6 weeks of gestation with us. She was on tablet hydroxyurea which she stopped 2 months prior to this conception. Amniocentesis was done at 15 weeks of gestation for prenatal diagnosis. Amniotic fluid DNA analysis suggested the presence of sickle cell trait in the fetus. She had history of admission at fifth month of gestation for H1N1 infection with anemia which was managed conservatively with parenteral antibiotics and hydration. She received four packed cell transfusions during this admission.

At 32 weeks of gestation, she came with fever with chills and generalized body ache since one day. On examination, she was febrile (temperature of 39 degree celsius), pulse rate was 100 beats/ minute and blood pressure was 110/70 mm Hg. On auscultation, chest was clear, S1S2 were normal. On abdominal examination uterus was relaxed, 30-32 weeks in size, cephalic presentation, FHS were 140 beats per minute. She was admitted for the above complaints in medical unit and was managed. She was treated conservatively by the physician with injection ceftriaxone and metronidazole for 14 days and adequate hydration. Peripheral smear showed no evidence of malarial parasite, tests for malarial antigen, IgG, IgM antibodies for dengue, tests to detect NS1 antigen, IgG, IgM antibodies for leptospirosis and Widal test were negative. Urine culture showed no growth. Her hemoglobin (Hb) on admission was 6.8 gm%, WBC counts were 24,100/ cumm and platelets were 2 lakhs cumm. Her liver function tests were mildly deranged with SGOT 92 U/L, SGPT 27 U/L, total bilirubin 4.7 mg%, direct bilirubin 2.8 mg% and INR 1.03 seconds. Her renal function tests were normal. Ultrasound (USG) abdomen was suggestive of moderate splenomegaly. Hematologist opined to maintain Hb between 8-9 gm% and exchange transfusion to be considered only if new infiltrate on chest X-ray/ hypoxia/ breathlessness / chest pain occurred.  Two units of packed cells were transfused. Liver function tests and INR were monitored every third day. They were in the decreasing trend. Deranged liver function tests with moderate splenomegaly was due to hemolysis. She was closely monitored for development of maternal and fetal risk factors. Two doses of 12 mg injection betamethasone were given. Serial USG scans were done to detect early evidence of fetal/ maternal compromise. USG doppler was suggestive of severe oligohydramnios (AFI 2) without materno-fetal insufficiency. Fetal well being was monitored by performing biweekly non stress test and weekly doppler. Two weeks later, she again developed fever spikes. She was started on injection piperacillin/ tazobactum for 7 days and artisunate was given for 3 days. Peripheral smear showed no evidence of malarial parasite, tests for malarial antigen, IgG, IgM antibodies for dengue, tests to detect NS1 antigen, IgG, IgM antibodies for leptospirosis and Widal test were negative. Urine culture showed no growth. She went into spontaneous onset of labor at 34 weeks of gestation. Her Hb was 8.6 gm%, WBC counts were 10,400/ cumm, platelets were 2.35 lakhs/ cumm, SGOT was 51 U/L, SGPT was 24 U/L, total bilirubin was 2.2 mg%, direct bilirubin of 1.0 mg%, and INR was 0.93.  An emergency lower segment cesarean section was done and she delivered a male child of 2.002 Kg with Apgar score of 9/10. One unit packed cell was transfused intraoperatively. Post cesarean  section, she was continued on parenteral piperacillin/ tazobactum for 14 days, metronidazole for 5 days and gentamycin for 3 days. She was closely monitored for symptoms of sickle cell crisis post cesarean section. She had fever spikes of 39 degree celsius on day 3 postpartum and she also complained of breathlessness. She was managed conservatively on same antibiotics, adequate hydration and nasal oxygen to maintain optimal oxygen saturation. She received one packed cell transfusion post-delivery on Hb 7.6 gm%. She was monitored for two weeks postpartum and was discharged in consultation with the hematologist.

Discussion

Sickle cell disease is characterized by formation of abnormal hemoglobin structure leading to development of fragile sickle cells. These fragile sickle cells are prone to breakdown thereby leading to hemolytic anemias. Sickle cell disease is associated with increased risk of maternal and foetal complications. Our patient suffered from infections several times during her pregnancy. She also went into premature labor.

Women with sickle cell disease should undergo preconceptual screening regarding advice about partner screening, vaccinations, medications and avoidance of crisis. If a partner is a carrier or is affected by a major hemoglobinopathy, the couple must be explained about the risk of having affected offspring and also the choice regarding termination of pregnancy.  As our patient was regularly following up with the hematologist, husband’s electrophoresis was done prior to this conception which revealed no evidence of hemoglobinopathy in the partner. 
Penicillin prophylaxis is beneficial for women with sickle cell disease as they are hyposplenic and are at greater risk of infection with capsulated organisms.[7] Our patient suffered from H1N1 infection at fifth month of gestation and was managed conservatively. Women with sickle cell disease should receive influenza and swine flu vaccine annually.[7] 
Hydroxyurea, a drug used to decrease the incidence of painful crisis[8]should be stopped 3 months prior to conception. Hydroxyurea has been found to be teratogenic in animals, however there are published reports that show no adverse effects in babies of women who have taken hydroxyurea throughout their pregnancy.[9,10] Termination of pregnancy is not indicated based on exposure to hydroxurea alone, however a level 3 ultrasound must be performed to detect structural abnormalities.[11] Our patient stopped the drug two months prior to this conception, however she continued with the drug in her previous two pregnancies. Low threshold for seeking medical help is advisable for women with sickle cell disease. Antenatal care must be provided by a multidisciplinary team including an obstetrician, hematologist and a general physician. Precipitating factors of sickle cell crisis like extreme temperature, hypoxia, and dehydration must be avoided by pregnant women. Iron supplementation is recommended for them only if there is laboratory evidence of iron deficiency. Low dose aspirin (75 mg OD) must be provided from 12 weeks of gestation as they are at mild risk of pre-eclampsia.[12] Administration of low molecular weight heparin is also recommended in these women during their antenatal admissions to avoid thromboembolism.[13] Blood pressure and urinalysis must be done at every antenatal visit, midstream urine for culture should be done monthly. Serial growth scans should be done at every 4 weeks after 24 weeks of gestation to detect early fetal growth restriction. The role of prophylactic blood transfusion in pregnant women with sickle cell disease is inconclusive.[14] Some studies have shown prophylactic transfusion to decrease the maternal painful crisis however it has not shown to influence maternal or fetal outcome.[15] The decision for blood transfusion must be taken after correlating with clinical findings and after consulting experienced obstetrician and hematologist. Prophylactic transfusion must be considered in multiple gestation as they are associated with higher complication rate. Transfusion must be continued in pregnancy for women who are on a transfusion regimen before pregnancy for prevention of severe disease complications. Top up transfusion is recommended for women with previous serious medical, obstetric or fetal complications and to treat acute anemia. Exchange transfusion is the accepted method to manage acute chest syndrome and acute stroke.[7, 16]. Blood should be cross matched for extended phenotype as alloimmunization is common in women with sickle cell disease and it renders women untransfusable. Acute painful crisis should be treated with appropriate analgesia. Mild pain is treated with paracetamol and NSAIDS. Recommended use of NSAIDS is between 12 and 28 weeks of gestation for mild to moderate pain. Weak opioids are used for moderate pain whereas stronger opioids like morphine are used for severe pain. Pethidine should be avoided as it is associated with seizures in women with sickle cell disease.[17] Fluid of at least 60 ml/ kg/ 24 hours should be ensured. Oxygen supplementation is recommended if saturation drops below 95%. Women should be assessed for infection. Therapeutic antibiotics must be started if febrile or there is clinical suspicion of infection. Thromboprophylaxis is given if patient is admitted with painful crisis.

Vaginal delivery between 38 to 40 weeks is the recommended mode of delivery for women with sickle cell disease.[18] Cesarean section should be reserved for obstetric indication. Our patient underwent cesarean section as she had undergone LSCS in previous two pregnancies. Regional anesthesia is recommended for cesarean section. Blood should be cross matched. Concerned hematologist, physician as well as anesthetists must be informed while taking the patient for delivery. Patient must be kept warm and well hydrated during labor. Continuous fetal monitoring should be done as there are high chances of fetal distress. Prophylactic antibiotics is not recommended but the threshold to start broad spectrum antibiotics should be low and the patient should be closely monitored for increase in temperature.

Same level of care and vigilance should be given to women in the post-partum period as the risk of sickle cell crisis remains. Adequate hydration and maternal saturation above 94% is required. Thromboprophylaxis is recommended for 7 days postpartum following vaginal delivery and for 6 weeks postpartum following cesarean section. In women with high risk of sickle cell disease in newborn, early testing for sickle cell disease must be offered. Hematology opinion was taken for the newborn and they advised to do Hb electrophoresis at six months of age. Women need to be counseled regarding modes of contraception. Progesterone only pill and injection DMPA are recommended for women with sickle cell disease.[19, 20]

Expert knowledge of the condition, proper intervention at the time of crisis and appropriate pre-conceptional, antenatal and postpartum management can result in successful maternal and fetal outcome in sickle cell disease in pregnancy. 

References
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Citation

Parihar AS, Warke HS, Mali K. Sickle cell disease in pregnancy.  JPGO 2017. Volume 4 No.12. Available from: http://www.jpgo.org/2017/12/sickle-cell-disease-in-pregnancy.html