ISSN: 2320-5407
Int. J. Adv. Res. 4(10), 1245-1250
Journal Homepage: -www.journalijar.com
Article DOI:10.21474/IJAR01/1917
DOI URL: http://dx.doi.org/10.21474/IJAR01/1917
RESEARCH ARTICLE
PREGNANCY COMPLICATED WITH HEREDITARY SPHEROCYTOSIS – LESSONS LEARNT FROM
A CASE AND REVIEW OF LITERATURE.
1.
2.
Parul Verma1 and Shashikant R. Kulkarni2.
Junior Resident, Department of Obstetrics and Gynaecology, Dr. D.Y. Patil Medical College,Kolhapur,
Maharashtra-416003, India.
Professor and Head, Department of Obstetrics and Gynaecology, Dr. D.Y. Patil Medical College, Kolhapur,
Maharashtra-416003, India.
……………………………………………………………………………………………………....
Manuscript Info
Abstract
…………………….
………………………………………………………………
Manuscript History
Received: 12 August 2016
Final Accepted: 22 September 2016
Published: October 2016
Key words:Hereditary spherocytosis, Pregnancy,
Splenectomy
Hereditary spherocytosis (HS) also known as Minkowski-Chauffard
syndrome is a genetically determined disorder of the red blood cell
membrane cytoskeleton complex causing Hemolytic anemia. There is
a wide spectrum of clinical presentation ranging from mild anemia to
severe anemia with splenomegaly and jaundice. Increased Mean
Corpuscular Hemoglobin Concentration (MCHC), spherocytes in
peripheral blood smear and increased osmotic fragility favour the
diagnosis of HS.No causal treatment is yet available for this disease.
Mild disease warrants no treatment. Folic acid, supportive treatment
and regular annual check up usually suffice for moderate disease
while frequent hematological supervision and splenectomy is prudent
for severe disease.Pregnancy complicates the management of HS and
very limited data is available in the literature regarding this.
Case Presentation:-Authors hereby report a case of 24-year-old 36weeksgestational age primigravida withintrauterine fetal demise.
Workup revealed patient to be suffering from Hereditary
Spherocytosis that resulted in hemolysis ultimately causing fetal
demise. Pregnancy was terminated and patient was subsequently
referred to the Department of Surgery for splenectomy.
Conclusion:- Hereditary Spherocytosis, one of the commonest
congenital hemolytic anemia may get decompensated during
pregnancy. Due to paucity of data in literature regarding management
of HS during pregnancy, it is hard to formulate guidelines for
indications of splenectomy during pregnancy. However, authors
recommend Splenectomy preferably in second trimester in any
pregnant women with HS who is experiencing hemolysis or having
symptoms, signs and complications thereof. Obstetricians should
exercise high index of suspicion to diagnose this not so uncommon
entity as early as pregnancy is diagnosed to yield better outcomes.
Copy Right, IJAR, 2016,. All rights reserved.
……………………………………………………………………………………………………....
Corresponding Author:-Parul Verma.
Address:-Junior Resident, Department of Obstetrics and Gynaecology, Dr. D.Y. Patil Medical
College,Kolhapur, Maharashtra-416003, India.
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Introduction:Hereditary spherocytosis (HS) is a genetically determined disorder of the red blood cell membrane cytoskeleton
complex causing Hemolytic anemia. The estimated frequency of HS varies from 1:2000 to 1:5000. 1-3 Minkowski
and Chauffard in the late 19th century reported families whose peripheral blood revealed numerous spherocytes and
have been thus duly credited with the discovery of this not so uncommon disorder.4,5The red cells were abnormally
susceptible to lysis in hypotonic media as revealed by in vitro studies, thereby establishing osmotic fragility test
virtually diagnostic of HS.
There is a wide spectrum of clinical presentation ranging from mild anemia to severe anemia with splenomegaly and
jaundice. Increased Mean Corpuscular Hemoglobin Concentration (MCHC), spherocytes in peripheral blood smear
and increased osmotic fragility favour the diagnosis of HS.Sodium dodecyl sulphate polyacrylamide gel
electrophoresis (SDS-PAGE) is usually confirmative.1,2
No causal treatment is yet available for this disease. Mild disease warrants no treatment. Folic acid, supportive
treatment and regular annual check up usually suffice for moderate disease while frequent hematological supervision
and splenectomy is prudent for severe disease. 6 It is a well known fact that intercurrent conditions like, pregnancy
and infections may cause decompensation in a previously well compensated disease but unfortunately very limited
data is available regarding the course of HS during pregnancy with very few cases reported in the literature till date.7
Authors hereby report a case of pregnancy complicated with intrauterine fetal demise who was later diagnosed to be
suffering from HS.
Case report:A 24-year-old 36-weeks gestational age primigravida presented in the emergency department with the complaints of
decreased fetal movement since morning.She was married for 11 months and had normal menstrual cycles.Past
history was insignificant except for one unit Packed red blood cell transfusion at the age of 12 years. Examination
revealed pallor and icterus. Abdominal examination showed gravid uterus with fundal height corresponding to 32-34
weeks gestational age with longitudinal lie and cephalic presentation. Head was found to be floating. No fetal
movements were felt during examination. Fetal Heart sounds could not be auscultated. Patient was relaxed and there
was no evidence of uterine contractions. Per speculum examination showed Cervix and Vagina to be healthy. There
was no evidence of per vaginal discharge or bleeding. Per vaginum examination revealed os to be closed, posteriorly
placed and was uneffaced.
Obstetric Ultrasonography examination revealed single intrauterine fetus of 38 weeks 0 day in cephalic presentation
with absent fetal cardiac activity and fetal movements suggestive of fetal demise. Complete blood count showed
anemia with 9.9 g Hemoglobin/dL, leukocytosis with 15600 total leucocyte counts/ cubic mm. Mean Corpuscular
Volume (MCV) was 95.9 fL,Mean Corpuscular Hemoglobin (MCH)was 33.9 pg and Mean Corpuscular
Hemoglobin Concentration (MCHC)was 35.4 g/dL. Peripheral blood smear showed increased number of
spherocytes (++) with few polychromatophils. Spherocytes were uniform in size and density without any central
pallor. Platelets were adequate in number with 2.81 lacs/ cubic mm. Reticulocytosis was present with 8.0 %
reticulocytes. Liver function tests revealed indirect hyperbilirubinemia with 5.7 mg total serum bilirubin/dL and 0.9
mg direct serum bilirubin/dL. Liver enzymes were normal.Renal Function Tests were normal. Serum Lactate
dehydrogenase was found to be raised with values of 566.9 Units/L. Iron studies,Glucose-6-Phosphate
Dehydrogenase (G6PD) assay and Hemoglobin electrophoresis were normal. Patient tested negative for antinuclear
antibody (ANA), Indirect and Direct Coomb’s test. The above findings were strongly suggestive of Hemolytic
anemia most probably as a result of Hereditary Spherocytosis. Subsequently Osmotic fragiltiy test was done which
concluded Initial lysis (minimal resistance) in 0.745 % NaCl, Complete lysis (maximum resistance) in 0.33 % NaCl
and Mean corpuscular fragilty in 0.515 % NaCl, thereby confirming the diagnosis of Hereditary Spherocytosis.
While enquiring about the old records, patient showed six months old reports. Complete blood counts showed
anemia with 10.6 g Hb / dL, leucocytosis with 12130 TLC/ cumm and 2.64 lacs Platelets / cumm. MCV was 89.6
fL, MCH was 30.0 pg and MCHC was 33.5%.Indirect hyperbilirubinemia with 3.2 mg/dL total serum bilirubin and
1.6 mg/dL direct fraction was seen in LFT. USG abdomen done at the periphery showed minimal hepatomegaly
with multiple calculi in Gall bladder with moderate splenomegaly and a single live early intrauterine pregnancy of
gestational age 12 weeks 5 days.
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A diagnosis of 36 weeks pregnancy with Hereditary Spherocytosis with Intrauterine fetal demise was made and was
planned to terminate the pregnancy.
Treatment and outcome:Induction of labour was started with Dinoprostone (Prostaglandin E2) gel followed by insertion of intracervical
catheter. Labour was augmented by Oxytocin infusion and dead fetus was delivered. Postpartum period was
uneventful. Patient was prescribed Folic acid 5 mg per day and thereafter was referred to the Department of Surgery
for Splenectomy.
Table1:-Classification of Hereditary Spherocytosis.
CLASSIFICATION
Trait
Hemoglobin (g/dL)
Normal
Reticulocyte count (%)
Normal (<3%)
Bilirubin (μmol/L)
<17
Spectrin per erythrocyte (% of 100
normal)
Mild
11-15
3-6
17-34
80-100
Moderate
8-12
>6
>34
50-80
Severe
6-8
>10
>51
40-60
Discussion:Hereditary spherocytosis (HS) is one of the commonest congenital hemolytic anemia caused by genetic mutations in
genes encoding red blood cell (RBC) membrane proteins. Various membrane proteins can be affected in HS like
spectrin, ankyrin, band 3, and protein 4.2 but spectrin deficiency is reported to be the commonest culprit resulting in
HS. Autosomal dominant pattern of inheritance is the most frequent mode of transmission of this genetically
heterogeneous disease but few cases of autosomal recessive inheritance have also been reported. The estimated
prevalence as reported in various systematic reviews range from 1 in 2000 to 1 in 5000 people. 1-3
Clinically, there is a wide spectrum of presentation ranging from asymptomatic mild anemia to fulminant hemolytic
anemia with pallor, jaundice and splenomegaly requiring aggressive treatment. Gallstones of pigment type caused
by increased unconjugated bilirubin may be the first presentation of this disorder. Family history is variably present
with patients reporting history of splenectomy and cholecystectomy in family member. Environmental triggers, like,
fatigue, infections, emotional distress and pregnancy have been reported to unmask the previously compensated
disease.7
The HS is characterized by mild to moderate anemia with increased mean corpuscular hemoglobin concentration
(MCHC). Increased MCHC due to cellular dehydration is a hallmark of HS. Reticulocytosis is invariablypresent
signifying increased cell production. Peripheral blood smear revealspherocytes, which in contrast to spherocytes
seen in immune hemolytic anemia and thermal injury are quite uniform in size and density (Fig.–1). Unconjugated
hyperbilirubinemia is frequently observed due to hemolysis. Incubated osmotic fragility test is the most sensitive test
for HS (Fig.–2).8 Other tests infrequently used are Acidified glycerol lysis time (AGLT), Flow cytometry (Eosin-5maleimide binding), Osmotic gradient ektacytometry and membrane analysis by SDS-PAGE.9
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Fig.1:- Peripheral smear shows increased number of spherocytes (black arrow) and few polychromatophils (red
arrow). Spherocytes are uniform in size and density without any central pallor.
Fig. 2:- Osmotic Fragility Curve of the patient. The whole curve is shifted to the right. Please note the tailing of
fragile erythrocytes, which are lysed at higher concentration of saline (0.7-0.8 %). Normally no lysis occurs at these
concentrations.
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This disorder despite being discovered almost 2 centuries back, unfortunately, there is still no causative treatment to
correct the basic disorder. Decision to offer treatment to the patients suffering from HS is based on the severity of
clinical symptoms and complications (Table–1).10 Folate supplements have been routinely prescribed to the patients
suffering from chronic hemolysis and folate therapy is recommended in moderate and severe HS but not in mild HS
in the dose of 5 mg per day.
Splenectomy has long been the standard treatment for patients with clinically severe HS and is considered in those
with moderate HS. It should not be performed in mild HS. 1,2,6 Splenectomy is a double edged sword, at one end it
eliminates the sign and symptoms of hemolysis and at the other end it makes individual susceptible for life long risk
of infections with capsulated organism, especially, Pneumococci with a mortality of 0.1-0.4%. 11,12However, this
risk has been reduced by vaccination against pneumococcus, meningococcus and Hemophilus influenzae coupled
with prophylactic antibiotics. It has been recommended to vaccinate patients undergoing splenectomy two weeks
prior to surgery. 1-3,13 Recently, a largest single center study done by Thomas Pincez etal reported safety and success
of subtotal splenectomy over total splenectomy in children.14Concurrent cholecystectomy is advocated if the patient
has symptoms of gall stone disease. 1,2,12
Pregnancy complicates the management of hereditary spherocytosis. Traditionally, many authors have held the view
of avoiding splenectomy during pregnancy due to fear of perioperative morbidity associated with the surgery to both
mother and fetus. There is paucity of data in literature in this regard but the studies although few have been contrary
to the long held concept of avoiding splenectomy during pregnancy.Second trimester is usually preferred for
splenectomy, although it can be performed at any gestational age. Less invasive laparoscopic splenectomy is
routinely preferred due to its obvious advantages over open splenectomy. 3
Moore etal (1976) have reported two cases of pregnant women in the second trimester with HS who underwent
successfulsplenectomy and reviewed 5 such cases in literature.15Ho-Yen DO (1984) described a family with HS in
which 3 sisters had hemolytic episodes during their 6 pregnancies but none was treated with splenectomy and each
pregnancy resulted in birth of mature and live infant. 16Maberry etal (1992) reported 23 women with HS during their
50 pregnancies, none requiring splenectomy during pregnancy. Maternal complications were infrequent and
perinatal outcomes were excellent.17Pajor etal (1993) have reported 8 patients with HS whohad 19 pregnancies in
total, 10 before splenectomy and 9 after splenectomy. Allwere managed conservatively and was found that fetal
outcome was more favourable after splenectomy than before splenectomy.18Brabec V etal (1999) studied the
influence of pregnancy on the course of HS in 21 women during their 44 pregnancies and found that pregnancy
caused no problems in the majority, even when complications developed they were not serious. Anemia deteriorated
in one-third pregnancies in non-splenectomized women due to increased hemolysis, while complaints were minimal
in splenectomized patients.19Only two instances of successful laparoscopic splenectomy in a pregnant woman
suffering from HS have been reported in literature yet. 3,20
The case presented by the authors seems to have been undergoing hemolysis since last six months as evident by
anemia and unconjugated hyperbilirubinemia in routine hematological reports and also there was evidence of
hepatosplenomegaly in Ultrasonography study of abdomen but unfortunately it could not be recognized at the
periphery. It was sad that patient presented to the authors when fetal demise already occurred. Had she been
previously worked up and diagnosed as a case of HS and underwent splenectomy, authors feel that it would have
been possible to save the life of fetus.
Conclusion:Hereditary Spherocytosis one of the commonest congenital hemolytic anemia may get decompensated during
pregnancy and pregnancy complicates the management of Hereditary Spherocytosis. Pregnancy is usually well
tolerated and need for splenectomy doesn’t arise frequently. Although there is a consensus to subject patient to
splenectomy and its inherent risks in clinically moderate and severe HS, the management is still controversial during
pregnancy. Given the few studies in literature regarding management of HS during pregnancy, it is hard to formulate
guidelines for indications of splenectomy during pregnancy at this juncture. The decision to perform splenectomy in
pregnancy is guided at best by the indications in non-pregnant patients of HS. However, authors recommend
splenectomy in any pregnant women with HS who is experiencing hemolysis or having symptoms, signs and
complications thereof. Second trimester should be preferred for splenectomy. Of note, Obstetricians should exercise
high index of suspicion to diagnose this not so uncommon entity as early as pregnancy is diagnosed if a present with
signs and symptoms suggestive of hemolysis and plan out further management along with discussing the option of
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splenectomy with patient and her attendants for better perinatal outcome. Not surprisingly, earlier diagnosis and
management can commensurate into better outcomes.
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