Pregnancy In A Case Of Pyruvate Kinase Deficiency

Author Information

Kumar M*, Mali K**, Warke HS***.
(* Junior Resident, ** Assistant Professor, *** Associate Professor, Department of Gynecology and Obstetrics, Seth G S Medical College and K E M Hospital, Mumbai, India.)


There is a wide variety of congenital disorders which can affect pregnancy. One such rare condition is pyruvate kinase deficiency. It can result in hemolytic anemia of varying severity. A case of pyruvate kinase deficiency and its outcome in pregnancy is presented here.


Pyruvate kinase deficiency (PKD) is the second most common heredity hemolytic anemia. Inheritence is mainly autosomal recessive. Pyruvate kinase is the rate limiting enzyme of Embden Meyeroff glycolytic pathway. Its deficiency results in build up of the intermediates of this pathway making erythrocytes susceptible to hypoxic injury. Homozygote carriers for PKD experience multiple episodes of hemolysis requiring multiple transfusions and sometimes splenectomy. Heterozygous carriers are usually less affected but may experience hemolysis under stressful conditions.[1]

Case Report

A 30 year old gravida 5 with 4 prior spontaneous abortions at 35 weeks of gestation presented to the emergency with epigastric discomfort, and episodes of vomiting along with yellow discolouration of eyes and urine. She had these symptoms from 2 months of gestation with minimal improvement, but had not consulted any physician for the same. She had no complaints of pain in abdomen or itching. On admission her total bilirubin was 21 mg/ dl of which indirect bilirubin was 10 mg/ dl. Her haemoglobin was 8.5 gm%, leukocyte count of 11400 cu/ mm, and platelet count was 2 lakhs/ cu mm. Hematology advice was taken regarding increased indirect bilirubin. Complete hemogram was normal. Both DCT and ICT were negative, but serum LDH levels were high (2251units). ANA, anti dsDNA, aCLA, and anti beta-2 glycoprotein 1 IgM and IgG were negative. Viral markers were negative. She was monitored as a case of Coombs negative hemolytic anaemia. Over ten days, total bilirubin dropped down to 5.6 mg/ dl with indirect bilirubin 3.5 mg/ dl, but never normalized. Her hemoglobin was always in the range of 7-8.0 gm %. In view of persistent hemolysis in the absence of autoimmune abnormality, hematologists advised red blood corpuscle enzyme studies (done using enzyme assay in the hematology laboratory of our institute).  This revealed a normal G6PD enzyme activity, but surprisingly, revealed a pyruvate kinase deficiency. This confirmed the underlying pathology.
Two units packed cell transfusion was given in the antenatal period as she was approaching term. Liver function test and complete blood count were monitored every other day. Biweekly non-stress test was done which was reactive. Obstetric Doppler showed normal flow studies. Her predelivery hemoglobin was 8.5 gm %. At 37 weeks of gestation she went into spontaneous labor. Amniotic fluid was meconium stained and intrapartum monitoring was non-reassuring, for which a lower segment cesarean section was performed. She delivered a healthy male child of 2.8 kg with of Apgar score of 9/10. On third post-operative day, she experienced two episodes of fever following which injection amoxicillin-clavulanate was converted to injection piperacillin-tazobactum, which resulted in fever resolution. She was discharged uneventfully on day 15. She was advised to follow up with hematologists regularly.


Pyruvate kinase deficiency causing hemolytic anaemia is an uncommon disease and is rare in pregnancy. In humans, the pyruvate kinase gene is found at chromosome 1q212.[2] Deficiency or dysfunction of the enzyme results in hemolysis. Most common complication of hemolytic anaemia in pregnancy is fetal growth restriction. However, it was not seen in this pregnancy. Heterozygous carriers are usually not affected but may experience hemolysis under stress conditions. Hence our patient was never diagnosed prior. She underwent investigations and diagnosis for the first time at 30 years of age and in her 5th pregnancy. Apart from pregnancy itself, there appeared to be no other stress factor.
Pre-pregnancy counseling is essential in patients with known pyruvate kinase deficiency for boosting immunity to encapsulated microorganisms and maternal screening for hepatitis B, C, HIV and CMV. Our patient did not have any of these infections. Cardiac investigations include echocardiography and MRI to exclude cardiac siderosis, due to iron overload. The carrier status of the partner should be determined to allow proper prenatal counseling.[3] Our patient was herself diagnosed late in pregnancy, and hence prenatal counseling was not a possibility.
Antenatal folic acid therapy is required to alleviate folate deficiency due to chronic hemolysis. Increased risk of impaired fetal growth is common in these patients and necessitate the need of regular fetal monitoring.[4,5] Our patient was on bi-weekly non-stress tests.  Placental dysfunction may also increase the risk of hypertensive disorders. Uterine artery Doppler may be used as a screening tool to identify risk of preeclampsia.[6] However, our patient was also normotensive.
In established cases of severe pyruvate kinase deficiency, splenectomy is indicated in patients with severe anaemia. However, in our patient, who did not have severe anemia, the hematologists had decided to follow up the patient and assess for further management after the completion of puerperal period. Although there is no research to confirm, breastfeeding is safe when patient has pyruvate kinase deficiency.


The occurrence of hyperbilirubinemia in pregnancy could be the first presentation of rare conditions such as RBC enzyme disorders. A successful pregnancy outcome with pyruvate kinase deficiency in the mother is presented. Close coordination with hematologists helped in improving outcomes.
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Kumar M, Mali K, Warke HS. Pregnancy In A Case Of Pyruvate Kinase Deficiency. JPGO 2018. Volume 5 No.9. Available from: