Journal of Obstetrics and Gynaecology
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
A rare cause of anaemia in pregnancy B. Chisnall & D. Webster To cite this article: B. Chisnall & D. Webster (2014) A rare cause of anaemia in pregnancy, Journal of Obstetrics and Gynaecology, 34:8, 742-743 To link to this article: http://dx.doi.org/10.3109/01443615.2014.935728
Published online: 14 Jul 2014.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijog20 Download by: [University of Florida]
Date: 06 November 2015, At: 04:20
742
Obstetrics Case Reports
heart chambers were dilated, without any signs of decompensation. The fetal liver had homogeneous hepatomegaly. The woman did not attend for any further follow-up until delivery, therefore we could not determine if cardiac failure ever developed. No additional anomalies were found in an ultrasonographic evaluation. The prenatal history was unremarkable.
Case report 2 A 29-year-old, G1P0, woman was referred to our unit at 34 weeks’ gestation, due to a previous diagnosis of cardiomegaly in the fetus. Fetal echocardiography showed a large aberrant umbilical vein coursing in the anterior thorax, crossing the diaphragm and connecting directly to the right atrium. The course, connection and sizes of the inferior vena cava and hepatic vein were normal. Ductus venosus was not visualised (Figure 1). Detailed ultrasonographic examination yielded an additional diagnosis of anorectal malformation. At 37 weeks’ gestation, a female baby was delivered by caesarean section. The postnatal examination was consistent with cloaca anomaly. An ileostomy, vesicostomy and a vaginostomy operation was performed for cloaca anomaly on the 3rd day following the birth.
References Berg C, Kamil D, Geipel A et al. 2006. Absence of ductus venosus-importance of umbilical venous drainage site. Ultrasound in Obstetrics and Gynecology 28:275–281. Contratti G, Banzi C, Ghi T et al. 2001. Absence of the ductus venosus: report of 10 new cases and review of the literature. Ultrasound in Obstetrics and Gynecology 18:605–609. Fasouliotis SJ, Achiron R, Kivilevitch Z et al. 2002. The human fetal venous system: normal embryologic, anatomic, and physiologic characteristics and developmental abnormalities. Journal of Ultrasound in Medicine 21:1145–1158. Hofstaetter C, Plath H. Hansmann M. 2000. Prenatal diagnosis of abnormalities of the fetal venous system. Ultrasound in Obstetrics and Gynecology 15: 231–241. Perles Z, Nir A, Nadjari M et al. 2003. Absent ductus venosus in the fetus: review of the literature and first report of direct umbilical venous drainage to the coronary sinus. Fetal Diagnosis and Therapy 18:247–251. Sau A, Sharland G. Simpson J. 2004. Agenesis of the ductus venosus associated with direct umbilical venous return into the heart – case series and review of literature. Prenatal Diagnosis 24:418–423. Sothinathan U, Pollina E, Huggon I et al. 2006. Absence of the ductus venosus. Acta Paediatrica 95:620–621. Tutar E, Fitoz S. 2010. Absent ductus venosus associated with persistent truncus arteriosus: prenatal diagnosis. Cardiology in the Young 20:345–348.
Journal of Obstetrics and Gynaecology 2014.34:742-743.
Discussion The DV, which is developed in the 5–6th gestational week, connects the left umbilical vein with the inferior vena cava, leading 20–30% of the umbilical vein blood to bypass the hepatic sinusoids and to enter the heart directly. The well-oxygenated blood from the ductus venosus reaches to the left atrium through the foramen ovale and supplies the arteries leading to the brain (Fasouliotis et al. 2002). Absence of DV may be presented by three different patterns of abnormal UV connection: (1) UV bypassing the liver and connecting directly to the inferior vena cava; in these cases marked dilatation of the inferior vena cava is a discriminating feature. (2) UV bypassing the liver and connecting directly to the right atrium; in these cases a long aberrant vessel coursing between the liver and right abdominal wall and crossing the diaphragm is observed. (3) UV connecting to the portal vein without giving rise to the ductus venosus. Diagnosis is confirmed by the absence of a connection between the portal veins and the inferior vena cava. UV entering directly to the heart or inferior vena cava is usually associated with fetal cardiac failure. In most of the series, direct portal vein connection has the most favourable prognosis for cardiac failure. The exact mechanism for cardiac compromise cannot be elucidated. However, chronic volume overload due to the absence of DV regulatory mechanism may lead to high-output cardiac failure and hydrops fetalis (Contratti et al. 2001; Tutar and Fitoz 2010). Absence of DV might be expected on fetal USG by unexplained cardiomegaly and abnormal course of the UV. The diagnosis can be confirmed by blood flow of the UV with colour Doppler ultrasonography (USG) (Contratti et al. 2001). In the two cases reported here, the diagnosis was suspected due the visualisation of an abnormal course of the UV on two-dimensional echocardiography and then confirmed by following the route of this abnormal vein via colour Doppler USG. Many cardiac and extracardiac anomalies might be present in fetuses with ductus venosus agenesis. The association of cardiac anomalies, such as ventricular septal defect, atrial septal defect, interrupted inferior vena cava, hypoplastic left heart syndrome and heterotaxia syndrome, was observed with ductus venosus agenesis. There is also an important risk for associated chromosomal anomalies, such as Turner syndrome (Sau et al. 2004; Sothinathan et al. 2006; Perles et al. 2003). Perinatal prognosis of DV agenesis is closely related to associated anomalies and chromosomal abnormalities. In Case 2, we defined additional cloaca anomalies antenatally, which were confirmed by postnatal examinations. Unfortunately, karyotype analysis were not available for both cases. In summary, in every fetus with unexplained cardiomegaly, ductus venosus agenesis should be kept in mind. As presented here, a detailed ultrasonographic evaluation of the fetus for associated pathologies is essential once the diagnosis of ductus venosus agenesis is confirmed. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
A rare cause of anaemia in pregnancy B. Chisnall1 & D. Webster2 1King’s College London, London, UK and 2Department of Obstetrics and Gynaecology, Poole Hospital NHS Foundation Trust, Poole, UK
DOI: 10.3109/01443615.2014.935728 Correspondence: B. Chisnall, King’s College London, Hodgkin Building, Guy’s Campus, Great Maze Pond, London, SE1 1UL, UK. E-mail: [email protected]
Introduction Haemoglobinopathies in pregnancy can have severe consequences for mother and baby. Milder haemoglobin mutations may give a more reassuring clinical picture, but these have associated risks which must be anticipated and managed by obstetricians. These are discussed in this case report, using the example of a carrier of the haemoglobin North Shore-Caracas variant.
Case review
A 38-year-old woman, para 1 ⫹ 1, gravida 3, was found, during her first pregnancy in 2009, to have a low haemoglobin (107 g/l), a low MCV (75 fl) and a low MCHC (24.6 pg). Upon liquid chromatography (HPLC) analysis, a haemoglobin variant was detected, eluting before adult haemoglobin (HbA0) and constituting around 27% of the sample. Raised levels of HbA2 (4.6%) and HbF (1.1%) were also detected. The patient was sent for alkaline haemoglobin electrophoresis, and was found to have a slightly faster band than HbA. A diagnosis of haemoglobin North Shore-Caracas, a rare unstable haemoglobin variant, was made. There were no atypical red blood cell antibodies present, and the patient’s blood group was A-Rh(D)-negative. Presenting for her second pregnancy in 2013, the patient had not experienced any symptoms of anaemia, and was clinically well. Iron supplementation was given, but no improvement followed. At 28 weeks’ gestation, her blood results were as shown in Table I. On ultrasound at 27 ⫹ 2 weeks’ gestation, the fetus showed normal growth (head circumference 50th centile, abdominal circumference 75th centile, femur length 30th centile, estimated fetal weight 40th centile) and amniotic fluid index normal. The placenta was anterior and high. The patient had a family history of thromboembolic disease: her mother, who was also a North Shore-Caracas carrier, suffered a deep vein thrombosis (DVT) after a flight. The patient had also previously suffered a 1st trimester miscarriage, although no direct cause had been found for this. Due to her unstable haemoglobinopathy, the patient was advised to avoid blood products because of the potential for
Obstetrics Case Reports 743 Table I. Blood results for the patient at 28 weeks’ gestation. Component Haemoglobin (g/l) Haematocrit (%) Platelets (⫻ 103/μl) Mean corpuscular volume (fl) Mean corpuscular haemoglobin (pg) Nucleated red blood cells (⫻ 103/μl) Ferritin (ng/ml) Folate (ng/ml) Vitamin B12 (pg/ml) Iron (μmol/l) Total iron binding capacity (μmol/l) Transferrin saturation (%)
Patient’s blood values
Normal range
93 28.2 205 77.9 25.3 0.00 75.6 13.4 514 14 60 23
115–160 36.0–47.0 150–400 80.0–100.0 27.0–32.0 0.00 13–150 4.6–18.7 191–663 6.6–30.4 45–81 12–45
Journal of Obstetrics and Gynaecology 2014.34:742-743.
adverse reactions. Accordingly, she would be allowed to labour but not deliver vaginally, instead having a caesarean section at the onset of labour.
Discussion Haemoglobin North Shore-Caracas is a rare haemoglobinopathy characterised by low haemoglobin, low MCV and MCH, with normal serum ferritin levels and a raised reticulocyte count. The haemoglobin North Shore molecule has a substitution of valine to glutamine or glutamic acid at position 134 on the beta chain, causing impaired beta chain synthesis (Smith et al. 1983). Patients also have increased HbA2 levels, with normal or slightly raised HbF levels. The clinical picture is similar to that of mild beta-thalassaemia trait, and carriers of the North Shore-Caracas variant may be asymptomatic. Previous case reports have described a recurrent unexplained purpuric rash in a carrier, as well as clinical manifestations of iron deficiency anaemia (Gurney et al. 1987). Due to the rarity of the North Shore-Caracas variant, there is no robust data on its effects in pregnancy. Obstetricians must be aware
of the need to avoid blood products in pregnancy or labour, and to discuss this and its implications with the patient. Studies on mothers who are carriers of the beta-thalassaemia minor trait have suggested an association with intrauterine growth restriction, oligohydramnios and increased frequency of urinary tract infections in pregnancy, alongside increased rates of caesarean section. (Sheiner et al. 2004; Jans et al. 2010) There may also be an increased risk of preeclampsia in nulliparous and obese women with beta-thalassaemia trait (Hanprasertpong et al. 2013). As the North Shore-Caracas trait gives a similar clinical and haematological manifestation to mild beta-thalassaemia trait, obstetricians may want to be vigilant for these potential complications in this and other rare haemoglobinopathies.
Conclusion Patients presenting in pregnancy with a microcytic anaemia may not just have iron deficiency or dilutional anaemia but may need investigation for haemoglobinopathies, especially if their anaemia is unresponsive to iron supplementation. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Gurney H, Baig I, Gordon S et al. 1987. A second Australian family with hemoglobin North Shore (beta 134 Val----Glu). Pathology 19:62–63. Hanprasertpong T, Kor-Anantakul O, Leetanaporn R et al. 2013. Pregnancy outcomes amongst thalassemia traits. Archives of Gynecology and Obstetrics 288:1051–1054. Jans SM, de Jonge A, Lagro-Janssen AL. 2010. Maternal and perinatal outcomes amongst haemoglobinopathy carriers: a systematic review. International Journal of Clinical Practice 64:1688–1698. Sheiner E, Levy A, Yerushalmi R et al. 2004. Beta-thalassemia minor during pregnancy. Obstetrics and Gynecology 103:1273–1277. Smith CM, Hedlund B, Cich JA et al. 1983. Hemoglobin North Shore: a variant hemoglobin associated with the phenotype of beta-thalassemia. Blood 61:378–383.
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
A rare cause of anaemia in pregnancy B. Chisnall & D. Webster To cite this article: B. Chisnall & D. Webster (2014) A rare cause of anaemia in pregnancy, Journal of Obstetrics and Gynaecology, 34:8, 742-743 To link to this article: http://dx.doi.org/10.3109/01443615.2014.935728
Published online: 14 Jul 2014.
Submit your article to this journal
Article views: 47
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijog20 Download by: [University of Florida]
Date: 06 November 2015, At: 04:20
742
Obstetrics Case Reports
heart chambers were dilated, without any signs of decompensation. The fetal liver had homogeneous hepatomegaly. The woman did not attend for any further follow-up until delivery, therefore we could not determine if cardiac failure ever developed. No additional anomalies were found in an ultrasonographic evaluation. The prenatal history was unremarkable.
Case report 2 A 29-year-old, G1P0, woman was referred to our unit at 34 weeks’ gestation, due to a previous diagnosis of cardiomegaly in the fetus. Fetal echocardiography showed a large aberrant umbilical vein coursing in the anterior thorax, crossing the diaphragm and connecting directly to the right atrium. The course, connection and sizes of the inferior vena cava and hepatic vein were normal. Ductus venosus was not visualised (Figure 1). Detailed ultrasonographic examination yielded an additional diagnosis of anorectal malformation. At 37 weeks’ gestation, a female baby was delivered by caesarean section. The postnatal examination was consistent with cloaca anomaly. An ileostomy, vesicostomy and a vaginostomy operation was performed for cloaca anomaly on the 3rd day following the birth.
References Berg C, Kamil D, Geipel A et al. 2006. Absence of ductus venosus-importance of umbilical venous drainage site. Ultrasound in Obstetrics and Gynecology 28:275–281. Contratti G, Banzi C, Ghi T et al. 2001. Absence of the ductus venosus: report of 10 new cases and review of the literature. Ultrasound in Obstetrics and Gynecology 18:605–609. Fasouliotis SJ, Achiron R, Kivilevitch Z et al. 2002. The human fetal venous system: normal embryologic, anatomic, and physiologic characteristics and developmental abnormalities. Journal of Ultrasound in Medicine 21:1145–1158. Hofstaetter C, Plath H. Hansmann M. 2000. Prenatal diagnosis of abnormalities of the fetal venous system. Ultrasound in Obstetrics and Gynecology 15: 231–241. Perles Z, Nir A, Nadjari M et al. 2003. Absent ductus venosus in the fetus: review of the literature and first report of direct umbilical venous drainage to the coronary sinus. Fetal Diagnosis and Therapy 18:247–251. Sau A, Sharland G. Simpson J. 2004. Agenesis of the ductus venosus associated with direct umbilical venous return into the heart – case series and review of literature. Prenatal Diagnosis 24:418–423. Sothinathan U, Pollina E, Huggon I et al. 2006. Absence of the ductus venosus. Acta Paediatrica 95:620–621. Tutar E, Fitoz S. 2010. Absent ductus venosus associated with persistent truncus arteriosus: prenatal diagnosis. Cardiology in the Young 20:345–348.
Journal of Obstetrics and Gynaecology 2014.34:742-743.
Discussion The DV, which is developed in the 5–6th gestational week, connects the left umbilical vein with the inferior vena cava, leading 20–30% of the umbilical vein blood to bypass the hepatic sinusoids and to enter the heart directly. The well-oxygenated blood from the ductus venosus reaches to the left atrium through the foramen ovale and supplies the arteries leading to the brain (Fasouliotis et al. 2002). Absence of DV may be presented by three different patterns of abnormal UV connection: (1) UV bypassing the liver and connecting directly to the inferior vena cava; in these cases marked dilatation of the inferior vena cava is a discriminating feature. (2) UV bypassing the liver and connecting directly to the right atrium; in these cases a long aberrant vessel coursing between the liver and right abdominal wall and crossing the diaphragm is observed. (3) UV connecting to the portal vein without giving rise to the ductus venosus. Diagnosis is confirmed by the absence of a connection between the portal veins and the inferior vena cava. UV entering directly to the heart or inferior vena cava is usually associated with fetal cardiac failure. In most of the series, direct portal vein connection has the most favourable prognosis for cardiac failure. The exact mechanism for cardiac compromise cannot be elucidated. However, chronic volume overload due to the absence of DV regulatory mechanism may lead to high-output cardiac failure and hydrops fetalis (Contratti et al. 2001; Tutar and Fitoz 2010). Absence of DV might be expected on fetal USG by unexplained cardiomegaly and abnormal course of the UV. The diagnosis can be confirmed by blood flow of the UV with colour Doppler ultrasonography (USG) (Contratti et al. 2001). In the two cases reported here, the diagnosis was suspected due the visualisation of an abnormal course of the UV on two-dimensional echocardiography and then confirmed by following the route of this abnormal vein via colour Doppler USG. Many cardiac and extracardiac anomalies might be present in fetuses with ductus venosus agenesis. The association of cardiac anomalies, such as ventricular septal defect, atrial septal defect, interrupted inferior vena cava, hypoplastic left heart syndrome and heterotaxia syndrome, was observed with ductus venosus agenesis. There is also an important risk for associated chromosomal anomalies, such as Turner syndrome (Sau et al. 2004; Sothinathan et al. 2006; Perles et al. 2003). Perinatal prognosis of DV agenesis is closely related to associated anomalies and chromosomal abnormalities. In Case 2, we defined additional cloaca anomalies antenatally, which were confirmed by postnatal examinations. Unfortunately, karyotype analysis were not available for both cases. In summary, in every fetus with unexplained cardiomegaly, ductus venosus agenesis should be kept in mind. As presented here, a detailed ultrasonographic evaluation of the fetus for associated pathologies is essential once the diagnosis of ductus venosus agenesis is confirmed. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
A rare cause of anaemia in pregnancy B. Chisnall1 & D. Webster2 1King’s College London, London, UK and 2Department of Obstetrics and Gynaecology, Poole Hospital NHS Foundation Trust, Poole, UK
DOI: 10.3109/01443615.2014.935728 Correspondence: B. Chisnall, King’s College London, Hodgkin Building, Guy’s Campus, Great Maze Pond, London, SE1 1UL, UK. E-mail: [email protected]
Introduction Haemoglobinopathies in pregnancy can have severe consequences for mother and baby. Milder haemoglobin mutations may give a more reassuring clinical picture, but these have associated risks which must be anticipated and managed by obstetricians. These are discussed in this case report, using the example of a carrier of the haemoglobin North Shore-Caracas variant.
Case review
A 38-year-old woman, para 1 ⫹ 1, gravida 3, was found, during her first pregnancy in 2009, to have a low haemoglobin (107 g/l), a low MCV (75 fl) and a low MCHC (24.6 pg). Upon liquid chromatography (HPLC) analysis, a haemoglobin variant was detected, eluting before adult haemoglobin (HbA0) and constituting around 27% of the sample. Raised levels of HbA2 (4.6%) and HbF (1.1%) were also detected. The patient was sent for alkaline haemoglobin electrophoresis, and was found to have a slightly faster band than HbA. A diagnosis of haemoglobin North Shore-Caracas, a rare unstable haemoglobin variant, was made. There were no atypical red blood cell antibodies present, and the patient’s blood group was A-Rh(D)-negative. Presenting for her second pregnancy in 2013, the patient had not experienced any symptoms of anaemia, and was clinically well. Iron supplementation was given, but no improvement followed. At 28 weeks’ gestation, her blood results were as shown in Table I. On ultrasound at 27 ⫹ 2 weeks’ gestation, the fetus showed normal growth (head circumference 50th centile, abdominal circumference 75th centile, femur length 30th centile, estimated fetal weight 40th centile) and amniotic fluid index normal. The placenta was anterior and high. The patient had a family history of thromboembolic disease: her mother, who was also a North Shore-Caracas carrier, suffered a deep vein thrombosis (DVT) after a flight. The patient had also previously suffered a 1st trimester miscarriage, although no direct cause had been found for this. Due to her unstable haemoglobinopathy, the patient was advised to avoid blood products because of the potential for
Obstetrics Case Reports 743 Table I. Blood results for the patient at 28 weeks’ gestation. Component Haemoglobin (g/l) Haematocrit (%) Platelets (⫻ 103/μl) Mean corpuscular volume (fl) Mean corpuscular haemoglobin (pg) Nucleated red blood cells (⫻ 103/μl) Ferritin (ng/ml) Folate (ng/ml) Vitamin B12 (pg/ml) Iron (μmol/l) Total iron binding capacity (μmol/l) Transferrin saturation (%)
Patient’s blood values
Normal range
93 28.2 205 77.9 25.3 0.00 75.6 13.4 514 14 60 23
115–160 36.0–47.0 150–400 80.0–100.0 27.0–32.0 0.00 13–150 4.6–18.7 191–663 6.6–30.4 45–81 12–45
Journal of Obstetrics and Gynaecology 2014.34:742-743.
adverse reactions. Accordingly, she would be allowed to labour but not deliver vaginally, instead having a caesarean section at the onset of labour.
Discussion Haemoglobin North Shore-Caracas is a rare haemoglobinopathy characterised by low haemoglobin, low MCV and MCH, with normal serum ferritin levels and a raised reticulocyte count. The haemoglobin North Shore molecule has a substitution of valine to glutamine or glutamic acid at position 134 on the beta chain, causing impaired beta chain synthesis (Smith et al. 1983). Patients also have increased HbA2 levels, with normal or slightly raised HbF levels. The clinical picture is similar to that of mild beta-thalassaemia trait, and carriers of the North Shore-Caracas variant may be asymptomatic. Previous case reports have described a recurrent unexplained purpuric rash in a carrier, as well as clinical manifestations of iron deficiency anaemia (Gurney et al. 1987). Due to the rarity of the North Shore-Caracas variant, there is no robust data on its effects in pregnancy. Obstetricians must be aware
of the need to avoid blood products in pregnancy or labour, and to discuss this and its implications with the patient. Studies on mothers who are carriers of the beta-thalassaemia minor trait have suggested an association with intrauterine growth restriction, oligohydramnios and increased frequency of urinary tract infections in pregnancy, alongside increased rates of caesarean section. (Sheiner et al. 2004; Jans et al. 2010) There may also be an increased risk of preeclampsia in nulliparous and obese women with beta-thalassaemia trait (Hanprasertpong et al. 2013). As the North Shore-Caracas trait gives a similar clinical and haematological manifestation to mild beta-thalassaemia trait, obstetricians may want to be vigilant for these potential complications in this and other rare haemoglobinopathies.
Conclusion Patients presenting in pregnancy with a microcytic anaemia may not just have iron deficiency or dilutional anaemia but may need investigation for haemoglobinopathies, especially if their anaemia is unresponsive to iron supplementation. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Gurney H, Baig I, Gordon S et al. 1987. A second Australian family with hemoglobin North Shore (beta 134 Val----Glu). Pathology 19:62–63. Hanprasertpong T, Kor-Anantakul O, Leetanaporn R et al. 2013. Pregnancy outcomes amongst thalassemia traits. Archives of Gynecology and Obstetrics 288:1051–1054. Jans SM, de Jonge A, Lagro-Janssen AL. 2010. Maternal and perinatal outcomes amongst haemoglobinopathy carriers: a systematic review. International Journal of Clinical Practice 64:1688–1698. Sheiner E, Levy A, Yerushalmi R et al. 2004. Beta-thalassemia minor during pregnancy. Obstetrics and Gynecology 103:1273–1277. Smith CM, Hedlund B, Cich JA et al. 1983. Hemoglobin North Shore: a variant hemoglobin associated with the phenotype of beta-thalassemia. Blood 61:378–383.
