Arch Gynecol Obstet DOI 10.1007/s00404-014-3240-6
Case Report
Prenatal renal vein thrombosis in dichorionic twin pregnancy Sarah K. Weber · Andreas Müller · Annegret Geipel · Christoph Berg · Ulrich Gembruch
Received: 19 March 2014 / Accepted: 28 March 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Background Prenatal renal vein thrombosis is a rarely described diagnostic finding. The etiology is unclear in the majority of cases, although thrombophilia was found in some affected fetuses. Precise ultrasound scan can improve detection rate of neonatal thrombosis due to characteristic findings. Case report We present the unusual case of a dichorionic twin pregnancy in 31 weeks of gestation with one affected fetus, showing already intrauterine a bilaterally enlarged kidney and absence of renal venous flow. Additionally, the fetus showed signs of circulatory compromise and fetal distress, while dichorionic male co-twin was healthy. The postnatal thrombophilia investigations revealed a heterozygous factor V Leiden mutation. Conclusion Fetal renal vein thrombosis may occur bilateral and may also involve the inferior vena cava. Rapid deterioration of fetal condition, abnormal fetal Doppler, appearance of hydrops fetalis, may accompany fetal venous thrombosis. By color Doppler flow mapping abnormal arterial and absent venous perfusion of the affected kidney may be demonstrated in addition. Keywords Renal vein thrombosis · Hyperechogenic kidney · Hydrops · Fetus · Prenatal diagnosis
S. K. Weber (*) · A. Geipel · C. Berg · U. Gembruch Department of Obstetrics and Prenatal Medicine, University of Bonn, Sigmund‑Freud Str 25, 53105 Bonn, Germany e-mail: [email protected]‑bonn.de U. Gembruch e-mail: [email protected]‑bonn.de A. Müller Department of Neonatology, University of Bonn, Bonn, Germany
Introduction Renal venous thrombosis is not rare in the neonatal period, but there are few data about etiology and incidence of this phenomenon in prenatal time. However, some risk factors, which are known to predisposing renal venous thrombosis are, e.g., diabetes mellitus or preeclampsia of the mother or maternal and/or fetal thrombophilia [1, 2]. In this article, we describe a special case of a renal vein thrombosis in one fetus of a dichorionic twin pregnancy by presenting the ultrasound findings, the clinical presentation, and possible differential diagnosis.
Case description A 32-year-old gravida IV, para I with a dichorial-diamniotic twin pregnancy was presenting at 31 weeks of gestation. The prenatal care was normal up to this point and included normal second trimester scan. At the 29 weeks, the woman had an application of antenatal corticosteroids for the prevention of respiratory distress syndrome and tocolysis with fenoterol, a beta-2-sympathomimetic, was done due to premature contractions. In the women’s obstetrical history, there was a spontaneous birth of a healthy boy 2001 and two interruptions in early gestation. There was no family history of thrombophilia or other maternal health risks. Ultrasound examination showed two fetuses without any abnormal findings regarding development, size, amnion fluid index, and biophysical profile. However, fetus I showed fetal centralization of circulatory with decreased pulsatility in middle cerebral artery (PI 1.09, RI 0.65, PSV 41.0 cm/s) and reverse flow in the ductus venosus during atrial contraction (PVIV 1.43) in spite a normal Doppler flow velocity waveform in the umbilical artery (PI 1.06, RI
13
0.63). In addition, ultrasound revealed bilaterally enlarged kidneys with hyperechogenic parenchyma, blurred corticomedullary distinction, and a renal volume of about 30 cm3 on left side, mild ascites, mild bilateral pleural effusion, and hyperechogenic bowel (Figs. 1, 2, 3). In fetal echocardiography, there was a holosystolic tricuspid regurgitation but no other structural and hemodynamic anomalies, also in pulmonary, arterial ductal, and aortic flow. Two days later, color Doppler could not show any blood flow neither in the renal artery nor in the renal and inferior caval veins and there were signs of low cardiac output with reduced preload in fetus I. Both kidneys showed a more blurred cortico-medullary distinction and a slightly increased volume. Still, there was a decreased pulsatility in the middle cerebral artery (PI 1.36, RI 0.66, PSV 41.6 cm/s), ductus venosus showed increased pulsatility, but positive flow during atrial contraction (PVIV 0.79). The fetal movement as well as fetal heart rate monitor was without pathological
Fig. 1 Ultrasound scan showing the enlarged and hyperechogenic left kidney at 30 + 1 weeks of gestation
Fig. 2 Both kidneys are enlarged and with blurred cortico-medullary distinction at 30 + 4 weeks of gestation
13
Arch Gynecol Obstet
Fig. 3 Mild pleural effusion of the fetus at 30 + 4 weeks of gestation
findings. Fetus II was still presenting with normal findings in ultrasound examination and biophysical profile. The patient underwent an urgent cesarean section under spinal anesthesia. Two male fetuses were delivered. Birth weights were 1,830 and 2,005 g, Apgar score 8, 9, 9, and 9, 9, 9, umbilical artery pH 7.30 and 7.39, and umbilical artery base excess −1.6 mmol/l and +0.6 mmol/l, respectively. Both newborns were immediately supplied. Physical examination of fetus I revealed an afebrile, well-developed male infant with regular heartbeat, palpable pulse on all extremities, and slight intercostal retractions. The neonate’s abdomen was distended and showed an enlargement of the liver, palpable 3 cm under the costal arch. The infant was supplied with CPAP. Intravenous access was established; complete blood count was drawn. A chest X-ray performed on the first day of life demonstrated a respiratory distress syndrome II°; ultrasound of the brain was without pathological findings. Echocardiography revealed normal anatomy and function. Ultrasound of the abdomen confirmed the diagnosis of a bilateral renal vein thrombosis of fetus I, especially the left kidney was enlarged, hyperechogenic, with blurred cortico-medullary distinction, pathological renal arterial Doppler with diastolic reverse flow, and absence of renal venous flow. Angiography performed by a catheter-based puncture of the V. femoralis, and selective demonstration of V. renalis revealed thrombosis of the infrahepatic part of the inferior vena cava with collateral circulation through the azygos vein in the superior vena cava. Laboratory investigations showed a hematocrit of 57 % with a hemoglobin concentration of 20.4 g/dl, a thrombocytopenia of 29,000/μl, white blood cell count of 11,080/μl, and a mild renal failure with a highest creatinine level of 1.8 mg/dl at the third day of life. A thrombolytic therapy with tissue-type plasminogen activator, t-PA (Actilyse®), and unfractionated heparin was initialized. Under this treatment, a bleeding of the adrenal cortex occurred as side effect, so
Arch Gynecol Obstet
that the thrombolytic therapy was paused for 1 day. According to soon recovery of renal function, therapy with unfractionated heparin (100 IE/kg BW/day heparin) was changed into low molecular weight heparin (4 mg/kg/day enoxaparin) after 9 days. The sibling had unremarkable findings in physical examination, laboratory investigations, and ultrasound of the brain. Chest X-ray showed respiratory distress syndrome IV°. The siblings were transferred in another hospital in the parent’s neighborhood 18 days after birth. This mutation was not detected in the parents and the co-twin. In search of etiology of antenatal renal vein thrombosis, serological and PCR-based diagnostic procedure of the mother and the neonate excluded infections with entero-, rubella-, hepatitis-, parvo-, cytomegaly-, varicella zoster-, herpes simplex viruses, HIV, and toxoplasmosis. The thrombophilia investigations of neonatal blood sample (protein C and protein S activity, antithrombin III activity, activated protein C resistance, prothrombin mutation, and factor V Leiden) revealed a heterozygous factor V Leiden mutation. Currently, the child has a thrombosis prophylaxis with enoxaparin. Even at the age of 4 years, the left kidney is smaller than the right one. However, there is no restriction of renal function (creatinine 0.32 mg/dl, cystatin C 0.96 mg/l).
Discussion The actual incidence of prenatal renal vein thrombosis is still unknown. However, neonatal renal vein thrombosis is a well-known clinical picture with a probably higher incidence of 2.2 per 100.000 live births [3] and even 13 per 100.000 live births in preterm neonates. Some possible theories of pathogenesis of intrauterine thrombosis have been discussed in previous reviews. Reported maternal conditions are, e.g., diabetes, preeclampsia, lupus erythematodes, and corticosteroid therapy or cytomegaly virus infection during pregnancy [1, 2]. In our case, apart from antenatal corticosteroid therapy with 12 mg betamethasone i.m. on 2 days, none of the mentioned risk factors affected the mother. Treatment with beta-2-sympathomimetics and corticosteroids is widely used and safe; however, it maybe has been triggered occurrence of thrombosis in the dichorionic twin, which was predisposed to thrombosis due to thrombotic disorder. A further common reason for prenatal thrombosis could be fetal thrombophilia. In a study with 23 neonates with renal vein thrombosis [4], prothrombotic abnormalities were detected in 44 % of all patients. Factor V Leiden mutations were the most commonly reported defects in their report and also in those of other infant thrombosis series [5, 6]. One case described a fetal and maternal
antithrombin deficiency [7] and another one with maternal antiphospholipid syndrome [8]. Interestingly, the affected child in our case had a de novo mutation of factor V Leiden, while the twin brother and the parents had not a factor V Leiden mutation. In a review of the literature, Smorgick and coworkers (2007) describe 12 cases of renal thrombosis in the fetus [9]: in 33.3 %, the fetuses presented hydrops fetalis; in 41.6 %, there were signs of “fetal distress” like abnormal fetal heartbeat in cardiotocography; and in 25 %, diagnosis was made by incidental findings on prenatal ultrasound. In four cases, there were no associated maternal conditions; the others had either acute or chronic disease in their maternal history such as acute gastroenteritis [10] or acute pyelonephritis [11], chronic hypertension [12], and diabetes mellitus [11]. Referring to this case, a special thrombophilic disorder concerning mother or fetus was found in two cases: antiphospholipid antibody syndrome [8] and antithrombin III deficiency [7]. To the best of our knowledge, there is only one case describing a similar situation of a twin pregnancy with a stillborn fetus showing bilateral thrombosis of renal and inferior caval veins. While the male dichorionic co-twin was healthy, a homozygous mutation of the gene encoding for 5,10 methylene tetrahydrofolate reductase (MTHFR) was diagnosed, but there was also a premature closure of the foramen ovale and also a previous application of beta-2-sympathomimetics and corticosteroids as relevant risk factors [13]. It is noteworthy that all fetuses showed signs of stress; retrospectively, it seems difficult to verify that the renal thrombosis was the reason for the fetal stress or if the fetal stress was caused by the thrombosis. Prenatal ultrasound examination in our case showed bilaterally enlarged kidneys with left-sided predominance and a volume of about 30 cm3, hyperechogenic parenchyma, blurred cortico-medullary distinction, mild ascites, mild bilateral pleural effusion, and hyperechogenic bowel. Absent venous and arterial flow in renal vessels were additional Doppler signs. Brandao et al. [2] describe in their review typical ultrasound findings of in utero onset RTV, such as renal enlargement and hyperechogenicity with or without calcifications of the renal venous system. In a further case of bilateral renal venous thrombosis, a progressive development of atrophy of both kidneys occurred [14]. In follow-up ultrasound examinations after 4 weeks, both kidneys showed progressive growth and improved resistive indices. Postnatally, the classical triad of hematuria, palpable mass, and thrombocytopenia is not present in all cases of renal venous thrombosis. In a cohort of 23 patients, only 22 % showed all three mentioned features [4]. One further case report described that diagnosis of renal vein thrombosis of a newborn was confirmed by kidney biopsy, whereas
13
sonography was unspecific in this case [16]. Left-sided predominance and male newborns were more often affected by all congenital renal malformations [16]. The left-sided predominance could be a result of the anatomic circumstances, due to the anatomic course of the renal vein underneath the aorta. There is a significantly correlation between renal size and outcome [2, 4]. Using ultrasound, a functional radionuclide scan and a chromium-51 ethylenediamine tetraacetic acid (Cr51-EDTA) glomerular filtration rate (GFR), they detected that larger neonatal kidneys had a reduced longterm function. This fact may be helpful to identify those patients who benefit from more aggressive or intensive treatment. To confirm this assumption and the renal longterm outcome, further studies are required.
Conclusion A precise ultrasound screen should be performed in order to detect abnormalities in case of unclear fetal distress and/ or hydrops. Typical findings of prenatal RVT in ultrasound evaluation are uni- or bilateral nephromegaly and blurred cortico-medullary distinction and in color Doppler, reduced or absent renal perfusion. Nevertheless, its clinical presentation can vary from polyhydramnios, ascites, or hydrops fetalis to suspicious CTG. Procoagulant screening should be done, considering the fact that recent studies have highlighted the importance of underlying prothrombotic alterations in renal vein thrombosis [5, 16]. In this case report, we described a dichorionic twin pregnancy with one affected fetus, showing already intrauterine a bilaterally enlarged kidney and absence of renal venous flow in combination with signs of circulatory compromise and fetal distress, while dichorionic male co-twin was healthy. Conflict of interest We declare that we have no conflict of interest.
References 1. Oppenheimer EH, Esterly JR (1965) Thrombosis in the newborn: comparison between infants of diabetic and non diabetic mothers. J Pediatr 67:549–556 2. Brandão LR, Simpson EA, Lau KK (2011) Neonatal renal vein thrombosis. Semin Fetal Neonatal Med 16:323–328
13
Arch Gynecol Obstet 3. Bökenkamp A, von Kries R, Nowak-Göttl U, Göbel U, Hoyer PF (2000) Neonatal renal venous thrombosis in Germany between 1992 and 1994: epidemiology, treatment and outcome. Eur J Pediatr 159:44–48 4. Winyard PJD, Bharucha T, de Bruyn R, Dillon MJ, van’t Hoff W, Trompeter RS, Liesner R, Wade A, Rees L (2006) Perinatal renal venous thrombosis: presenting renal length predicts outcome. Arch Dis Child Fetal Neonatal Ed 91:F273–F278 5. Kosch A, Kuwertz-Broking E, Heller C, Kurnik K, Schobess R, Nowak-Göttl U (2004) Renal venous thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Blood 104:1356–1360 6. Heller C, Schobess R, Kurnik K, Junker R, Günther G, Kreuz W, Nowak-Göttl U (2000) Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors: a multicenter case control study, for the childhood thrombophilia study group. Br J Haematol 111:534–539 7. Weissmann-Brenner A, Ferber A, O’Reilly-Green C, Avila C, Grassi A, Divon MY (2004) Inferior vena cava thrombosis presenting as non-immune hydrops in the fetus of a women with diabetes. Ultrasound Obstet Gynecol 23(2):194–197 8. Hage ML, LIU R, Marcheschi DG, Bowie JD, Allen NB, Macik BG (1994) Fetal renal vein thrombosis, hydrops fetalis and maternal lupus anticoagulant: a case report. Prenat Diagn 14:873–877 9. Smorgick N, Herman A, Wiener Y, Halperin R, Sherman D (2007) Prenatal thrombosis of the inferior vena cava and the renal veins. Prenatal Diagn 27:603–607 10. Diallo A, Boog GJ, Moussally F, Quere MP (1998) Fetal renal venous thrombosis: a typical ultrasonographic aspect. J Gynecol Obstet Biol Reprod (Paris) 27:445–447 11. Sanders LD, Jequier S (1989) Ultrasound demonstration of prenatal renal vein thrombosis. Pediatr Radiol 19:133–135 12. Patel RB, Connors JJ (1988) In utero sonographic findings in fetal renal vein thrombosis with calcifications. J Ultrasound Med 7:349–352 13. Stanek J, Bove KE, Bofinger M, Needham D, Saldana LR, Mutema GK, Meyer R (2000) Premature closure of foramen ovale and renal vein thrombosis in a stillborn twin homozygous for methylene tetrahydrofolate reductase gene polymorphism: a clinicopathologic case study. J Perinat Med 28:61–68 14. Lau KK, Fernandez y Garcia E, Kwan WY, Albrecht L, SteinWexler R (2007) Bilateral renal venous thrombosis and adrenal hemorrhage: sequential prenatal US with postnatal recovery. Pediatr Radiol 37:912–915 15. Prelog M, Fischer H, Gassner I, Tzankov A, Glatz-Krieger K, Mihatsch M, Zimmerhackl LB (2006) Bilateral renal vein thrombosis in a twin newborn without known risk factors. Clin Nephrol 66:135–139 16. Kuhle S, Massicotte P, Chan A, Mitchell L (2004) A case series of 72 neonates with renal vein thrombosis: data from the 1-800-NOCLOTS registry. Thromb Haemost 92:729–733
Case Report
Prenatal renal vein thrombosis in dichorionic twin pregnancy Sarah K. Weber · Andreas Müller · Annegret Geipel · Christoph Berg · Ulrich Gembruch
Received: 19 March 2014 / Accepted: 28 March 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Background Prenatal renal vein thrombosis is a rarely described diagnostic finding. The etiology is unclear in the majority of cases, although thrombophilia was found in some affected fetuses. Precise ultrasound scan can improve detection rate of neonatal thrombosis due to characteristic findings. Case report We present the unusual case of a dichorionic twin pregnancy in 31 weeks of gestation with one affected fetus, showing already intrauterine a bilaterally enlarged kidney and absence of renal venous flow. Additionally, the fetus showed signs of circulatory compromise and fetal distress, while dichorionic male co-twin was healthy. The postnatal thrombophilia investigations revealed a heterozygous factor V Leiden mutation. Conclusion Fetal renal vein thrombosis may occur bilateral and may also involve the inferior vena cava. Rapid deterioration of fetal condition, abnormal fetal Doppler, appearance of hydrops fetalis, may accompany fetal venous thrombosis. By color Doppler flow mapping abnormal arterial and absent venous perfusion of the affected kidney may be demonstrated in addition. Keywords Renal vein thrombosis · Hyperechogenic kidney · Hydrops · Fetus · Prenatal diagnosis
S. K. Weber (*) · A. Geipel · C. Berg · U. Gembruch Department of Obstetrics and Prenatal Medicine, University of Bonn, Sigmund‑Freud Str 25, 53105 Bonn, Germany e-mail: [email protected]‑bonn.de U. Gembruch e-mail: [email protected]‑bonn.de A. Müller Department of Neonatology, University of Bonn, Bonn, Germany
Introduction Renal venous thrombosis is not rare in the neonatal period, but there are few data about etiology and incidence of this phenomenon in prenatal time. However, some risk factors, which are known to predisposing renal venous thrombosis are, e.g., diabetes mellitus or preeclampsia of the mother or maternal and/or fetal thrombophilia [1, 2]. In this article, we describe a special case of a renal vein thrombosis in one fetus of a dichorionic twin pregnancy by presenting the ultrasound findings, the clinical presentation, and possible differential diagnosis.
Case description A 32-year-old gravida IV, para I with a dichorial-diamniotic twin pregnancy was presenting at 31 weeks of gestation. The prenatal care was normal up to this point and included normal second trimester scan. At the 29 weeks, the woman had an application of antenatal corticosteroids for the prevention of respiratory distress syndrome and tocolysis with fenoterol, a beta-2-sympathomimetic, was done due to premature contractions. In the women’s obstetrical history, there was a spontaneous birth of a healthy boy 2001 and two interruptions in early gestation. There was no family history of thrombophilia or other maternal health risks. Ultrasound examination showed two fetuses without any abnormal findings regarding development, size, amnion fluid index, and biophysical profile. However, fetus I showed fetal centralization of circulatory with decreased pulsatility in middle cerebral artery (PI 1.09, RI 0.65, PSV 41.0 cm/s) and reverse flow in the ductus venosus during atrial contraction (PVIV 1.43) in spite a normal Doppler flow velocity waveform in the umbilical artery (PI 1.06, RI
13
0.63). In addition, ultrasound revealed bilaterally enlarged kidneys with hyperechogenic parenchyma, blurred corticomedullary distinction, and a renal volume of about 30 cm3 on left side, mild ascites, mild bilateral pleural effusion, and hyperechogenic bowel (Figs. 1, 2, 3). In fetal echocardiography, there was a holosystolic tricuspid regurgitation but no other structural and hemodynamic anomalies, also in pulmonary, arterial ductal, and aortic flow. Two days later, color Doppler could not show any blood flow neither in the renal artery nor in the renal and inferior caval veins and there were signs of low cardiac output with reduced preload in fetus I. Both kidneys showed a more blurred cortico-medullary distinction and a slightly increased volume. Still, there was a decreased pulsatility in the middle cerebral artery (PI 1.36, RI 0.66, PSV 41.6 cm/s), ductus venosus showed increased pulsatility, but positive flow during atrial contraction (PVIV 0.79). The fetal movement as well as fetal heart rate monitor was without pathological
Fig. 1 Ultrasound scan showing the enlarged and hyperechogenic left kidney at 30 + 1 weeks of gestation
Fig. 2 Both kidneys are enlarged and with blurred cortico-medullary distinction at 30 + 4 weeks of gestation
13
Arch Gynecol Obstet
Fig. 3 Mild pleural effusion of the fetus at 30 + 4 weeks of gestation
findings. Fetus II was still presenting with normal findings in ultrasound examination and biophysical profile. The patient underwent an urgent cesarean section under spinal anesthesia. Two male fetuses were delivered. Birth weights were 1,830 and 2,005 g, Apgar score 8, 9, 9, and 9, 9, 9, umbilical artery pH 7.30 and 7.39, and umbilical artery base excess −1.6 mmol/l and +0.6 mmol/l, respectively. Both newborns were immediately supplied. Physical examination of fetus I revealed an afebrile, well-developed male infant with regular heartbeat, palpable pulse on all extremities, and slight intercostal retractions. The neonate’s abdomen was distended and showed an enlargement of the liver, palpable 3 cm under the costal arch. The infant was supplied with CPAP. Intravenous access was established; complete blood count was drawn. A chest X-ray performed on the first day of life demonstrated a respiratory distress syndrome II°; ultrasound of the brain was without pathological findings. Echocardiography revealed normal anatomy and function. Ultrasound of the abdomen confirmed the diagnosis of a bilateral renal vein thrombosis of fetus I, especially the left kidney was enlarged, hyperechogenic, with blurred cortico-medullary distinction, pathological renal arterial Doppler with diastolic reverse flow, and absence of renal venous flow. Angiography performed by a catheter-based puncture of the V. femoralis, and selective demonstration of V. renalis revealed thrombosis of the infrahepatic part of the inferior vena cava with collateral circulation through the azygos vein in the superior vena cava. Laboratory investigations showed a hematocrit of 57 % with a hemoglobin concentration of 20.4 g/dl, a thrombocytopenia of 29,000/μl, white blood cell count of 11,080/μl, and a mild renal failure with a highest creatinine level of 1.8 mg/dl at the third day of life. A thrombolytic therapy with tissue-type plasminogen activator, t-PA (Actilyse®), and unfractionated heparin was initialized. Under this treatment, a bleeding of the adrenal cortex occurred as side effect, so
Arch Gynecol Obstet
that the thrombolytic therapy was paused for 1 day. According to soon recovery of renal function, therapy with unfractionated heparin (100 IE/kg BW/day heparin) was changed into low molecular weight heparin (4 mg/kg/day enoxaparin) after 9 days. The sibling had unremarkable findings in physical examination, laboratory investigations, and ultrasound of the brain. Chest X-ray showed respiratory distress syndrome IV°. The siblings were transferred in another hospital in the parent’s neighborhood 18 days after birth. This mutation was not detected in the parents and the co-twin. In search of etiology of antenatal renal vein thrombosis, serological and PCR-based diagnostic procedure of the mother and the neonate excluded infections with entero-, rubella-, hepatitis-, parvo-, cytomegaly-, varicella zoster-, herpes simplex viruses, HIV, and toxoplasmosis. The thrombophilia investigations of neonatal blood sample (protein C and protein S activity, antithrombin III activity, activated protein C resistance, prothrombin mutation, and factor V Leiden) revealed a heterozygous factor V Leiden mutation. Currently, the child has a thrombosis prophylaxis with enoxaparin. Even at the age of 4 years, the left kidney is smaller than the right one. However, there is no restriction of renal function (creatinine 0.32 mg/dl, cystatin C 0.96 mg/l).
Discussion The actual incidence of prenatal renal vein thrombosis is still unknown. However, neonatal renal vein thrombosis is a well-known clinical picture with a probably higher incidence of 2.2 per 100.000 live births [3] and even 13 per 100.000 live births in preterm neonates. Some possible theories of pathogenesis of intrauterine thrombosis have been discussed in previous reviews. Reported maternal conditions are, e.g., diabetes, preeclampsia, lupus erythematodes, and corticosteroid therapy or cytomegaly virus infection during pregnancy [1, 2]. In our case, apart from antenatal corticosteroid therapy with 12 mg betamethasone i.m. on 2 days, none of the mentioned risk factors affected the mother. Treatment with beta-2-sympathomimetics and corticosteroids is widely used and safe; however, it maybe has been triggered occurrence of thrombosis in the dichorionic twin, which was predisposed to thrombosis due to thrombotic disorder. A further common reason for prenatal thrombosis could be fetal thrombophilia. In a study with 23 neonates with renal vein thrombosis [4], prothrombotic abnormalities were detected in 44 % of all patients. Factor V Leiden mutations were the most commonly reported defects in their report and also in those of other infant thrombosis series [5, 6]. One case described a fetal and maternal
antithrombin deficiency [7] and another one with maternal antiphospholipid syndrome [8]. Interestingly, the affected child in our case had a de novo mutation of factor V Leiden, while the twin brother and the parents had not a factor V Leiden mutation. In a review of the literature, Smorgick and coworkers (2007) describe 12 cases of renal thrombosis in the fetus [9]: in 33.3 %, the fetuses presented hydrops fetalis; in 41.6 %, there were signs of “fetal distress” like abnormal fetal heartbeat in cardiotocography; and in 25 %, diagnosis was made by incidental findings on prenatal ultrasound. In four cases, there were no associated maternal conditions; the others had either acute or chronic disease in their maternal history such as acute gastroenteritis [10] or acute pyelonephritis [11], chronic hypertension [12], and diabetes mellitus [11]. Referring to this case, a special thrombophilic disorder concerning mother or fetus was found in two cases: antiphospholipid antibody syndrome [8] and antithrombin III deficiency [7]. To the best of our knowledge, there is only one case describing a similar situation of a twin pregnancy with a stillborn fetus showing bilateral thrombosis of renal and inferior caval veins. While the male dichorionic co-twin was healthy, a homozygous mutation of the gene encoding for 5,10 methylene tetrahydrofolate reductase (MTHFR) was diagnosed, but there was also a premature closure of the foramen ovale and also a previous application of beta-2-sympathomimetics and corticosteroids as relevant risk factors [13]. It is noteworthy that all fetuses showed signs of stress; retrospectively, it seems difficult to verify that the renal thrombosis was the reason for the fetal stress or if the fetal stress was caused by the thrombosis. Prenatal ultrasound examination in our case showed bilaterally enlarged kidneys with left-sided predominance and a volume of about 30 cm3, hyperechogenic parenchyma, blurred cortico-medullary distinction, mild ascites, mild bilateral pleural effusion, and hyperechogenic bowel. Absent venous and arterial flow in renal vessels were additional Doppler signs. Brandao et al. [2] describe in their review typical ultrasound findings of in utero onset RTV, such as renal enlargement and hyperechogenicity with or without calcifications of the renal venous system. In a further case of bilateral renal venous thrombosis, a progressive development of atrophy of both kidneys occurred [14]. In follow-up ultrasound examinations after 4 weeks, both kidneys showed progressive growth and improved resistive indices. Postnatally, the classical triad of hematuria, palpable mass, and thrombocytopenia is not present in all cases of renal venous thrombosis. In a cohort of 23 patients, only 22 % showed all three mentioned features [4]. One further case report described that diagnosis of renal vein thrombosis of a newborn was confirmed by kidney biopsy, whereas
13
sonography was unspecific in this case [16]. Left-sided predominance and male newborns were more often affected by all congenital renal malformations [16]. The left-sided predominance could be a result of the anatomic circumstances, due to the anatomic course of the renal vein underneath the aorta. There is a significantly correlation between renal size and outcome [2, 4]. Using ultrasound, a functional radionuclide scan and a chromium-51 ethylenediamine tetraacetic acid (Cr51-EDTA) glomerular filtration rate (GFR), they detected that larger neonatal kidneys had a reduced longterm function. This fact may be helpful to identify those patients who benefit from more aggressive or intensive treatment. To confirm this assumption and the renal longterm outcome, further studies are required.
Conclusion A precise ultrasound screen should be performed in order to detect abnormalities in case of unclear fetal distress and/ or hydrops. Typical findings of prenatal RVT in ultrasound evaluation are uni- or bilateral nephromegaly and blurred cortico-medullary distinction and in color Doppler, reduced or absent renal perfusion. Nevertheless, its clinical presentation can vary from polyhydramnios, ascites, or hydrops fetalis to suspicious CTG. Procoagulant screening should be done, considering the fact that recent studies have highlighted the importance of underlying prothrombotic alterations in renal vein thrombosis [5, 16]. In this case report, we described a dichorionic twin pregnancy with one affected fetus, showing already intrauterine a bilaterally enlarged kidney and absence of renal venous flow in combination with signs of circulatory compromise and fetal distress, while dichorionic male co-twin was healthy. Conflict of interest We declare that we have no conflict of interest.
References 1. Oppenheimer EH, Esterly JR (1965) Thrombosis in the newborn: comparison between infants of diabetic and non diabetic mothers. J Pediatr 67:549–556 2. Brandão LR, Simpson EA, Lau KK (2011) Neonatal renal vein thrombosis. Semin Fetal Neonatal Med 16:323–328
13
Arch Gynecol Obstet 3. Bökenkamp A, von Kries R, Nowak-Göttl U, Göbel U, Hoyer PF (2000) Neonatal renal venous thrombosis in Germany between 1992 and 1994: epidemiology, treatment and outcome. Eur J Pediatr 159:44–48 4. Winyard PJD, Bharucha T, de Bruyn R, Dillon MJ, van’t Hoff W, Trompeter RS, Liesner R, Wade A, Rees L (2006) Perinatal renal venous thrombosis: presenting renal length predicts outcome. Arch Dis Child Fetal Neonatal Ed 91:F273–F278 5. Kosch A, Kuwertz-Broking E, Heller C, Kurnik K, Schobess R, Nowak-Göttl U (2004) Renal venous thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Blood 104:1356–1360 6. Heller C, Schobess R, Kurnik K, Junker R, Günther G, Kreuz W, Nowak-Göttl U (2000) Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors: a multicenter case control study, for the childhood thrombophilia study group. Br J Haematol 111:534–539 7. Weissmann-Brenner A, Ferber A, O’Reilly-Green C, Avila C, Grassi A, Divon MY (2004) Inferior vena cava thrombosis presenting as non-immune hydrops in the fetus of a women with diabetes. Ultrasound Obstet Gynecol 23(2):194–197 8. Hage ML, LIU R, Marcheschi DG, Bowie JD, Allen NB, Macik BG (1994) Fetal renal vein thrombosis, hydrops fetalis and maternal lupus anticoagulant: a case report. Prenat Diagn 14:873–877 9. Smorgick N, Herman A, Wiener Y, Halperin R, Sherman D (2007) Prenatal thrombosis of the inferior vena cava and the renal veins. Prenatal Diagn 27:603–607 10. Diallo A, Boog GJ, Moussally F, Quere MP (1998) Fetal renal venous thrombosis: a typical ultrasonographic aspect. J Gynecol Obstet Biol Reprod (Paris) 27:445–447 11. Sanders LD, Jequier S (1989) Ultrasound demonstration of prenatal renal vein thrombosis. Pediatr Radiol 19:133–135 12. Patel RB, Connors JJ (1988) In utero sonographic findings in fetal renal vein thrombosis with calcifications. J Ultrasound Med 7:349–352 13. Stanek J, Bove KE, Bofinger M, Needham D, Saldana LR, Mutema GK, Meyer R (2000) Premature closure of foramen ovale and renal vein thrombosis in a stillborn twin homozygous for methylene tetrahydrofolate reductase gene polymorphism: a clinicopathologic case study. J Perinat Med 28:61–68 14. Lau KK, Fernandez y Garcia E, Kwan WY, Albrecht L, SteinWexler R (2007) Bilateral renal venous thrombosis and adrenal hemorrhage: sequential prenatal US with postnatal recovery. Pediatr Radiol 37:912–915 15. Prelog M, Fischer H, Gassner I, Tzankov A, Glatz-Krieger K, Mihatsch M, Zimmerhackl LB (2006) Bilateral renal vein thrombosis in a twin newborn without known risk factors. Clin Nephrol 66:135–139 16. Kuhle S, Massicotte P, Chan A, Mitchell L (2004) A case series of 72 neonates with renal vein thrombosis: data from the 1-800-NOCLOTS registry. Thromb Haemost 92:729–733
