Idiopathic neonatal aortic thrombosis
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《美国医学杂志》
Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
We report a term neonate with severe aortic thrombosis involving the aorto-iliac segment and leading to renal failure. This patient did not have any predisposing risk factors. The authors have also reviewed the literature on neonatal aortic thrombosis and discuss the need for evolving evidence based consensus guidelines for management of this catastrophe.
Keywords: Neonatal; Aortic; Thrombosis
Aortic thrombosis in an apparently healthy term newborn, in absence of risk factors like umbilical artery catheterization, is a rarity. The authors report a term neonate with extensive thrombosis of abdominal aorta and iliac arteries, without any identifiable risk factors for the same.
This 7-day-old term born boy, presented to us with complaints of poor feeding, irritability, decreased urine output and dusky discoloration of both lower limbs for 2 days. The child was born at a private hospital and natal course was uneventful. There was no history of birth asphyxia, or umbilical arterial catheterization in this child. Antenatal period was uneventful and there was no maternal history of recurrent abortions, oral ulcers, alopecia, skin rash, photosensitivity, leg pain and swelling or arthralgia. There was no family history of premature thrombotic events.
On examination, the child was active but irritable. Lower limb pulses, including the femorals, were not palpable, and there was dusky discoloration of both the feet. Blood pressure was elevated in both upper limbs (>95th centile). Lower limb blood pressure was not recordable. Abdominal examination did not reveal any mass or bruit. Systemic examination including the cardiovascular examination was normal.
Investigations showed a positive septic screen (microESR 22 mm in 1st hr, I/T ratio of 0.22 and positive C reactive protein assay), deranged renal function (urea 290 mg/dl and creatinine 7 mg/dl), low calcium and elevated phosphate levels (7.0 mg/dl, 7.0 mg/dl respectively) and hyperkalemia (7.0 meq/L). Child's chest radiograph and electrocardiogram (ECO) were both normal. As coarctation of aorta was the main differential diagnosis, echocardiographic evaluation was performed which did not reveal any congenital cardiac abnormality including coarctation of aorta but Doppler ultrasonography of abdomen suggested massive aortic thrombosis extending from suprarenal segment to bilateral common iliac arteries.
The authors started the child on intravenous urokinase (4000 U bolus followed by continuous infusion at the rate of 4000 U/hr) and antimicrobials; peritoneal dialysis was also done over the next 72 hours. Repeat Doppler USG of abdomen 24 hrs after starting urokinase infusion showed persistence of the aortic thrombus.
Clinical presentation strongly suggested a hypercoagulable state, and authorsinvestigated the child for the same. Lupus anticoagulant was negative, C3 level was 90 (normal 77-190) mg/dl, Factor V Leiden mutation was negative and homocysteine level was 8 (normal 3.3-11.3) mmol/L. Disseminated intravascular coagulation profile was also negative. Protein C, Protein S and Antithrombin III levels were all low.
The child's renal functions failed to improve with therapy and he is currently on renal replacement therapy.
Discussion
Aortic thrombosis in newborn period is an infrequent but catastrophic event which is associated with predisposing conditions like umbilical arterial catheterization[1], dehydration[2], polycythemia[3], cyanotic congenital heart disease[3], patent ductus arteriosus[4], sepsis[5], lupus anticoagulant[6] and inherited defects in coagulation.[7] Umblical arterial catheterization (UAC) has emerged as one of the most important risk factors for aortic thrombosis. Studies show that almost 20-30% patients with umbilical arterial catheter show ultrasonographic evidence of aortic thrombosis. Factors which increase the risk of UAC associated thrombosis include calcium infusion through the UAC, placement of catheter above the renal arteries and use of 3.5 Fr gauge catheter[8], However, Boo et al showed that the duration of catheter placement was the only significant risk factor for UAC associated thrombosis.[1] They also found that infusion of 1.0 U/ml of heparin did not decrease the risk of thrombosis and recommended removal of UAC as soon as it was not required.[1]
Signs of aortic obstruction can be variable and include absent lower extremity pulses, lower limb ischemia ranging from pallor, poikilothermia to cyanosis and gangrene, renal failure, congestive heart failure and hypertension. It is important to differentiate this condition from coarctation of aorta which is also characterized by absent lower etremity pulses.[9] Signs of lower extremity ischemia (Pallor, Pain, Poikilothermia, Pulselessness) are the key clinical features that help in this differentiation.
Colour flow Doppler ultrasonography is the investigation of choice to diagnose aortic thrombosis.[10] It is non-invasive, inexpensive and involves minimum risk to the patient. However, this technique is provides imprecise anatomic detail and is dependent upon the skill of the operator. Aortography has the advantage of providing precise outline of aortic thrombus, but it can be dangerous in these sick children.
It is important to have a homogenous classification system for patients with neonatal aortic thrombosis, as that would help in comparing outcomes and devising specific recommendations. Colburn et al[8] have proposed a classification system for neonates with aortic thrombosis [Table - 1].
Historically, aortic thrombosis has been treated with three different approaches: supportive, thrombolytic and surgical, each with variable degree of success. Adelman et al recommended conservative management in infants with hypertension secondary to thrombotic renal artery stenosis.[11] Malin et al also reported successful conservative management of 3 infants with aortic thrombosis.[12] There are numerous reports that describe successful management of neonatal aortic thrombosis with surgical therapy.[8],[13] There is also evidence that indicates that medical management is equally effective. Drugs which have been found useful in this regard include thrombolytics[14],[15] and low molecular weight heparin.[16] The patient was treated with intravenous urokinase infusion and showed some improvement in peripheral perfusion after starting the infusion but thrombolysis could not be demonstrated.
Long term consequences of aortic thrombosis include hypertension and impaired limb growth.[8],[17] Limb length discrepancy of more than 2 cm usually manifests as gait disturbance, and this, along with claudication, are indications for surgical treatment.[8]
This case highlights the clinical features and catastrophic consequences of neonatal aortic thrombosis. There is a need to evolve evidence based consensus guidelines to ensure uniform and appropriate management of these patients.
References
1.Boo N-Y, Wong N-C, Syed Zulfikli SZ, Lye M-S. Risk factors associated with umblical vascular catheter-associated thrombosis in newborn infants. J Pediatr Child Health 1999; 35: 460-465.
2.Suri M, Ramji S, Thirupuram S, Sharma BK. Spontaneous aortic thrombosis in a neonate. Indian Pediatr 1994; 31: 846-849. [PUBMED]
3.Tugrul Kural I, Tinaztepe K, Yurdakul Y. Aortic thrombosis in the newborn infant. J Cardiovasc Surg 1984; 25: 246-248. [PUBMED]
4.GT Knowlson, HB Mardsen. Aortic thrombosis in the newborn period. Arch Dis Child 1978; 53: 164-166.
5.Szymankiewicz M, Oszkinis G, Uchman J. Abdominal aortic-iliac thrombosis as a .complication of newborn's bacterial sepsis. Ginekol Pol 2005; 76: 61-66.
6.Sheridan-Pereira M, Porreco RP, Hays T, Burke MS. Neonatal aortic thrombosis associated with the lupus anticoagulant. Obstet Gynecol 1988; 71: 1016-1018.
7.Sanchez J, Velasco F, Alvarez R, Roman J, Torres A. Aortic thrombosis in a neonate with hereditary antithrombin III deficiency: successful outcome with thrombolytic and replacement treatment. Acta Pediatr 1996; 85: 245-247.
8.Colburn MD, Gelabert HA, Quinones-Baldrich W. Neonatal aortic thrombosis. Surgery 1992; 111: 21-28.
9.Rodriguez M, Sosenko I. Catheter- induced aortic thrombus masquerading as coarctation of the aorta. Clin Pediatr 1989; 28: 581-584.
10.Deeg KH, Wolfel D, Rupperecht Th. Diagnosis of neonatal aortic thrombosis by colour coded Doppler ultrasonography. Peditr Radiol 1992; 22: 62-63.
11.Adelman RD, Merten D, Vogel J, Goetzman BW, Wennberg RP. Nonsurgical management of renovascular hypertension in the neonate. Pediatrics 1978; 62: 71-76.
12.Malin SW, Baumgart S, Rosenberg HK, Foreman J Nonsurgical management of obstructive aortic thrombosis complicated by renovascular hypertension in the neonate. J Pediatr 1985; 106: 630-634.
13.Flanigan DP, Stolar CJ, Pringle KC, Schuler JJ, Fisher E, Vidyasager D. Aortic thrombosis after umbilical artery catheterization. Arch Surg 1982; 117: 371-374.
14.Cheah FC, Boo NY, Rohana J, Yong SC. Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses. J Pediatr Child Health 2001; 37: 479-482.
15.Giacoia GP. High-dose urokinase therapy in newborn infants with major vessel thrombosis. Clin Pediatr 1993; 32: 231-237.
16.Klinger G, Hellmann J, Daneman A. Severe aortic thrombosis in the neonate-successful treatment with low-molecular-weight heparin: two case reports and review of the literature. Am J Perinatol 2000; 17: 151-158.
17.Seibert JJ, Northington FJ, Miers JF, Taylor BJ. Aortic thrombosis after umbilical artery catheterization in neonates: prevalence of complications on long-term follow-up. AJR Am J Roentgenol 1991; 156: 7-9.(Kohli Utkarsh, Lodha Rakesh)
We report a term neonate with severe aortic thrombosis involving the aorto-iliac segment and leading to renal failure. This patient did not have any predisposing risk factors. The authors have also reviewed the literature on neonatal aortic thrombosis and discuss the need for evolving evidence based consensus guidelines for management of this catastrophe.
Keywords: Neonatal; Aortic; Thrombosis
Aortic thrombosis in an apparently healthy term newborn, in absence of risk factors like umbilical artery catheterization, is a rarity. The authors report a term neonate with extensive thrombosis of abdominal aorta and iliac arteries, without any identifiable risk factors for the same.
This 7-day-old term born boy, presented to us with complaints of poor feeding, irritability, decreased urine output and dusky discoloration of both lower limbs for 2 days. The child was born at a private hospital and natal course was uneventful. There was no history of birth asphyxia, or umbilical arterial catheterization in this child. Antenatal period was uneventful and there was no maternal history of recurrent abortions, oral ulcers, alopecia, skin rash, photosensitivity, leg pain and swelling or arthralgia. There was no family history of premature thrombotic events.
On examination, the child was active but irritable. Lower limb pulses, including the femorals, were not palpable, and there was dusky discoloration of both the feet. Blood pressure was elevated in both upper limbs (>95th centile). Lower limb blood pressure was not recordable. Abdominal examination did not reveal any mass or bruit. Systemic examination including the cardiovascular examination was normal.
Investigations showed a positive septic screen (microESR 22 mm in 1st hr, I/T ratio of 0.22 and positive C reactive protein assay), deranged renal function (urea 290 mg/dl and creatinine 7 mg/dl), low calcium and elevated phosphate levels (7.0 mg/dl, 7.0 mg/dl respectively) and hyperkalemia (7.0 meq/L). Child's chest radiograph and electrocardiogram (ECO) were both normal. As coarctation of aorta was the main differential diagnosis, echocardiographic evaluation was performed which did not reveal any congenital cardiac abnormality including coarctation of aorta but Doppler ultrasonography of abdomen suggested massive aortic thrombosis extending from suprarenal segment to bilateral common iliac arteries.
The authors started the child on intravenous urokinase (4000 U bolus followed by continuous infusion at the rate of 4000 U/hr) and antimicrobials; peritoneal dialysis was also done over the next 72 hours. Repeat Doppler USG of abdomen 24 hrs after starting urokinase infusion showed persistence of the aortic thrombus.
Clinical presentation strongly suggested a hypercoagulable state, and authorsinvestigated the child for the same. Lupus anticoagulant was negative, C3 level was 90 (normal 77-190) mg/dl, Factor V Leiden mutation was negative and homocysteine level was 8 (normal 3.3-11.3) mmol/L. Disseminated intravascular coagulation profile was also negative. Protein C, Protein S and Antithrombin III levels were all low.
The child's renal functions failed to improve with therapy and he is currently on renal replacement therapy.
Discussion
Aortic thrombosis in newborn period is an infrequent but catastrophic event which is associated with predisposing conditions like umbilical arterial catheterization[1], dehydration[2], polycythemia[3], cyanotic congenital heart disease[3], patent ductus arteriosus[4], sepsis[5], lupus anticoagulant[6] and inherited defects in coagulation.[7] Umblical arterial catheterization (UAC) has emerged as one of the most important risk factors for aortic thrombosis. Studies show that almost 20-30% patients with umbilical arterial catheter show ultrasonographic evidence of aortic thrombosis. Factors which increase the risk of UAC associated thrombosis include calcium infusion through the UAC, placement of catheter above the renal arteries and use of 3.5 Fr gauge catheter[8], However, Boo et al showed that the duration of catheter placement was the only significant risk factor for UAC associated thrombosis.[1] They also found that infusion of 1.0 U/ml of heparin did not decrease the risk of thrombosis and recommended removal of UAC as soon as it was not required.[1]
Signs of aortic obstruction can be variable and include absent lower extremity pulses, lower limb ischemia ranging from pallor, poikilothermia to cyanosis and gangrene, renal failure, congestive heart failure and hypertension. It is important to differentiate this condition from coarctation of aorta which is also characterized by absent lower etremity pulses.[9] Signs of lower extremity ischemia (Pallor, Pain, Poikilothermia, Pulselessness) are the key clinical features that help in this differentiation.
Colour flow Doppler ultrasonography is the investigation of choice to diagnose aortic thrombosis.[10] It is non-invasive, inexpensive and involves minimum risk to the patient. However, this technique is provides imprecise anatomic detail and is dependent upon the skill of the operator. Aortography has the advantage of providing precise outline of aortic thrombus, but it can be dangerous in these sick children.
It is important to have a homogenous classification system for patients with neonatal aortic thrombosis, as that would help in comparing outcomes and devising specific recommendations. Colburn et al[8] have proposed a classification system for neonates with aortic thrombosis [Table - 1].
Historically, aortic thrombosis has been treated with three different approaches: supportive, thrombolytic and surgical, each with variable degree of success. Adelman et al recommended conservative management in infants with hypertension secondary to thrombotic renal artery stenosis.[11] Malin et al also reported successful conservative management of 3 infants with aortic thrombosis.[12] There are numerous reports that describe successful management of neonatal aortic thrombosis with surgical therapy.[8],[13] There is also evidence that indicates that medical management is equally effective. Drugs which have been found useful in this regard include thrombolytics[14],[15] and low molecular weight heparin.[16] The patient was treated with intravenous urokinase infusion and showed some improvement in peripheral perfusion after starting the infusion but thrombolysis could not be demonstrated.
Long term consequences of aortic thrombosis include hypertension and impaired limb growth.[8],[17] Limb length discrepancy of more than 2 cm usually manifests as gait disturbance, and this, along with claudication, are indications for surgical treatment.[8]
This case highlights the clinical features and catastrophic consequences of neonatal aortic thrombosis. There is a need to evolve evidence based consensus guidelines to ensure uniform and appropriate management of these patients.
References
1.Boo N-Y, Wong N-C, Syed Zulfikli SZ, Lye M-S. Risk factors associated with umblical vascular catheter-associated thrombosis in newborn infants. J Pediatr Child Health 1999; 35: 460-465.
2.Suri M, Ramji S, Thirupuram S, Sharma BK. Spontaneous aortic thrombosis in a neonate. Indian Pediatr 1994; 31: 846-849. [PUBMED]
3.Tugrul Kural I, Tinaztepe K, Yurdakul Y. Aortic thrombosis in the newborn infant. J Cardiovasc Surg 1984; 25: 246-248. [PUBMED]
4.GT Knowlson, HB Mardsen. Aortic thrombosis in the newborn period. Arch Dis Child 1978; 53: 164-166.
5.Szymankiewicz M, Oszkinis G, Uchman J. Abdominal aortic-iliac thrombosis as a .complication of newborn's bacterial sepsis. Ginekol Pol 2005; 76: 61-66.
6.Sheridan-Pereira M, Porreco RP, Hays T, Burke MS. Neonatal aortic thrombosis associated with the lupus anticoagulant. Obstet Gynecol 1988; 71: 1016-1018.
7.Sanchez J, Velasco F, Alvarez R, Roman J, Torres A. Aortic thrombosis in a neonate with hereditary antithrombin III deficiency: successful outcome with thrombolytic and replacement treatment. Acta Pediatr 1996; 85: 245-247.
8.Colburn MD, Gelabert HA, Quinones-Baldrich W. Neonatal aortic thrombosis. Surgery 1992; 111: 21-28.
9.Rodriguez M, Sosenko I. Catheter- induced aortic thrombus masquerading as coarctation of the aorta. Clin Pediatr 1989; 28: 581-584.
10.Deeg KH, Wolfel D, Rupperecht Th. Diagnosis of neonatal aortic thrombosis by colour coded Doppler ultrasonography. Peditr Radiol 1992; 22: 62-63.
11.Adelman RD, Merten D, Vogel J, Goetzman BW, Wennberg RP. Nonsurgical management of renovascular hypertension in the neonate. Pediatrics 1978; 62: 71-76.
12.Malin SW, Baumgart S, Rosenberg HK, Foreman J Nonsurgical management of obstructive aortic thrombosis complicated by renovascular hypertension in the neonate. J Pediatr 1985; 106: 630-634.
13.Flanigan DP, Stolar CJ, Pringle KC, Schuler JJ, Fisher E, Vidyasager D. Aortic thrombosis after umbilical artery catheterization. Arch Surg 1982; 117: 371-374.
14.Cheah FC, Boo NY, Rohana J, Yong SC. Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses. J Pediatr Child Health 2001; 37: 479-482.
15.Giacoia GP. High-dose urokinase therapy in newborn infants with major vessel thrombosis. Clin Pediatr 1993; 32: 231-237.
16.Klinger G, Hellmann J, Daneman A. Severe aortic thrombosis in the neonate-successful treatment with low-molecular-weight heparin: two case reports and review of the literature. Am J Perinatol 2000; 17: 151-158.
17.Seibert JJ, Northington FJ, Miers JF, Taylor BJ. Aortic thrombosis after umbilical artery catheterization in neonates: prevalence of complications on long-term follow-up. AJR Am J Roentgenol 1991; 156: 7-9.(Kohli Utkarsh, Lodha Rakesh)