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Aortic thrombosis in the neonate
J
THORAC CARDIOVASC SURG
81:334-337, 1981
Aortic thrombosis in the neonate The case histories of two infants with aortic thrombosis are presented. Clinically. an obstructive aortic arch lesion was suspected because of a systolic pressure gradient between the upper and lower extremities in one infant and unequal peripheral pulses with lower limb cyanosis in the other. Noninvasive studies were inconclusive. the only abnormality noted echocardiographically being severe left ventricular dysfunction. Cardiac catheterization including angiography defined the severity of the obstruction and location of the thrombus in both babies. The thrombus originated within a ductus arteriosus aneurysm in one infant and was located in the ascending aorta and transverse arch in the other. Although successful surgical removal was accomplished. both babies died unexpectedly in the early postoperative period.
Richard C. McFaul, M.D., John F. Keane, M.D., Edward R. Nowicki, M.D., and Aldo R. Castaneda, M.D., Ph.D., Portland. Maine, and Boston, Mass.
Arterial occlusions are rare in the neonate, in contrast to adults. These obstructions almost invariably are limited to peripheral vessels and usually occur in infants with sepsis. Physical signs of these occlusions usually are localized to the areas supplied by these vessels; for example, seizures or a hemiparesis suggests involvement of a central nervous system vessel, ischemia or gangrene indicates occlusion of an extremity vessel, I and hematuria or hypertension is associated with renal artery thrombosis. 2 Large obstructive thrombi within the aorta also have been described, L 3-7 with physical signs tending to be generalized and obscured by manifestations of sepsis, dehydration, or shock. This lesion, first described more than a century ago," heretofore has been diagnosed only at postmortem examination. This report (1) describes our recent experience with two infants in whom aortic thrombosis was diagnosed preoperatively and (2) reviews the literature concerning this rare entity.
Case reports CAS E I. A female infant weighing 4.6 kg was born at term to a diabetic mother. Because the second stage of labor was prolonged, the Apgar rating was 5 at I minute after birth.
From the Departments of Pediatric Cardiology of Maine Medical Center, Portland, Maine, and Children's Hospital Medical Center, Boston, Mass. Received for publication June 20, 1980. Accepted for publication Aug. 4, 1980. Addressfor reprints: Richard C. McFaul, M.D., c/o Pediatric Center, 229 Vaughan St., Portland, Maine04102.
334
Shortly thereafter the blood glucose level dropped to 12 mg/dl, dextrose was administered peripherally through a scalp vein, and the infant's condition improved. On the third day of life, tremors and tachypnea occurred, and blood noted in the anterior chamber of the right eye raised the possibility of an intracranial hemorrhage. Investigations including a computed tomographic scan excluded significant intracranial bleeding. A chest x-ray film revealed cardiomegaly and pulmonary venous congestion, and digoxin and oxygen therapy were commenced. However, because of the persistence of tachypnea and clinical evidence of low cardiac output, the infant was transferred on the eleventh day to the Maine Medical Center, Portland, Maine. The most striking features on physical examination were absent femoral pulses, a peak systolic gradient of 80 mm Hg between the upper and lower extremities, and congestive heart fail ure, all consistent with severe coarctation of the aorta. The electrocardiogram revealed right ventricular hypertrophy and an echocardiogram identified a large, poorly functioning left ventricle. At cardiac catheterization, oxygen saturation data identified a left-to-right atrial shunt, believed to be the result of elevated left atrial pressure. The right ventricular systolic pressure was 100 mm Hg, identical to that in the lower extremities, but the left ventricular value ranged from 180 to 200 mm Hg. The left ventricular cineangiogram excluded a ventricular septal defect and, although a typical discrete coarctation at the aortic isthmus was not visualized, a web or membrane-like obstruction was noted in that area, distal to the origin of the left subclavian artery (Fig. I). At operation, the distal transverse arch, upper descending aorta, and ductus arteriosus were explored. The latter structure narrowed in normal fashion at its attachment to the pulmonary artery but was aneurysmal at its aortic end. Opening this aneurysmal segment revealed a large, organized thrombus which occupied both the aneurysm and the upper descending aorta (Fig. 2). The thrombus was removed, and identical systolic pressures of 140 mm Hg were measured in the aorta above and below the ligated aneurysm at the conclusion of the procedure.
0022-5223/811030334+04$00.40/0 © 1981 The C. V. Mosby Co.
Volume 81 Number 3
Aortic thrombosis in neonate
335
March,1981
Fig. 1. Left ventricular angiogram. Arrows outline negative shadow created by the aortic thrombus.
Fig. 3. Left ventricular angiogram. Arrow indicates proximal end of totally occlusive thrombus in the ascending aorta.
Fig. 2. Thrombus removed from the ductal aneurysm and aorta (scale in centimeters).
The infant's condition remained stable for only several hours before severe irreversible metabolic acidosis and hypotension ensued and the baby died. At postmortem examination, the aorta and its major branches were free of thrombi, and the heart, although dilated, was structurally normal and contained no thrombi. Microemboli were identified throughout the viscera and hemorrhagic infarcts were evident in the adrenal glands, death being attributed to the latter. CA SE 2. A male infant, weighing 2.8 kg, was born after 38 weeks' gestation. The pregnancy, labor, and delivery were uncomplicated except for an upper respiratory tract infection during the third trimester. After 24 hours, generalized cyanosis and a murmur in the pulmonic area were noted, and the infant was transferred to the Children's Hospital Medical Center, Boston, Massachusetts. The right brachial and both carotid pulses were not palpable. The left brachial and both femoral pulses were easily felt and equal, with a pressure of 83/46 mm Hg being recorded in the descending aorta through an umbilical arterial line. In addition, congestive heart failure was evident. The chest x-ray film revealed cardiomegaly and pulmonary venous congestion, and the electrocardiogram identified left ventricular hypertrophy and a strain pattern consistent with outflow obstruction. The two-dimensional
The Journal of
336 McFaul et al.
Thoracic and Cardiovascular Surgery
echocardiogram showed the left ventricle to be enlarged and poorly functioning, whereas the aortic valve, ascending aorta, and transverse arch appeared normal. Because of oxygen saturation evidence of right-to-Ieft shunting via a patent ductus, echocardiographic findings of a structurally normal heart, and unequal pulses, obstruction in the region of the aortic arch was suspected and cardiac catheterization was carried out. At this study, right-to-Ieft shunting through a patent ductus arteriosus was confirmed. The right ventricular, pulmonary arterial, and descending aortic systolic pressures were identical, whereas pressure in the left ventricle was 64 mm Hg higher and the left ventricular end-diastolic value was 25 mm Hg. A left ventricular cineangiogram demonstrated in dramatic fashion complete occlusion by an intraluminal mass of the distal ascending aorta and transverse arch with involvement of the origins of both carotid arteries (Fig. 3). Cerebral perfusion occurred largely through a dilated left vertebral artery. By means of deep hypothermic circulatory arrest, a large, loosely adherent clot was removed from the ascending aorta and transverse arch and the ductus arteriosus was ligated. Postoperatively, the infant's condition improved and was quite stable. He was extubated after 24 hours. However, on the second postoperative day, cardiac arrest occurred unexpectedly and all resuscitative measures were unsuccessful. At autopsy, rethrombosis of the ascending aorta and transverse arch had occurred with extension of the thrombus into the aortic end of the ligated ductus arteriosus. Although no thrombi were present in the left ventricle, microscopic examination revealed hemorrhagic infarction of the papillary muscles with patchy fibrosis throughout the myocardium. Results of histologic examination of the aorta were normal.
Discussion Aortic thrombosis is rare, often is associated with other illnesses such as sepsis, and in the past has been diagnosed only at autopsy. Further analysis of these previous reports reveals that clinical evidence of severe aortic obstruction, including congestive heart failure, hypertension, absent femoral pulses, and lower limb ischemia, was observed in some. I. 5. 6 Our first patient manifested the majority of these physical findings, whereas the unequal pulses, echocardiographic evidence of a structurally normal heart, and cyanosis of the lower extremities suggested an aortic arch obstruction in our second patient. More important, our patients illustrate that following identification of these physical findings, use of cardiac catheterization allows diagnosis of this lesion. The pathogenesis of aortic thrombosis is unknown. Sepsis has been suspected in some infants, although other associated entities or lesions have been described. Infants of diabetic mothers are predisposed to thrombotic events. In a report by Oppenheimer and Esterly" concerning 83 infants born to diabetic mothers, 14 were found to have thrombosis of large veins and one had
aortic thrombosis. Also, our first patient had a large aneurysm of the ductus arteriosus. The occurrence of thrombosis of the aorta related to this lesion was first described in 1859 8 and was later reported by others." 7.10 Since thrombosis together with fibrosis and intimal proliferation normally contribute to anatomic closure of the ductus, it is possible that extension of thrombus originating within an aneurysm of this structure may result in eventual obstruction of the aorta with or without embolization. Histologic examination of the aneurysm in our patient revealed deficiency of smooth muscle fibers, which may have prevented the normal contraction which occurs after birth. Aortic thrombosis also has been described in association with a deficiency in antithrombin 3,5 a plasma protein which inhibits thrombin and prevents platelet aggregation. Whether or not this contributed to the thrombosis in our patients we do not know, although results of limited hematologic studies consisting of platelet counts, prothrombin time, and partial thromboplastin time were normal. The occurrence of thrombosis of the ascending aorta and transverse arch in one of our patients has not been described previously. The origin of the original and recurrent thrombi is unknown but clearly was not related to the ductus arteriosus. Although a paradoxical embolus via the atrial septum is a possibility, no definite site of origin including the ductus venosus could be identified. Systemic embolization from the left ventricle in infants and children with idiopathic congestive cardiomyopathy has been reported"; however, no evidence of intracardiac thrombi, endocardiofibrosis, myocardial inflammation, or necrosis was identified in either of our patients at autopsy. The critical condition of these infants requires that these large thrombi be surgically removed. Steroids might be helpful to combat adrenal insufficiency, a potential sequela of adrenal infarction and hemorrhage. Heparin administration after operation might prevent rethrombosis if the surgeon were to identify injury to the intimal surface of the aorta.
2 3 4 5
REFERENCES Gross RE: Arterial embolism and thrombosis in infancy. Am J Dis Child 70:61-73, 1945 Dimmick JE, Patterson, MWH, Wu KWA: Systemic hypertension in a newborn infant, J Pediatr 95:321-324, 1979 Stout C, Koehl G: Aortic embolism in a newborn infant. Am J Dis Child 120:74-76, 1970 Marks C, Fehler BM: Aortic occlusion in infancy. Br Med J 1:709-710, 1953 Bjarke B, Herin P, Blomback M: Neonatal aortic thrombosis. Acta Paediatr Scand 63:297-301, 1974
Volume 81 Number 3 March,1981
6 Heggtveit HA, Hill DP: Thromboaortitis in the newborn. Arch Pathol (Chicago) 76:578-580, 1963 7 Knowlson GT, Marsden MB: Aortic thrombosis in the newborn period. Arch Dis Child 53:164-166, 1978 8 Klob J: Thrombosis ductus botalli. Z Gesellsch Aerzte Wien 15:4, 1859 9 Oppenheimer EH, Esterly JR: Thrombosis in the new-
Aortic thrombosis in neonate
337
born. Comparison between infants of diabetic and nondiabetic mothers. J Pediatr 67:549-556, 1965 IO Ordway NK, Stout LC: Thromboembolus to abdominal aorta in a neonate. J Pediatr 82:143-148, 1973 II Harris LC, Powell G, Brown OW III: Primary myocardial disease. Pediatr Clin North Am 25:847-867, 1978
THORAC CARDIOVASC SURG
81:334-337, 1981
Aortic thrombosis in the neonate The case histories of two infants with aortic thrombosis are presented. Clinically. an obstructive aortic arch lesion was suspected because of a systolic pressure gradient between the upper and lower extremities in one infant and unequal peripheral pulses with lower limb cyanosis in the other. Noninvasive studies were inconclusive. the only abnormality noted echocardiographically being severe left ventricular dysfunction. Cardiac catheterization including angiography defined the severity of the obstruction and location of the thrombus in both babies. The thrombus originated within a ductus arteriosus aneurysm in one infant and was located in the ascending aorta and transverse arch in the other. Although successful surgical removal was accomplished. both babies died unexpectedly in the early postoperative period.
Richard C. McFaul, M.D., John F. Keane, M.D., Edward R. Nowicki, M.D., and Aldo R. Castaneda, M.D., Ph.D., Portland. Maine, and Boston, Mass.
Arterial occlusions are rare in the neonate, in contrast to adults. These obstructions almost invariably are limited to peripheral vessels and usually occur in infants with sepsis. Physical signs of these occlusions usually are localized to the areas supplied by these vessels; for example, seizures or a hemiparesis suggests involvement of a central nervous system vessel, ischemia or gangrene indicates occlusion of an extremity vessel, I and hematuria or hypertension is associated with renal artery thrombosis. 2 Large obstructive thrombi within the aorta also have been described, L 3-7 with physical signs tending to be generalized and obscured by manifestations of sepsis, dehydration, or shock. This lesion, first described more than a century ago," heretofore has been diagnosed only at postmortem examination. This report (1) describes our recent experience with two infants in whom aortic thrombosis was diagnosed preoperatively and (2) reviews the literature concerning this rare entity.
Case reports CAS E I. A female infant weighing 4.6 kg was born at term to a diabetic mother. Because the second stage of labor was prolonged, the Apgar rating was 5 at I minute after birth.
From the Departments of Pediatric Cardiology of Maine Medical Center, Portland, Maine, and Children's Hospital Medical Center, Boston, Mass. Received for publication June 20, 1980. Accepted for publication Aug. 4, 1980. Addressfor reprints: Richard C. McFaul, M.D., c/o Pediatric Center, 229 Vaughan St., Portland, Maine04102.
334
Shortly thereafter the blood glucose level dropped to 12 mg/dl, dextrose was administered peripherally through a scalp vein, and the infant's condition improved. On the third day of life, tremors and tachypnea occurred, and blood noted in the anterior chamber of the right eye raised the possibility of an intracranial hemorrhage. Investigations including a computed tomographic scan excluded significant intracranial bleeding. A chest x-ray film revealed cardiomegaly and pulmonary venous congestion, and digoxin and oxygen therapy were commenced. However, because of the persistence of tachypnea and clinical evidence of low cardiac output, the infant was transferred on the eleventh day to the Maine Medical Center, Portland, Maine. The most striking features on physical examination were absent femoral pulses, a peak systolic gradient of 80 mm Hg between the upper and lower extremities, and congestive heart fail ure, all consistent with severe coarctation of the aorta. The electrocardiogram revealed right ventricular hypertrophy and an echocardiogram identified a large, poorly functioning left ventricle. At cardiac catheterization, oxygen saturation data identified a left-to-right atrial shunt, believed to be the result of elevated left atrial pressure. The right ventricular systolic pressure was 100 mm Hg, identical to that in the lower extremities, but the left ventricular value ranged from 180 to 200 mm Hg. The left ventricular cineangiogram excluded a ventricular septal defect and, although a typical discrete coarctation at the aortic isthmus was not visualized, a web or membrane-like obstruction was noted in that area, distal to the origin of the left subclavian artery (Fig. I). At operation, the distal transverse arch, upper descending aorta, and ductus arteriosus were explored. The latter structure narrowed in normal fashion at its attachment to the pulmonary artery but was aneurysmal at its aortic end. Opening this aneurysmal segment revealed a large, organized thrombus which occupied both the aneurysm and the upper descending aorta (Fig. 2). The thrombus was removed, and identical systolic pressures of 140 mm Hg were measured in the aorta above and below the ligated aneurysm at the conclusion of the procedure.
0022-5223/811030334+04$00.40/0 © 1981 The C. V. Mosby Co.
Volume 81 Number 3
Aortic thrombosis in neonate
335
March,1981
Fig. 1. Left ventricular angiogram. Arrows outline negative shadow created by the aortic thrombus.
Fig. 3. Left ventricular angiogram. Arrow indicates proximal end of totally occlusive thrombus in the ascending aorta.
Fig. 2. Thrombus removed from the ductal aneurysm and aorta (scale in centimeters).
The infant's condition remained stable for only several hours before severe irreversible metabolic acidosis and hypotension ensued and the baby died. At postmortem examination, the aorta and its major branches were free of thrombi, and the heart, although dilated, was structurally normal and contained no thrombi. Microemboli were identified throughout the viscera and hemorrhagic infarcts were evident in the adrenal glands, death being attributed to the latter. CA SE 2. A male infant, weighing 2.8 kg, was born after 38 weeks' gestation. The pregnancy, labor, and delivery were uncomplicated except for an upper respiratory tract infection during the third trimester. After 24 hours, generalized cyanosis and a murmur in the pulmonic area were noted, and the infant was transferred to the Children's Hospital Medical Center, Boston, Massachusetts. The right brachial and both carotid pulses were not palpable. The left brachial and both femoral pulses were easily felt and equal, with a pressure of 83/46 mm Hg being recorded in the descending aorta through an umbilical arterial line. In addition, congestive heart failure was evident. The chest x-ray film revealed cardiomegaly and pulmonary venous congestion, and the electrocardiogram identified left ventricular hypertrophy and a strain pattern consistent with outflow obstruction. The two-dimensional
The Journal of
336 McFaul et al.
Thoracic and Cardiovascular Surgery
echocardiogram showed the left ventricle to be enlarged and poorly functioning, whereas the aortic valve, ascending aorta, and transverse arch appeared normal. Because of oxygen saturation evidence of right-to-Ieft shunting via a patent ductus, echocardiographic findings of a structurally normal heart, and unequal pulses, obstruction in the region of the aortic arch was suspected and cardiac catheterization was carried out. At this study, right-to-Ieft shunting through a patent ductus arteriosus was confirmed. The right ventricular, pulmonary arterial, and descending aortic systolic pressures were identical, whereas pressure in the left ventricle was 64 mm Hg higher and the left ventricular end-diastolic value was 25 mm Hg. A left ventricular cineangiogram demonstrated in dramatic fashion complete occlusion by an intraluminal mass of the distal ascending aorta and transverse arch with involvement of the origins of both carotid arteries (Fig. 3). Cerebral perfusion occurred largely through a dilated left vertebral artery. By means of deep hypothermic circulatory arrest, a large, loosely adherent clot was removed from the ascending aorta and transverse arch and the ductus arteriosus was ligated. Postoperatively, the infant's condition improved and was quite stable. He was extubated after 24 hours. However, on the second postoperative day, cardiac arrest occurred unexpectedly and all resuscitative measures were unsuccessful. At autopsy, rethrombosis of the ascending aorta and transverse arch had occurred with extension of the thrombus into the aortic end of the ligated ductus arteriosus. Although no thrombi were present in the left ventricle, microscopic examination revealed hemorrhagic infarction of the papillary muscles with patchy fibrosis throughout the myocardium. Results of histologic examination of the aorta were normal.
Discussion Aortic thrombosis is rare, often is associated with other illnesses such as sepsis, and in the past has been diagnosed only at autopsy. Further analysis of these previous reports reveals that clinical evidence of severe aortic obstruction, including congestive heart failure, hypertension, absent femoral pulses, and lower limb ischemia, was observed in some. I. 5. 6 Our first patient manifested the majority of these physical findings, whereas the unequal pulses, echocardiographic evidence of a structurally normal heart, and cyanosis of the lower extremities suggested an aortic arch obstruction in our second patient. More important, our patients illustrate that following identification of these physical findings, use of cardiac catheterization allows diagnosis of this lesion. The pathogenesis of aortic thrombosis is unknown. Sepsis has been suspected in some infants, although other associated entities or lesions have been described. Infants of diabetic mothers are predisposed to thrombotic events. In a report by Oppenheimer and Esterly" concerning 83 infants born to diabetic mothers, 14 were found to have thrombosis of large veins and one had
aortic thrombosis. Also, our first patient had a large aneurysm of the ductus arteriosus. The occurrence of thrombosis of the aorta related to this lesion was first described in 1859 8 and was later reported by others." 7.10 Since thrombosis together with fibrosis and intimal proliferation normally contribute to anatomic closure of the ductus, it is possible that extension of thrombus originating within an aneurysm of this structure may result in eventual obstruction of the aorta with or without embolization. Histologic examination of the aneurysm in our patient revealed deficiency of smooth muscle fibers, which may have prevented the normal contraction which occurs after birth. Aortic thrombosis also has been described in association with a deficiency in antithrombin 3,5 a plasma protein which inhibits thrombin and prevents platelet aggregation. Whether or not this contributed to the thrombosis in our patients we do not know, although results of limited hematologic studies consisting of platelet counts, prothrombin time, and partial thromboplastin time were normal. The occurrence of thrombosis of the ascending aorta and transverse arch in one of our patients has not been described previously. The origin of the original and recurrent thrombi is unknown but clearly was not related to the ductus arteriosus. Although a paradoxical embolus via the atrial septum is a possibility, no definite site of origin including the ductus venosus could be identified. Systemic embolization from the left ventricle in infants and children with idiopathic congestive cardiomyopathy has been reported"; however, no evidence of intracardiac thrombi, endocardiofibrosis, myocardial inflammation, or necrosis was identified in either of our patients at autopsy. The critical condition of these infants requires that these large thrombi be surgically removed. Steroids might be helpful to combat adrenal insufficiency, a potential sequela of adrenal infarction and hemorrhage. Heparin administration after operation might prevent rethrombosis if the surgeon were to identify injury to the intimal surface of the aorta.
2 3 4 5
REFERENCES Gross RE: Arterial embolism and thrombosis in infancy. Am J Dis Child 70:61-73, 1945 Dimmick JE, Patterson, MWH, Wu KWA: Systemic hypertension in a newborn infant, J Pediatr 95:321-324, 1979 Stout C, Koehl G: Aortic embolism in a newborn infant. Am J Dis Child 120:74-76, 1970 Marks C, Fehler BM: Aortic occlusion in infancy. Br Med J 1:709-710, 1953 Bjarke B, Herin P, Blomback M: Neonatal aortic thrombosis. Acta Paediatr Scand 63:297-301, 1974
Volume 81 Number 3 March,1981
6 Heggtveit HA, Hill DP: Thromboaortitis in the newborn. Arch Pathol (Chicago) 76:578-580, 1963 7 Knowlson GT, Marsden MB: Aortic thrombosis in the newborn period. Arch Dis Child 53:164-166, 1978 8 Klob J: Thrombosis ductus botalli. Z Gesellsch Aerzte Wien 15:4, 1859 9 Oppenheimer EH, Esterly JR: Thrombosis in the new-
Aortic thrombosis in neonate
337
born. Comparison between infants of diabetic and nondiabetic mothers. J Pediatr 67:549-556, 1965 IO Ordway NK, Stout LC: Thromboembolus to abdominal aorta in a neonate. J Pediatr 82:143-148, 1973 II Harris LC, Powell G, Brown OW III: Primary myocardial disease. Pediatr Clin North Am 25:847-867, 1978