Case 7 -

Thrombosis and Calcification of Portal Vein and Intra-hepatic Portal Vein Branches Complicating Central Venous Catheter Alan G. Rose

Clinical History The patient was a 3 ½ month old female with Noonan syndrome who was extremely cyanotic from birth and underwent neonatal repair of the following cardiovascular defects: pulmonary valvar stenosis, aortico-pulmonary window defect, atrial septal defect, aortic valvar stenosis, patent ductus arteriosus and coarctation of the aorta. The patient also had a perimembranous ventricular septal defect. The thoracic duct was ligated due to a chylothorax. Her postoperative recovery was complicated by delayed chest closure, total body edema and she required significant vasopressor support. She was placed on a respirator and developed renal failure of uncertain etiology for which peritoneal dialysis was administered. Prior to death she had increasing need for larger amounts of vasopressors and mechanical ventilation. Autopsy revealed the patient to be status post repair of the congenital defects listed above. The umbilical vein was obliterated and both umbilical artery vestiges were identified on either side of the obliterated urachus. The liver (310 grams) appeared large relative to the other organs and it extended 6 cm below the right costal margin in the mid-clavicular line. An intra-peritoneal catheter indented the liver's capsular surface and a small (less than 1 cm diameter) area of hemorrhage was present nearby. Multiple small, discrete foci of calcification were scattered throughout the liver. The major portal vein, prior to reaching the hepatic hilum, showed occlusive thrombosis with signs of organization and early peripheral recanalization. Calcification was evident in the media and adventitia of the thrombosed portal vein. The seminar slide shows widespread thrombosis of many intra-hepatic branches of the portal vein. The situation of these venules within the portal tracts clearly distinguishes them as portal vein branches and distinguishes them from central, sub-lobular and larger hepatic veins. Some portal venous tributaries are totally occluded by organized thrombi with minimal recanalization, while others show less severe luminal occlusion. Calcification, which appears to be dystrophic in nature, is prominent in the wall of affected portal venules as well as in the organized thrombus to a limited extent. The liver parenchyma shows fatty change and areas of sclerosis. The key element in this patient was the trans-umbilical venous cannulation via the ductus venosus into the inferior vena cava and thence into the right atrium for parenteral nutrition in the initial postoperative period. This led to thrombosis of the main portal vein with extension of the thrombotic process to involve many of the intra-hepatic branches of the portal vein in the portal tracts. No calcification was noted in portal venous branches unaffected by thrombosis. As is commonly noted in children in a variety of pathologic conditions, there was a great propensity for calcification to occur in relation to the vessels affected by organized thrombi. Calcification in children occurs commonly in bioprostheses [1] and is commonly observed in ischemic myocardial lesions in the young. This propensity for calcification has been attributed to differences in calcium metabolism in the young, who tend to have an elevated alkaline phosphatase level. In infants, portal vein thrombosis may result from umbilical cord infection or cannulation of the umbilical vein. In adults it usually is a complication of liver cirrhosis. Pyelophlebitis (e.g. due to appendix abscess) may also lead to portal vein thrombosis. Pancreatic tumor, pancreatitis, or diseases of adjacent lymph nodes may induce extrinsic thrombosis. Intrahepatic obstruction of the portal circulation may be due to lesions in the portal venules (as in our patient) or within the liver sinusoids due to reticuloendothelial disease, sarcoidosis, congenital hepatic fibrosis, or bilharziasis. If portal vein thrombosis occurs rapidly and completely (e.g. due to trauma) it may produce hemorrhagic infarction of the intestine. In some patients in whom the portal vein thrombosis is not fatal, extensive recanalization of the vein may occur; which is termed cavernous transformation of the portal vein. [2] The causes of portal hypertension are listed in Table 1. Table 1: Causes of Portal Hypertension Presinusoidal Lesions Extrahepatic obstruction Intrinsic thrombosis of portal vein Neonatal sepsis Increased blood coagulability Pyelophlebitis Extrinsic thrombosis of portal vein Pancreatic tumor Pancreatitis Diseases of adjacent lymph nodes Intrahepatic obstruction Lesions in the portal vein branches Sinusoidal Lesions Cirrhosis Reticuloendothelial diseases Sarcoidosis Congenital hepatic fibrosis Bilharziasis Postsinusoidal Lesions Obstruction of hepatic veins Hepatic veno-occlusive disease Webs in suprahepatic inferior vena cava Increased Blood Flow into Portal System Arteriovenous fistula A number of papers have reviewed the complications (Table 2) that may arise in neonates from the use of vascular catheters. [3, 4, 5] The commonest complication is infection, which is related to birth weight, male sex and duration of catheter placement. [3] Other complications include venous thrombosis (e.g. superior vena cava syndrome), edema, thrombosis, ischemia and catheter obstruction. [5] Dislocations and thromboembolic complications may occur. [6] Cardiac tamponade (following cardiac rupture due to catheter tip injury), pneumothorax, hydrothorax and hemothorax have also been reported. [7] Correct placement of the catheter tip in the superior vena cava poses little risk of cardiac perforation. [8 ]Transjugular intrahepatic portosystemic shunt (TIPS) has been used to treat Budd-Chiari syndrome or portal vein thrombosis. [9] Table 2: Complications of Transvenous Cannulation in the Young Infection Venous Thrombosis Thromboembolism Catheter Dislocation Cardiac Rupture Pneumothorax Hydrothorax, Hemothorax Zahn Infarct Acute thrombotic occlusion of an intra-hepatic portal vein radicle does not cause ischemic infarction, but produces a Zahn infarct that is characterized by sinusoidal distention, hepatocellular atrophy and hemostasis. Obstruction of Blood Flow Through the Liver May also Occur at the Sinusoidal Level This is seen in cirrhosis, sickle cell disease, disseminated intravascular coagulopathy (e.g. in eclampsia) or in diffuse spread of carcinoma. Miscellaneous Lesions of Veins Venous Aneurysms / Ectasias Aneurysms of arteries are common and also occasionally occur in the heart. Owing to the low blood pressure within veins, aneurysms are seldom encountered. If they occur, they take the form of an aneurysmal varix (due to a direct communication between an artery and a vein without an intervening false sac), or a varicose aneurysm (an indirect communication between an artery and a vein via a false sac). 1. Portal vein aneurysm Venous aneurysms, including portal vein aneurysms are rarely encountered in clinical practice. Portal vein aneurysms [10] may be intra-hepatic or extra-hepatic, and their origin may be congenital [11] or acquired. Acquired aneurysms are associated with liver disease, trauma or degenerative changes. Methods of management include observation, resection, thrombectomy, or portal venous decompression. Extrahepatic portal vein aneurysms can thrombose and lead to portal hypertension, they may rupture or they may compress the portal vein itself. Portal thromboembolism to the liver from a thrombosed portal vein aneurysm is a theoretical possibility. The aneurysm may also compress the bile duct or other organs e.g. the duodenum or inferior vena cava. Rupture of a portal aneurysm may occur, but is fortunately rare due to the low intra-vascular pressure. Venous aneurysms are uncommon in clinical practice, but should be included in the differential diagnosis of a subcutaneous mass. [12] Venous aneurysms of the popliteal, jugular and saphenous veins have been described most often. Other sites include intracranial veins, internal jugular vein, [13]superior vena cava, inferior vena cava, renal vein, [14]forearm veins, femoral vein and the portal vein. Most of the aneurysms are thought to be congenital in origin and are asymptomatic. Thus, surgery is usually not indicated. Popliteal aneurysms appear to be an exception to this rule. Aneurysms of the popliteal vein appear to be more prone to thrombosis and recurrent pulmonary embolism. Popliteal venous aneurysms should be sought for in patients with pulmonary emboli and no evidence of lower extremity deep-vein thrombosis. Venography, ultrasonography, angiography or magnetic resonance imaging may make the diagnosis. Excision of the popliteal venous aneurysm with venous reconstruction is recommended. Some confusion exists in the literature between aneurysms and varices of renal veins. [14] Varices are usually multiple, smaller, serpiginous and not typically saccular in appearance and usually have a better blood flow through them than venous aneurysms, which comprise solitary sacs filled with stagnant blood. Recognition of an aneurysm is important in order to avoid percutaneous biopsy, which may be complicated by retroperitoneal hemorrhage. Barzilai and Kleckner [15] reported a case of persistent gastrointestinal bleeding as a result of portal vein aneurysmal rupture into the extrahepatic bile duct. The differential diagnosis of the particular venous aneurysm will depend on the site of the aneurysm. Those situated in veins in the upper half of the body will enlarge with the Valsalva maneuver. Like a cavernous hemangioma, venous aneurysms may exhibit a hum on auscultation. It is not known whether the alterations of elastase activity [16] that may favor arterial aneurysm development (see case 4 in this seminar) are also operative in venous aneurysm formation. 2. Aneurysm of inferior vena cava I have had personal experience with an idiopathic aneurysm of the inferior vena cava which killed a young girl due to massive, sudden pulmonary thromboembolism by bulky thrombus, which had filled much of the (probably congenital) aneurysm. [17] The aneurysm lay below the level of the renal veins and was lined by endothelial cells resting upon collagen apart from at an area of mural tearing, where exposure of the underlying tissue had led to intra-aneurysmal massive thrombosis. Local bleeding had occurred around the aneurysm at the tear site. The aneurysm had the appearance of a 'true' aneurysm with remnants of the muscle coat of the inferior vena cava being represented in the aneurysm wall. 3. Rupture of the splenic vein in portal hypertension Abdominal apoplexy is a rare condition characterized by usually idiopathic massive, spontaneous retroperitoneal or intra-abdominal hemorrhage. A cause may be found in some cases, most being due to arterial rupture (e.g., dissection, segmental mediolytic arteriopathy, or aneurysmal rupture). Rupture of the splenic vein is very rare indeed and only about 15 cases have been reported in the literature. Eight of these have been associated with pregnancy [18] and the remaining 7 occurred in cirrhotic patients with portal hypertension. [19] We have encountered such a case, in a 47-year-old woman with primary biliary cirrhosis, who had repeated intestinal bleeding. The low venous pressure led to more protracted fatal retroperitoneal bleeding than that associated with arterial rupture. Rupture of the splenic vein is probably under-diagnosed. It is an unfamiliar concept and the splenic vein is often not examined in detail at autopsy. Splenectomy and ablation of the affected portion of the splenic vein holds the only chance for survival in such patients. The rarity of splenic vein rupture in portal hypertension suggests that some vascular conditioning factor must be operative in affected patients. Rupture of the splenic vein has also been reported as a fatal complication of catheterization via the umbilical vein in which echocardiography was not adequately used to guide the catheter below the diaphragm. [20] We have come full circle since we started this case discussion with a consideration of complications following umbilical vein catheterization. Venular Thrombosis in Hyperacute Cardiac Rejection Venular thrombosis appears to be the key event in the pathogenesis of hyperacute and delayed xenograft rejection. [21] Understanding of the sequential features of hyperacute rejection has led to a grading system [22] for hyperacute rejection that may have clinical application once it becomes feasible to use xenografts in clinical practice. References Rose AG. Pathology of heart valve replacement. Lancaster, MTP Press Ltd, 1987, pp 147-151. Rose AG. Diseases of veins. In Silver MD (ed): Cardiovascular pathology, 2nd edition, New York, Churchill Livingstone, 1991, pp195-223. Hogan MJ. Neonatal vascular catheters and their complications. Radiol Clin North Am 1999; 37: 1109-1125. Pandit PB, Pandit FA, Govan J, O-Brien K. Complications associated with surgically placed central venous catheters in low birth weight neonates. J Perinatol 1999; 19: 106-109. Henschel R, Wiescholek U, von Lengerke J, Harms E, Jorch G. Coagulation- associated complications of indwelling arterial and central venous catheters during heparin-prophylaxis – a prospective study. Europ J Pediatr 1999; 158 Suppl 3: S126-S129. Rand T, Kirschner L, Puig S, Ponhold W, Vergesslich K, Imhof H. "Lines and tubes" in neonatal intensive care patients. Radiologe 2000; 40: 52-57. Bagwell CE, Salzberg AM, Sonnino RE, Haynes JH. Potentially lethal complications of central venous catheter placement. J Pediatr Surg 2000; 35: 709-713. Andropoulos DB, Stayer SA, Bent ST, Campos CJ, Bezold CLI, Alvarez M, Fraser CD. A controlled study of transesophageal echocardiography to guide central venous catheter placement in congenital heart surgery patients. Anesth Analg 1999; 89: 65-70. Ganger DR, Klapman JB, McDonald V, Matalon TA, Kaur S, Rosenblate H, Kane R, Saker M, Jensen DM. Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis: review of indications and problems. Am J Gastroenterol 1999; 94: 603-608. Brock PA, Jordan PH, Barth MH, Rose AG. Portal vein aneurysm: a rare but important vascular condition. Surgery 1997;121: 105-108. Thompson PB, Oldham KT, Bedi DG, Guice KS, Davis M. Aneurysmal malformation of the extrahepatic portal vein. Am J Gastroenterol 1986; 81: 695-697. Friedman SG, KrishnasastryKV, Doscher W, Deckoff SL. Primary venous aneurysms. Surgery 1990; 108: 92-95. Levin SE, Govendrageloo K, Harrisberg JR. Aneurysm of the internal jugular vein. Cardiovasc J South Afr 1995; 6: 147-14148. Val-Bernal JF, Fernandez N, Lopez-Rasines. Symptomatic solitary right renal vein aneurysm: a case report. Cardiovasc Pathol 2000; 9: 29-32. Brasilia R, Kleckner MS. Hemocholecyst following ruptured aneurysm of portal vein. Arch Surg 1985; 72: 725-727. Cohen JR, Mandell C, Chang JB, Wise L. Elastin metabolism of the infrarenal aorta. J Vasc Surg 1988; 7: 210-214. van Ieperen L, Rose AG. Idiopathic aneurysm of the inferior vena cava. S Afr Med J 1990; 77: 535-536. Madhavan P, Hegarty P, Akram M, Drumm J. Spontaneous rupture of the splenic vein in pregnancy. Ir Med J 1998; 91:64. Almgren B, Bowald S. Spontaneous rupture of the splenic vein secondary to hepatic cirrhosis. Acta Chir Scand 1983; 149: 109-111. de Moor M, Pribut H, Hugo-Hamman C. The switch to balloon atrial septostomy with echocardiographic guidance – a severe complication. S Afr Med J 1996; 86 Suppl 2: C97-C99. Rose AG, Cooper DKC. Venular thrombosis is the key event in the pathogenesis of antibody-mediated cardiac rejection. Xenotransplantation 2000; 7: 31-41. Rose AG, Cooper DKC. A histologic grading system of hyperacute (humoral, antibody-mediated) cardiac xenograft and allograft rejection. J Heart Lung Transplant 1996; 15: 804-817.