* University of Connecticut Health Center, Dept of Ob-Gyn, Division of Maternal-Fetal Medicine, 263 Farmington Avenue, Farmington, CT 06030-2202 Ph: 203-679-3267, Fax: 203-679-1271. Neonatology, Dept of Ob-Gyn and Reproductive Sciences, Robert Wood Johnson Medical School, New Brunswick, NJ

Synonyms: None.

Definition: Thrombus within lumen of the inferior vena cava.

Prevalence: Unknown but assumed to be rare.

Pathogenesis: Vascular endothelial defects, hyperviscosity or congenital hypercoagulable conditions may be predisposing factors. A thrombus may be primary or an extension of renal vein thrombus.

Associated anomalies: Rarely reported: hydrops, renal vein thrombosis, porencephaly,

Differential diagnosis: Hematogenous extension of neoplasm such as neuroblastoma, renal cell carcinoma, or Wilm"s tumor. Vascular endothelial neoplasm such as a myxoma.

Prognosis: Generally good, but is dependent on the presence of embolic disease or renal vein thrombosis.

Recurrence risk: Unknown, but probably dependent upon the underlying etiology.

Management: Expectant, with serial evaluation of fetal intracranial anatomy looking for sonographic evidence for embolic events or renal vein thrombosis.

MESH Inferior vena cava, Thrombosis ICD9 747.49 CDC 747.490

Introduction

Thrombus formation within the inferior vena cava (IVC) in infants and children is an uncommon, but well-described event^l-17. It can occur in conjunction with renal vein thrombosis. Characteristic ultrasound findings of an IVC thrombus have been described^I0-13. The majority of these reports represent the identification of a mature organized thrombus, usually with calcification. In utero IVC thrombosis is presumed to be rare. There has been only I previous report of the prenatal diagnosis of an IVC thrombusig. Sonographic findings of early IVC thrombus formation and progression have not been previously reported. We report an unusual case of isolated IVC thrombosis in a twin gestation complicated by Stuck Twin syndrome, Progressive IVC occlusion due to the thrombus in one twin was documented by serial ultrasound examinations.

Case report

The patient was a 36 year-old, Caucasian, G₉P_7-0-1­7. She had one previous first trimester spontaneous abortion and 7 uncomplicated spontaneous vaginal deliveries at term. Her medical and family history were unremarkable. She was initially referred for a routine ultrasound examination at 17 weeks which demonstrated a normally grown twin gestation, a single placenta, like sex fetuses, and a thin dividing membrane suggestive of diamniotic monochorionic placentation. Her next examination at 23 weeks identified severe oligohydramnios for Twin A and polyhydramnios for Twin B consistent with the “Stuck Twin” syndrome. A therapeutic amniocentesis was performed with removal of 640 ml of amniotic fluid from the sac of Twin B. The amniotic fluid volumes equalized over a two week period. Premature uterine contractions were treated with oral terbutaline, Weekly steroids (Celestone 12mg intramuscularly) were given to promote fetal lung maturity beginning at 24 weeks in anticipation of possible preterm delivery. Twice weekly antenatal fetal heart rate testing and amniotic fluid volume assessments were instituted at 26 weeks. Serial ultrasound examinations demonstrated appropriate growth for both twins with normal amniotic fluid volumes.

During a routine antenatal testing visit at 31 weeks a homogenous echogenic mass was identified within the IVC of Twin B at the level of the fetal liver (fig. 1).

Figure 1:  Initial oblique longitudinal (top) and transverse

Flow around the mass within the IVC could be demonstrated on color Doppler examination (figs. 2-4). Daily ultrasound examinations were performed to monitor the mass and also monitor for possible embolic phenomena (i.e. porencephalic cyst, nephromegaly, etc.). Over the next three days the size, consistency, and distance of the mass from the right atrium changed significantly (fig. 5) Daily non­stress tests were also instituted. On the third day after initial identification of the mass, intermittent spontaneous decelerations for Twin B were noted despite a reactive non-stress test. The patient was admitted for continuous fetal heart rate monitoring. The decelerations resolved and the patient remained hospitalized for twice daily non-stress tests and daily ultrasound evaluations of the IVC mass.

Figure 2: Gray-scale image of thrombus within the inferior vena cava. Note central sonolucency of thrombus (day 1).

Figure 3: Color Doppler demonstrating patency of the inferior vena cava around the thrombus (day 1).

Figure 4: Color Doppler demonstrating flow around the thrombus and within the cephalic portion of the inferior vena cava. Note distance from the right atrium (day 1).

Figure 5: Progressive elongation of the thrombus with extension towards the right atrium. Note the presence of flow within the caudal

Figure 6: Thrombus (arrows) with prominent sonolucency close to the right atrium (day 3).

Figure 7: Complete occlusion of the inferior vena cava with extension

Complete IVC occlusion was noted 7 days after initial identification of the mass. (fig. 8) At that time flow could not be identified within the distal IVC at the junction of the right atrium. Significant collateral venous flow was also identified. The mass was felt to be a thrombus with the observed changes representing various stages of organization and propagation. The mother was evaluated for thrombogenic conditions including protein S, protein C and anti thrombin Ill deficiencies, (Table I) She was also tested for ANA, anticardiolipin antibody, and lupus anticoagulant which were negative.

Table 1:  Results of laboratory evaluation for inherited disorders of fibrinolysis. Normal values are in parenthesis. (* Note the low maternal free protein S is consistent with physiologic changes due to pregnancy. Repeat testing 8 weeks postpartum resulted in normal free and total protein S levels.)

Daily monitoring remained reassuring until 33 weeks when Twin B demonstrated persistent late decelerations with regular uterine contractions. She underwent an uncomplicated primary low transverse cesarean section. Twin A was male, 1730g, and had an Apgar score of 8 at 1 minute and 9 at 5 minutes. Twin B was male, 1635g, and had an Apgar score of 8 at 1 minute and 9 at 5 minutes, Umbilical cord blood gases were normal for both twins. The placenta was diamniotic monochorionic and demonstrated evidence for intraplacental vaso-occlusion with the disk for Twin B having significantly more extensive changes than the disk for Twin A. The placenta for Twin B was noted to have extensive endothelial damage in some of the larger fetal stem vessels with erythrocyte fragmentation. Focal areas of avascular villi were thought to be secondary to regional occlusion of fetal stem vessels.

The neonatal course for Twin A was complicated by apnea of prematurity (requiring 11 days of theophylline) in addition to hyperbilirubinemia (requiring 5 days of phototherapy). The initial hematocrit was 33.8% and the platelets were 272,000. Twin B (IVC thrombus twin) had a hematocrit of 47,9%, PT/PTT-11.6/31.7, fibrinogen of 173, and platelets of 292,000, The protein S, protein C and antithrombin Ill levels were normal. (Table I) This infant"s neonatal course was also complicated by apnea of prematurity and hyperbilirubinemia for which appropriate treatment was provided. Sonographic evaluation of Twin B was performed at I day of age. An IVC thrombus was visualized at the level of the liver extending to the custacean valve at the juncture of the IVC and the right atrium. No flow was seen in the caudal portion of the IVC, The hepatic and renal veins were normal in appearance. The hemiazygos-azygos veins were significantly dilated consistent with increased collateral circulation due to the occluded IVC, similar to the prenatal finding. An echocardiogram revealed a structurally and functionally normal heart. A renal scan was performed on day 6 of life which was reported as normal "with mild retention of tracer in the left renal collecting system. Twin B"s vital signs including blood pressure were monitored and remained within the normal range throughout the hospitalization, Since the infant was asymptomatic, thrombolytic therapy was not initiated. Both twins were discharged home on day 20 in stable condition.

Discussion

The prenatal diagnosis of IVC thrombus formation is rare. Rypens et al. reported a case of ultrasound identification of an IVC thrombus associated with calcification and renal vein thrombosis in a 38 week gestation^l8. The neonatal diagnosis of IVC thrombosis has been well-described^2,6-9,12-15. Several of these neonatal cases identified calcified IVC thrombi which is highly suggestive of in utero thrombosis^6-9,13.

Etiology

The origin of IVC thrombi is generally considered unknown. Maternal and fetal conditions which have been associated with this diagnosis are listed in Table II.

It has been suggested that conditions which increase the viscosity of blood in the fetus or neonate may increase the risk for clot formation. Hyperviscosity may be present in the “Stuck-Twin” syndrome if the condition is due to so-called Twin-Twin transfusion. In that circumstance the recipient twin is usually polyoythemic which may contribute to a hypercoagulable state. The higher hematocrit of Twin B at birth suggests that this may have been a contributing factor for the IVC thrombus in this case, Other etiologies for a potential thrombogenic state in the fetus include congenital deficiencies of the fetal or maternal thrombolytic system (antithrombin III or protein S and protein C deficiencies) and acquired hypercoagulable conditions (anticardiolipin antibodies, lupus anticoagulant) ^14,19. Evaluation of the mother and affected infant failed to identify any of these abnormalities.

Table 2: Maternal and fetal conditions reported to be associated with inferior vena cava thrombosis.

Associated anomalies

Little is known about the natural history of a fetal IVC thrombus. Several cases of IVC thrombosis in neonates have been reported in association with renal vein thrombosis^2,9,12-14. In these cases it is unclear whether the thrombus originated in the renal vein and extended to the IVC or if the IVC formed a thrombus first with subsequent occlusion of the renal vein. McDonald et al. has documented by venogram progressive extension of a renal vein thrombus resulting in complete occlusion of the IVC²⁰. Ultrasound findings associated with fetal and neonatal renal vein thrombosis have been previously described and should be evaluated in fetuses suspected of having an IVC thrombus^l2.

Ultrasound diagnosis

When the prenatal diagnosis of a fetal IVC thrombus is suspected, a careful sonographic evaluation of the fetus should be performed. Attention should be given to the intracranial anatomy looking for evidence of embolic events (por­en­ce­phalic cysts) as well as the fetal kidneys and renal vasculature looking for evidence of" renal vein thrombosis. The mother should be evaluated for evidence of diabetes, preeclampsia, antiphospholipid antibodies, and deficiencies of protein S, protein C, or antithrombin III, If the fetus has reached a gestational age consistent with viability then antenatal testing is suggested for evaluation of fetal well-being.

Prognosis

In the absence of major medical conditions, an IVC thrombus in infants and children is considered to be relatively benign. In these cases expectant management is usually advocated^8,9. The main risk to infants and children with an IVC thrombus appears to be renal infarction due to renal vein thrombosis with subsequent decreased renal function or systemic hypertension. Close observation for these complications is recommended. Occlusion of the IVC in infants and children usually results in a well-developed collateral circulation which includes the azygos-hemiazygos veins and other retroperitoneal vesselsl⁷. In our case, the prominent collateral venous return to the superior vena cava demonstrated in the antenatal, as well as neonatal monographic examinations suggests that adequate collaterals develop in the fetus when the IVC is occluded in utero. Recanalization of an IVC occluded by a thrombus has been reported²⁰.

The risk for embolization has been stated as low, but extension of a renal vein thrombus into the IVC has been associated with pulmonary emboli⁵. Interestingly, two infants reported to have calcified IVC thrombi also had intracranial porencephalic cysts which are lesions known to be associated with thrombotic or embolic events^8,9. In utero emboli from an IVC thrombus could cross the foramen ovale and enter the fetal systemic circulation, increasing the risk of intracranial embolization. In the present case there was further concern that emboli from Twin B could theoretically reach the placenta and possibly Twin A through vascular anastamoses- No evidence for embolic phenomena was found on fetal or neonatal evaluation of Twin A, However, the placenta had lesions consistent with focal fetal stem vessel occlusion which could be secondary to emboli.

Management

Consideration was given for premature delivery of the twins at the time of the initial diagnosis of the IVC thrombus. Therapies discussed included thrombectomy and anticoagulation. After consultation with neonatologists and pediatric cardiothoracic surgeons, it was felt that surgical treatment of the thrombus was not feasible in the setting of prematurity, although IVC thrombectomy in term infants has been reported as successful in two of four attemptsl^,16,17. Anticoagulation of a premature infant was also believed to present significant risks for intraventricular hemorrhage2l, These factors along with the other risks of iatrogenic prematurity for both twins formed the basis of our decision for expectant non-interventional management. No specific etiology was found for the persistent late decelerations which ultimately prompted delivery. As of the time of this writing, the twin with the IVC thrombus was doing well clinically, and had early evidence for recanalization of the thrombus at the level of the right atrium.

References

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2.Avery ME, Oppenheimer GH, Gordon H14. Renal vein thrombosis in the newbom infants of diabetic mothers, N Eng J Med 256:1134-9, 1957.

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19. Corrigaii JJ. Neonatal thrombosis and thethrombolytic system; Pathophysiology and therapy. Am JPerdiatr Hematol Oncol 10:83-91, 1988.

20.  McDonald P, Tarar R, Gilday D, Reilly BJ. Some radiologic observations in renal vein thrombosis, Am J. Rocntgenol Radium Ther Nucl Med 120:368-88, 1974.

21. Andrew M, Schmidt B. Use of heparin in newborn infants. Semin Thromb Hemost 14:28-31, 1988.