A case report of hemothorax due to intrathoracic variceal rupture linked to Budd-Chiari syndrome

Abstract

Background

Budd-Chiari syndrome (BCS) is a hepatic venous system disease caused by obstruction of the hepatic blood flow outflow tract. The definition of hemothorax is that blood accumulates in the chest cavity, and the hematocrit value of the effusion exceeds 50%. Hemothorax caused by intrathoracic variceal rupture associated with BCS is rare.

Case presentation

A 43-year-old female patient with just 69 g/L hemoglobin, complaining of shortness of breath for 2 days, was admitted to gastroenterology department. The chest computed tomography (CT) revealed right pleural effusion and contrast-enhanced CT in portal venous phase revealed portal hypertension and multiple tortuous veins. The ratio of red blood cells to white blood cells in bloody pleural effusion was about 500:1, and the neuron-specific enolase (NSE) and cytokeratin 19 fragment antigen 21 − 1 (CYFRA21-1) in the pleural effusion were significantly increased. Therefore, the patient was transferred to the respiratory medicine department to exclude malignant pleural effusion. The enhanced chest CT reexamination showed a continuous enhanced soft tissue-like lump in the thoracic cavity, which was a varicose vein. The vascular interventional physician reviewed the contrast-enhanced CT in portal venous phase to see a stenosis between the hepatic vein and the inferior vena cava, so BCS was suspected. Vascular interventional surgery was performed, and identified obstructed blood flow at the upper end of the inferior vena cava, which significantly improved after thrombolysis. Therefore, the intrathoracic variceal rupture linked to BCS was the source of the patient’s pleural effusion.

Conclusions

when there is unexplained bloody pleural effusion and the tumor index of pleural effusion increases, thoracoscopic pleural biopsy should not be blindly performed, and pleural effusion caused by vascular rupture should be further excluded.

Background

Budd-Chiari syndrome (BCS) is a rare and life-threatening hepatic vascular disease caused by obstruction of hepatic venous blood flow, with retrohepatic portal hypertension and inferior vena cava hypertension as the main clinical manifestations. The obstruction site may occur anywhere from the level of the hepatic vein to the intersection of the inferior vena cava and the right atrium. BCS can manifest as portal hypertension such as liver function damage, splenomegaly, peritoneal effusion, esophageal and gastric varices, and inferior vena cava hypertension syndrome such as varices of the lower extremities, pigmentation of foot, and chronic ulcers [1]. Hemothorax is defined as an accumulation of blood in the chest cavity with an effusion that has a hematocrit percentage greater than 50% [2]. This paper reports in detail a case of hemothorax caused by an intrathoracic variceal rupture caused by BCS.

Case presentation

A 43-year-old female patient with no underlying diseases was admitted to the hospital due to shortness of breath for 2 days. The patient had no recent history of hematemesis and thoracic trauma. Physical examination revealed spider nevus in the chest, low respiratory sound in the right lung, and edema in both lower extremities. The blood routine showed the white blood cell count was 2.88 × 10⁹ /L (normal range: 3.5–9.5 × 10⁹ /L), the hemoglobin was 69 g/L (normal range: 115–150 g/L), and the platelet count was 92 × 10⁹/L (normal range: 125–350 × 10⁹ /L). The coagulation function indicated that the prothrombin time was 14.3 s (normal range: 9.8–12.1 s), and the international normalized ratio was 1.23 (normal range: 0.85–1.15). A chest computed tomography (CT) scan at the local hospital showed right pleural effusion with lung atelectasis, venous varicose wall of the abdomen, cirrhosis and splenomegaly (Fig. 1a-c). Therefore, the patient was admitted to the gastroenterology department.

Fig. 1

Chest computed tomography (CT). (a) Right pleural effusion and lung atelectasis; (b) subcutaneous varicose vein of the abdominal wall (white arrow); (c) Cirrhosis and splenomegaly

After admission, the liver function showed 32.4 g/L albumin (normal range: 40–55 g/L), 261 U/L lactate dehydrogenase (normal range: 120–250 U/L), aspartate aminotransferase and alanine aminotransferase were normal. Five indexes of hepatitis B indicated the surface antibody and core antibody were positive, and the others were negative. Antibodies against hepatitis A, C, E and autoimmune liver diseases were negative. Blood tumor markers displayed no abnormalities. The liver fibrosis markers showed type IV collagen at 164.8 ng/mL (normal range: 0.02–30 ng/mL), type III collagen at 45.82 ng/mL (normal range: 0–30 ng/mL), laminin at 79.71 ng/mL (normal range: 0–50 ng/mL), and glycocholic acid at 10.6 µg/mL (normal range: 0–2.7 µg/mL). Gastroscopy revealed chronic superficial gastritis with no esophagogastric varices. Colonoscopy showed no abnormalities. Contrast-enhanced CT in portal venous phase indicated abdominal wall vein dilatation, cirrhosis, portal hypertension, splenomegaly, splenic vein dilatation, and paravertebral vein dilatation and communication with left renal vein (Fig. 2a-c).

Fig. 2

Contrast-enhanced CT in portal venous phase. (a) Dilated abdominal wall vein; (b) Dilated splenic veins (white arrow), splenomegaly, cirrhosis and portal hypertension; (c) Dilated paravertebral vein and communicated with the left renal vein (white arrow)

The patient received 3.5 U of red blood cell suspension once for low hemoglobin. The hemoglobin gradually increased and stabilized at about 100 g/L after regular review. Thoracic ultrasound revealed right pleural effusion, up and down by 126 mm, anteroposterior diameter of 103 mm, and floating the lung tissue (Fig. 3). The bloody pleural effusion was extracted by thoracentesis. Pleural effusion routine revealed positive rivalta test, red blood cell count of 2,709,000 /µL (normal range: 0 /µL), and white blood cell count of 5369 /µL (normal range: leakage < 100 /µL, exudate > 500 /µL). Data regarding the hematocrit of pleural effusion was not collected. Pleural effusion biochemistry indicated 29.9 g/L albumin (normal range: 0 g/L) and 2466 U/L lactate dehydrogenase (normal range: leakage < 200 U/L, exudate > 200 U/L). The tumor markers of pleural effusion showed that neuron-specific enolase (NSE) was 248.84 ng/ml (reference range within our center: < 16.5 ng/ml), cytokeratin 19 fragment antigen 21 − 1 (CYFRA21-1) was 113.60 ng/ml (reference range within our center: < 3.3 ng/ml), and alpha fetoprotein, carbohydrate antigen 125, and carbohydrate antigen 153 were normal. No tumor cells were found in pleural effusion smears. Thus, the patient was referred to the respiratory medicine department to rule out malignant pleural effusion and undergo thoracoscopy if necessary.

Fig. 3

Thoracic ultrasound. Right pleural effusion, up and down by 126 mm, anteroposterior diameter of 103 mm, and floating the lung tissue

Reexamination of the enhanced chest CT revealed a continuous soft tissue-like lump in the posterior mediastinum (Fig. 4a-b). After enhancement, the parenchymal and delayed phases showed obvious enhancement, suggesting the lump was a varicose vein rather than an expanded lymph node and closely connected to the inferior vena cava. Because the extracted pleural effusion was bloody, the ratio of red blood cells to white blood cells in pleural effusion was 500:1 and the patient had anemia, suggesting hemothorax caused by intrathoracic variceal rupture.

Fig. 4

Enhanced chest CT. (a and b) A continuous enhanced soft tissue-like lump in the posterior mediastinum, which was a varicose vein (white arrow)

The vascular interventional physician was invited and reviewed the contrast-enhanced CT in portal venous phase, who found a stenosis between the hepatic vein and the inferior vena cava, and the upper and lower segments of the stenosis were seen to be tortuous and thickened (Fig. 5a-b). The patient had portal hypertension, multiple tortuous and dilated veins, so BCS was suspected.

Fig. 5

Contrast-enhanced CT in portal venous phase: sagittal (a) and coronal (b) view. A stenosis (white arrow) between the hepatic vein and the inferior vena cava

Vascular interventional surgery was performed after 10 days. Intraoperative inferior vena cava angiography demonstrated obstructive blood flow at the upper end of the inferior vena cava (Fig. 6a). Numerous branch circulations surrounded the inferior vena cava. The inferior vena cava’s occlusive portion was slowly dilated with Futhrouth balloon catheter, and 200,000 U of urokinase was administered for thrombolysis. Blood flow in the occlusive region improved markedly after re-angiography (Fig. 6b), confirming BCS. Therefore, considering the patient’s hemothorax was due to BCS-related variceal bleeding.

Fig. 6

Vascular interventional surgery. (a) The blood flow at the upper end of the inferior vena cava was blocked. (b) The blood flow in the inferior vena cava occlusion segment was significantly improved after 200,000 U of urokinase thrombolysis

Two months after vascular interventional surgery, re-examination of enhanced upper abdominal CT showed a greatly reduced varicose vein in the thoracic cavity (Fig. 7).

Fig. 7

Two months after vascular interventional surgery, re-examination of the enhanced upper abdominal CT revealed significant reduction of the intrathoracic varicose vein (white arrow)

Discussion and conclusion

In 1845, the British doctor George Budd first proposed that the syndrome characterized by clinical symptoms such as abdominal pain, ascites, and hepatomegaly was called BCS [3]. But it was not until 1959 that Parker proposed that the pathophysiological mechanism of BCS formation was related to thrombosis conditions [4]. BCS is a rare entity characterized by obstruction of hepatic venous blood flow. In western countries, studies have shown that paroxysmal nocturnal hemoglobinuria [5], myeloproliferative neoplasms [6], high homocysteine, antiphospholipid antibodies, pregnancy [7] and puerperium are high risk factors for BCS, but the above risk factors are not common in China [8]. The patient in the case had no underlying disease before admission, and no history of tumor, paroxysmal nocturnal hemoglobinuria and other diseases was found after admission. Therefore, it is considered that the patient’s disease is mainly due to hypercoagulable state of blood, and the specific cause is not known.

The clinical manifestations of BCS are not specific and may be diverse. Most BCS patients have no obvious manifestations in the early stage of onset. Portal vein pressure rises due to hepatic vein blood flow restriction, forming intrahepatic and extrahepatic collateral circulation. The establishment of intrahepatic and extrahepatic collateral circulation significantly improves patient symptoms. Decompensated liver function can cause portal and inferior vena cava hypertension. Portal hypertension usually causes esophageal and gastric varices, liver damage, splenomegaly, refractory ascites, and periumbilical and abdominal wall vein enlargement. Inferior vena cava hypertension can cause lower extremity edema, varicose veins, even lower extremity skin pigmentation and chronic ulcers. The patient in the case experienced recurring lower limb edema and chest spider nevus before admission. The contrast-enhanced CT in portal venous phase demonstrated tortuous enlargement of splenic, paravertebral, paraumbilical, and abdominal wall veins, consistent with BCS symptoms.

Several causes of bloody pleural effusion include chest trauma [9], intrathoracic vascular rupture, and malignant tumor metastasis. Intrathoracic vascular rupture can be caused by aortic dissection rupture hemorrhage [10, 11] and pulmonary arteriovenous fistula hemorrhage. Varicose bleeding is the main complication of portal hypertension in cirrhosis. Hemorrhage occurs mainly in the gastrointestinal tract, while extraluminal bleeding is very rare, so hemothorax caused by an intrathoracic variceal rupture linked to BCS is relatively rare [12]. Paparoupa M et al. reported in detail a case of bilateral hemothorax caused by variceal bleeding in a patient with liver cirrhosis [12]. Similar to our case, both patients had an unexplained mass shadow found in the mediastinal window of the enhanced chest CT. The hemothorax in both cases was caused by extraluminal variceal rupture and neither of the two patients had hematemesis, and no gastrointestinal bleeding was found in the upper gastrointestinal endoscopy. Different from our case, the patient in the case reported by Paparoupa M et al. suffered a large amount of blood loss, which caused hemorrhagic shock and required immediate embolization of the ruptured vein. Fortunately, the patient’s hemoglobin in our case gradually increased and stabilized after the infusion of red cell suspension, indicating that the intrathoracic varicose vein rupture gradually healed, providing more time for the patient’s diagnosis. The patient’s pleural effusion tumor markers showed significantly elevated NSE and CYFRA21-1, so malignant pleural effusion was deemed possible. When the primary tumor could not be identified, thoracoscopic biopsy of the intrathoracic soft tissue-like lump was even needed to further confirm the diagnosis. Now it seems that thoracoscopic biopsy may induce significant hemorrhage and death in the patient. NSE derived from neurons and peripheral neuroendocrine cells, is a biomarker of neuroendocrine tumors or ischemic brain damage. However, as platelets and erythrocytes contain NSE, hemolysis causes falsely elevated NSE [13]. Due to the rupture of the varicose vein in the chest cavity, the blood flowing into the chest cavity had hemolysis, so the patient’s pleural effusion NSE increased. Unfortunately, the reason for the elevation of CYFRA21-1 in the patient’s pleural effusion has not been found so far, the hemolysis of the specimen may also cause the increase of CYFRA21-1.

The diagnosis of BCS mainly depends on color doppler ultrasound (CDUS), contrast-enhanced CT in portal venous phase, magnetic resonance imaging (MRI), digital subtraction angiography (DSA) and other imaging examinations. CDUS performed by an experience operator, has a sensitivity > 75% and should be the first choice option [14]. Contrast-enhanced CT in portal venous phase and MRI have a role in diagnostic confirmation or in the absence of an experienced operator. DSA is the gold standard for diagnosing BCS, showing inferior vena cava lesions, occlusion length, thrombus, and collateral circulation. However, DSA is invasive radiographic testing that increases bleeding and thrombosis risk, so it is relatively few dedicated to diagnosis BCS [15]. Interventional therapy for BCS has gradually been considered the preferred treatment in recent years. In the case, the patient underwent inferior vena cava balloon dilatation and catheter thrombolysis in time. The operation significantly increased the blood flow to the occluded segment of the inferior vena cava and had good therapeutic effects. Wang Z et al. reported a large-sample, single-center retrospective study on the first recurrence of BCS after endovascular treatment [8]. Among the 450 patients included in the study, 102 patients relapsed during follow-up and the recurrence rates in years 1, 3, 5, and 10 were 9.11%, 17.35%, 20.10% and 23.06%, respectively. In my opinion, if the probability of recurrence after BCS interventional therapy is higher, the risk of bleeding recurrence inside the pleural cavity will also increase. To date, the literature on BCS-associated vascular rupture hemothorax is rare, so the risk of bleeding recurrence inside the pleural cavity is unknown.

In the process of diagnosing and treating of this patient, we obtained the following conclusions: First, when there is unexplained bloody pleural effusion and the tumor index of pleural effusion increases, thoracoscopic pleural biopsy should not be blindly performed, and pleural effusion caused by vascular rupture should be further excluded. Non-malignant pleural effusion can also cause elevated tumor markers. Second, BCS combined with bloody pleural effusion is relatively rare, which provides a new idea for the diagnosis of patients with portal hypertension combined with bloody pleural effusion. Third, when encountering difficult patients, communication between multiple departments should be carried out in time. Fourth, fortunately, the patient’s varicose veins healed spontaneously after rupture. Hemoglobin gradually increased and stabilized after the infusion of red blood cell suspension. If the patient repeatedly relapsed pleural effusion, and the hemoglobin decreased again, it should not wait for spontaneous hemostasis, the ruptured varicose vein should be embolized in time to improve the prognosis of the patient. We hope that our case report will help more clinicians.