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Exp Clin Cardiol. 2010 Summer; 15(2): e33–e35.
PMCID: PMC2898533
Clinical Cardiology: Case Report

Successful management of hemopericardium and cardiac tamponade secondary to occult malignancy and anticoagulation

David H Hsi, MD FACC,1,2 Mahesh Krishnamurthy, MD,1 Gerald F Ryan, MD,1,2 Pifu Luo, MD PhD,1 and Timothy J Woodlock, MD1,2


In patients presenting with pericarditis or pericardial effusion without known malignancy, the likelihood of finding previously undiagnosed cancer in different publications typically ranges from 4% to 7%. Cardiac tamponade due to malignant pericardial effusion is thus a rare clinical entity and often acutely life threatening. The present report describes an unusual case of large pericardial bleeding causing tamponade in the setting of fondaparinux anticoagulation, heterozygous factor V Leiden mutation and eventual discovery of meta-static adenocarcinoma.

Keywords: Adenocarcinoma of unknown primary, Factor V Leiden mutation, Fondaparinux, Malignant pericardial effusion, Pericardial tamponade


A 49-year-old Caucasian man initially presented with an unprovoked left popliteal deep venous thrombosis (DVT). The patient had a sedentary career as an engineer on desk duty. He was treated with enoxaparin and simultaneously initiated on warfarin therapy. He eventually required up to 15 mg of warfarin per day for therapeutic international normalized ratio (INR). Hypercoagulability studies were ordered for further evaluation. Three weeks later, he presented with bilateral extensive pulmonary embolism confirmed by computed tomography (CT). The patient was again treated with enoxaparin and warfarin, with the goal of keeping his INR in the 2.5 to 3.5 range. An inferior vena cava filter was placed. Test results showed normal activity levels of protein C, protein S, anticardiolipin antibodies and antithrombin III, and normal homocysteine level. He tested positive for heterozygous factor V Leiden abnormality. (His mother and son also tested positive for a similar gene mutation.) Due to concerns for underlying malignancy, the patient underwent CT scans of the chest, abdomen and pelvis, which were normal. During the next few weeks, the patient had one episode of right upper extremity cephalic vein thrombosis with therapeutic INR. The patient was started on subcutaneous fondaparinux injection (7.5 mg daily) because of warfarin failure. The patient did well for approximately seven months. He then presented with progressively worsening shortness of breath and orthopnea of one-day duration. He had upper respiratory viral symptoms with fever and malaise for one week before admission. The patient had severe dyspnea and orthopnea, with a resting heart rate of 120 beats/min and a blood pressure of 112/70 mmHg. A physical examination revealed distant heart sounds and significantly distended internal jugular vein to the jaw level. An electrocardiogram revealed sinus tachycardia and borderline low-voltage QRS complexes. A CT scan of the chest revealed a large pericardial effusion, but no evidence of pulmonary embolism, aortic dissection, aneurysm or mass. A bedside echo-cardiogram confirmed large pericardial effusion, as well as evidence of right atrial and right ventricular diastolic collapse, which is highly consistent with life-threatening cardiac tamponade (Figure 1). Despite the risk of bleeding, a clinical decision was made to proceed with echocardiography-guided pericardiocentesis, removing 1300 mL of dark nonclotting blood. There was excellent re-expansion of the cardiac chambers and resolution of pericardial effusion. The patient’s heart rate decreased to 86 beats/min and his systolic blood pressure increased by 24 mmHg immediately after the pericardiocentesis. A pericardial catheter was left in place for extended drainage (five days), with resolution of bleeding and obvious effusion.

Figure 1)
Echocardiographic image in apical four-chamber view showing large pericardial effusion (PE) and right ventricle (RV) diastolic collapse (arrow). LA Left atrium; LV Left ventricle; RA Right atrium

Viral studies of seasonal influenza A and B, and H1N1 were negative. The cytology from both pericardial and pleural effusion was positive for metastatic adenocarcinoma (Figure 2). He underwent a total body CT scan, revealing a small lesion (6 mm to 7 mm) in the left occipital lobe and a 10 mm lesion in the right lobe of the liver, which was suspicious for metastasis. Cancer antigen 19-9 and carcinoembryonic antigen levels were elevated at this time, raising the concern for hidden pancreatic primary cancer.

Figure 2)
Cytology slide of the pericardial fluid showing malignant cells of adenocarcinoma (arrows). The background red colour and cells indicate blood plasma and red blood cells, respectively

The patient received single-agent cytotoxic chemotherapy with gemcitabine on days 1, 8, 15, 22, 29, 36 and 43, followed by one week of rest (1). He opted to resume fondaparinux injection (10 mg once daily), which was increased to 10 mg and 15 mg daily, on alternate days, for new onset of right leg DVT. The patient did not want to take twice daily injection of enoxaparin. The patient underwent close clinical and echo-cardiographic monitoring for possible pericardial bleeding, which was negative. His cancer antigen 19-9 and carcinoembryonic antigen levels improved on chemotherapy, although his legs were edematous, which is consistent with DVT and post-phlebitic syndrome. His overall performance status was fair and he returned to work within two months. Six months later, there was re-accumulation of pericardial effusion, which required that he undergo the pericardial window procedure. The cytology was again positive for adenocarcinoma of unknown primary origin. The patient eventually passed away 7.5 months after cardiac tamponade and diagnosis of cancer, and 14.5 months after the initial presentation of leg DVT and finding of factor V Leiden abnormality.


The present unusual case illustrated complex problems in a young individual who presented with cardiac tamponade and previous episodes of DVT and pulmonary embolism even after initiation of anticoagulation therapy. His gene abnormality of heterozygous factor V Leiden variation certainly contributed to underlying hypercoagulability, as well as, in retrospect, the cancer-induced thrombosis-Trousseau’s syndrome. The patient’s presentation of pericardial bleeding and tamponade was probably due to a combination of inflamed pericardium in the setting of viral illness, baseline anticoagulation by fondaparinux injection and metastatic adenocarcinoma invading the pericardium. Quick action with pericardiocentesis was both life-saving and diagnostic of underlying pathology.

Malignancies, especially adenocarcinoma, have a propensity for causing a hypercoagulable state and subsequent thrombosis mostly in the venous circulation as part of Trousseau’s syndrome. There are major concerns for underlying malignancy, such as lung, breast and gastrointestinal cancer, despite unremarkable initial workup. On rare occasions, cardiac involvement may be the first or only expression of a non-cardiac primary neoplasm. The most common cardiac sign is tamponade (26). Pericardial fluid cytology has variable sensitivity for malignant cells. The presence of pericardial malignant cells usually indicates a shortened survival of approximately seven weeks compared with a mean survival of 29 weeks in other cancer patients with pericardial effusion (7). Our patient did have recurrent malignant pericardial effusion and survived seven months after the initial diagnosis. In patients presenting with cardiac tamponade, malignancy accounts for 65% of primary etiology, and one-year mortality was 76.5% in patients with malignant disease and 13.3% in those without malignant disease (8). The patient’s overall presentation was consistent with previous reports of poor long-term outcomes in this population.


Occult malignancy remains an important concern in patients presenting with unprovoked DVT. Fondaparinux anticoagulation treatment of our patient was complicated by spontaneous pericardial bleeding and life-threatening tamponade with underlying adenocarcinoma of unknown primary origin. Aggressive management, including pericardiocentesis, in the setting of full anticoagulation saved the patient’s life during the acute stage. Judicious initiation of chemotherapy, in conjunction with other medical and surgical interventions, afforded the patient additional duration of meaningful survival.


The authors thank Bryana A Levitan RDCS for providing high-quality echocardiographic images.


FINANCIAL DISCLOSURE: The authors have no financial associations to declare.


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