Case report
A 67-year-old female patient with metastatic pancreatic carcinoma was admitted to the department of gastro-oncology in our university medical center for the initiation of palliative chemotherapy. The carcinoma was first detected by CT and diagnosed by confirmatory histology using ultrasound guided biopsy two weeks prior to the admission. In addition to the primary tumor, CT-scans had detected multiple liver metastases (Figure 1), so palliative chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, leucovorin and fluorouracil) was recommended. Initially, the therapy was planed in an outpatient setting, but due to dyspnea and progressive thrombocytopenia, the patient was admitted to the hospital.
On admission, the patient reported worsening dyspnea for about two weeks which now met the criteria of NYHA stage III. Furthermore, she reported that a deep vein thrombosis of the left lower leg had been diagnosed 10 days before admission. Anticoagulant treatment with apixaban 5mg twice daily had been initiated, but recently discontinued by her family physician due to severe thrombocytopenia of so far unknown origin. The patient had no history of cardiovascular disease. During physical exam, we did not find typical clinical sings of heart failure or deep vein thrombosis but petechiae on different sites of the skin on both lower legs.
Laboratory findings confirmed severe thrombocytopenia and highly elevated D-dimer levels reflecting a hypercoagulatory state. Given the severe shortness of breath and the deep vein thrombosis, an immediate CT-angiogramm of the chest was planned to rule out pulmonary embolism.
In order to apply intravenous contrast medium and after multiple attempts at inserting a peripheral venous catheter had failed, a central venous catheter was inserted into the right internal jugular vein. Following insertion, bedside ultrasound was used for confirmation of the central venous placement by visualizing bubble artifacts in the right atrium after injection of agitated saline through the distal port3.
Unexpectedly, during visualization of the right atrium and right ventricle in subcostal view, transthoracic echocardiography (using a Philips Affinity 70 ultrasound system) revealed large masses adherent to the tricuspid valve leaflets (Figure 2 A/B). The differential diagnosis included thrombi, bacterial vegetations and metastases. A CT was obtained immediately and demonstrated a hypodense lesion of 28 x 20 mm with predominantly intra-ventricular and only a small intra-atrial proportion (Figure 3). The lesion was irregularly configured and showed multiple stripy foothills to the ventricle walls. Furthermore, bilateral segmental and subsegmental pulmonary embolisms were detected.
After an interdisciplinary discussion of the echocardiography and CT results, we interpreted the tricuspid mass as most consistent with non-bacterial thrombotic endocarditis. We explained the findings to the patient and outlined the risks and benefits of initiating the planned chemotherapy. Specifically, we were concerned that chemotherapy might destabilize the intracardial mass, causing massive pulmonary embolism On the other hand, anticoagulative therapy was deemed riskful because of the marked thrombocytopenia. Finally, not acting at all would allow the tumor to grow in an uncontrolled manner. The patient opted for the chemotherapy which was initiated the next day. During the treatment, several sets of blood cultures as well as serum procalcitonin were negative indicating no hint for infectious endocarditis. Therapeutic anticoagulation was not possible due to persistent severe thrombocytopenia and spontaneous intracutaneous and catheter-related bleeding.
Several days later, the patient developed arterial thromboses in both lower extremities with critical ischemia, reflecting an overall deranged coagulation with parallel hypercoagulation and bleeding disorder consistent with disseminated intravascular coagulation. We performed a short time echocardiographic control after the first course of chemotherapy.
Unfortunately, the masses covering the tricuspid valve leaflets increased with signs of valve dysfunction and severe tricuspid insufficiency (Figure 4). Despite severe thrombozytopenia, continuous heparin and alprostadil were started. Within a few days, the thrombocyte count reached normal levels, and serum D dimer levels declined. Naturally, toe necroses did not resolve. The patient was discharged on low molecular-weight heparin in order to continue palliative chemotherapy in the outpatient department.