Keywords
hemorrhagic cholecystitis - warfarin - anticoagulation - cholecystitis - deep vein
thrombosis
Hemorrhagic cholecystitis is an uncommon form of acute cholecystitis which can be
rapidly fatal. It may be hard to detect as it frequently presents with symptoms found
in other, more common diagnoses. Here, we report the case of a 63-year-old man recently
started on anticoagulation who initially presented with suspicion for pneumonia versus
pulmonary embolism, but was found to have hemorrhagic cholecystitis instead.
Case Report
A 63-year-old man with a deep vein thrombosis diagnosed 5 days prior, presented with
fever, tachycardia, and nausea/vomiting. The patient had a past medical history of
cerebrovascular accident 9 years prior with residual left-sided weakness, epilepsy,
hypertension, and hyperlipidemia. The patient denied smoking, alcohol, or drug use.
The patient was transferred from an acute rehab center where a left lower extremity
deep vein thrombosis had been found on ultrasound 5 days prior, and anticoagulation
started. He was bridged from enoxaparin to oral warfarin. Initial laboratories were
as follows: white blood cell count 12,600/mL3, hemoglobin 14.0 g/dL, platelet 302,000/mL3, total bilirubin 2.1 mg/dL, aspartate aminotransferase 68 IU/L, alanine aminotransferase
56 IU/L, prothrombin time 20.3 seconds, international normalized ratio (INR) 1.95,
albumin 3.1, fibrin degradation products > 10 and < 40, blood urea nitrogen 14, and
serum creatinine 0.83. Initial physical exam showed left lower lobe decreased breath
sounds, and an unremarkable abdominal exam. At that time, the patient denied any pain,
current nausea/vomiting, shortness of breath, constipation, or diarrhea. Chest X-ray
suggested consolidation in the left lower lobe. The decision was made to admit the
patient as he met the criteria for systemic inflammatory response syndrome, possibly
due to a left lower lobe pneumonia versus pulmonary embolism. For further evaluation,
a chest computed tomography (CT) scan was ordered. While the CT scan showed no evidence
of pulmonary embolism or pneumonia, it did incidentally reveal a distended appearance
to the gallbladder ([Fig. 1]). Ultrasound showed distended gallbladder with a heterogeneous mixture of intermediate
and low echogenic material with no evidence of stones, which was concerning for possible
pus or hemorrhage. Liver was of normal size and echogenicity. Patient was started
on ceftazidime, clindamycin, and vancomycin empirically for systemic inflammatory
response syndrome/sepsis. The patient was initially ruled out as a surgical candidate
due to his elevated INR, and given his extensive deep vein thrombosis, it was felt
that the risk of stopping anticoagulation outweighed the benefits and he was recommended
for interventional radiology (IR)-guided cholecystostomy. Repeat physical exam on
hospital day #2 revealed a firm, tender right upper quadrant of the abdomen, with
all other quadrants being soft and nontender. The patient's INR spiked to 6.28 on
hospital day #2 and his hemoglobin dropped to 9.8 g/dL. This elevation of his INR
was attributed to his continued anticoagulation, which was subsequently discontinued.
INR on hospital day #3 was 4.53, and 4.94 on hospital day #4, at which point vitamin
K and fresh frozen plasma were administered. INR improved to 1.69 on hospital day
#5. IR-guided cholecystostomy was attempted on hospital day #4. The decision to proceed
with an IR-guided approach had been made earlier as it was felt he was at high risk
for surgery and septic. However, there was an organized clot with no drainable material
and subsequently no drain left in place. An inferior vena cava filter was placed on
hospital day #8. The family and patient had also up to this point refused surgery
due to his history of stroke, do not resuscitate/do not intubate status, and their
perceived risk of surgery. However, they eventually agreed to have surgery. On hospital
day #11, laparoscopic cholecystectomy was performed, and revealed dense adhesions
surrounding the gallbladder including the omentum and bowel. These adhesions were
taken down to reveal a very large distended gallbladder with areas of necrosis and
perforation. The contents of the gallbladder contained approximately 1,000 cubic centimeters
of old clot which had perforated near the infundibulum with clot extending out into
Morison's pouch and the right upper quadrant causing dense adhesions to the liver.
The gallbladder was freed from these adhesions and the clot was removed. The gallbladder
was dissected and freed from surrounding adhesions. The cystic duct was secured with
a “PDS Endoloop” made by Ethicon. During the course of the operation, patient experienced
significant bleeding and required four units of packed red blood cells. The operation
was converted to an open cholecystectomy to obtain hemostasis, and a Jackson-Pratt
drain was left in place. Pathology of the gallbladder specimen showed extensive hemorrhage,
acute inflammation, and necrosis. Pathology of a liver specimen showed moderate fibrosis,
which was suggestive of cirrhosis. However, hepatitis serology was all negative, and
ultrasound of the liver showed a liver of normal size and echogenicity. No other investigation
showed signs of chronic liver disease. Patient had one episode of bleeding from his
drain which required transfusion, but the remainder of his hospital course was otherwise
uneventful. The patient was considered too high risk for further anticoagulation and
was discharged with an inferior vena cava filter in place.
Fig. 1 Computed tomography (CT) of abdomen and pelvis showing distended hemorrhagic appearance
of gallbladder, no stones.
Discussion
Hemorrhagic cholecystitis is a rare disease but has been previously associated with
blunt trauma, anticoagulation, spontaneous hemorrhage in patients with cirrhosis and
renal failure, and angiosarcomas.[1]
[2]
[3] The presentation of hemorrhagic cholecystitis can be easily confused with a variety
of more common diagnoses. As with any form of acalculous cholecystitis, hemorrhagic
cholecystitis can present with leukocytosis and unexplained fever. Clots can form
inside the gallbladder, leading to gallbladder distention and right upper quadrant
pain, possibly leading to perforation into the abdomen. If this occurs, the patient
could present with symptoms of frank peritonitis. Blood could flow freely and enter
the bowel lumen, presenting with hematemesis or melena. Finally, it can present with
signs of obstructive jaundice.[4]
Initially, the patient in this case only presented with fever and leukocytosis. Given
his history and presentation, hemorrhagic cholecystitis was not suspected immediately.
The patient in this case did have hemorrhage into the gallbladder and out into the
immediate peritoneal cavity. However, he did not display any signs of peritonitis
likely due to the containment of the bleeding to just the right upper quadrant and
the gallbladder itself. The cystic duct was completely obstructed by clot formation,
preventing hemorrhage into the intestinal lumen. Consequently, our patient did not
experience any hematemesis or melena which would have signaled the presence of a hemorrhage.
His exam was also normal until hospital day #2, when his INR jumped significantly.
We believe that the starting of anticoagulation triggered his hemorrhage, which was
then exacerbated when his INR increased. At the time of discharge, there was no clear
explanation for why his INR had suddenly increased. Although we initially suspected
a previously unknown liver disease as a cause for his sudden increase in INR, none
of his laboratory work and imaging showed signs of significant cirrhosis. He was referred
to follow-up with outpatient hepatology for further evaluation.
Hemorrhagic cholecystitis is associated with high morbidity and mortality rates, particularly
when it is complicated by perforation, necrosis, and potentially massive hemorrhage.
Empiric antibiotic therapy should be initiated as secondary infection by enteric pathogens
is common in the setting of acute acalculous cholecystitis.[5] Definitive treatment for cholecystitis is typically a cholecystectomy, although
a percutaneous cholecystostomy may be performed for acute management in a patient
with significant comorbidities preventing a cholecystectomy. If necessary, a delayed
cholecystectomy can then be performed.[6]
[7] Percutaneous cholecystostomy is not indicated in the presence of gallbladder gangrene
or perforation, but this may be challenging to determine through imaging alone.[8]
In summary, hemorrhagic cholecystitis is a rare finding but its complications are
often fatal. Because its presentation may be similar to many other conditions, a high
index of suspicion is necessary for its diagnosis, particularly in the setting of
an acutely ill patient with other comorbidities or on anticoagulation. Timely diagnosis
is important to allow for early surgical management.
Conclusion
The above case presents a rare presentation of hemorrhagic cholecystitis secondary
to warfarin use for deep vein thrombosis treatment. Although rare, this disease entity
should be considered in patients presenting with abdominal pain who are on anticoagulation.
Early diagnosis and treatment can improve outcomes.
