A 71-Year-Old Woman With Anemia Thrombocytopenia and Coagulopathy

A 71-year–old woman with a medical history of Graves’ disease presented to the emergency department after sustaining a mechanical fall with subsequent right-sided hip pain. She denied a head strike, loss of consciousness, bleeding, bruising, weakness, numbness, tingling, shortness of breath, and chest pain. There was no personal or family history of malignancy or known blood disorders.

On arrival, the patient was afebrile, normotensive, and tachycardic, with a heart rate of 140 beats per minute. Electrocardiogram and physical exam showed new-onset atrial fibrillation with rapid ventricular rate, which improved with use of intravenous diltiazem. She had decreased range of motion of her right hip, with X-rays and computed tomography (CT) revealing a comminuted right intertrochanteric fracture. Surgical repair was delayed due to the presence of coagulopathy and anemia of unknown origin. Her laboratory results are listed in the table below.

A peripheral blood smear (PBS) revealed normocytic, normochromic red blood cells (RBCs) with frequent stomatocytes and no schistocytes. Coagulation factor assays revealed factors II, V, VII, IX, and X activity below 50% (decreased), with elevated factor VIII activity of 275%. An initial CT of the chest, abdomen, and pelvis (with contrast) showed moderate anasarca but was negative for findings suggestive of cirrhosis, nodules, masses, or abscesses. A CT angiogram of the chest was negative for pulmonary embolism. The differential diagnosis for the patient’s normocytic anemia, thrombocytopenia, and coagulopathy included thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and liver disease including cirrhosis and congestive hepatopathy.

Given her ascites on presentation, lack of schistocytes on the PBS, and normal lactate dehydrogenase levels, the patient’s care team had a lower suspicion for thrombotic microangiopathies such as TTP or HUS. Her PLASMIC score was 4, which translates to a low probability of severe ADAMTS13 deficiency. Even though her fibrinogen was in the lower limit of normal, her normal factor VIII activity lowered the suspicion for DIC, which would have caused consumption and low levels of all coagulation factors, including factor VIII.

The team then opted to pursue further investigation of the patient’s suspected liver injury, which included an autoimmune workup. She was found to have positive anti-mitochondrial antibodies and was diagnosed with primary biliary cholangitis (PBC). A liver biopsy was not obtained; however, a repeat CT of her abdomen and pelvis with contrast showed findings supportive of early liver cirrhosis. She was started on ursodeoxycholic acid therapy (UDCA), with improvement in her hepatic function. She also required three doses of 10 mg of oral phytonadione, one unit of pre-pooled cryoprecipitate, three units of fresh-frozen plasma, and three units of packed RBCs for the management of her anemia and coagulopathy. Intramedullary nail insertion into her injured femur was eventually performed after medical optimization, with the patient subsequently discharged to a subacute rehabilitation facility.

PBC is a chronic cholestatic autoimmune disorder that primarily affects women aged 40 to 70. The disease progresses slowly and is characterized by cholestasis with elevated liver enzymes, anti-mitochondrial antibodies or primary biliary cholangitis-specific anti-nuclear antibodies (anti-SP100 or anti-GP210), and intrahepatic bile duct destruction on histology.¹,² Significant hepatocellular dysfunction and cholestatic environments can result in vitamin K malabsorption causing elevated prothrombin time due to decreased levels of vitamin K-dependent factors II, VII, IX, and X.³ UDCA is the current standard-of-care therapy for PBC and has been shown to significantly decrease mortality and liver-transplant risk.⁴ Patients with PBC should have regular screenings with bone mineral densitometry, liver ultrasound, thyroid-stimulating hormone, fat-soluble vitamins, and upper endoscopy due to association with osteopenia/osteoporosis, portal hypertension, hepatocellular carcinoma, and thyroid disease.⁵ This case emphasizes that PBC and other liver diseases should always be considered in the differential for cytopenias and coagulopathy.

1. Tanaka A, Ma X, Takahashi A, et al. Primary biliary cholangitis. Lancet. 2024;404(10457):1053-1066.
2. Rodríguez Lugo DA, Coronado Tovar JJ, Solano Villamarin GA, et al. Primary biliary cholangitis, part 1: state of the art, epidemiology, physiopathology and clinical manifestations. Rev Gastroenterol Peru. 2017;37(4):357-364.
3. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.
4. Harms MH, van Buuren HR, Corpechot C, et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J Hepatol. 2019;71(2):357-365.
5. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419.

Disclosure Statement: Drs. Brik and Thor indicated no relevant conflicts of interest.

Acknowledgment: This article was reviewed by Christopher Wanjiku, MD, and Alfred Lee, MD, PhD.