Case Presentation: A 48-year-old male with past medical history significant for hypertension, alcohol use disorder in remission, known grade I esophageal varices, and cirrhosis who presented with confusion and oral mucosa bleeding. He was tachycardic to 100 but had adequate blood pressure of 106/68. Initial labs remarkable for hemoglobin 9.4 g/dL and platelet count 1 x10^3/uL. EGD at admission showed esophageal varices and gastric ulcers neither with evidence of recent bleeding. He received empiric treatment for spontaneous bacterial peritonitis but blood culture and peritoneal fluid, both were negative. Despite receiving multiple platelet transfusions (>20), he continued to be profoundly thrombocytopenic with platelet count as low as 0k/uL. On several occasions, he received a unit of platelets without a subsequent increase in platelet count (Corrected Count Increment of 0). Immature platelet count was elevated at 29.1% (normal 1-7.9%). This prompted additional work up which included: included positive ANA (titer 1:1,280), positive platelet antibody IgG and IgM, positive H. pylori stool screen, negative hepatitis panel, negative nutritional panel, and normal ADAMSTS-13. Bone marrow biopsy was normal. Due to elevated platelet antibodies and ongoing destruction, the patient was treated for ITP. Initial treatments, specifically four doses of IVIG, eltrombopag, and dexamethasone, were without response. Due to refractory nature, the patient received romiplostim followed by rituximab. After receiving second doses of both medications the patient had platelet recover to 163×10^3/uL and was discharged with outpatient follow up with hematology.
Discussion: Thrombocytopenia affects a large number of hospitalized patients and has a broad differential. Differentiating underlying etiology is essential to effective management. Thrombocytopenia in liver disease has several underlying etiologies, specifically increased platelet sequestration within the spleen secondary to portal hypertension, decreased production of thrombopoietin, and in some cases such as viral or alcohol induced hepatitis bone marrow suppression. It is marked by decreased production of most anticoagulation factors except for von Willebrand factor which is produced by endothelial cells and often elevated in chronic liver disease. In patients undergoing low bleeding risk procedures, no platelet directed therapies should be given. In the event of a high-risk procedure and platelets less than 50,000, then thrombopoietin receptor agonists or platelet transfusion should be considered. There are no definitive diagnostic tests for ITP; it is a diagnosis of exclusion. Diagnosis can be confirmed by response to treatment. Steroids and IVIG are first line treatments. Second line treatments include thrombopoietin receptor agonists (romiplostim), and CD20 antagonists (rituximab). Patients are considered refractory to platelet transfusions when a 1-hour post-transfusion platelet count fails to increase after at least two separate transfusions. ITP will resolve 40-60% percent of time in adults.
Conclusions: Thrombocytopenia occurs frequently in hospitalized patients. Chronic liver disease can cause thrombocytopenia, but platelet transfusions should only be done prior to procedures with high bleeding risk. ITP is a less common diagnosis but should be considered in cases of profound thrombocytopenia when patients do not respond as expected. Understanding the underlying etiology is an essential skill as a hospitalist.