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PATIENT 
Ms. W is a 56-year-old woman who comes to the office complaining of poor appetite for several weeks and black, tarry stools with generalized weakness for 1 day.
She has no prior history of bleeding, and her 3 prior obstetric deliveries were uncomplicated. Her past history is notable for cirrhosis due to chronic hepatitis C. Her medications include spironolactone and metoprolol; additionally, she has been taking ibuprofen for back pain.
On examination, she is pale. Her blood pressure is 110/80 mm Hg, pulse is 112 bpm, RR is 16 breaths per minute, temperature is 37.1°C. Her conjunctivae are pale, mucous membranes moist, lungs clear, heart regular rhythm with a systolic flow murmur at the left sternal border, liver minimally enlarged with a nodular edge, spleen palpable 3 cm below the left costal margin in the anterior axillary line, and she has no edema. Digital rectal examination discloses black stool that is Hemoccult-positive.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
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Ms. W’s presentation suggests that she is having an upper GI bleed. In addition to the specific GI causes of upper GI bleeding discussed in Constructing a Differential Diagnosis, it is important to consider whether patients who are bleeding have an underlying platelet or coagulation disorder contributing to the bleeding. Ms. W does have cirrhosis with splenomegaly that could lead to thrombocytopenia due to splenic sequestration; however, the large volume of the bleeding suggests a coagulation factor disorder.
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The prothrombin time (PT) measures what is commonly called the “extrinsic” clotting pathway (Figure 8-2), wherein tissue factor from an injury activates factor VII, followed by activation of the coagulation cascade through the “common pathway” factors (factors V, X, II [prothrombin] and I [fibrinogen]). Because the source of tissue factor reagents used in the laboratory to trigger the cascade vary, the PT will vary among different laboratories when testing the same sample. To overcome this problem of PT results not being comparable from one laboratory to another, the international normalized ratio (INR) was developed, to standardize PT results based on a constant associated with each laboratory reagent. The INR, which is routinely reported along with the PT, allows the clinician to be confident that the data from different laboratories are comparable.
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