A 40-year-old woman with a history of obesity, smoking and oral contraceptive use sustains minor knee injury and avoids her regular walking activity. Three days later, she complains of lightheadedness and progressive respiratory distress over a twelve hour period, and collapses upon arrival in the emergency room. Despite extensive resuscitative efforts she dies, and an autopsy is performed. The source of her terminal event is shown below.





What is the pathologic process responsible for her death?

A. Congestive heart failure
B. Mesenteric ischemia
C. Infection
D. Venous thrombosis
E. Hemorrhage





(Scroll down for the answer)






The diagnosis in this case is pulmonary thromboembolism (Answer D). Pulmonary thromboemboli occur when blood in the deep veins of the legs forms a thrombus (blood clot), and then pieces of that clot break off and travel through the venous system. Once a chunk of clot starts traveling it also becomes an embolus. An embolus is just a traveling blob of stuff in a blood vessel – it can be made of fat, air bubbles, tumor, built-up cholesterol (from atherosclerosis), or as in this case, a thrombus. That’s why we call it a thromboembolus, and it is the most common type of embolus.

After forming and breaking off, thromboemboli are carried up through the large veins and through the right side of the heart before hitting the end of the road by getting lodged in the pulmonary arteries of the lungs, where they may straddle the branching point of the left and right main arteries (called a saddle embolus), or may go further down, even breaking off into a “shower” of smaller emboli in the smaller arterial branches. The patient in this case had large thromboemboli in the main arteries of both lungs, as well as a number of smaller fragments in the lower lobes (as seen in the picture).

A key histologic feature of a thrombus are the “lines of Zahn,” which are very pretty alternating stripes of fibrin and red blood cell layers. These stripes form when the blood is flowing by and forming the thrombus layer by layer, and they tell us that the clot happened while the patient was still alive, unlike thrombi which form after death, and are a boring solid color.

What makes a thrombus form? There are many reasons, and a detailed discussion could go on for hundreds of pages, but the key features which predispose to thrombosis were neatly summarized back in the 1800’s by Rudolph Virchow, the “Father of Modern Pathology”. Virchow described three main conditions that make a thrombus likely to happen:

  1. Endothelial injury of the blood vessels. This can happen in many disease states, including infection and hypertension. Damage to the endothelial cells activates a variety of factors which promote the clotting of platelets.
  2. Changes in blood flow. Blood that is moving slowly or stopped, or that has increased turbulence (as can happen with atherosclerotic plaques, if you imagine the flow of blood being similar to turbulent water over rocks in a stream) is more likely to clot and to form a thrombus.
  3. Hypercoagulability. This category, loosely defined, includes anything that predisposes a patient to thrombus formation. A whole bunch of things fall into this category, from genetic factors, to certain medications (oral contraceptives can increase risk, especially in combination with smoking and advancing age), to sedentary lifestyle.

Sometimes the thrombi form and resolve on their own without breaking off, and sometimes if they are small they never cause clinical symptoms even when they embolize. But if they are big enough, or get stuck in a key location, they can be rapidly deadly.

* A huge thanks to Michelle Stoffel, MD PhD, PGY2 Pathology Resident at the University of Wisconsin, for this great case and wonderful post!

If you liked this case, here are more unknown cases to check out:

  • Case 1: 20-year-old male who died suddenly
  • Case 2: 72-year-old male with right calf mass
  • Case 3: 67-year-old female with pancytopenia
  • Case 4: 59-year-old male with severe headaches
  • Case 5: 38-year-old female with deep venous thrombi
  • Case 6: 13-year-old male with cerebellar mass
  • Case 7: 45-year-old male with pulmonary emphysema
  • Case 8: 38-year-old male with AIDS and headaches
  • Case 9: 25-year-old male with arm mass
  • Case 10: 57-year-old male with fatigue and left upper quadrant heaviness
  • Case 11: 62-year-old male with hepatosplenomegaly, skin lesions and cardiomyopathy
  • Case 12: 16-month-old infant with failure to thrive
  • Case 13: 36-year-old female with painless lower leg nodule
  • Case 14: 58-year-old female with several-year history of pelvic pain
  • Case 15: 52-year-old male with abdominal pain and bloody diarrhea
  • Case 16: 42-year-old female with tinnitus, hearing loss, and a mass at the cerebellopontine angle
  • Case 17: 52-year-old male with HIV with profuse, watery diarrhea
  • Case 18: 44-year-old male with history of progressive weakness and visual changes
  • Case 19: 20-year-old male with large, deep thigh mass
  • Case 20: 60-year-old male with multiple lung nodules
  • Case 21: 3-year-old boy with 7 cm abdominal mass
  • Case 22: 15-year-old male with large thigh mass
  • Case 23: 7-year-old male with headache, vomiting and gait ataxia
  • Case 24: 16-year-old male with a nagging cough
  • Case 25: 30-year-old male with deep thigh mass
  • Case 26: 48-year-old female with persistent headaches