Here’s a nice boards – type question that requires you to put together some clinical and laboratory data to form a diagnosis, and then describe what the blood smear would look like.

A previously-healthy 32-year-old woman presents with recurrent headaches. She develops nausea, vomiting, weakness, and easy bruisability. Her laboratory values are as follows:

Hgb = 6.9
MCV = 80
Plt = 30,000
WBC=15,000

She is immediately admitted to the hospital. Over a two day period, she becomes lethargic, and lapses into a coma. A peripheral blood smear is most likely to show which of the following?

A. Macrocytes
B. Spherocytes
C. Schistocytes
D. Sickle cells
E. Target cells

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This question describes a patient with marked anemia and thrombocytopenia (but the WBC is normal – even above normal – so you can rule out the causes of pancytopenia). Her clinical symptoms include various non-specific findings, like nausea and vomiting, but also the specific finding of neurologic deficits.

Her symptoms and laboratory values are consistent with TTP (thrombotic thrombocytopenic purpura), which is a disorder that’s part of a group of disorders called “thrombotic microangiopathies.” Thrombotic microangiopathies are a group of syndromes, including TTP and HUS, in which something triggers platelet activation, and the patient ends up with thrombi all over the place – with resultant thrombocytopenia (the patient is using the platelets up in making the thrombi) and microangiopathic hemolytic anemia (red cells are getting snagged on the fibrin strands as they go through the thrombi-laden vessels).

In TTP, the “something” that triggers platelet activation is abnormal von Willebrand factor. It turns out that normally, when von Willebrand factor is released into the circulation, it’s in a big, long multimer (called “unusually large vWF.” In this state, it causes platelet aggregation! But we have an enzyme called ADAMTS13 that cleaves unusually large vWF into smaller, less active pieces, which work well (but not too well).

Patients with TTP lack this enzyme (either they’re making antibodies to it, or they are missing it from birth) – so they have this unusually large vWF floating around, which traps platelets and causes thrombi.

The symptoms in TTP are usually described as a pentad: 1) hematuria and jaundice (from the microangiopathic hemolytic anemia), 2) bleeding and bruising (from the thrombocytopenia), 3) fever (who knows why), 4) bizarre behavior or neurologic deficits (from thrombi in the brain), and 5) decreased urine output (from thrombi in the kidneys leading to kidney failure). In reality, not all patients have all of the symptoms – so you don’t need to have all 5 by any means to diagnose it. Treatment depends on whether it’s acquired or hereditary. Acquired cases tend to be more severe for some reason, and the treatment involves daily plasmapheresis (to get rid of the antibodies to ADAMTS13). The hereditary cases are usually treated with plasma infusions every three weeks or so (to replace the missing enzyme).

So: the answer to the question is C, schistocytes. Schistocytes are a special type of fragmented red cells (they are small, with pointy outlines, and no central pallor) that are characteristic of microangiopathic hemolytic anemia (you can see a whole bunch of these in the image above!). Sometimes you can see things that look sort of similar to schistocytes in other anemias – such as the bite cells you see in glucose 6 phosphate dehydrogenase deficiency. But any time you see something you even think might be a schistocyte, you need to explore the possibility of a microangiopathic hemolytic process, because some of the things that cause microangiopathic hemolytic anemia are very dangerous (like TTP!), and you would not want to miss them.

Note: the very nice image of a microangiopathic hemolytic anemia (see all the schistocytes?) was taken by Ed Uthman and can be found at http://commons.wikimedia.org/wiki/File:DIC_With_Microangiopathic_Hemolytic_Anemia_(301920983).jpg.