Jake Hardie’s* head was pounding. He showed up at his local emergency room complaining of a splitting headache, emesis and hematuria. At 29, Jake was an ill-looking, pale young man. He told the ER staff that he had been plagued by persistent headaches for the past three months. However, the headaches had worsened over the previous week, complete with several episodes of vomiting and hematuria.

The ER staff treated Mr. Hardie with intravenous fluids and pain medications, which alleviated his headache. He was then sent home.

We Get a Look
The next day, Mr. Hardie’s headache returned and he came to the emergency department at the University of Iowa. In addition to the headaches, his concerns included paresthesias and a new-onset “blind spot” in his left eye. His medical history was significant for hypertension treated with amlodipine (Lotrel, Norvasc) and losartan (Cozaar). He had neither a personal nor a family history of ophthalmic problems.

On examination, his BCVA was 20/20 in both eyes. His pupils were equal and reactive without a relative afferent pupillary defect. Ocular motility examination was normal. Confrontation visual field testing appeared normal in each eye; however, Amsler grid testing detected a small paracentral scotoma in his left eye. The slit-lamp exam was notable for bilateral vesicular and bandlike lesions with scalloped borders on the corneal endothelium consistent with posterior polymorphous dystrophy. The dilated exam revealed numerous large cotton-wool spots along the superior and inferior arcades in both eyes (Fig. 1), corresponding to the subjective visual field deficits. The optic discs appeared normal. Mr. Hardie’s blood pressure was 169/109, which was in his reported “normal” range.

Caption: Fig. 1: The dilated exam found numerous cotton-wool spots in both eyes.  

Testing Tells the Story
Cotton-wool spots in a patient with uncontrolled hypertension are not an unusual finding. However, Mr. Hardie was very ill with poorly controlled hypertension, worsening headache, paresthesias and a recent history of hematuria.

We requested a complete blood count (CBC) with platelets and a differential as well as an electrolyte panel and urinalysis. The findings were as follows: Mr. Hardie’s platelet count was low at 32, while his hemoglobin was 14.1 grams per deciliter and thus within the normal range. As for his electrolyte panel, both creatinine and blood urea nitrogen were slightly high, at 1.6 milligrams per dL and 26 mg/dL, respectively. A peripheral blood smear revealed 1+ schistocytes (fragmented red blood cells). His lactate dehydrogenase level was high at 752 international units per liter. Urinalysis indicated 3+ hematuria and proteinuria. Fibrinogen and fibrinogen degradation products were normal (making disseminated intravascular coagulation an unlikely diagnosis).

Mr. Hardie was admitted and initiated on plasmapheresis. Two days after his admission, his platelet count continued to decrease to 13 and his hemoglobin dropped to 9 g/dL; however, both began to rebound after several days of therapy. Moreover, his headaches improved, his blood pressure was controlled and his perception of the visual field deficit diminished.

After seven days in the hospital, Mr. Hardie was discharged; when he returned for a follow-up exam, his hemoglobin, platelets and renal function were normal.

Too Close for Comfort
Although cotton-wool spots are a nonspecific finding, their presence in an ill, young patient should elicit a thorough medical evaluation.

Given the clinical presentation, our patient was diagnosed with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). Although TTP and HUS were once thought to be separate pathologic entities, it is now felt that they represent a spectrum of a single disorder. TTP-HUS presents as a thrombocytopenia and microangiopathic hemolytic anemia associated with thrombi composed primarily of platelets in affected organs. Patients may present with thrombocytopenia, microangiopathic hemolytic anemia, neurologic signs and symptoms (such as headache, vision changes and paresthesias), renal insufficiency and fever.

TTP-HUS is a deadly disorder with mortality rates over 90 percent in untreated patients. Plasma exchange with fresh frozen plasma is the treatment of choice and reduces the mortality rate to below 50 percent.¹ Patient survival is dependent on prompt diagnosis, hospital admission and treatment.

While Mr. Hardie came to our attention due to a new scotoma in his visual field from large cotton-wool spots, other ophthalmic manifestations in patients with TTP-HUS include serous macular detachments, choriocapillaris occlusion due to fibrin-platelet thrombi, retinal or vitreous hemorrhages, optic disc edema, neovascularization of the disc and central retinal vein occlusion.^2-5

Rare but Deadly
Cotton-wool spots can be a sign of serious systemic disease and warrant further evaluation in certain clinical scenarios. Initial testing should include blood pressure measurement, a CBC with platelets and a differential and an evaluation for diabetes.

In this case, a life-threatening illness was discovered. Although TTP-HUS is rare, it should be considered in patients who present with vaso-occlusive disease of the retina, neurologic decline, renal insufficiency and hematologic abnormalities such as thrombocytopenia.

Evaluation and management of TTP-HUS should be done in conjunction with internists and hematologists. Because the mortality rate of this condition can be exceedingly high without prompt intervention, ophthalmologists may play a key role in its timely diagnosis and thus improve the likelihood of patient survival.
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* Patient name is fictitious.
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1 Rock, G. A. et al. N Engl J Med 1991;325(6): 393–397.
2 Patel, M. R. et al. Arch Ophthalmol 2001; 119(9):1388–1389.
3 Melton, R. C. and R. F. Spaide. Retina 1996; 16(1):78–80.
4 Black, R. L. and J. E. Terry. J Am Optom Assoc 1991;62(6):457–461.
5 Jellie, H. G. et al. Can J Ophthalmol 1984; 19(6):279–283.
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Dr. Doan is a third-year ophthalmology resident at the University of Iowa; Dr. Kitchens is a fellow and chief ophthalmology resident at the University of Miami; and Dr. Farjo is in private practice at Davis Duehr Dean in Madison, Wisc.

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Differential Diagnosis for Cotton-Wool Spots