Ophthalmologic Manifestations of Thrombotic Thrombocytopenic Purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz disease, is an uncommon hematologic disease characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia with purpura, acute kidney injury (AKI), neurologic abnormalities with fluctuating mental status, and fever. Though these are the classic symptoms, this article will focus on ocular manifestations, which have been reported to be present in 14-20% of cases.
TTP is generally believed to be caused by a decrease in activity of A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13). This can occur secondary to a variety of genetic mutations that affect ADAMTS13 activity or, in cases of acquired TTP, autoimmune inhibitors of ADAMTS13 are the most common culprit. Low levels of ADAMTS13 have also been seen in sepsis, disseminated intravascular coagulopathy (DIC), liver disease, and plasmodium falciparum infection. TTP has also been reported to be triggered by certain medications, including tyrosine kinase inhibitors.
ADAMTS13 is a protease that cleaves large multimers of von Willebrand factor. When these multimers are not cleaved properly, they build up in the bloodstream in comparison to normal von Willebrand factor. This leads to platelet-rich microthrombus formation and mechanical hemolysis. This can disrupt the blood supply to any organ, including the retina if the choroid or retinal vasculature is involved. Involvement of cranial nerves has also been reported, thought to be secondary to thrombotic ischemia. Due to concomitant kidney failure, hypertensive emergency (i.e., malignant hypertension) may accompany TTP, which can lead to papilledema.
TTP is diagnosed by the presence of microangiopathic hemolytic anemia (MAHA) in conjunction with thrombocytopenic purpura (the two major criteria). ADAMTS13 activity can support the diagnosis, but if the two major criteria are present, treatment should not be withheld waiting for the results. When ocular signs or symptoms are present, physicians should take a thorough history to ensure the patient does not have other systemic symptoms that may indicate a systemic disorder such as TTP. If other pieces of the classic pentad are present, TTP along with other unifying systemic causes should be investigated.
Ophthalmologic signs of TTP may be retinal including hemorrhage, arterial or venous occlusion, or serous retinal detachment. Anisocoria or ocular misalignment may be present if cranial nerves are involved. Papilledema (optic disc edema due to increased intracranial pressure) as well as hypertensive choroidopathy, retinopathy, and optic neuropathy have also been reported.
Symptoms of TTP can vary depending on the affected organ. Ocular symptoms may include acute loss of vision due to retinal pathology, diplopia if cranial nerves are affected, or blurring of vision secondary to papilledema.
Plasma exchange is the mainstay of treatment for acquired TTP.
Plasma exchange is often successful as levels of ADAMTS autoimmune inhibitors tend to decrease over time.
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