A 60-year-old woman is evaluated for occasional short-lived episodes of dizziness. She has had no headaches, blurry vision, muscle weakness, or syncope. The patient has no history of heart disease or stroke. She takes over-the-counter acetaminophen for low back pain and is a lifetime nonsmoker.
Blood pressure is 144/90 mm Hg and pulse is 82/min. There are no rashes. Neurologic examination shows no abnormalities.
Laboratory results are as follows:
Further workup shows the presence of the JAK2 V617F mutation.
Because of her current condition, this patient is at greatest risk for which of the following?

Question

A 60-year-old woman is evaluated for occasional short-lived episodes of dizziness.  She has had no headaches, blurry vision, muscle weakness, or syncope.  The patient has no history of heart disease or stroke.  She takes over-the-counter acetaminophen for low back pain and is a lifetime nonsmoker.
Blood pressure is 144/90 mm Hg and pulse is 82/min.  There are no rashes.  Neurologic examination shows no abnormalities.
Laboratory results are as follows:
 Further workup shows the presence of the JAK2 V617F mutation.
Because of her current condition, this patient is at greatest risk for which of the following?

Quizplus · Accepted Answer

This patient likely has essential thrombocythemia (ET), a chronic myeloproliferative disorder characterized by the clonal proliferation of platelets, leading to peripheral thrombocytosis (>450,000/mm³). Most cases are associated with a driver mutation to JAK2 V617F (60%-65%), CALR, or MPL. JAK2 mutations are also seen with polycythemia vera and primary myelofibrosis. Median age at diagnosis is 60. ³ Patients with ET are often asymptomatic but can develop vasomotor symptoms (eg, headaches, dizziness, chest pain), thrombosis (eg, deep venous thrombosis), and/or hemorrhage (eg, mucosal bleeding). Physical examination often reveals splenomegaly. Hemoglobin and leukocyte count are typically normal. The diagnosis is confirmed with bone marrow aspirate/biopsy and testing for typical driver mutations; other myeloproliferative disorders (eg, chronic myeloid leukemia) must be excluded. Patients at low risk for thrombosis (age <60, no previous thrombosis) are treated with aspirin; higher-risk patients usually receive hydroxyurea. Approximately 20% of patients with ET develop acquired von Willebrand disease (VWD). This is likely due to the consumption of large von Willebrand factor multimers secondary to platelet activation and proteolysis. Acquired VWD is associated with increased risk for skin and mucosal bleeding, which limit the ability to use aspirin for treatment. However, cytoreduction often resolves or improves the condition. (Choice B) Amyloidosis is characterized by the extracellular deposition of low-molecular-weight protein components and is typically seen with plasma cell dyscrasias (eg, multiple myeloma) or chronic inflammatory diseases (eg, rheumatoid arthritis). ET is not usually associated with amyloidosis. (Choice C) Disseminated intravascular coagulation is usually characterized by oozing from mucosal sites, thrombocytopenia, and prolonged coagulation times. Although DIC can be associated with malignancies, including acute promyelocytic leukemia, mucinous tumors (eg, pancreatic), and brain tumors, it is not usually linked to ET. (Choice D) Niacin deficiency (pellagra) is usually seen in alcoholics and those with chronic malnutrition. It is usually marked by the "4 Ds" of photosensitive dermatitis, diarrhea, and dementia, which can lead to death. Pellagra is not associated with ET. (Choice E) Tumor lysis syndrome usually occurs when a patient with a rapidly proliferative tumor undergoes cytotoxic chemotherapy. It is most common in those with non-Hodgkin lymphoma or acute lymphoblastic leukemia. ET is not associated with tumor lysis syndrome. Educational objective: Essential thrombocythemia is a clonal myeloproliferative disorder characterized by platelet counts >450,000/mm³. Patients may be asymptomatic or have vasomotor symptoms, thrombosis, and/or hemorrhage. Approximately 20% of patients develop acquired von Willebrand disease, which may limit the ability to use aspirin in treatment. ³ __________ References: How I treat the acquired von Willebrand syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/21540459) Management of essential thrombocythemia. (http://www.ncbi.nlm.nih.gov/pubmed/22160037)

A 60-Year-Old Woman Is Evaluated for Occasional Short-Lived Episodes of Dizziness