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Chapter 69 Essential Thrombocythemia 1111

TABLE Frequency of Neurologic Complaints Associated With
69.1 Essential Thrombocythemia
Manifestations Patients (n)
Headache 13
Paresthesias 10
Posterior cerebral circulatory ischemia 9
Anterior cerebral circulatory ischemia 6
Visual disturbances 6
Epileptic seizures 2
Total number of patients 33
Data from Jabaily J, Iland HJ, Laszlo J, et al: Neurologic manifestations of
essential thrombocythemia. Ann Intern Med 99:513, 1983.

Fig. 69.3 GANGRENE OF THE TOE IN A PATIENT WITH ESSEN-
was the most common, with paresthesias of the extremities a close TIAL THROMBOCYTHEMIA.
second. There was an extremely high incidence of transient ischemic
attacks involving both the anterior and posterior cerebral circulation.
These attacks have a sudden onset, last for a few moments, and are result in the development of nephrotic syndrome. Splanchnic vein
frequently associated with a pulsatile headache. The various symp- thromboses occur predominantly in young women with ET. Patients
toms occur sequentially rather than simultaneously and can be pre- with this complication are at a high risk of having a poor survival
ceded or followed by erythromelalgia. Transient neurologic symptoms because of hepatic failure or transformation to MF or acute leukemia.
include unsteadiness, dysarthria, dysphoria, motor hemiparesis, It is worth noting that a fraction of patients with idiopathic splanch-
scintillating scotomas, amaurosis fugax, vertigo, dizziness, migraine- nic vein thrombosis may present with normal or near-normal blood
like symptoms, syncope, and seizures. The syndrome is caused by counts but have an occult MPN based on genetic or histopathologic
platelet-mediated ischemia and thrombosis in end-arterial microvas- abnormalities. In a review of more than 800 patients with splanchnic
culature. It is not unusual for these symptoms to eventually progress vein thrombosis without a diagnosis of an MPN, a mean of 32.7%
to definitive cerebral infarcts. of patients were JAK2V617F positive. More than 50% of these
Microvascular circulatory insufficiency involving the toes and patients were subsequently diagnosed with an MPN. In addition,
fingers is frequent. Such events can lead to digital pain, enhanced by 2.6% of patients with a cerebral sinus and vein thrombosis were also
warmth; distal-extremity gangrene; and classic erythromelalgia. The shown to be JAK2V617F positive. These studies suggest that all cases
term erythromelalgia refers to a syndrome of redness and burning pain of splanchnic vein thrombosis and likely cerebral sinus and vein
in the extremities. Erythromelalgia, which is characterized by a thrombosis should be tested for JAK2V617F to identify patients with
burning pain and a dusky congestion of swollen extremities, is usually an occult MPN. Occasional patients with idiopathic splanchnic vein
preceded by paresthesias. Cold provides relief to these symptoms, and thromboses with CALR mutations have been reported. In those
heat intensifies the symptoms. Patients prefer to wear shoes or slippers patients who are JAK2V617F negative it is prudent to also search for
without socks and elevate their feet. These symptoms may progress CALR mutations. Priapism is a rare complication of ET, presumably
in intensity and lead to peeling of the skin in affected appendages or caused by platelet sludging in the corpus cavernosum. In addition,
affected toes or fingers, which then may become cold and ischemic myocardial ischemia and infarction associated with normal coronary
with a dark purplish tinge. Erythromelalgia symptoms are asym- angiograms has been reported in patients with ET, as has a high
metric in the majority of cases. Symptoms related to coronary artery incidence of anginal symptoms. Acute renal failure has been observed
disease or transient ischemic attacks may precede or accompany the after thrombosis of renal arteries and veins in patients with ET.
onset of erythromelalgia. Occasionally, hemorrhagic episodes may Pulmonary hypertension secondary to alveolar capillary plugging
occur in patients experiencing erythromelalgia. Platelet counts in by platelets and megakaryocytes has also been reported in patients
9
patients with erythromelalgia are frequently below 1000 × 10 /L. The with ET.
relief of such pain for several days after a single dose of aspirin is Hemorrhagic events occur in 3–11% of patients with ET; the
diagnostic of erythromelalgia. The specific microvascular syndrome primary site of bleeding is the gastrointestinal tract. Other sites of
of erythromelalgia is readily explained by platelet-mediated arteriolar bleeding may be the skin, eyes, urinary tract, gums, tooth sockets
inflammation and occlusive thrombosis leading to acrocyanosis and (after extraction), joints, or brain. A high incidence of bleeding epi-
even gangrene. Skin biopsies from affected sites reveal arteriolar sodes during the immediate postoperative period is likely caused by
lesions without involvement of venules, capillaries, or nerves. The postsurgical thrombocytosis and the development of acquired von
arteriolar endothelial cells are swollen and the vessel walls thickened Willebrand syndrome or the use of antithrombotic prophylaxis
by cellular swelling and deposition of intracellular material. Com- therapy. Bleeding is closely correlated with a significant increase in
9
pared with atherosclerotic circulatory obstruction, arterial pulses in platelet counts in excess of 1500 × 10 /L and is associated with
patients with erythromelalgia remain normal. Other patients develop pseudohyperkalemia. It is important to emphasize that individual
platelet-mediated acral inflammation and arterial thrombosis, which patients can experience both thrombotic and hemorrhagic episodes.
can progress to ischemic acrocyanosis or necrosis of fingers, toes, and, Appreciation of the risk of developing thrombohemorrhagic
rarely, the tip of the nose (Fig. 69.3). events in asymptomatic patients with ET who are younger than 40
Although thrombosis of the microvasculature is generally more years of age is imprecise at best. Such patients are thought to be at a
frequent, thrombosis of large veins and arteries in patients with ET low risk of developing thrombotic episodes unless they have experi-
still occurs commonly. Patient symptoms frequently occur related to enced a prior thrombotic episode or have associated cardiovascular
large-vessel thrombosis, mostly in the arteries of the legs, the coronary risk factors. The most common thrombotic complications include
arteries, and the renal arteries. Involvement of the carotid, mesenteric, migraine headaches in 20% and erythromelalgia in 5% of the
and subclavian arteries is frequent, and patients characteristically have patients. Life-threatening hemorrhagic episodes are rare. The degree
venous thromboses involving the splenic vein, hepatic veins, or veins of leukocytosis has been suggested by some investigators to be useful
of the legs and pelvis. Unexplained thrombosis of the hepatic veins in discriminating between young patients with a low or high risk to
leads to Budd-Chiari syndrome, and thrombosis of the renal vein can develop a thrombotic episode.