Page 1244 - Hematology_ Basic Principles and Practice ( PDFDrive )

1090 Part VII Hematologic Malignancies

factor V Leiden, or protein C deficiency. The JAK2V617F mutation particularly susceptible to thrombosis. Cerebrovascular thrombosis
has been reported in 32.7% patients of 831 patients with an idio- occurs more often in PV patients than in the general population.
pathic splanchnic vein thrombosis. The mutation was present in 49% Symptoms caused by intermittent carotid or vertebral basilar artery
of patients at diagnosis of the idiopathic form of splanchnic vein insufficiency (or both) occur so frequently in PV that it is suggested
thrombosis, of which 60% were diagnosed as having a coexisting that every patient with focal cerebrovascular insufficiency should at
MPN; more than 52% of the remaining patients went on to develop least have a complete blood count test to exclude the diagnosis of an
an MPN after a median of 49 months. JAK2V617F was detected in underlying MPN.
45% of patients with BCS, and at least in one series, neither exon Thrombosis of the dural sinus or cerebral veins (CVT) is an
12 JAK2 mutations nor MPL mutations were observed. Furthermore, uncommon form of stroke, usually affecting young individuals. CVT
additional patients (6.9%) who have idiopathic splanchnic vein represents about 0.5–1% of all strokes. While 3.8% of CVT patients
thrombosis have a BM histopathologic picture diagnostic of an MPN are diagnosed with MPNs, 0.4% of MPN patients have a CVT
but are JAK2V617F negative. The diagnostic value of low serum EPO during their clinical course. Headache, generally indicative of an
level in BCS has been questioned because elevated levels have been increase in intracranial pressure, is the most common symptom in
attributed in JAK2V617F-positive patients with necrotic liver tissue. CVT. Clinical manifestations of CVT may also depend on the loca-
There are fulminant, acute, subacute, and chronic forms of BCS. tion of the thrombosis. The superior sagittal sinus is most commonly
These clinical manifestations depend on the extent and rapidity of involved, which may lead to headache, increased intracranial pressure,
hepatic vein occlusion and the development of venous collaterals to and papilledema. A motor deficit, sometimes with seizures, can also
decompress the venous sinusoids. One should always consider a occur. Scalp edema and dilated scalp veins may be seen on examina-
diagnosis of BCS in any patient with an MPN with ascites, upper tion. For lateral sinus thromboses, symptoms related to an underlying
abdominal pain, and liver function abnormalities. This syndrome is condition (middle-ear infection) may be noted, including constitu-
characterized by hepatosplenomegaly, ascites, edema of the peripheral tional symptoms, fever, and ear discharge. Pain in the ear or mastoid
extremities, and distention of superficial abdominal veins caused by region and headache are typical. Hemianopia, contralateral weakness,
resultant portal hypertension. Routine biochemical determinations of and aphasia may sometimes be seen owing to cortical involvement.
hepatocellular function and injury are frequently of little diagnostic Approximately 16% of patients with CVT have thrombosis of the
value in patients with suspected BCS. Doppler ultrasonography is the deep cerebral venous system (internal cerebral vein, vein of Galen,
best tool for screening patients for BCS. This test has a sensitivity and straight sinus), which can lead to thalamic or basal ganglial
and specificity of 85%. Characteristic findings include an absence of infarction. Cavernous sinus thrombosis is usually associated with a
flow in the hepatic veins or nonvisualization of the hepatic vein. primary infectious etiology involving a focus in the face, throat,
Contrast-enhanced computed tomography scanning and magnetic mouth, ear, or sinuses. Aseptic cavernous sinus thrombosis is an
resonance imaging (MRI) are useful in better defining the hepatic extremely rare phenomenon that has been reported in patients with
venous anatomy. Hepatic venous and inferior vena caval catheteriza- PV. These patients present with monocular blindness and the char-
tion is a key diagnostic procedure indicating the sites of venous acteristic features of ipsilateral cavernous sinus thrombosis, and only
obstruction. The diagnosis can be definitively made by a spider web retrospectively is the diagnosis of PV made. Therefore, patients found
pattern on hepatic venography. Transjugular liver biopsy specimens to have this symptom complex who have no known infectious pre-
usually reveal intense congestion and cellular atrophy. disposing causes should be carefully evaluated to rule out this diag-
It has been emphasized that patients with PV can present with nosis. The most sensitive diagnostic technique is MRI in combination
portal or hepatic vein thrombosis with normal hemoglobin or hema- with magnetic resonance venography.
tocrit values. Such patients may have leukocytosis, thrombocytosis, Thrombosis of large-caliber arteries is a relatively rare event in PV
or splenomegaly. Screening for the JAK2 mutation should be system- patients, but there have been case reports of thromboses within the
atically carried out in such situations and may substitute for BM chambers of the heart, leading to refractory congestive heart failure
examinations in individuals who are JAK2V617F positive. In patients and acute aortic occlusion. Such catastrophic thrombotic events in
with an idiopathic form of splanchnic vein thrombosis but who are the heart or large vessels would suggest that cardiac catheterization
JAK2V617F negative, a BM aspirate and biopsy are recommended to be performed with some caution.
exclude the possibility of a JAK2V617F-negative MPN. Gastro- PV frequently manifests with symptoms caused by peripheral
intestinal bleeding or an increase in plasma volume that is a conse- vascular disease. In these cases, patients may first be seen by surgeons
quence of splenomegaly often accounts for the normal blood counts or dermatologists. Intense redness or cyanosis of the digits with or
in such patients with BCS. The factors operational in the PV patient without burning, classic erythromelalgia, digital ischemia with pal-
that lead to the development of hepatic vein thrombosis are believed pable pulses, or thrombophlebitis without another known cause may
to be multiple. Whereas splenomegaly causes increased portal blood be the presenting symptoms.
flow, extramedullary hematopoiesis within the hepatic sinusoids fre- Erythromelalgia is characterized by burning pain in the digits, an
quently obstructs hepatic blood flow, and JAK2V617F-positive objective sensation of increased temperature, and relief by cooling.
endothelial cells might affect adhesion to monocytes, leading to PV is the most common cause of erythromelalgia and is one of the
aggregation of blood elements. These processes are surely important few disorders in which digital ischemia with or without ulceration
contributory factors in addition to the other previously discussed risk may exist in the presence of palpable pulses. Other disorders that can
factors that lead to the development of thrombosis in this patient lead to this abnormality include embolism, trauma, cutaneous infarc-
population. tion, neuritis, infection, and various types of arteritis. Painful and
Neurologic abnormalities occur in almost 60–80% of untreated ulcerating toes and fingers have frequently been observed to be pre-
or poorly controlled PV patients and include TIAs, cerebral infarc- senting symptoms in patients with PV. The likelihood that arterial
tion, cerebral hemorrhage, fluctuating dementia, confusional states, insufficiency is the cause of such ulceration is quite small in patients
and choreic syndromes. PV associated chorea has been reported as a who have a palpable dorsalis pedis and posterior tibialis pulses; in this
presenting complaint, primarily in older females, which typically situation, the possibility of an underlying hematologic disorder such
involves the orolingual or appendicular musculature and often as PV should be entertained. Foot pain at rest is a distressing but not
resolves with phlebotomy or cytoreductive therapy. In addition, widely recognized symptom of PV. In patients with this complaint,
complaints of dizziness, paresthesias, visual disturbances, tinnitus, peripheral pulses are of normal character, and cutaneous circulation
and headaches have been attributed to the increased blood viscosity appears to be adequate. The pain is most severe at night, is dull in
and reduced cerebral blood flow caused by erythrocytosis. The nature, and occurs primarily in the feet or legs. These symptoms have
transient neurologic symptoms can also be the consequence of small been shown to be the results of platelet activation and aggregation in
infarcts in the region of the basal ganglia, which can be detected by vivo, which preferentially occur in arterioles. If untreated, erythro-
computed tomography. These small infarcts are known as lacunae and melalgia can progress to ischemic acrocyanosis or gangrene. Phle-
result from the occlusion of small penetrating arteries, which are botomy alone in PV does not improve erythromelalgia. These