History and exam
Key diagnostic factors
common
history of radiation exposure
A high incidence of primary myelofibrosis (PMF) has been reported in patients exposed to thorium dioxide-based radiographic contrast medium (used in x-ray diagnostics in the 1930s to 1950s), and in survivors of the Hiroshima atomic bomb.[7][8]
PMF was observed at 15 to 20 times the expected incidence rate in Hiroshima survivors (on average 6 years after the incident).[8]
history of industrial solvents exposure
Benzene, toluene, and many other aromatic solvents have been associated with hematologic malignancies, including primary myelofibrosis.[9]
symptoms of anemia (fatigue, weakness, dyspnea, palpitations)
In patients with primary myelofibrosis (PMF), the malignant hematopoietic stem cell clone impairs hematopoiesis and subsequently causes anemia, extramedullary hematopoiesis, and splenomegaly.
Splenomegaly also contributes to anemia due to red cell sequestration and hemodilution.
Increased folate consumption from chronic myeloproliferation may lead to folate deficiency, which may contribute to anemia.
constitutional symptoms (weight loss, night sweats, low-grade fever, cachexia, fatigue, and pruritus)
High cell turnover rate in primary myelofibrosis results in a hypercatabolic state that manifests as constitutional symptoms.
splenomegaly ± hepatomegaly
In patients with primary myelofibrosis (PMF), the malignant hematopoietic stem cell clone impairs hematopoiesis and subsequently causes anemia, extramedullary hematopoiesis, and splenomegaly.
Splenomegaly is a hallmark of PMF and is present in virtually every patient with PMF at diagnosis. If absent, other causes of the clinical abnormalities should be considered. The degree of splenomegaly varies but is frequently substantial. Because the rate of splenic enlargement is variable, spleen size cannot be used as an indication of disease duration.[36]
Splenomegaly may result in early satiety, generalized abdominal discomfort, and left upper quadrant discomfort. Splenic infarcts, perisplenitis, or subcapsular hematoma may cause severe left upper quadrant or left shoulder pain.
Hepatomegaly may be present, invariably of a lesser extent than the splenomegaly (e.g., in 40% to 70% of patients).[37]
uncommon
features of extramedullary hematopoiesis
In patients with primary myelofibrosis (PMF), the malignant hematopoietic stem cell clone impairs hematopoiesis and subsequently causes anemia, extramedullary hematopoiesis, and splenomegaly.
Extramedullary hematopoiesis is a hallmark of PMF.
Depending on the organ or site of involvement, extramedullary hematopoiesis may result in hemorrhage (gastrointestinal tract hemorrhage, cutaneous petechiae, hemoptysis, hematuria), spinal cord compression, focal seizures, symptoms related to increased intracranial pressure, ascites, pericardial or pleural effusion, pulmonary hypertension, and respiratory failure.
Other diagnostic factors
uncommon
features of portal hypertension
May occur as a result of markedly increased splenoportal blood flow and decreased hepatic vascular compliance.
Portal hypertension can present without signs and symptoms, or manifest as ascites, esophageal and gastric varices, gastrointestinal bleeding, hepatic encephalopathy, and hepatic or portal vein thrombosis.
joint and bone pain
Manifestation of osteosclerosis or gout.
hearing loss
Due to otosclerosis. An interesting but often nonelicited symptom.
bleeding
Bleeding can occur due to extramedullary hematopoiesis and portal hypertension, and varies in severity from insignificant cutaneous petechiae to severe, life-threatening gastrointestinal bleeding. Platelet dysfunction, acquired factor V deficiency, thrombocytopenia, and disseminated intravascular coagulation may occur, contributing to bleeding.
infections
Caused by deficiencies in humoral immunity. Pneumonia is the most common infection.
Risk factors
strong
radiation exposure
High incidence of primary myelofibrosis (PMF) has been reported in patients exposed to thorium dioxide-based radiographic contrast medium (used in x-ray diagnostics in the 1930s to 1950s), and in survivors of the Hiroshima atomic bomb.[7][8]
PMF was observed at 15 to 20 times the expected incidence rate in Hiroshima survivors (on average 6 years after the incident).[8]
industrial solvents exposure
Benzene, toluene, and many other aromatic solvents have been associated with hematologic malignancies, including primary myelofibrosis.[9]
weak
age ≥65 years
cytogenetic abnormalities
Somatic driver mutations in the Janus kinase 2 (JAK2), myeloproliferative leukemia virus oncogene (MPL), or calreticulin (CALR) genes are commonly present in patients with primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs, e.g., polycythemia vera, essential thrombocythemia).[14][15]
The V617F mutation in the JAK2 gene (located on chromosome 9p) has been identified in approximately 58% of patients with PMF.[14][15]
Mutations in the MPL gene (on chromosome 1p) have been identified in approximately 8% of patients with PMF.[14][15]
Mutations in the CALR gene (on chromosome 19) have been identified in approximately 25% of patients with PMF.[15]
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