History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors are history of exposure to radiation and industrial solvents.
symptoms of anaemia (fatigue, weakness, dyspnoea, palpitations)
In patients with primary myelofibrosis (PMF), the malignant haematopoietic stem cell clone impairs haematopoiesis and subsequently causes anaemia, extramedullary haematopoiesis, and splenomegaly.
Splenomegaly also contributes to anaemia due to red cell sequestration and haemodilution.
Increased folate consumption from chronic myeloproliferation may lead to folate deficiency, which may contribute to anaemia.
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 haematopoietic stem cell clone impairs haematopoiesis and subsequently causes anaemia, extramedullary haematopoiesis, 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, generalised abdominal discomfort, and left upper quadrant discomfort. Splenic infarcts, perisplenitis, or subcapsular haematoma 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 haematopoiesis
In patients with primary myelofibrosis (PMF), the malignant haematopoietic stem cell clone impairs haematopoiesis and subsequently causes anaemia, extramedullary haematopoiesis, and splenomegaly.
Extramedullary haematopoiesis is a hallmark of PMF.
Depending on the organ or site of involvement, extramedullary haematopoiesis may result in haemorrhage (gastrointestinal tract haemorrhage, cutaneous petechiae, haemoptysis, haematuria), 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, oesophageal 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 non-elicited symptom.
bleeding
Bleeding can occur due to extramedullary haematopoiesis 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 haematological malignancies, including primary myelofibrosis.[9]
weak
age ≥65 years
cytogenetic abnormalities
Somatic driver mutations in the Janus kinase 2 (JAK2), myeloproliferative leukaemia virus oncogene (MPL), or calreticulin (CALR) genes are commonly present in patients with primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs, e.g., polycythaemia vera, essential thrombocythaemia).[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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