Diagnosis

While a person may have certain signs and symptoms of myleofibrosis (MF), laboratory tests are needed to confirm the diagnosis. There is no one test that can diagnose a person as having MF; the diagnosis is based on findings from a bone marrow biopsy exam, blood cell counts and chemistry, and physical exam.

In people who have no symptoms, MF may be suspected when a routine medical checkup reveals an enlarged spleen and abnormal blood test results. However, a doctor will consider other conditions first to determine if “reactive myelofibrosis” is causing the patient’s disorder. Reactive myelofibrosis also results in scarring in the bone marrow, but unlike MF, it does not begin in the bone marrow. Instead, reactive myelofibrosis is a reaction to another problem in the body such as:

Infection
Autoimmune disorder
Other Chronic inflammatory conditions
Hairy cell leukemia or other lymphoid neoplasm

Medical History and Physical Examination

Evaluation of an individual with suspected MF should start with a detailed medical history and a physical examination.The medical history should include information about the patient’s

Cardiovascular risk factors
Past illnesses
Injuries
Treatments
Medications
History of thrombosis (the formation or presence of a blood clot inside a blood vessel) or hemorrhagic events (loss of blood from damaged blood vessels)
History of blood relatives—some illnesses run in families
Current symptoms

After the medical history, the doctor will conduct a physical examination. During the physical examination, the doctor may:

Listen to the patient's heart and lungs
Examine the patient's body for signs of disease
Check different organs of the body

Blood Tests

Complete Blood Count (CBC)

This test is used to measure the number red blood cells, white blood cells and platelets in a sample of blood. It also measures the amount of the iron-rich protein that carries oxygen in red blood cells (hemoglobin) and the percent of whole blood made up of red blood cells (hematocrit). People with MF often have abnormally low levels of red blood cells. White blood cell counts are usually higher than normal (called “leukocytosis”), but in some patients, the white blood cell counts may be lower than normal (called “leukopenia”). Platelet counts may be higher or lower than normal.

Peripheral Blood Smear

A procedure in which a sample of blood is viewed under a microscope. A pathologist examines the size, shape, and appearance of blood cells in the sample, and also checks for the presence of blast cells (immature blood cells). Blast cells are normally found in the bone marrow and are not typically found in the peripheral blood of healthy individuals. People with MF often have abnormal teardrop-shape red blood cells and immature blasts in the blood.

Comprehensive Metabolic Panel

This test measures the levels of certain substances released into the blood by organs and tissues in the body, including electrolytes (such as sodium, potassium and chloride), fats, proteins, glucose (sugar) and enzymes. This provides important information about how well a person’s kidneys, liver and other organs are working. Individuals with MF often have elevated serum levels of uric acid, lactic dehydrogenase (LDH), alkaline phosphatase and bilirubin. The doctor may also check the levels of serum erythropoietin level, serum ferritin, iron, and total iron binding capacity.

Bone Marrow Tests

Your doctor tests your bone marrow to help confirm a diagnosis. Bone marrow testing involves two steps usually performed at the same time in a doctor's office or a hospital:

A bone marrow aspiration to remove a liquid marrow sample
A bone marrow biopsy to remove a small amount of bone filled with marrow

A pathologist studies the samples under the microscope and examines the chromosomes inside the cells. This is necessary to differentiate MF from other MPNs. Patients with MF have increased numbers of megakaryocytes that are also unusual in size and shape, and there is scarring of the bone marrow (fibrosis).

Molecular Testing

Molecular genetic tests are very sensitive tests that look for specific gene mutations. The 2016 World Health Organization diagnostic criteria now include molecular testing for JAK2, CALR, and MPL mutations for individuals suspected of having MF. If the patient does not have one of these mutations, the doctor may test for other mutations.

Imaging tests

Ultrasound tests may be used to determine the size of the spleen. Magnetic resonance imaging (MRI) tests may be used to identify changes in the bone marrow that indicate MF.

HLA Typing

HLA typing should be performed for patients who are candidates for an allogeneic stem cell transplantation. HLAs play an important role in the body’s immune response to foreign substances by helping the body distinguish its own cells from foreign cells. HLA matching is done prior to a donor stem cell transplantation to find out if tissues between the donor and the person receiving the transplant match.

Criteria for Diagnosing Primary Myelofibrosis

According to the 2016 World Health Organization criteria for diagnosing primary MF, a diagnosis of primary MF requires meeting all three major criteria and at least one minor criterion below.

Major Criteria

Proliferation of abnormal megakaryocytes accompanied by fibrosis in the bone marrow
Exclusion of other diseases defined by World Health Organization criteria, such as essential thrombocythemia, polycythemia vera, BCR-ABL1+ chronic myeloid leukemia, myelodysplastic syndromes or other myeloid neoplasms
Presence of JAK2, CALR, or MPL mutation or another clonal marker (gene mutation) such as genes ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1, or the absence of reactive myelofibrosis

Minor Criteria

Presence of at least one of the following, confirmed in two consecutive tests

Anemia not caused by another condition, or
White blood cell count greater than or equal to 11 × 10⁹/L
Palpable enlarged spleen, or
Lactate dehydrogenase (LDH) level above upper normal limits, or
Presence of immature blood cells in the peripheral blood (called "leukoerythroblastosis")