What happens in the bone marrow
The disease is based on an acquired mutation in a blood stem cell, most often in the JAK2, CALR or MPL genes. Modified megakaryocytes and other cells release growth factors that cause connective tissue cells to lay down collagen fibers. The bone marrow gradually turns into dense scar tissue, with no room for normal cells to grow. Hematopoiesis partially moves to the spleen and liver - this is called extramedullary hematopoiesis. It is this that explains the significant enlargement of the spleen and the appearance of immature and deformed cells in the blood.
- JAK2, CALR, or MPL mutations in a stem cell
- Excessive production of fibrosis growth factors
- Replacement of bone marrow with collagen fibers
- Hematopoiesis moves to the spleen and liver
- Drop-shaped red blood cells and immature forms appear in the smear
Symptoms
Some patients find out about the disease by chance through changes in a blood test. Over time, the manifestations of anemia increase: pallor, weakness, shortness of breath and palpitations during normal exercise. The enlarged spleen puts pressure on the stomach, which is why a person eats several spoonfuls of food and feels heaviness and pain on the left side, sometimes radiating to the shoulder. A separate group consists of general symptoms associated with inflammatory substances: night sweats, low-grade fever, itching, bone pain and noticeable weight loss. Both thrombosis and bleeding may occur.
- Weakness, pallor, shortness of breath on exertion
- Heaviness and pain in the left hypochondrium
- Quick satiation with a small amount of food
- Night sweats and low-grade fever
- Pain in bones and joints
- Weight loss and itchy skin
- Tendency to thrombosis and bleeding
Diagnostics
The starting point is a general blood test with a mandatory examination of the smear: teardrop-shaped red blood cells, immature cells of both lineages, and an altered platelet count are characteristic. The key test is bone marrow biopsy, which evaluates the degree of fibrosis; Aspirate is often not obtained due to the density of the tissue, and this in itself is a clue. It is imperative to determine mutations in JAK2, CALR and MPL, and also exclude chronic myeloid leukemia by analyzing BCR-ABL. Ultrasound shows the size of the spleen and liver. Additionally, LDH, uric acid, ferritin and renal function are assessed.
- General blood test with smear and leukemia formula
- Trephine biopsy of bone marrow with assessment of fibrosis
- JAK2, CALR, MPL mutations
- BCR-ABL test to rule out myeloid leukemia
- Ultrasound of the spleen and liver
- LDH, uric acid, ferritin
Complications and prognosis
The severity of the disease is assessed using special scales that take into account age, hemoglobin and leukocyte levels, the proportion of blast cells, general symptoms and molecular features. The choice of treatment depends on the risk group. The most common problems are increasing anemia with the need for transfusions, infections due to a lack of neutrophils, bleeding with low platelets, thrombosis, portal hypertension due to an enlarged spleen. In some patients, the disease eventually develops into acute leukemia, which requires separate tactics and regular monitoring.
- Progressive anemia and transfusion dependence
- Infectious complications
- Bleeding due to thrombocytopenia
- Thrombosis, including abdominal vessels
- Portal hypertension
- Transition to acute leukemia in some patients
Treatment and support
The only method that can cure the disease is donor bone marrow transplantation, but it is not suitable for everyone due to age, concomitant diseases and the risks of the procedure. JAK inhibitors have become the basis of drug treatment: they significantly reduce the size of the spleen and relieve general symptoms, improving well-being. For anemia, erythropoiesis stimulants, drugs that support hematopoiesis, and red blood cell transfusions are used. Concomitant therapy is also important: prevention of gout with high uric acid, treatment of infections, adequate nutrition. The regimen is always selected by a hematologist taking into account the risk group.
- JAK inhibitors to reduce spleen and symptoms
- Allogeneic bone marrow transplantation in selected patients
- Maintenance therapy for anemia and red blood cell transfusions
- Uric acid control
- Early treatment of infections
- Regular monitoring of blood tests and spleen size
- Avoid abdominal trauma if you have a large spleen
