Myeloproliferative disorders Flashcards
Myeloproliferative disorders : Definition
Myeloproliferative disorders involve the uncontrolled proliferation of a single type of stem cell.
- Cause irreversible replacement of the bone marrow with fibrous tissue (fibrosis)
- Considered a form of cancer occurring in the bone marrow, although they tend to develop and progress slowly.
They have the potential to transform into acute myeloid leukaemia.
Myeloproliferative disorders : Types
- Primary myelofibrosis
- Polycythaemia vera
- Essential thrombocythaemia
Myeloproliferative disorders : Genetics
- JAK2 gene mutation : Mostly associated with Polycythemia Vera
- MPL
- CALR
contribute to abnormal signaling pathways and increased proliferation of hematopoietic cells.
Primary Myelofibrosis : Definition
Clonal proliferation of hematopoietic stem cells,
Single mutated stem cell gives rise to a population of abnormal cells
Primary Myelofibrosis : Pathophysiology
1 . Gene mutation
Abnormal cell signally - increases proliferation of stem cells
2 . Abnormal hematopoietic stem cells proliferation in bone marrow
* Leukocytosis
* Thrombocytosis
3 . Excessive GF and Cytokines released - triggers fibrosis
4 . Bone marrow fibrosis
* Fibrobroblasts replace bone marrow with collagen scar tissue
5 . Bone marrow dysfunction
* Lack of erythrocytes produced - Anaemia
6 . Extramedullary Hematopoiesis
* Due to bone marrow fibrosis - haemtopoesis progresses in Spleen and Liver
* Splenomegaly, Hepatomegaly
Primary Myelofibrosis : Blood findings
- Anaemia - impaired erythropoesis particularly extramedullar
- Leukocytosis - raised WCC due to initial proliferation
- Thrombocytosis -raised platelets due to intial proliferation
When extramedullary haematopesis progresses - will cause drop in WCC and platelets also.
Primary Myelofibrosis : Management
- No active treatment for mild disease with minimal symptoms
- Supportive management of complications, such as anaemia, splenomegaly and portal hypertension
- Chemotherapy (e.g., hydroxycarbamide) to help control the disease
- Targeted therapies, such as JAK2 inhibitors (ruxolitinib)
- Allogeneic stem cell transplantation (risky but potentially curative)
Essential Thrombocytopenia : Definition
Chronic myeloproliferative neoplasm characterized by abnormal proliferation of ;
* Megakaryocytes in the bone marrow, which produce platelets
Essential Thrombocytopenia :Pathophysiology
1 . JAK 2 mutation - promote abnormal proliferation of megakaryoblasts
2 . Bone Marrow Hyperplasia
Increased production of abnormal platelets
3 . Platelet overproduction
4 . Splenomegaly
* High number of platelet sequester in the spleen
- Thrombotic complications
* Increased coagulability due to + platelets in the blood leads to - high risk of PE, DVT, arterial thrombosis - Haemorrhagic complications
* Abnormal plateltes - dysfunctional in controlling bleeding
Essential Thrombocytopenia : Complications
- Thrombotic complications
* Increased coagulability due to + platelets in the blood leads to - high risk of PE, DVT, arterial thrombosis - Haemorrhagic complications
* Abnormal platelets - dysfunctional in controlling bleeding
Essential Thrombocytopenia : Blood findings
- Raised platelet count
- Megakaryoblasts
Essential Thrombocytopenia : Management
Management of essential thrombocythaemia may involve:
- Aspirin to reduce the risk of thrombus formation
- Chemotherapy (typically hydroxycarbamide) to help control the disease
- Anagrelide is a specialist platelet-lowering agent
Polycythemia vera : Definition
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the excessive production of red blood cells, white blood cells, and platelets in the bone marrow.
Polycythemia vera : Pathophysiology
- JAK 2 mutation
* Mainly affects the erythropoietin receptor, leading to increased sensitivity of hematopoietic cells to erythropoietin
* Also effects - lymphoblasts and megakaryocytes to some degree - Erythrocytosis - main compoenent
* Overproduction of RBCs
* Hyperviscosity of blood - Bone Marrow Hyperplasia:
* Hyperplasia of the erythroid, myeloid, and megakaryocytic lineages
4, Leukocytosis and Thrombocytosis present
* Increased megakaryocytes
- Splenomegaly
* High RBCs, increased sequesteration in the spleen
Polycythemia vera : Complications
Increased risk of thrombosis - due to high viscosity of blood
Leading to : myocardial infarction, stroke or venous thromboembolism
Polycythemia vera : Clinical presentation
Clinical signs of polycythaemia include:
- Ruddy complexion (red face)
- Conjunctival plethora (the opposite of conjunctival pallor)
- Splenomegaly
- Hypertension
- Pruritus - worst after taking hot showers
- Tingling, burning and numbness in arms, hands and feet
Polycythemia vera : Blood findings
- Elevated Hematocrit and Hemoglobin:
Polycythemia vera : Management
- Venesection - keep the haemoglobin in the normal range
- Aspirin - reduce the risk of thrombus formation
- Chemotherapy (typically hydroxycarbamide) to help control the disease
Myelofibrosis : Definition
Myelofibrosis can result from primary myelofibrosis, polycythaemia vera or essential thrombocythaemia.
Myelofibrosis is where the proliferation of a single cell line leads to bone marrow fibrosis,
Myelofibrosis : Pathophysiology
- Proliferation of a single cell line (Any of the myeloproliferative disorders)
- Triggers - Fibroblast growth factor and cytokine release
- Bone marrow replaced with fibrotic tissue
- Fibrosis leads to dysfunctional production of Blood cells;
low haemoglobin (anaemia),
low white blood cells (leukopenia)
low platelets (thrombocytopenia). - Extramedullar haematopesis - due to bone marrow non function
Production of blood cells in the;
* liver and spleen causes hepatomegaly, splenomegaly, and portal hypertension.
* Around the spine, it can cause spinal cord compression.
Myelofibrosis : Clinical presentation
Systemic symptoms
- Fatigue
- Weight loss
- Night sweats
- Fever
There may be signs and symptoms of underlying complications:
- Anaemia (tiredness, shortness of breath and dizziness)
- Splenomegaly (abdominal pain)
- Portal hypertension (ascites, varices and abdominal pain)
- Low platelets (bleeding and petechiae)
- Raised haemoglobin (itching, headaches and a red face)
- Low white blood cells (infections)
- Gout is a complication of polycythaemia
Myelofibrosis : Diagnosis
Gold standard : Bone marrow biopsy
Aspiration may be “dry” with myelofibrosis, as the bone marrow has turned to scar tissue
Blood film
- Teardrop-shaped red blood cells
- Anisocytosis (varying sizes of red blood cells)
- Blasts (immature red and white cells)
Myelofibrosis : Main complication
It has the potential to transform into Acute Myeloid Leukaemia.
Myelodisplastic syndrome : Definition
Myelodysplastic syndrome is a form of cancer caused by
* mutation in the myeloid cells in the bone marrow,
* resulting in ineffective haematopoiesis
Myelodisplastic syndrome : Pathophysiology
1 . Mutations
* contribute to the dysregulation of hematopoiesis.
2 . Myeloid stem cells - abnormal development and maturation of myeloid precursor cells
3 . Ineffective Hematopoiesis:
* Abnormal myeloid precursor cells produced in the bone marrow are often nonfunctional and ineffective.
* This results in inadequate production of mature, fully functional blood cells.
4 . Peripheral Blood Cytopenias
* > 1 blood lineage of Myeloid precursor cells affected
Myelodisplastic syndrome : Clinical presentation
They may present with symptoms of:
- Anaemia (fatigue, pallor or shortness of breath)
- Neutropenia (frequent or severe infections)
- Thrombocytopenia (bleeding and purpura)
Myelodisplastic syndrome : Diagnosis
- Full blood count will be abnormal. There may be blasts on the blood film.
- Bone marrow biopsy is required to confirm the diagnosis.
Myelodisplastic syndrome : Management
Management
- Watchful waiting
- Supportive treatment (e.g., blood or platelet transfusions)
- Erythropoietin (stimulates red blood cell production)
- Granulocyte colony-stimulating factor (stimulates neutrophil production)
- Chemotherapy and targeted therapies (e.g., lenalidomide)
Myelodisplastic syndrome : Complication
Increased risk of : Acute Myeloid Leukaemia devlopment
