DIFFERENCES BETWEEN

DISEASES OF PLATELETS/VESSEL WALL OR OF

COAGULATION FACTORS.

PATHOGENESIS OF MYELODYSPLASIA

MYELODYSPLASIA
(CLINICAL FEATURES)
 joints or soft tissue

• Clonal disorder of hematopoietic stem cells with

• Increasing bone marrow failure (ineffective hematopoiesis)
• Dysplastic changes in >= 1 cell line
• simultaneous proliferation and apoptosis of hemopoietic cell
• Hypercellular BM, peripheral pancytopenia

1. Genetic changes in multipotent hemopoietic progenitor cell resulting in

• Clonal hematopoiesis, clonal expansion, morphology dysplasia, ineffective hematopoiesis

2. Genetic changes
• Chromosome abnormalities 50% - del(5q) present in 15% mds
• Epigenetic process
• DNA Methylation – TET2, DNMT3A
• Chromatin modification – ASXL1
• RNA splicing

• MDS genome – global DNA hypomethylation with concomitant hypermethylation of gene promoter region.

• Other cause – stromal abnormalities and T cell dysregulation

• ATRX mutation – acquired Hb H disease – 8% of MDS

Function of white cells and platelets are impaired

1. Anemia
2. Infection
3. Bleeding
4. Spleen is not usually enlarged
 MYELODYSPLASIA
(LAB FEATURES)

MYELODYSPLASIA
(BONE MARROW FINDING)

MYELODYSPLASIA
(5q- syndrome, monosomy 7 syndrome)
• FBC
• RBC
• inappropriately low reticulocyte count
• Macrocytic/normocytic
• RDW increased
• Normal MCHC
• WBC – leukopenia
• Platelet
• thrombocytopenia – del(20q)
• Thrombocytosis (less common) – 5q- syndrome

• FBP
• RBC
• Normo/macrocytic
• Ovalomacrocytosis
• Alteration in cytoskeletal protein – elliptocytosis, teardrops, stomatocytes, acanthocytes
• Basophilic stippling, howel jolly body
• If reticulocytosis – superimposed autoimmune
• WBC
• leukopenia
• pseudopelger huet, abnormality, with hypogranulation
• Platelet – usually normal

Serum iron, ferritin, transferrin saturation, all increased – increase in body iron stores. Bilirubin raised - hemolysis

• Hypercellular, BLAST < 20%, HYPOCELLULAR IN THEREAPY RELATED OR CHILDREN WITH MDS
• 10% of cell in a lineage must be dysplastic

• ERYTHROID PRECURSOR
• internuclear bridges, multinucleated normobloast, nuclear budding.
• coarse or fine periodic acid ‐Schiff‐positive granules, or a "necklace"
• ring sideroblasts detected with Prussian blue staining

• myeloid
• abnormally large size, abnormal nuclear shape
• Defective granulation

• MEGAKARYOCYTES
• Normal/increased in number, occur in clusters.
• micromegakaryocytes,
• megakaryocytes with multiple dispersed nuclei ("Pawn ball" changes),
• hypogranular megakaryocytes
• mononuclear megakaryocytes in association with the 5q ‐ syndrome.

• TREPHINE BIOPSY: ALIPs Abnormal localization of immature precursors – Granulopoiesis may be displaced from its normal
paratrabecular location to more central marrow spaces.

• Cytochemistry immunophenotyping, flow cytomertry and genotyping

• Deletion of long arm of chromosome 5 (5q-) (bands 5q31 to 5q33) in older women.
• Present as
• refractory anemia with marked dyserythropoiesis,
• hypolobulated, small (“dwarf”) megakaryocytes.
• Carry good prognosis.

• Monosomy 7 Syndrome
• Second most frequent cytogenetic abnormality.
• Carry poor prognosis and rapid transformation to AML
 MYELODYSPLASIA
(CLASSIFICATION)

MYELODYSPLASIA
(POOR PROGNOSIS)

MULTIPLE MYELOMA
(TREATMENT – SUPPORTIVE CARE)
• Differential diagnosis

• Other causes of anaemia—haematinic defi ciency, haemolysis, blood loss, renal failure.

• Other causes of neutropenia—drugs, viral infection.

• Other causes of thrombocytopenia—drugs, ITP.

• Other causes of bi-/pancytopenia—drugs, infection, aplastic anaemia.

• Reactive causes of BM dysplasia—megaloblastic anaemia, HIV infection, alcoholism, recent cytotoxic therapy,

• Other causes of marrow hypoplasia in hypoplastic MDS—aplastic anaemia, PNH.

• Anaemia of chronic disease.

 MYELODYSPLASIA
(COURSE)

MYELODYSPLASIA
(PROGNOSIS)

MYELODYSPLASIA
(LOW RISK - TREATMENT)
• Survival ranged from 1-5 years.
• ~ 50 % died of infection due to severe neutropenia
• ~ 20 % died of bleeding complications of thrombocytopenia.
• ~ 30 % of cases evolved into AML.
• Over a 10 year ~10 % of patients develop AML.

• Patient with less than 5% of blasts in the marrow and only

• one cytopenia and favourable cytogenetics are defined as
• having low‐grade MDS.

• Patient is not treated

• improve marrow function with haemopoietic growth factors,
• Erythropoietin
• G-CSF
• thrombomimetics
• Transfusion support
• Iron chelation

• Lenalidomide is particularly effective in MDS associated with del(5q) where it can often reduce the size of the del(5q) clone and
reduce transfusion requirements.

• In selected patients standard or low‐intensity allogeneic

• stem cell transplantation (SCT) offers a permanent cure.
 MYELODYSPLASIA
(HIGH RISK - TREATMENT)
• Stem cell transplantation
• complete cure possible. Chemotherapy given prior to the transplant in patients with >10% blasts in the marrow.

• Intensive chemotherapy
• as given in AML , prolonged pancytopenia may occur as normal stem cells are not present.

• Hypomethylating agents
• Azacytidine (azacitidine) and decitabine are DNA methyltransferase inhibitors - inhibit methylation of newly formed
DNA.
• improve blood counts in a minority of high ‐risk MDS patients.
• Azacitidine can improve survival by approximately 9 months.

• General support care only

• in elderly patients with other major medical problems.
• Transfusions of red cells and platelets, and therapy with antibiotics and antifungals.