MYELODYSPLASTIC AND MYELOPROLIFERATIVE DISORDERS Pediatric Hemato-Oncology Division Medical Faculty University of Sumatera Utara 1
MYELODYSPLASIA SYNDROME A group of disorder defect in hematopoetic cell development Progresses from dysplastic ineffective hematopoesis to aggressive overt myelogenous leukemia 2
These are classified as : Refractory anemia (RA) Ra with ringed sideroblasts Ra with excess blasts Ra with excess blasts in transformation Chronic myelomonocytic leukemia (CML) Close relationship to aml patients treated with AML protocols 3
NORMAL BONE MARROW SMEAR, MAY-GIEMSA STAIN, X100 TAKEN FROM: bcl.med.harvard.edu/.../proj/raspap/bm-rars.jpg 4
400X MAGNIFICATION OF A BONE MARROW WITH PRIMARY REFRACTORY ANEMIA TAKEN FROM: www.academic.marist.edu/.../nrbc/nrbc22.jpg 5
REFRACTORY ANEMIA WITH RINGED SIDEROBLASTS (RARS) BONE MARROW SMEAR, IRON STAIN, X1000 TAKEN FROM: bcl.med.harvard.edu/.../proj/raspap/bm-rars.jpg 6
REFRACTORY ANEMIA WITH EXCESS OF BLASTS, BONE MARROW SMEAR TAKEN FROM: citylightsnews.com/.../raeb-excess_blasts.jpeg 7
REFRACTORY ANEMIA WITH EXCESS OF BLASTS IN TRANSFORMATION (RAEB-T) BONE MARROW SMEAR, MAY-GIEMSA STAIN, X200 TAKEN FROM: bcl.med.harvard.edu/.../proj/raspap/bm-rars.jpg 8
CHRONIC MYELOMONOCYTIC LEUKEMIA PERIPHERAL BLOOD TAKEN FROM: www.bekkoame.ne.jp/.../wbc/cmmol/cmmol-pb-h.jpg 9
ACUTE MYELOMONOCYTIC LEUKEMIA - MICROSCOPIC View TAKEN FROM:medicalimages.allrefer.com/large/acute-myelom. 10
These disorder are characterized by a single lineage myeloid proliferation that can progress to AML-like leukemia, include : CML Essential thrombocytopenia (ET) Policythemia Vera (PV) Agnogenic myeloid metaplasia Juvenile myelomonocytic leukemia 11
Treatment : Conservative management If failed or diseases progress to AML-like leukemic consider Stem cell transplantation 12
THROMBOCYTOSIS Thrombocyte count above the normal value for age Varies between platelet counts of > 400 - > 1000 x 10 9 /l Thrombocytosis are classified as : Mild : > 500 - < 700 x 10 9 / l Moderate : 700-900 x 10 9 / l Severe : > 900 x 10 9 / l Extreme : > 1000 x 10 9 / l 13
Cause of an increase in platelet count : 1. A primary disorder, such as myelo-proliferative or dysplastic syndrome ( An essential or primary thrombocytosis) 2. Increased production due to stimuli 3. A shift in platelets from the splenic pool into the peripheral circulation Reactive or secondary thrombocytosis 14
Table 1. differences between essential and reactive thrombocytosis Age ( years) Duration Origin Microvascular symptoms Thrombosis Bleeding Splenomegaly Platelet count ( x 10 9 /l ) Platelet morphology Platelet function Platelet distribution Iron stores Acute phase reagents such as IL-6, CRP, fibrinogen Essential (primary) Mostly > 20, often > 40 Over 2 years Stem cell defect Often Often Often Often Mostly > 1000 Large, dysmorphic Disturbed Elevated Normel Normal Reactive (secondary) Mostly < 20 Days or weeks, sometimes months Reaction to hypoxemia, infection, platelet loss; shift of platelet pool Extremely rare Extremely rare Extremely rare Rare Mostly < 1000 Large, normal appearance Normal Normal width Low High, if thrombocytosis caused by infection 15
ESSENTIAL THROMBOCYTOSIS Rare in children and young or middle-aged adults Most common in the fifth or sixth decade d of life Clinical i l manifestation ti persistent elevated platelet count > 1000x10 9 /l Splenomegali li Recurrent bleeding Microcirculatory disturbances : acrocyanosis, myocard infarction, transient ischemic attack (TIA) asypmtomatic 16
Treatment Platelet lowering therapy ( e.g. hydoxyurea, busulfan, anagrelide, interferon, radioactive phosphorous, platelet apheresis) Platelet aggregation inhibition ( e.g. aspirin and dipyridamole) 17
REACTIVE THROMBOCYTOSIS Pathophysiology Stimulation of thrombocyte production after peripheral loss of thrombocyte ( e.g. after immunologic, septic, oncogenic or traumatic events, blood loss or hypoxemia, of respiratory or cardiac origin ) Shift of pool into the peripheral blood (exercise, stress, inj. Epinephrine p and isoprenaline, asplenia) 18
Incidence More common than essential thrombocytosis Higher incidence in neonates, infants, and young children Incidence between 6-13% in hospitalized children, and 15% in pediatric outpatients = 78% mild thrombocytosis 15% moderate thrombocytosis 7% severe thrombocytosis 19
Table 2. Conditions associated with reactive thrombocytosis ( predominantly in infants and young children) Infection Respiratory Meningitis iti Gastrointestinal Tissue damage ( surgery, trauma) Splenectomy Hypoxemia Anemia Iron-deficiency anemia hemolytic anemia Anemia due to blood loss Anemia caused by nephrotic disease Respiratory disease Cardiac hypoxemia 20
Table 2. Conditions associated with reactive thrombocytosis ( predominantly in infants and young children) Autoimmune disease Juvenile rheumatoid arthritis Kawasaki syndrome Henoch-schoenlein disease Renal disease Malignancy hepatoblastoma Hodgkin s disease Histiocytosis Sarcoma Acute lymphoblastic leukemia and Non-hodgkin lymphoma Prematurity 21
Table 2. Conditions associated with reactive thrombocytosis ( predominantly in infants and young children) Stress situation Medication Epinephrine Corticosteroid Vinca alkaloids l Miconazole Penicillamine Methadone ( during pregnancy) Hydantoin ( during pregnancy ) Miscellaneous gastroesophegeal reflux cafley s disease 22
Complications Thrombosis Headache Confusion Convulsions Cerebral Infarction Intracranial hemorrhage Hemiparesis 23
Indications for prophylaxis Prophylaxis with anticoagulants or platelet aggregation inhibitors if risk factors exist : Immobilization in a cast Leukemia Alterations ti of other plasmatic thrombophilic hili factors 24
Indications for prophylaxis Iron-deficiency anemia Cyanotic heart disease Cardiac arrythmias after fontan surgery Splenectomy for a myeloproliferative syndrome or hematologic disease Post operative thrombocytosis after pancreas transplantation 25
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