Dasar Penyakit Hematologi

Tulus Widiyanto, MD Optima Bandung-Jakarta

Erytrocyte Disorders

ANEMIA Erythropoiesis Process

�  Hematopoiesis is the process by which the formed elements of the blood are produced.

�  The physiologic regulator of red cell production, the glycoprotein hormone EPO, is produced and released by peritubular capillary lining cells within the kidney.

Tulus Widiyanto, MD

ANEMIA Diagnostic Approach

�  The evaluation of the patient with anemia requires a careful history and physical examination.

�  Physical examination may demonstrate a forceful heartbeat, strong peripheral pulses, and a systolic “flow” murmur.

Tulus Widiyanto, MD

Classification: �  Marrow production defects

(hypoproliferation) �  Red cell maturation defects

(ineffective eryth ropoiesis) �  Decreased red cell survival

(blood loss/hemolysis). 1.  Reticulocyte production

index > 2.5; hemolysis 2.  A reticulocyte production

index < 2; hypoproliferative anemia or maturation disorder.

ANEMIA Diagnostic Approach

Tulus Widiyanto, MD

ANEMIA; Iron Deficiency Anemia

Iron Cycle Nutritional Requirement �  The balance of iron

metabolism in the or- ganism is tightly controlled and designed to conserve iron for reutilization.

�  Iron comes into the body is via absorption from food (dietary iron intake) or from medicinal iron taken orally.

Tulus Widiyanto, MD

ANEMIA; Iron Deficiency Anemia

Stages of Iron Deficiency

Tulus Widiyanto, MD

ANEMIA; Iron Deficiency Anemia

Diagnostic Approach

Treatment �  A dose of 200 to 300 mg of elemental iron per day should result in the absorption of iron up to 50 mg/d.

�  Typically, the reticulocyte count should begin to increase within 4 to 7 days after initiation of therapy and peak at 1½ weeks.

Tulus Widiyanto, MD

ANEMIA; Megaloblastic Anemia

Definition Pathophysiology �  The megaloblastic

anemias are disorders caused by impaired DNA synthesis.

�  Most megaloblastic anemias are due to a deficiency of cobalamin (vitamin B12) and/or folic acid.

Tulus Widiyanto, MD

ANEMIA; Megaloblastic Anemia

Diagnostic Approach

Laboratory �  If the macrocytosis is marked (MCV > 110 fL), the patient is much more likely to have a megaloblastic anemia.

�  Enhanced intramedullary destruction of erythroblasts results in an in- crease in unconjugated bilirubin and lactic acid dehydrogenase

Tulus Widiyanto, MD

ANEMIA Megaloblastic Anemia

Cobalamine deficiency: �  Oral replacement therapy with

2 mg crystalline B12 per day.

�  Parenteral treatment begins with 1000 μg cobalamin per week for 8 weeks, followed by 1000 μg cyanocobala- min intramuscularly every month for the rest of the patient’s life.

Tulus Widiyanto, MD

Folate deficiency: �  Oral folic acid

supplementation; the usual dose of folic acid is 1 mg/d.

�  Higher dose can be given for malabsorbtion.

�  Definitive treatment

Thalassemia Hemoglobin chain

�  The thalassemia syndromes are inherited disorders of α- or β-globin biosynthesis.

�  Unbalanced accumulation of α and βsubunits occurs because the synthesis of the unaffected globin proceeds at a normal rate.

�  Clinical severity varies widely.

Tulus Widiyanto, MD

THALLASAEMIA Clinical Manifestation

�  Hypochromia and microcytosis.

�  Shortening the RBC life span.

�  Massive bone marrow expansion.

�  Hemolytic anemia causes hepatosplenomegaly, leg ulcers, gallstones, and high-output congestive heart failure

Tulus Widiyanto, MD

THALLASAEMIA Workup & Treatment

Workup �  CBC; Anemia �  Peripheral blood

smear; hypochromasia and microcytosis, hypochromic macrocytes that represent the polychromatophilic cells, nucleated RBCs, basophilic stippling, and occasional immature leukocytes

�  HB electroforesis

Tatalaksana � Blood transfusion �  Iron-chelating

therapy � Hematopoietic

stem cell transplantation (HSCT)

Tulus Widiyanto, MD

Leucocyte Disorders

Tulus Widiyanto, MD

Myeloproliferation

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Acute Myelogenic Leukemia �  A group of diseases

characterized by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of the hematopoietic system.

�  Etiology; Heredity, radiation, drugs, chemical exposure

�  Symptoms resulting from bone marrow failure, symptoms resulting from organ infiltration with leukemic cells, or both.

Tulus Widiyanto, MD

Acute Myelogenic Leukemia Workup & Treatment

Workup �  Anemia and

thrombocytopenia �  presence of greater than

20% blasts in the marrow

Tatalaksana �  Anthracycline

(idarubicin or daunorubicin) or anthracenedione (mitoxantrone), combined with cytarabine

�  Blood transfusion �  Antibiotics �  Growth factor (G-CSF)

Tulus Widiyanto, MD

Acute Lymphocytic Leukemia �  A malignant (clonal) disease of

the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow.

�  Symptoms; direct infiltration of the marrow, decrease of marrow elements.

�  Palpable lymphadenopathy �  Splenomegaly

Tulus Widiyanto, MD

Acute Lymphocytic Leukemia Workup & Treatment

Workup �  Anemia,

thrombocytopenia, neutropenia

�  Presence of greater than 20% lymphoblastblasts in the marrow

�  myeloperoxidase (MPO) (or Sudan black) and terminal deoxynucleotidyl transferase (TdT)

Tatalaksana �  vincristine, prednisone,

anthracycline, and cyclophosphamide.

�  Transplantation; Allogenic, stem cell

Tulus Widiyanto, MD

Trombocyte Disorders

Tulus Widiyanto, MD

Hemofilia Definition & Pathophysiology

Definition Pathophysiology �  Hemofilia A:

Deficiency FVIII �  Hemofilia B;

Deficiency FIX �  History of

hemorrhage disproportionate to trauma, spontaneous hemorrhage, bleeding disorders in the family, concomitant illness

Tulus Widiyanto, MD

HEMOFILIA Workup & Treatment

Workup

� Complete blood cell count

� Coagulation studies (aPTT)

� Factor VIII, IX, von willebrand assay

Treatment

� Cryoprecipitates infusion

Immune Trombocytopenic Purpura

Definition Pathophysiology �  Clinical syndrome in which

a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency.

�  Splenic sequestration and phagocytosis by mononuclear macrophages

Tulus Widiyanto, MD

�  Acute & Chronic ITP

Immune Trombocytopenic Purpura

Workup Treatment �  Isolated thrombocytopenia �  Assays for platelet antigen–

specific antibodies �  ANA test

Tulus Widiyanto, MD

�  ITP has no cure, and relapses may occur years after seemingly successful medical or surgical management

�  Prevent remission; Cotricosteroids; Immunoglobulins