THROMBOCYTOPENIA Reduction in platelet count below 150 x 109 A smear of human perypheral blood, from :www.uoguelph.ca/zoology/ devobio/210labs/ct2.html

DIFFERENTIAL DIAGNOSIS OF THROMBOCYTOPENIA Destructive Thrombocytopenia Immunologic ITP Drug induced Post-tranfusion purpura Autoimmune disease Post-transplant Hyperthyroidism Lymphoproliferative disorders

Nonimmunologic Microanigopathic disease Hemolytic anemia and thrombocytopenia Hemolytic-uremic syndrome Thrombotic thrombocytopenic purpura Platelet Consumption/Destruction DIC Giant Hemangiomas Cardiac (prosthetic heart valves, repair of intra cardiac defects)

Neonatal Problems Pulmonary hypertension Polycythemia RDS/infection (viral, bacterial, protozoal, spirochetal) Sepsis/DIC Prematurity Meconium aspiration Glant hemangioma Neonatal alloimmune Neonatal autoimmune (maternal ITP) Erythroblastosis fetalis (Rh incompatibility)

Impaired Production Congenital & Hereditary Disorders Thrombocytopenia-absent radii (TAR) syndrome Fanconi’s anemia Bernard-Soulier syndrome Wiskott-Aldrich syndrome Glanzmann’s thrombasthenia May-Hegglin anomaly Amegakaryocytosis (congenital) Rubella syndrome Associated with Chromosomal Defect Trisomy 13 or 18

Metabolic disorders Marrow infiltration malignancies, storage disease, myelofibrosis Acquired processes Aplastic anemia Drug induced Severe iron deficiency Sequestration Hypersplenism (portal hypertension, neoplastic, infectious, glycogen storage disease, cyanotic heart syndrome) Hypothermia

Thrombocytopenia with neutropenia Figure 1. Approach to the child with thrombocytopenia with neutropenia or pancytopenia History Physical Examination CBC : differential platelet count Peripheral smear evaluation Thrombocytopenia with neutropenia or pancytopenia Consider : Marrow infiltration Marrow failure hypersplenism Asses: Bone marrow aspirate splenomegaly Dd/:aplastik anemia Fanconi’s anemia Malignancy Storage disease Hypersplenisme

Approach to the child with isolated thrombocytopenia Figure 2. Approach to the child with isolated thrombocytopenia History Physical Examination CBC : differential platelet count Peripheral smear evaluation Isolated thrombocytopenia Asses : platelet morphology normal abnormal Asses : splenomegaly or lymphadenopathy Bernard-Soulier syndrome Wiskott-Aldrich syndrome May-Hegglin anomaly Glanzmann’s thrombasthenia Gray platelet syndrome positive or negative bone marrow aspirate Normal examination Congenital anomalies dd/: malignancy infection HIV storage disease hypersplenism dd/: ITP (viral induced, drug induced) HIV Collagen vascular disease Infant : alloimmune, autoimmune Hemangiomas Aplastic anemia Fanconi’s anemia Familial skeletal abnormalitas fanconi’s anemia TAR cyanotic heart disease eczema : Wiskott-Aldrich syndrome hemangiomas Kasabach-Merritt syndrome

thrombocytopenia, anemia microangiopathic process Figure 3. Approach to the child with thrombocytopenia and anemia History Physical Examination CBC : differential platelet count Peripheral smear evaluation thrombocytopenia, anemia yes Asses : intravascular hemolisis red cell fragment microangiopathic process consumption no Coombs’ test dd/ : DIC HUS TTP Sepsis negative positive Reticulocyte count dd/: Evans syndrome HIV EBV Collagen vascular disease Drug induced high normal or low Assess physical lihat figure 2 bone marrow aspirate lihat figure 1

IMMUNE THROMBOCYTOPENIC PURPURA = IDIOPATHIC THROMBOCYTOPENIA PURPURA = AUTOIMMUNE THROMBOCYTOPENIC PURPURA = MORBUS WERLHOF = PURPURA HEMORRHAGICA

IDIOPATHIC THROMBOCYTOPENIC PURPURA ( ITP ) Acute ITP : - resolve within 6 months - usually occurs in children ages 2 to 4 years Chronic ITP : - persistent thrombocytopenia > 6 months - child < 1 year or > 10 years of age - may have an associated autoimmune disease or immunodeficiency state Neonatal Alloimmune Thrombocytopenic Purpura ( NATP )

PATHOPHYSIOLOGY Pathogenesis of epitop spread in ITP ( From Cines DB et al, Immune Thrombocytopenic Purpura, In : N Engl J med 2002 ; 346 )

CLINICAL MANIFESTATIONS Sudden onset of generalized petechiae & purpura Bleeding from the gums and mucous membrane ( paticularly with platelet < 10 x 109 / L ) History of preceding viral infection 1 to 4 week before No hepatosplenomegaly 1% of cases develop intracranial hemmorrhage Resolution within 6 months

ptechiae purpura conjunctival hemorrhage Howell–Jolly bodies ( From Cines DB et al, Immune Thrombocytopenic Purpura, In : N Engl J med 2002 ; 346 )

LABORATORY FINDINGS Low platelet count Giant platelet Hemoglobin maybe decreased if there have been profuse bleeding BMP : normal granulocytic & erythrocyte series with characteristically normal or increased numbers of megakaryocytes, some of the megakaryocytes may appear to be immature Platelet antibody (+)

TREATMENT Intravenous Immunoglobulin ( IVIG ) - Dose : 0,8 – 1 g / kg /day ; 1-2 days - Expensive and time consuming to administer - Adverse effect : headaches & vomitting suggestive of aseptic meningitis Prednison - Dose : 1-4 mg / kg / 24 hours ; 2-3 week or until a rise in platelet count > 20.000 / mm3 IV anti D therapy - Given to Rh positive individuals - Dose : 50 mikrogram / kg

Splenectomy - The older children ( > 4 years ) with severe ITP > 1 years ( chronic ITP ) - Life threatening hemorrhage ( intracranial hemorrhage ), if the platelet count cannot rapidly be corrected with tranfusion of platelets and administration of IVIG and corticosteroids

Mechanisms of Action of Therapies for Immune Thrombocytopenic Purpura ( From Cines DB et al, Immune Thrombocytopenic Purpura, In : N Engl J med 2002 ; 346 )

NEONATAL ALLOIMMUNE THROMBOCYTOPENIA ( NATP ) Caused by the development of maternal antibodies against antigens present on fetal platelets that are shared with the father and recognized as foreign by the maternal immune system  platelet equivalent of Rh disease of the newborn 1 in 4000 – 5000 live births

CLINICAL MANIFESTATIONS Generalized petechiae & purpura within the first few days after delivery Normal maternal platelet count, moderate to severe thrombocytopenia in the newborn No maternal thrombocytopenia in the past 30 % severe NATP may develop intracranial hemorrhage Early jaundice occurs in 20 % of cases as a results of resolution of intracranial or intraorgan hemorrhage The thrombocytopenia is transient, lasting up to 3 to 6 weeks

DIFFERENTIAL DIAGNOSIS Checking for the presence of maternal alloantibodies directed against the father’s platelets Specific studies to identify the target alloantigen DIFFERENTIAL DIAGNOSIS Transplacental transfer of maternal antiplatelet auto antibodies ( Maternal ITP ) Viral or bacterial infection

TREATMENT Transfusion with antigen – negatife patelets IVIG ( 1 g / kg /24 hours, 1-2 doses until platelet > 50.000 / mm3 ) PREVENTION IVIG 1 g / kg /week from midgestation until near term Delivery should be performed by cesarean section

Terima Kasih