Dr Heersh HMH Raof Saeed

 A rare chronic H.A.  it is an acquired disorder of hematopoiesis characterized by a defect in proteins of the cell membrane that renders the red blood cells (RBCs) and other cells susceptible to damage by normal plasma complement proteins  Pancytopenia is usually present;  Infection & venous thrombosis are known complications.  Splenectomy is of no value & blood transfusion may be only helpful when required

 60% of pediatric patients have marrow failure  Remainder have either ▪ intermittent ▪ chronic anemia  Nocturnal and morning hemoglobinuria is a classic finding in adults  Thrombocytopenia and leukopenia are often characteristic  Thrombosis and thromboembolic phenomena are serious complications  Abdominal, back, and head pain may be prominent.

 Laboratory Findings:  the acidified serum hemolysis (Ham ) test  the sucrose lysis test.  reduced levels of RBC acetylcholinesterase activity  Decrease decay accelerating factor  Flow cytometry  Treatment :  prednisone (2 m g/kg/24 hr) for hemolysis  Prolonged anticoagulation therapy  iron therapy  Androgens, antithymocyte globulin, cyclosporine.  Eculizumab

 A rare form of autoimune H.A.in which acute hemolysis may occur during viral illnesses on exposure to cold.  The disorder is due to the presence of hemolysins.  Coombs test is +ve.  Avoiding cold exposure is the only way to deal with this disease,  whole blood transfusion may precipitate hemolysis of both the patient and the transfused R.B.C.

 Aetiology:  Idiopathic.  Secondary  Drug  Hemolysis 2 major classes:  IgG or warm antibody (H.A. at 37C o)  IgM or cold antibody (H.A. at 32C o )

 Warm type A.H.A :  The autoantibody : is either  inappropriate immune response  molecular mimicry  infectious agent may alter the RBC membrane  In most instances of warm antibody hemolysis, no underlying cause can be found  Secondary : lymphoproliferative disorder, SLE, or immunodeficiency and drug  Clinical manifestation:  an acute type :80% in 2-12 years  transient type lasting 3-6 m. Splenomegaly.  good responce to steroid  chronic course:high mortality rate

 Cold type A.H.A :  They are primarily of the IgM class  require complement for hemolytic activity  They may occur in ▪ primary or idiopathic cold agglutinin disease ▪ secondary to infections such as those from Mycoplasma pneumoniae and Epstein-Barr virus  high titers of cold antibodies cause severe intravascular hemolysis  concomitant immune thrombocytopenic purpura sometimes occurs (Evans syndrome).  frequently results in an acute, self-limited episode of hemolysis  Patients should avoid exposure to cold and should be treated for underlying disease

 quantitative defects in the globin chain synthesis of Hb.  Beta thalassemia is caused by deceased production of beta –globin chains  while alpha thalassaemia is caused by deceased production of alpha globin chain.  Introduction  Normal Hb ; A, A2& F: ▪ Hb’F’ fetal blood & first few months of infancy. ▪ Hb A2 is present in extremely small quantities through out life. ▪ Hb "A" is the predominant form  Beta thalassemia: more in Mediterranean countries than alpha thalassemia.

 B- Thalassaemia:  marked reduction or complete absence of beta chain synthesis(Hb A)  Accordingly Hb F & A2 increase in amounts to compensate for the lack of Hb. A  alpha – thalassaemia :  due to deletions of the alpha-globulin genes  there are 4 alpha-globulin genes  The severity of alpha –thalassaemias is directly proportional to the number of missing genes

 Thalassemia trait ▪ misdiagnosed as iron deficiency in children ▪ have a persistently normal red cell distribution width ▪ low mean corpuscular volume (MCV ) ▪ hemoglobin analysis, they have an elevated Hb F and elevated Hb A2  Beta-Thalassemia minor :  mild form of Hypochromic Microcytic anaemia (Hb. Level of 2-3 gm. /dl. Less than the normal )  Some ovalocytes, target cells& basophilic stippling are seen  Elevation of Hb.A2 levels of more than 3.5% establishes the diagnosis of Beta- Thalassemia Minor  No therapy is required for this form of Thalassemia

 Thalassemia intermedia:  microcytic anemia with hemoglobin of about 7 g/dL  degree of medullary hyperplasia,  nutritional hemosiderosis perhaps requiring chelation,  splenomegaly,  other complications of β-thalassema is associated with excessive iron stores  Extramedullary hematopoiesis can occur in the vertebral canal  Splenectomy m ay be indicated

 Beta- Thalassemia Major (Coolys anemia) :  by progressive anemia during early infancy -blood transfusion necessary  Progressive hepato-splenomegaly  progressive bone changes resulting in the characteristic thalassemic facies  Delayed growth& puberty  If untreated affected children they die after age 3

 C.F:  thalassemic facies,  pathologic bone fractures  marked hepatosplenomegaly,  cachexia  Pallor, hemosiderosis, and jaundice can combine to produce a greenish brown complexion  Repeated transfusion and increase GIT iron absorption lead to iron toxicity  Endocrine dysfunction

 Laboratory Findings:  The infant is born only with Hb F  severe anemia, reticulocytopenia, numerous nucleated erythrocytes, and microcytosis  The hemoglobin level falls progressively to <5 g/dL unless transfusions are given  The reticulocyte count <8% ( inappropriately low)when compared to the degree of anemia due to ineffective erythropoiesis  unconjugated serum bilirubin level is usually elevated  elevated serum ferritin and transferrin saturation

 Treatment:  Transfusions: ▪ diagnosis of β-thalassemia major should be confirmed ▪ blood products that are leukoreduced and phenotypically matched for the Rh and Kell antigens are required for transfusion ▪ transfusion program generally requires monthly transfusions(9.5 and 10.5 g/dL)  repeated blood transfusions, most of them will have complications like; ▪ Iron deposition ▪ R.C. & HLA antibody formation. ▪ Infections

 Excessive iron stores can be prevented by the use of  deferoxamine (Desferal)  deferasirox (Ex jade)  The number of hours that deferoxamine is used daily is more important than the daily dosage.  Iron chelation have many complication  deferasirox has replaced deferoxamine  Hematopoietic stem cell transplantation  Splenectomy is often necessary after 5 years hypersplenism)

1: Silent carrier in which one alpha globin chain is deleted.Affected patients are asymptomatic 2: Alfa thalathemia minor in which 2 alpha globin chains are deleted & the affected patients have mild anemia. 3: Hb-H disease in which 3 alpha globin chains are deleted. Affected patents have sever anemia at birth with elevated haemoglobin Bart (this type of Hb binds oxygen very strongly and do not release it to tissues). Anemia is life long and severe. 4:Hydrops fetalis in which 4 alpha globin chains are deleted. Only Hb Bart is formed since antenatal period causing severe prenatal anemia, anasarca & death.

 Hemoglobin S (Hb S) is the result of a single base- pair change, thymine for adenine  encodes valine instead of glutamine in the sixth position in the β globin.  Sickle cell anemia, homozygous Hb S, occurs when both β globin genes have the sickle cell mutation  Sickle cell disease refers to not only patients with sickle cell anemia but also to compound heterozygotes (Hb S β-thalassemia,

 Clinical Manifestations :  functional asplenia  Bacterial sepsis  Human parvovirus B19 poses a unique threat  Dactylitis  Splenic Sequestration  Priapism  Neurologic complications  Lung disease