dr heersh hmh raof saeed. a rare chronic h.a. it is an acquired disorder of hematopoiesis...
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Hematology (lecture 3)
Dr Heersh HMH Raof Saeed
Paroxysmal nocturna hemoglobinurea (PNH):
A rare chronic H.A. it is an acquired disorder of
hematopoiesischaracterized 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
Clinical manifestation:
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
Paroxysmal cold hemoglobinurea (PCH):
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.
Autoimmune hemolytic anemia:
Aetiology: Idiopathic. Secondary Drug
Hemolysis 2 major classes: IgG or warm antibody (H.A. at 37Co)
IgM or cold antibody (H.A. at 32Co )
Autoimmune hemolytic anemia:
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
Autoimmune hemolytic anemia: 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
“The Thalassaemias “
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.
“The Thalassaemias “
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
Beta-Thalassema:
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-Thalassema:Beta- Thalassemia Major
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
Beta-Thalassema:Beta- Thalassemia Major
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
Beta-Thalassema:Beta- Thalassemia Major
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
Beta-Thalassema:Beta- Thalassemia Major
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
Beta-Thalassema:Beta- Thalassemia Major
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)
α -Thalassemia
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.
Sickle Cell Disease
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,
Sickle Cell Disease
Clinical Manifestations : functional asplenia Bacterial sepsis Human parvovirus B19 poses a unique
threat Dactylitis Splenic Sequestration Priapism Neurologic complications Lung disease