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 -Thalassemia1: 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