Thalassemia

Presenter: Abdul MushibINTERNAL MEDICINE

• Inherited autosomal recessive blood disorders• mutation or deletion• results in reduced rate of synthesis or no

synthesis of one of the globin chains that make up hemoglobin

• two major forms of the disease, alpha- and beta

Epidemiology

• Mediterranean origin, Arabs, and Asians• Bangladesh, China, India, Malaysia and

Pakistan.

Pathophysiology

• Normal hemoglobin is composed of four protein chains, two α and two β globin chains

• Thalassemia patients produce a deficiency of either α (16) or β (11) globin

• Unmatched globins precipitate, damaging RBC membranes causing hemolysis while still in marrow.

Beta Thalassaemias

• Point mutation leading to dec B chain production or no B chain production.

1_B T Minor: carrier state Asymptomatic or Mild well tolerated anemia Hb >9 Anemia worsen in pregnancy Often confused with Fe Deficiency

Anemia

2-B T Intermedia

Moderate anemia No transfusions Splenomegaly

3- B T Major (Cooleys Anaemia)Abnormalties in both B globulinsPresents in 1st year with severe anemia & failure to thrive.RBC forms outside the marrow causing cahacteristic headshape.

Skull bossing. Hepatosplenomegaly (due to Hemolysis) OsteopeniaLife long blood transfusions are needed.Iron overload/depositionFilm Show: very Hypochromic, microcytic cells+ target cells +

nucleated RBC.

RX

• Promote fitness, healthy diet, folate supps.• Regular (2-4 wkly) transfusions to keep Hb >9

to suppress extramedullary hematopoiesis• Iron chelators (Deferiprone)• Vit c- inc Urinary secretion of Fe• Hormal Rx of Dm, Hypo.• Histocompatable marrow transplant

Alpha T

• There are 4 genes• Mainly by gene deletions• If all 4 alpha delettion-death in utero (Barts

Hydrops)• Other features 3 genes deleted then:• Moderate anemia, hemolysis,

hepatosplenomagaly• 2 genes deleted: asymptomatic carrier• 1 gene deleted: clinical state is normal.

DX

• FBC• MCV• Iron• HB electrophoresis• Film

BLEEDING DISORDERS

• After injury 3 processors halt bleeding:

• 1-Vaso-constriction• 2-Gap-Plugging by platelets• 3-Coagualtion Cascade

Bleeding DisordersIs pattern of bleeding important?

• Prolonged bleeding from cuts

• easy bruising- purpura• epistaxis• gums• menorrhagia

VASCULAR & PLATELET DISORDERS

• Delayed bleeding into• Joints• Muscles

COAGULATION DISORDERS

• After injury 3 processors halt bleeding:

• 1-Vaso-constriction VASCULAR DEFECTS• 2-Gap-Plugging by platelets PLATELET DISORD• 3-Coagualtion Cascade COAGULATION DISORD

1-Vaso-constriction VASCULAR DEFECTS

• Congenital (connective tissue disease)Ehlers Danlos, Osler Weber Rendu Syndrome

2-Gap-Plugging by platelets PLATELET DISORDER

Decreased Production• Marrow Hypoplasia

(aplastic anemias, Fanconi’s Anemia)

• Marrow infiltration (Leukemia, myeloma

• Cytotoxic Drugs• Hematinic Deficiency (V

B12/folate)• Familial (Alports, Benard

Soulier Disease)

Increased consumption• Immune mechnisms (ITP,

Drug associated-quinnine)• Coagulation Activation (DIC)• Mechnical pooling

(hypersplenism)• Thrombotic

microangiopathies (Liver disease, Hemolytic Uraemic syndrome

• OTHERS (Von willie)

3-Coagualtion Cascade COAGULATION DISORDER

COngenital• Haemophilia• Von Willebrands

Acquired• Anticoagulants• Liver disease• DIC• Vitamin K defiecy

Approach to Bleeding

• QUESTION 1Is there an emergency?• QUESTION 2Why is the Px bleeding• QUESTION 3What is mechnism of bleeding

Is there an emergency?

• Is px dizzy, in shock, coma?• Is there hypovolemia (P Hypo, Oliguria)• Is there CNS bleeding (meningism, retinal

signs)• Underlying condition that is gonna be affected

eg Pregnancy

Why is the Px bleeding

• Is bleeding Normal ? (surgery, trauma or is it a bleeding disorder?

• Is there secondary cause? (drug (W), liver disease, sepsis?

• Past Family HX?• Pattern of bleeding?

What is mechnism of bleeding

• To help find answers do:FBCBlood FlimCoagulation profileSeptic Screeening

MX

• Depends on degree of bleeding• If shock_recucitate• FFP• Platelets• ITP: Steroids + Imunoglobulins

The End

DISCUSSION

Referance

• Oxford Handbook of clinical Medicine.• Davidson’s Principles of Internal Medicine.