Thalassemia

Presenter: Abdul Mushib INTERNAL 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 and two globin chains Thalassemia patients produce a deficiency of either (16) or (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

2-B T Intermedia Moderate anemia No transfusions Splenomegaly

3- B T Major (Cooleys Anaemia) Abnormalties in both B globulins Presents in 1st year with severe anemia & failure to thrive. RBC forms outside the marrow causing cahacteristic headshape. Skull bossing. Hepatosplenomegaly (due to Hemolysis) Osteopenia Life long blood transfusions are needed.

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

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 Disorders Is pattern of bleeding important?

Prolonged bleeding from cuts easy bruisingpurpura 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, Fanconis Anemia) Marrow infiltration (Leukemia, myeloma Cytotoxic Drugs Hematinic Deficiency (V B12/folate) Familial (Alports, Benard Soulier Disease) Increased consumption Immune mechnisms (ITP, Drug associatedquinnine) 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 1 Is there an emergency? QUESTION 2 Why is the Px bleeding QUESTION 3 What 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: FBC Blood Flim Coagulation profile Septic Screeening

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

The End

DISCUSSION

Referance
Oxford Handbook of clinical Medicine. Davidsons Principles of Internal Medicine.