Thalassaemia. Genetic based defect in synthesis of one of the normal chains.

Beta thalassaemia --->  reduced Hb A and increased HbF (α2, Y2) HBA2(α2)

Alpha thalassaemia  --->   reduced  Hb-A, Hb-A2 and Hb-F-with formation of Hb-H(β4) and Hb Barts (Y4).
Thalassaemia may manifest as trait or disease or with intermediate manifestation.

Features:
•    Microcytic hypochromic RBC is in iron deficjency.
•    Marked anisopoikilocytsis  with prominent target cells.
•    Reticulocytosis and nucleated RBC seen.
•    Mongoloid facies and X-ray findings characteristic of marrow hyperplasia
•    Decreased osmotic. fragility.
•    Increased marrow iron (important difference from iron deficiency anaemia).
•    Haemosiderosis, especially with repeated transfusions.

Diagnosis is by Hb electrophoresis and by Alkali denaturation test (for HbF).

Parvoviruses
 - smallest DNA virus
 - erythema infectiosum (fifth disease) is characterized by a confluent rash usually beginning on the cheeks ("slapped face") which extends centripetally to involve the trunk; fever, malaise and respiratory problems; and arthralgias and joint swelling (50%).
 
 other associations:
 - aplastic anemia in patients with chronic hemolytic anemias (e.g., sickle cell disease, spherocytosis).
 - repeated abortions associated with hydrops fetalis.
 - pure RBC aplasia by involving the RBC precursors (no reticulocytes peripherally).
 -chronic arthritis

Lymphopenia:
Causes

-As part of pancytopenia.
-Steroid administration.

Blood-Lymphatic Pathology

Disorders of primary hemostasis

1. General characteristics of disorders of primary hemostasis (due to problems of blood vessels or platelets):

a. Occur early in life.

b. Unlike secondary hemostasis, bleeding occurs in more superficial areas such as skin and mucous membranes rather than in secondary hemostasis.

c. Signs include petechiae.

d. Can be caused by vascular and platelet abnormalities or alterations in the plasma proteins required for adhesion of platelets to vascular subendothelium.

e. Laboratory findings include prolonged bleeding time, as seen in platelet disorders.

2. Vascular abnormalities

Scurvy

(1) Caused by a vitamin C deficiency leading to decreased synthesis of collagen. Note: vitamin C is necessary for the formation of collagen via hydroxylation of lysine and proline.

(2) Symptoms include:

- Delayed wound healing.

- Petechiae and ecchymosis.

- Gingival bleeding, swelling, and ulcerations.

3. Platelet abnormalities

a. Thrombocytopenia

(1) Characterized by a decreased number of platelets.

(2) The most common type of bleeding disorder.

(3) Can be caused by a number of diseases, such as irradiation, acute leukemia, disseminated intravascular coagulation (DIC), or idiopathic thrombocytopenic purpura (ITP).

b. Thrombocytopenic purpura

(1) Idiopathic: An autoimmune disease characterized by the presence of autoantibodies against platelets, resulting in the removal of platelets by splenic macrophages.

(2) May also be drug-induced.

Disorders of secondary hemostasis

1. General characteristics of disorders of secondary hemostasis (due to problems with clotting factors):

a. Symptoms occur later in life.

b. As compared to disorders of primary hemostasis, bleeding occurs in deeper areas and larger vessels (i.e., joint spaces).

c. Laboratory findings include abnormal:

- Partial thromboplastin time (PTT)—measures the intrinsic and common clotting pathway (i.e., tests all coagulation factors except factor 7).

- Prothrombin time (PT)—measures the extrinsic pathway.

- Does not affect the bleeding time.

Hemophilia

a. Caused by a deficiency of particular clotting factor(s).

b. All types of hemophilia affect the intrinsic pathway of the clotting cascade.

c. Signs and symptoms include:

- Prolonged PTT.

- Continuous bleeding from cuts or trauma, which can lead to excessive blood loss.

- Bleeding into joint cavities (hemarthroses) and muscle.

Two types:

(1) Hemophilia A (classic hemophilia)

- Caused by a deficiency of factor 8 (antihemophilic factor).

- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.

(2) Hemophilia B (Christmas disease)

- Caused by a deficiency of factor 9 (plasma thromboplastin).

- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.

- Lower incidence rate than hemophilia A.

(3). Vitamin K deficiency

- Causes include malnutrition and malabsorption of fats.

- A decrease in clotting factors 2, 7, 9, and 10 and prothrombin is observed.

- Prolonged PT.

Disorders of both primary and secondary hemostasis

1. von Willebrand’s disease

a. Characterized by a defective von Willebrand’s factor (vWF). Defective vWF affects both primary hemostasis by affecting platelet adhesion to

endothelium, and secondary hemostasis, by a defective factor 8.

b. Genetic transmission: autosomal dominant.

It is the most common hereditary bleeding disorder.

2. Liver disease—disease of the liver results in a decreased production of coagulation factors and therefore can lead to problems with hemostasis.

3. Disseminated intravascular coagulation a condition in which clots form throughout the vasculature. This uses up all available clotting factors and platelets, resulting in problems with bleeding.

Glycogen storage diseases (glycogenoses)

1. Genetic transmission: autosomal recessive.

2. This group of diseases is characterized by a deficiency of a particular enzyme involved in either glycogen production or degradative pathways.

Diseases include:
on Gierke disease (type I)
(a) Deficient enzyme: glucose-6-phosphatase.
(b) Major organ affected by the buildup of glycogen: liver.

Pompe disease (type II)

(1) Deficient enzyme: α-glucosidase(acid maltase).
(2) Major organ affected by the buildup of glycogen: heart.

Cori disease (type III)
(1) Deficient enzyme: debranching enzyme (amylo-1,6-glucosidase).
(2) Organs affected by the buildup of glycogen: varies between the heart, liver, or skeletal muscle.

Brancher glycogenosis (type IV)
(1) Deficient enzyme: branching enzyme.
(2) Organs affected by the buildup of glycogen: liver, heart, skeletal muscle, and brain.

McArdle syndrome (type V)
(1) Deficient enzyme: muscle phosphorylase.
(2) Major organ affected by the buildup of glycogen: skeletal muscle.

Eosinopenia:
Causes

-Corticoid effect (Cushing's syndrome or therapy).
-Stress.