Dr. MUBARAK ABDELRAHMAN

MD PEDIATRICS AND CHILD HEALTH

Assistant Professor

FACULTY OF MEDICINE -JAZAN

The student should be able:

» To identify the mechanism of homeostasis and the role of vessels, platelets and clotting factors.

» To recognize the different causes of bleeding disorders.

» To describe the hereditary basis and presentation of hemophilia and Von Willebrand disease.

The classic hemostatic mechanism include:

-vascular response

-platelets adhesion

-coagulation factor

» The vessel wall is first line of defense against blood loss.

» Local vasoconstriction is induced by a neurogenic reflex and is maintained by vaso constrictor substances released by platelets.

» 1- They stimulate vasoconstriction of injured vessels.

» 2-They form hemostatic plug to seal small vessel wall.

» 3- They play a role in fibrin clot formation.

» Depends on ionized calcium, platelets and coagulation factors.

» Clot formation pass through 3 phases:

PHASE 1: Activation of factor X mediated by intrinsic or extrinsic system.

PHASE 2: Conversion of pro-thrombin to active thrombin.

PHASE 3: Formation of fibrin clot from fibrinogen

1-Platelet disorder: A-↓ number (thrombocytopenia) due to:- #Decreased platelet production -Bone marrow depression Congenital: Fanconi`s anemia Acquired Drugs(chemotherapy) infection (hepatitis) -Bone marrow infiltration: Leukemia Neuroblastoma

B-Increased platelet destruction #Immune mechanism -ITP -Collagen vascular disorder e.g. SLE. #Non immune mechanism -↑ platelet consumption e.g. DIC -hypersplenism C-Abnormal platelet function 1-Hereditary : -Glanzmann Thrombasthenia -Bernard Soulier Disorder -von Willebrand Disorder 2-Acquired: -drugs e.g. Aspirin -CRF (chronic renal failure) -Leukemia

2-Vascular disorder a- Hereditary e.g. hemorrhagic , telangiectasis b-Acquired: 1-Henoch-Schonlein purpura. 2-Septicemia. 3-collagen disorder e.g. SLE

3- Coagulation Disorder Congenital -Hemophilia A, B, von Willebrand Acquired -DIC. -Hemorrhagic Disease of the newborn. -Liver Disease (Deficient Vit. K).

Factor VIII or factor IX deficiency

(Hemophilia A or B)

» It is the most common clotting disease.

» Considered together (similar clinical pictures and similar patterns of inheritance).

Classification:-

Hemophilia occurs in approx. 1:5,000 male with 85% having factor VIII deficiency

and 10-15% having factor IX.

Severe If factor VIII less than 1%

Moderate If factor VIII less than 1-5%

Mild If factor VIII less than 6-

30%

Laboratory Findings:-

1- Reduced level of factor VIII or factor IX.

2- aPTT is prolonged (normally 25-40 seconds).

3- Platelet count (150,000-450,000) , Bleeding time (4-8 minutes), PT (12-14 seconds) & Thrombin time (TT) (11-15 seconds) are normal.

4- Prolong clotting time.

5- ↑ thromoplastin generation time.

Treatment :

1- Prevention of trauma.

2- Careful dental hygiene & regular dental examination.

3- Avoid aspirin.

4- Vaccinate against hepatitis B.

5- Replacement therapy before surgery .

Replacement therapy:

-Mild hemophilia: Infusion of cryoprecipitate or desmopressin (DDAVP). -Moderate or severe type:

*Fresh Frozen Plasma

*Factor VIII, IX.

Factor Half-Life/ hour

VIII 8-12

IX 24

Complication of Hemophilia:-

1-Chronic joint destruction secondary to hemoarthrosis.

2-Transfusion transmitted infectious diseases e.g. A.I.D.S. , Hepatitis.

3- Development of inhibitor to factor XIII & IX in 10% of hemophiliacs.

- The most common hereditary bleeding disorder.

- Inherited as autosomal dominant.

Pathophysiology:-

von Willebrand factor has 2 major functions:

1- VWF acts as a bridge between subendothelial matrix & platelets.

2-VWF also serves as the carrier protein for plasma factor VIII .

Sub-Types:

Type 1: Is a simple deficiency of von Willebrand's Factor.

Type 2: There is a molecular defect in the structure of the factor protein.

Type 3: There is a complete lack of von Willebrand's Factor.

Lab. Findings:-

1-↑ Bleeding time.

2-↑ Clotting time.

3-↑ PTT.

4-↓ factor VIII & VWF.

5- Defective platelet adhesion but platelet number are normal.

Treatment:-

» Minor bleeding problems, may not require specific treatment.

» For more serious bleeding, desmopressin (DDAVP).

Hemophilia A Hemophilia B Von Willebrand

Disease

Inheritance X linked X linked Autosomal

dominant

Factor deficiency VIII IX VWF

Bleeding site(s) Muscle,joint

Surgical

Muscle ,joint Mucous

Skin

Prothrombin time Normal Normal Normal

Activated PTT Prolonged Prolonged Prolonged

Bleeding time Normal Normal Prolonged or

normal

Factor VIII Low Normal Normal

VWF Normal Normal Low

Factor IX Normal Low Normal

Platelet aggregation Normal Normal Normal

» A decrease of vitamin K dependent coagulation

factor (II,VII,IX,X) occur in newborn infants by 2nd or 3rd day gradual return to birth level by 7th –10th day of age.

Causes:-

1- Small amount of vit. K in the breast milk.

2- Immaturity of the infant liver.

3- Absence of bacterial flora in the intestine which is responsible for synthesis of vit. K.

The most common sites of bleeding are:

» The umbilicus, mucous membranes, GI tract, circumcision, venipuncture, trauma.

» Cephalhematoma and bruising, are also common findings.

» Intracranial bleeding can occur and is the main cause of mortality and long-term morbidity.

Investigations:-

1- Coagulation + PT + PTT = prolonged.

2- Bleeding time + platelet = normal.

3- Vitamin K direct assay is not useful because levels normally are low in newborns.

4- The diagnosis is confirmed if administration of vitamin K stopped the bleeding and reduced the PT value.

Prevention:-

-1 mg of vit. K is given I.M. after delivery for every newborn infant.

There are 2 abnormalities:

1- Function (thrombasthenia): Acquired and congenital.

2- Number (thrombocytopenia): Acquired and congenital.

» Congenital platelet function.

» It is not common.

Glanzmann

Thromasthenia

Bernard Soulier

Disorder (BSS)

Inheritance Autosomal

Recessive

Autosomal

Recessive, rarely

AD

Platelet

Count

Normal Low

Size Normal Giant

» Normal bone marrow.

» Thrombocytopenia in the absence of toxic exposure or a disease associated with a low platelet count.

» Usually 1-4 weeks following viral infection (EBV,HIV).

» A 2 distinct clinical syndromes acute condition in children and a chronic condition in adults.

Clinical Manifestation:-

1- The classic presentation of a child of 1-4 years with sudden onset of generalized petechiae & purpura.

2- Often there is bleeding from gums & mucous membrane.

Laboratory Finding:-

1- TWBC & differential should be normal but HB may be decreased.

2- Severe thrombocytopenia (platelet count < 20X10*9) is common .

3- Antinuclear antibody test is more often

positive in adolescents with chronic ITP.

4- PT & PTT are normal.

Differential Diagnosis:-

» Aplastic process e.g. Fanconi`s Anemia.

» Megakaryocytic thrombocytopenia

» Hypersplenism.

» Drug induced thrombocytopenia.

Treatment:-

» ABC.

» Platelet transfusion is indicated for controlling severe hemorrhage.

» High-dose steroids.

» IV immunoglobulin (IVIG).

There are many causes:-

1- Toxic metabolic product (e.g. in uremia)

2- Drugs (Aspirin, NSAIDs).

Definition:-

» It is a hypersensitivity vasculitis involving the small blood vessels of skin , joints, gut & kidneys.

Clinical Manifestation:-

1- Skin rash (100% of cases) 2- Arthritis(80% of cases) 3- Abdominal manifestation(65% of cases)

4- Renal manifestation(20% of cases)

5- C.N.S (not common, presented with convulsion,

paresis & coma).