Tutorial 10: Bleeding disorders in children

Physiology of haemostasis & coagulation pathways

Common bleeding disorders

Haemostasis of Blood

1. Vascular spasm and vasoconstriction

2. Formation of platelets plug

3. Blood coagulation

4. Formation of fibrin mesh

Blood Coagulation

Abnormal /normal bleeding? The onset of bleeding

- neonatal period (intrauterine or postnatal infection)

- 2nd to 5th day of life (hemorrhagic disease of newborn)

- Prolonged bleeding after trauma and dental extraction (congenital or acquired disorders)

The site of bleeding- Bleeding into joints or muscles (Hemophilia A & B)- The nose (epistaxis) mainly due to von-willebrand’s

disease- Abnormal bleeding involves gums, skin and under

periosteum of long bones (scurvy)

- GIT hemorrhage in neonatal period (hemorrhagic disease)

Clinical Approach To Diagnosis

The past history- Easy bruising, bruising at abnormal

sites, prolonged bleeding after trauma or invasive procedure

The family history- Hemophilia A, Christmas disease (sex-

linked recessive)- Von- Willebrand’ s disease &

hemorrhagic hereditary telangiectasia (autosomal dominant)

Drug ingestion (warfarin, heparin & aspirin) Diet ( vitamin C and Vitamin K) Splenomegaly (hypersplenism) – underlying causes like

leukemia Miscellaenous ( Wiskott-Aldrich Syndrome characterized

by eczema, thrombocytopenia and immunodeficiency & Ehlers-Danlos syndrome due to platelet aggregation failure)

Bleeding disorder in children

Defects / abnormalities in :

1. Vascular OR

2. Platelets ( qualitative/quantitative) OR

3. Coagulation

Bleeding Due to Vascular Defect

Anaphylactoid Purpura; Henoch-

Schonlein purpura

Infective states; meningococcaemia & dengue haemorrhaic

fever

Nutrition Deficiency; Vitamin C (Scurvy)

Miscellaenous; hereditary

haemorrhagic telangiectasia,

polyarteritis nodosa &Ehlers-Danlos Syndrome

Anaphylactoid purpura

Small vessel vasculitis by immune complexes

Combination of skin rashes (purpura), athralgia and abdominal pain.

Usually occur at age between 3-10 year old

Common in boys-preceded by pharyngitis

-Haemophilia -Von Willibrand Disease

Coagulation Disorder

HAEMOPHILIA-is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation

Classification :

-Haemophilia A is a recessive X-linked genetic disorder involving a lack of functional clotting Factor VIII and represents (80%)

-Haemophilia B is a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX. (20%)

-X-linked recessive,male predominance,qualitative/quantitative defect

Signs and symptomsPresent towards the end of first year of life(vary) Recurrent spontaneous bleeding into joints and muscles Large bruises and haematomas Internal or external bleedings

Three levels of hemophilia are recognized,

according to the level of clotting factor amounts in

the blood. These are often expressed as

percentages of normal: Above 5% - mild hemophilia 1% to 5% - moderate hemophilia Less than 1% - severe hemophilia

Diagnosis

History and signs Activated partial thromboplastin time

(prolonged) Factor VIII assay <10 IU Prenatal test-genetic testing have been

made available

Management• Regular infusions of recombinant FVIII or FIX

concentrates• IM injections, aspirin and NSAIDs and trauma

should be avoided in patients with haemophilia.

• Desmopressin (DDAVP) and cryoprecipitate for mild or moderate haemophilia A

• Specialised physiotherapy-pain,reabsorption and prevent/treat injury

Complications

• Deep internal bleeding

-Joint damage from haemarthrosis 

-Intracranial haemorrhage 

• Transfusion transmitted infection

VON WILLEBRAND DISEASE

-deficiency of von Willebrand factor. Von Willebrand factor facilitates platelet adhesion to damaged endothelium and also acts as the carrier protein for FVIII.

most common hereditary bleeding disorder, present in 1–2% of the general population.

Is usually inherited as an autosomal dominant trait and rarely as an autosomal recessive trait.

-Affects men and women equally

- Classification

Type 1- partial quantitative decrease of qualitatively normal von Willebrand factor

Type 2-qualitatively abnormal

Type 3-absent

Signs and Symptoms Varying degree of easy bleeding Mucosal bleeding such as epitaxis and gum

bleeding Bruising Menorrhagia Severe internal or joint bleeding uncommon

Diagnosis

• Bleeding time (is prolonged)

• APTT (prolonged)

• Ristocetin cofactor test (to measure vWF activity which uses the antibiotic ristocetin to induce vWF to bind to platelets. )

• von Willebrand factor level (level is reduced also act as APR)

Von Willebrand disease may be hard to diagnose.

Treatment

• DDAVP for milder form of vWD ( increase secretion of FVIII and vWD into plasma)

• Plasma derived FVIII concentrate for more severe types of vWD

• For women with heavy menstrual bleeding, the combined oral contraceptive pill may be effective in reducing bleeding or in reducing the length or frequency of periods

Contraindications Bleeding (hemorrhaging) may occur after

surgeries or other invasive procedures. If you have von Willebrand disease, do not

take nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen

Platelet Disorders

Leads to defects in primary haemostatic mechanism

Increased bleeding time Purpura and petechiae

Types of platelet disorders Qualitative (dysfunction)

Glanzman disease

Quantitative reduced (Thrombocytopenia)

Decreased production: aplastic anemia, leukemiaIncreased destruction: ITP, drugs, collagen disordersIncreased consumption: DIC, septicaemia

IMMUNE THROMBOCYTOPENIA

Classified according to antigenic stimulus Autoimmune

Immune/idiopathic thrombocytopenic purpura (ITP)

AlloimmunePosttransfusion purpuraNeontal alloimmune thrombocytopenia

Drug-induced Splenic destruction of antibody coated platelet

Acute ITP Affects young children (> 90% of cases) Acute in onset, usually self-limiting Majority of cases follow vaccinations or viral

infections ♂ : ♀ = 1:1 About 10% fail to recover within 6 months →

chronic ITP

Signs & Symptoms

<20,000/μl-admitted Spontaneous formation of purpura and

petechiae Epistaxis Bleeding gums Hematomas in mouth/mucous membranes

<5,000 /μl Subarachnoid/intracerebral hemorrhage Lower GI bleeding/internal bleeding

How to diagnose?

Low platelet count

No other blood abnormalities

Exclude 2 causes: leukemia, ⁰medications, lupus, cirrhosis, HIV etc

Findings

No splenomegaly

Prolonged bleeding time

Bone marrow examination: increased megakaryocytes

Full blood count Peripheral blood film Bleeding time (thrombocytopenia and dysfunction) Prothrombin time Activated Partial Thromboplastin Time

Coagulation factor assays (FXIII & FIX) aPTT & PT mixing studies Platelet funtion test & flow cytometry Thrombin time Liver & Renal Function Test D-dimers

Investigation of Bleeding