HEMOPHILIA

DR. TARIQ SAEEDAssistant ProfessorPaediatric DepartmentHoly Family Hospital Rawalpindi

Definition

Hemophilia A (factor VIII deficiency) and

hemophilia B (factor IX deficiency)

Rare bleeding disorders due to inherited deficiencies

of coagulation factors

Types

Haemophilia A (Classic) Factor VIII deficiency

Haemophilia B (Christmas Disease) Factor IX deficiency

Hemophilia A & B

clinically similar:

occur in approximately 1 in 5,000 male births

account for 90% of congenital bleeding disorders

Hemophilia A is approximately 5 times more common than B

Etiology

Inherited as a sex linked recessive trait with bleeding manifestations only in males

genes which control factor VIII and IX production are located on the x chromosome; if the gene is defective synthesis of these proteins is defective

female carriers transmit the abnormal gene

PATHOPHYSIOLOGY

Factors VIII and IX participate in a complex required for the activation of factor X.

After injury, the initial hemostatic event is formation of the platelet plug, together with the generation of the fibrin clot that prevents further hemorrhage. In hemophilia A or B, clot formation is delayed and is not robust.

Disease Severity

severity is dependent on blood levels of functioning factor VIII or IX

severity varies markedly between families but is relatively constant among family members in successive generations

remains relatively unchanged throughout life

Classification

% normal factor level

Causes of bleeding

Severe < 1% bleeding after trivial injury or spontaneous

Moderate 1 - 5% bleeding after minor injury; occasional spontaneous bleeds

Mild 6 - 30 % following major trauma, surgical or dental procedures

Clinical Features – Joint Bleeds

Joints (Hemarthrosis) Knees, ankles and elbows most common sites begin as the child begins to crawl and walk many bleeds occur between the ages of 6 and 15

years Single joint bleed: stiffness, swelling, pain, loose

pack position

Sub Acute Hemarthrosis

Develops after repeated bleeds into the joint Synovium becomes inflamed Hypertrophy, hyperplasia and increased

vascularity of synovial membrane Hemosiderosis: hemoglobin of intra articular

blood is degraded and iron deposited into the joint space

Chronic Arthropathy

Progressive destruction of a joint Pannus (inflammed synovium), & enzymes

begin to destroy articular cartilage Microfracture and cyst formation in

subchondral bone End stage: firbrous joint contracture, and

disorganization of articular surfaces

Clinical Features – Muscle Bleeds

Bleeding into muscle or soft tissue Less tendency to recurrent bleeds Sites: iliopsoas, calf, upper arm and forearm,

thigh, shoulder area, buttock Symptoms: pain, swelling, muscle spasm Complications: nerve compression,

contracture

Other Sites of Hemorrhage

Abdomen GI tract Intracranial bleeds Around vital structures in the neck

LABORATORY FINDINGS AND DIAGNOSIS

Factor VIII or factor IX deficiency leads to prolongation of APTT.

In severe hemophilia, APTT is usually 2–3 times the upper limit of normal.

All other screening tests of with in normal limit.

The specific assay for factors VIII and IX will confirm the diagnosis of hemophilia.

Management

Replacement of missing clotting factor Plasma products Cryoprecipitate Concentrates of Factor VIII Factor IX

Early, appropriate therapy is the hallmark of excellent hemophilia care.

Mild to moderate bleeding, levels of factor VIII or factor IX must be raised to hemostatic levels in the 35–50% range.

For life-threatening or major hemorrhages, the dose should aim to achieve levels of 100% activity.

Role of Desmopressin in Hemoplhilia A

With mild factor VIII hemophilia, the patient's endogenously produced factor VIII can be released by the administration of desmopressin acetate.

Other Medical Treatment

Analgesics (no aspirin) Good dental care Education – life long management Psychological counseling Acute and long term management of

musculoskeletal problems

Musculoskeletal Management

Acute Bleeds: Immediate replacement factor Immobilize joint No weight bearing Immediate medical attention if complications arise

Musculoskeletal Management

After 24 hours: Continue minimal or no weight bearing for lower

extremity bleed Active range of motion; gentle stretching Corrective positioning (splinting ??) Isometric strengthening; progress to isotonic

Musculoskeletal Management

Long term: Repeated musculoskeletal examination (annual or

biannual) Measurement of leg length, girth, ROM, strength,

gait, function Physiotherapy treatment: based on assessment

findings Prophylactic factor replacement

usually provided every 2–3 days to maintain a measurable plasma level of clotting factor (1–2%) when assayed just before the next infusion (trough level).

Education of Patient and Family

Importance of early factor replacement Use of helmet when riding tricycle/bicycle Sports: contact sports discouraged for

severe hemophiliacs; swimming, cross country skiing, tennis, golf, baseball, bicycling – generally considered safe

Footwear

CHRONIC COMPLICATIONS

Long-term complications of hemophilia A and B include

Chronic arthropathy Development of an inhibitor to either factor

VIII or factor IX, Risk of transfusion-transmitted infectious

diseases.