3. Definition
Hemophilia A (factor VIII deficiency) and
hemophilia B (factor IX deficiency)
Rare bleeding disorders due to inherited deficiencies
of coagulation factors
5. 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
6. 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
7.
8. 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.
9. 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
10. 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
11. 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
12. 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
13. 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
14.
15. 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
16. Other Sites of Hemorrhage
Abdomen
GI tract
Intracranial bleeds
Around vital structures in the neck
17. 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.
18. The
specific assay for factors VIII and IX will
confirm the diagnosis of hemophilia.
20. 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.
21. 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.
22. Other Medical Treatment
Analgesics (no aspirin)
Good dental care
Education – life long management
Psychological counseling
Acute and long term management of
musculoskeletal problems
24. 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
25. 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).
26. 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
27. 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.
Notes de l'éditeur
Von Willibrands Disease: RARELY REQUIRE PT
Autosomal dominant and therefore occurs in males and females
Clinical Features: Excessive bleeding from mucous membranes (nose bleeds, heavy menstrual bleeding, bleeding following dental procedures, cuts)
Risk of excessive bleeding following child birth, tooth extraction, surgery or trauma
Note:There are also more rare forms of factor deficiency – factor X and XI.
Affected male marries a normal female: none of sons will be affected, all daughters will be carriers
Female carrier marries normal male: 50% chance sons will be affected and 50% chance daughters will be carriers
70-80% of bleeds are into joints
Also shoulders and wrists; rarely small joints of the hands, feet, hips, TMJ or spine
Single joint bleed: prodrome of stiffness and/or pain followed by swelling (effusion) and increased temperature of the skin over the joint.
Joint held in a position of comfort – loose pack position
Responds rapidly to replacement of clotting factor; blood resorbs and there should be no residual joint problems.
Joint can quickly become a target joint – recurrent bleeds
Develop a thick boggy synovium (pannus); restriction of range of motion, muscle atrophy (Very common); little or not joint damage on xray
Treatment: often prophylactic factor replacment
Synovectomy – radiation, chemical or surgical
Children: epiphyses are involved resulting in growth disturbances of long bones.
Second most common site of bleeds but less tendency for recurrent bleeds.
Complications: Nerve compression – median, ulnar or femoral leading to transient or persistent sensory or motor impairment
If not treated adequately or if there are repeated bleeds into the same area – fibrosis and soft tissue contracture;
Some danger of compartment syndrome
NB: not necessarily a lot of bleeding from minor superficial cuts and abrasions (platelet function is normal)
Fresh whole blood: only treatment available prior to early 1950’s. If given within 24 hours of collection – contains all the clotting factors.
Largely ineffective in providing enough factor because of the large volumes needed . Life saving measure or given prior to unavoidable surgery.
Plasma Products: discovered in late 1940’s that plasma could be separated from cells and that fresh plasma had higher concentrations of factor than whole blood. Plasma could be given as a fresh product or frozen for later use. Volumes required were still very high – factor levels of 20-25% could be achieved.
Fresh frozen plasma (FFP) – treatment of choice for both factor VIII and IX deficiency until approx 1964.
Cryopecipitate: discovered that if plasma is frozen and then thawed most of the factor VIII remains in the sludge; this smaller quantity is then refrozen, stored for later use. Much less volume needed to treat factor VIII deficiency (one doner). Introduction of Cryoprecipitate coincided with beginning of home infusion – patients and families taught how to infuse at home – bleeds treated earlier. Some reduction in the joint damage due to recurrent bleeds.
Concentrates: both factor VIII and IX concentrates became available in early 1970’s. Obtained by rapid freezing and dehydration of plasma; kept in refrigerator, reconstituted with saline and given by IV. 10,000 to 20,000 doners per batch of concentrate. Rapidly became the treatment of choice in the 1970’s; easier to store and to do home infusion; allowed prophylactic treatment (I.e. prior to a sporting event).
PT along with other team members involved in educating family; Young child – parent does infusion; by age 10 – 12 most children can be taught to do this themselves.
Joints need to be rested in the loose pack position – room for effusion
Crutches or no weight bearing for lower extremity joint or muscle bleed
Ice helps with resorption of fluid
Need to be aware of complications – compartment syndrome or nerve compression in soft tissue bleeds
Important to regain ROM and muscle strength after a bleed.
Generally avoid splinting – except perhaps overnight to stretch soft tissues
Maintenance of physical fitness and muscle strength is important to prevent joint bleeds.
Soccer - ???
Footwear – good ankle support; high topped sneakers recommended
