Transcript Slide 1

‫ه‬
‫بسم ّللا الره حمن الره حیم‬
Hemophilia B
Bijan Keikhaei,
Ahvaz Jundishapur University
of
Medical Sciences
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Hemophilia B
Hemophilia B, or Christmas disease, is an inherited, X-linked,
recessive disorder that results in deficiency of
functional plasma coagulation factor IX.
As many as 1/3 of all cases are the result of spontaneous
mutation.
Hemophilia B occurs in about one in 25,000 male births and
affects about 3,300 people in the United States.
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Severity of Hemophilia B
The normal range of FVIII and FIX is between 50% and 150%.
Hemophilia severity is classified as follows:
Hemophilia B constitutes about 20% of hemophilia cases,
about 50% of cases→ factor IX <l%= Severe
30% of cases→ factor IX <l-5%= Moderate
20 %of
cases→ factor IX >6-40%= Mild
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Hemophilia B-Inheritance
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Hemophilia B-Inheritance
Hemophilia B-Inheritance
Women with Hemophilia B
There are circumstances, however, when females can
experience bleeding symptoms.
Symptomatic carriers
Daughters of a father with hemophilia and a carrier
mother
Turner’s syndrome
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Hemophilia B-Signs &
Symptoms
Neonates: Prolonged bleeding and/or
severe hematoma following procedures
such as circumcision, phlebotomy, and/or
immunizations; intracranial hemorrhage.
Toddler: Trauma-related soft-tissue
hemorrhage; oral bleeding during teething
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Hemophilia B-Signs &
Symptoms
Children and Adults: Hemarthrosis and
hematomas with increasing physical
activity; chronic arthropathy (late
complication); traumatic intracranial
hemorrhage (life threatening)
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Diagnosis
1-Personal history of bleeding.
2-Family history of bleeding and its inheritance pattern.
3-Laboratory testing.
Usually, the activated partial thromboplastin time (aPTT) is
prolonged; however, a normal aPTT does not exclude mild or
even moderate hemophilia because of the relative
insensitivity of the test. The aPTT is significantly prolonged in
severe hemophilia.
FVIII deficiency or hemophilia A can be diagnosed at birth
because newborns should have normal levels of FVIII. In
contrast, FIX levels are low during the newborn period and
may take 6 months to reach normal levels.
The diagnosis of mild FIX deficient hemophilia, therefore, may
be more difficult in the newborn period.
Sites of bleeding in hemophilia
Life-threatening
Intracranial
Neck/throat
Gastrointestinal
Serious
Joints (Hemarthrosis)
Muscles, especially deep compartments (iliopsoas,calf, and
forearm)
Mucous membranes in the mouth, gums, nose, and
genitourinary tract
Joint hemorrhage (Hemarthrosis)
A joint bleed is defined as an episode characterized by
rapid loss of range of motion as compared with
baseline that is associated
with any combination of the following: pain or an
unusual sensation in the joint, palpable swelling
and warmth of the skin over the joint.
The onset of bleeding in joints is frequently
described by patients as a tingling sensation and
tightness within the joint. This “aura” precedes
the appearance of clinical signs.
Joint hemorrhage (Hemarthrosis)
A target joint is a joint in which
3 or more spontaneous bleeds
have occurred within a
consecutive 6-month period.
Arthrocentesis
Arthrocentesis (removal of blood from a joint)
may be considered in the following situations:
a bleeding, tense, and painful joint, which shows no
improvement 24 hr after conservative Treatment .
evidence of neurovascular compromise of the limb
unusual increase in local or systemic temperature and
other evidence of infection (septic arthritis).
When necessary, arthrocentesis should be performed
under factor levels of at least 30– 50 IU Dl for 48–72
Bleeds requiring admission
Suspected intracranial haemorrhage.
Bleeding into neck/throat.
Forearm/calf bleed with suspicion or evidence
of compartment syndrome.
Bleeding into hip or inguinal area, suspected
iliopsoas haemorrhage.
Undiagnosed abdominal pain.
Persistent hematuria.
Bleeds causing severe pain.
General Measures - Joint and Muscle
Bleeds
R = Rest (in position of comfort)
I = Ice (Cold pack to reduce bleeding and
pain)
C = gentle compression bandage
E = Elevation
S = splint
Treatment
Mild hemorrhages (ie, early Hemarthrosis, epistaxis,
gingival bleeding): Maintain a FIX level of 30%
Major hemorrhages (ie, Hemarthrosis or muscle bleeds
with pain and swelling, prophylaxis after head trauma
with negative findings on examination): Maintain a FIX
level of 50%
Life-threatening bleeding episodes (ie, major trauma or
surgery, advanced or recurrent Hemarthrosis): Maintain
a FIX level of 80-90%. Plasma levels are maintained
above 40-50% for a minimum of 7-10 days .
Recommended clotting factor dosage
Type of bleed
Haemophilia A
Recombinant FVIII
40 units/kg Day 1
Haemophilia B
Recombinant FIX
50 units/kg Day 1
20 units/kg or usual home
prophylaxis dose Day 2 & 4
25 units/kg or usual home prophylaxis
dose Day 2 & 5
Muscle (minor)
Muscle (major)
30 units/kg
50 units/kg
50 units/kg
75 units/kg
Oral Mucosa & Dental
Epistaxis (active)
30 units/kg
30 units/kg
50 units/kg
50 units/kg
Gastrointestinal
50 units/kg
75 units/kg
Haematology and gastroenterology review
required. Lesion is usually found. Antifibrinolytic
therapy may be helpful.
Genitourinary
50 units/kg
75 units/kg
Evaluate for all causes however lesion not usually
found. Antifibrinolytic therapy contraindicated in
haematuria.
CNS/head
75 units/kg
125 units/kg
Always treat with factor replacement prior to CNS
imaging. Haematology & Neurosurgical review.
Trauma or surgery
50 - 75 units/kg
75 - 125 units/kg
Joint
Comment
Factor replacement may be modified when
intravenous access is difficult, particularly in
toddlers. E.g. 40 units/kg Day 1 & Day 2.
Intravenous cannula may be left insitu with
patient returning for Day 2 dose. (As an
outpatient, intravenous cannula should not be left
insitu for > 24 hours.)
Calf and forearm bleeds may lead to compartment
syndrome and be limb threatening. Arrange
haematology and surgical reviewInvolvement of
ileopsoas muscle may be associated with
significant blood loss and mandates haematology
review.
Antifibrinolytic therapy is critical.
Apply local measures (pressure). Antifibrinolytic
therapy effective in preventing recurrence.
Consultation with haematologist essential.
Analgesia
Paracetamol/codeine is sufficient in most cases,
however morphine, tramadol can be used for
severe pain .
Splinting/immobilisation is an effective adjunct for
reducing pain .
Do not use products containing aspirin or NSAIDS
(eg. ibuprofen, diclofenac).
Antifibrinolytic Therapy (tranexamic acid),
Adjunctive management
Reduces breakdown of blood clots and is effective for
treating and preventing recurrence of mouth
bleeds and epistaxis.
Contraindicated for treatment of haematuria.
Dose of tranexamic acid 25mg/kg/dose
(max:1.5g/dose) tds orally for 5-7 days.
Tranexamic acid should not be given to patients
with FIX deficiency receiving prothrombin complex
concentrates, as this will exacerbate the risk
of thromboembolism.
Antifibrinolytic Therapy (tranexamic acid)
Weight (kg)
<20 Kg
20 – 30 Kg
30 – 40 Kg
> 40 Kg
Tranexamic acid
250 mg tds
500 mg tds
750 mg tds
1 g tds
Definitions of factor replacement therapy
protocols
Protocol
Episodic
Definition
Treatment given at the time of clinically
evident bleeding
Continuous prophylaxis :primary,Secondary,Tertiary,Intermittant
Surgery and invasive procedures
Preoperative assessment should include inhibitor screening and
inhibitor assay, particularly if the recovery of the replaced
factor is significantly less than expected.
Surgery should be scheduled early in the week and early in the
day .
Adequate quantities of clotting factor concentrates.
Infusion of factor concentrates/hemostatic agents
is necessary before invasive diagnostic procedures
such as lumbar puncture, arterial blood gas determination,
or any endoscopy with biopsy.
Plasma
derived FIX
Monofix
Recombinant Benefix
FIX
500, 1000
250, 500,
1000, 2000
Hemophilia –B Factor IX
In absence of an inhibitor, each unit of FIX per
kilogram of body weight infused intravenously
will raise the plasma FIX level approximately 1
IU Dl.
The half-life is approximately. 18–24 hr.
Recombinant FIX (rFIX) :each unit of FIX per kg
body weight infused will raise the FIX activity by
approximately 0.8 IU dL in adults and 0.7 IU dL1
in children under15 years of age.
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Prophylaxis-long acting
The long-acting recombinant
Fc fusion factor IX (rFIXFc),
Alprolix, was approved by
the FDA in March 2014 for
patients with hemophilia
B.
Improvement of health and quality of
life of people with hemophilia
Joint and muscle damage and other sequelae
of bleeding.
Inhibitor development.
Viral infection(s) transmitted through blood
Products.
obligate carrier of hemophilia B
The biological daughter of a man who has hemophilia.
The biological mother of more than one son with
hemophilia.
The biological mother of at least one son with
hemophilia and has at least one other blood
relative with the disorder.
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Definition of response to treatment of
acute Hemarthrosis
Excellent :Complete pain relief within 8 hours and/or complete resolution of signs of
bleeding after the initial injection and not requiring any further replacement
therapy within 72 hours.
Good :Significant pain relief and/or improvement in signs of bleeding within
approximately 8 hours after a single injection, but requiring more than one dose of
replacement therapy within 72 hours for complete resolution
Moderate :Modest pain relief and/or improvement in signs of bleeding within
approximately 8 hours after the initial injection and requiring more than one
injection within 72 hours but without complete resolution
None :None or minimal improvement, or condition worsens, within approximately 8 h
after the initial injection.
Muscle hemorrhage
Sites of muscle bleeding that are associated with
neurovascular compromise, such as the deep flexor
muscle groups of the limbs, require immediate
management to prevent permanent damage and loss
of function. These groups include:
the iliopsoas muscle (risk of femorocutaneous,crural, and
femoral nerve palsy)
the superior-posterior and deep posterior compartments
of the lower leg (risk of posterior tibial and deep peroneal
nerve injury).
the flexor group of forearm muscles (risk of Volkmann’s
ischemic contracture).
Principles of care
The primary aim of care is to prevent and treat
bleeding with the deficient clotting factor.
2. Whenever possible, specific factor deficiency
should be treated with specific factor concentrate.
3. People with hemophilia are best managed in a
comprehensive care setting .
4. Acute bleeds should be treated as quickly as possible,
preferably within 2 h. If in doubt, treat
Definitions of factor replacement
therapy protocols
Secondary prophylaxis
Regular continuous treatment
started after2 or more bleeds into large joints and
before the onset of joint disease documented by
physical examination and imaging studies.
Tertiary prophylaxis
Regular continuous treatment
started after the onset of joint disease documented by
physical examination and plain radiographs of the
affected joints.
Intermittent (periodic) prophylaxis: Treatment given to
prevent bleeding for periods not exceeding 45 weeks in
a year.
Vein Access
They are the lifelines for a person with hemophilia.
23- or 25-gauge butterfly needles are
recommended.
Never cut down into a vein, except in an
emergency.
Apply pressure for 3–5 min after venipuncture.
Venous access devices should be avoided
whenever possible, but may be required in
some children.
Severity of Hemophilia B
Mild hemophilia : bleeding typically occurs only after injury,
trauma, or surgery. About 25% of the hemophilia population
has mild deficiency.
Moderate hemophilia :bleeding tends to occur after minor
injuries, though spontaneous bleeding episodes may occur.
About 15% of the hemophilia population has moderate
deficiency.
Severe hemophilia :may experience not only bleeding after
injury, trauma, or surgery, but also spontaneous bleeding into
joints and muscles. About 60% of the hemophilia population
has37severe factor deficiency.
Joint hemorrhage (Hemarthrosis)
The goal of treatment of acute Hemarthrosis is
to stop the bleeding as soon as possible. This should
ideally occur as soon as the patient recognizes the
“aura”, rather than after the onset of overt swelling
and pain.
Further evaluation is necessary if the patient’s
symptoms continue longer than 3 days. The presence
of inhibitors, septic arthritis, or fracture
should be considered if symptoms and findings
persist.
Hemophilia B-Signs &
Symptoms
The hallmark of hemophilia is hemorrhage
into the joints(typically the ankles in
children, and the ankles, knees, and
elbows in adolescents and adults).
This bleeding is painful.
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Management
Most bleeds will require factor replacement except
for bruises and minor soft tissue injuries that do not
impact on function and mobility.
Invasive procedures such as arterial puncture, lumbar
puncture must only be performed after clotting
factor replacement.
Do not give IM injections.
Physical activity
Non-contact sports such as
swimming,
walking,
golf,
badminton,
archery,
cycling,
rowing,
sailing,
table tennis