Inherited Coagulation Disorders Flashcards
Haemophilia A
➢Haemophilia A is an _________
bleeding disorder caused by
__________ or ________ factor _____ molecules or a combination of both
X-linked
defective synthesis
synthesis of dysfunctional
VIII
____________ is the commonest inherited
bleeding disorder after ______
Haemophilia A
vWD
Haemophilia A
➢F8 gene is located on ________
➢ pathophysiology is based on
insufficient generation of _______
by the ______ complex of the
_______ pathway
Xq28
thrombin
IXa/VIIIa
intrinsic
Haemophilia A
➢All sons of haemophilic males
with non-carrier wives are _____
➢All daughters of haemophilic males
with non-carrier wives are _______
normal
obligatory carriers
Haemophilia A
➢Sons of carriers have ____%
chance of being affected
➢Daughters of carriers have 50%
chance of being ______ if ________
50
carriers
father is normal.
Haemophilia A
✓Can result from multiple
alterations in the ____ gene:
✓Over _____ mutations noted
F8
142
Haemophilia A
Carrier detection can be as below:
•Family history
•Carriers usually have _____% or (more or less?) of _______ levels
•________ technique to detect
the ____________
•Prenatal diagnosis through ________
50; less
factor VIII
Southern blot
intron 22 inversion
DNA analysis
Haemophilia A: Carrier detection
vWF:FVIII is (lower or higher?) in carriers
Higher
Clinical classification of haemophilia A
- Mild: factor level is _____% of normal
(0.06-0.3 U/ml); _______ spontaneous bleeds, secondary to _____ or ____ - Moderate: factor level is ___-___% of
normal (0.01-0.05 U/ml); ____
spontaneous bleeds, secondary to ______ or _______ - Severe: factor level is ____% of
normal (≤ 0.01 U/ml); spontaneous
bleeds from _______, requires
factor replacement
6-30; extremely rare ; trauma or surgery
1-5; occasional; trauma or surgery
≤ 1; early infancy
Haemarthrosis in Haemophilia A:
➢Accounts for approximately ____% of
bleeding episodes
➢_______ beneath the _____ easily damaged
75
Numerous capillaries; synovium
Haemarthrosis in Haemophilia A:
Affects which joint more?
Hinge or ball and socket
Hinge joints > ball & socket joints
Haemarthrosis in Haemophilia A:
Hips, knees, shoulder, elbows, wrists, ankles
➢arrange the joints in order of deacresing frequency:___,______,_____,______ ,_____,_____
knees, elbows, ankles,
shoulders, wrists and hips
Haemarthrosis in Haemophilia A:
➢Occurs when affected child ___________
begins
to walk
Haemarthrosis
➢Heralded by aura of ____ discomfort which progresses in _____-____ to _____ pains
➢Joint ———, (cold or warm?) , ____ motion
➢May experience (mild, moderate, severe?) fever
mild; minutes-hours ; severe
swells; warm; limited ; limited
Mild
Haemarthrosis
➢Repeated bleeds destroys the ———- and leads to ____________
articular cartilage ; synovial hyperplasia
Haemarthrosis
➢A major complication is ____________, associated ________ and ____________ and —————-
joint deformity
muscle atrophy
soft tissue contractures and chronic
synovitis
Haematomas
✓Characteristic of __________
✓Bleeding into ________ is not
common
clotting factor deficiencies
myocardium
Haematomas
occurs only with known traumas
T/F
F
May occur with or without known
traumas
Haematomas
✓May stabilize and __________
Or
✓May ____________ and ______________, thereby ___________
slowly resorb
enlarge progressively
dissect in all planes
compressing vital organs
____________ is the most dangerous haemorrhagic event
Intracranial bleeds
Neurologic complications of Haemophilia A
Spontaneous or following trivial
trauma in _________ patients
severely deficient
Neurologic complications of Haemophilia A
➢Suspect if _________ persists
➢ Immediate __________ following suspicion (before or after?) CT scan
or MRI
unusual headaches
factor replacement
Even before
Neurologic complications of Haemophilia A
Bleeding into the spinal canal is
(Common or uncommon?)
Bleeding into the spinal canal may produce _________
uncommon
paraplegia
Lab features of Haemophilia A
✓APTT: ———-
✓PT: ________
✓BT: ________
✓TT: is ________
prolonged
normal
normal
normal
Lab features of Haemophilia A
✓__________ assay: definitive
diagnosis
Factor VIII
Lab features of Haemophilia A
FVIII antigen is measured by _________.
immunologic assays
If FVIII antigen level is normal and APTT is prolonged then the patient has _____________
dysfunctional FVIII molecule
Treatment of Haemophilia A
✓Avoid ____,_____
✓May use ______,______,________ in moderate doses
✓__________ with caution
✓_____ injections should be avoided
✓Replacement therapy ASP
✓Home treatment facilities
✓________ for the severely deficient
ASA, NSAIDs,
acetaminophen, celecoxib,
rofecoxib
Addictive narcotics
IM; Prophylaxis
Factor VIII replacement
Several plasma products are available for use to raise VIII levels
➢_______
➢ __________
➢_____________ from pooled donors
➢Plasma-derived VIII produced by ______ techniques
➢VIII produced by _______ techniques
e.g ______
➢______ VIII is useful in patients with VIII
_________
FFP
Cryoprecipitate
Lyophilized VIII
monoclonal antibody
recombinant DNA ; ADVATE
Porcine; antibodies
VIII replacement
✓____ U per ml of plasma is considered 100% of normal
✓Required dose depends on patient’s _________ and _________
✓½ life of VIII is _____-______
1
plasma volume (approx 5% wt in kg) and the desired level
8-12 hrs
_________
• Commonest inherited bleeding disorder
vWD
vWD
•approx 1 in _____
•Types ________
•__________ pattern of inheritance
100
1, 2 and 3
Autosomal recessive
vWF is a central component of haemostasis
T/F
T
Relationship between VWF and F8
VWF is a carrier protein for VIII in circulation
VWF
•Provides ______ interphase between _____ and _______
adhesive
platelets and
injured vessel wall
vWF produced exclusively in ______
and ________
endothelial cells
Mgks
Treatment of VWD is by _______, DDAVP
replacement
