Transcript Factor X levels 10-40% is usually adequate. Fresh frozen plasma

Inherited Bleeding Disorders
Factor X Deficiency
Galila Zaher, MRCPath
Assistant Professor
Consultant Hematologist
KAUH
Stuart-Prower Deficiency.
ii.
Inherited bleeding disorder.
It is due :
A lower than normal amount of FX
or FX which does not work properly.

Bleeding when the FX level below 10%


i.
Incidence







Rare factor deficiency.
Only 50 cases identified in the world.
1 in 500,000 people.
More frequent :consanguinity
“Autosomal recessive" disorder.
Affects males and females equally
No known racial or ethnic predilection.
Factor Level
More than 10% : Few problems
 1-10% :Mild to moderate bleeding
 Less than 1% : Severe bleeding

Clinical Presentation








Age: can present at any age.
More severe cases present during infancy
Umbilical cord stump bleeding
Bleeding after circumcision
Hemarthroses
Nose bleeds
Easy bruising
Bleeding in soft tissues and in muscles
Clinical Presentation







Gastrointestinal bleeding
Heavy and prolonged menstrual period
Hematuria
Intracranial bleeding (rare)
First-trimester miscarriage &Post-partum
bleeding
Post surgical traumatic bleeding
Petechiae, ecchymoses.
Replacement Therapy
Fresh frozen plasma
 Prothrombin Complex Concentrate

Physiology
Vitamin K–dependent serine protease
 First enzyme in the common pathway
 Inherited or acquired.
 In 1950s, Telfer reported woman
named Prower 1956; Hougie reported
man named Stuart 1957.
 Factor designated Stuart-Prower .

Clinical Features





Heterozygotes : asymptomatic.
Homozygous : hemorrhagic symptoms
Long arm ch 13, downstream FVII gene
It is composed of 8 exons
Signal region, a propeptide region, a
glutamic acid domain, an ”aromatic stack”
region, 2 regions homologous to epidermal
growth factor, and a catalytic domain
Physiology







FX Xa (intrinsic & extrinsic clotting
cascades).
Activation by the :TF-F VIIa.
Or by :FIXa and F VIIIa.
FXa :Prothrombin  thrombin
Positive feedback loop by activating FV,
VII, and VIII.
Inactivating both FVIII and tissue factor.
FXa is ultimately inactivated by AT
Factor X Deficiency
Type I deficiency :reduced synthesis
 Type II deficiency :production of a
dysfunctional molecule
 Complete absence is incompatible
with life.
 Missense mutations

Several Specific Mutations
Gamma-carboxylation
 Altering cleavage site of factor X
 Interference with protein folding

Acquired Deficiency












Vitamin K deficiency, Sodium valproate
Oral Anticoagulant
liver disease
Amyloidosis :8%
Myeloma
Mycoplasma pneumoniae infection ,URTI
Lupus anticoagulant
Leprosy
Children with severe burns
Topical thrombin administration
Leukemia and malignancy
intestinal malabsorption
Lab Studies





PT, APTT
The Russell viper venom time cleaves FX
FXa.
Type I : Functional & antigenic are
decreased
Type II :functional is decreased and
antigenic level varies
Vitamin K deficiency :other clotting
factors reveal decreases
Treatment


i.
ii.

i.
ii.
iii.
iv.
v.
vi.
Factor X levels 10-40% is usually adequate.
Fresh frozen plasma
Initial dose :15-20 mL/kg
Maintenance doses of 3-6 mL/kg q 12-24 hours.
PCCs
Contains F II, VII, IX, and X and protein C.
Trace of heparin to guard against thrombosis.
Dose calculated depending on concentration of protein C
50-125 U/kg
No more than 2-3 doses in the first 36-48 h
Thrombotic complications
Acquired , treat underlying cause
i. Vitamin K :acquired deficiency
ii.
Amyloidosis :splenectomy
Monitor

i.
ii.
iii.






Thrombotic complications
Administered with rFVIIa,
OR antifibrinolytics
FX levels >50%
Hypersensitivity reaction
Clinical response
PT, and aPTT should be closely monitored
Vit K Adult Dose 10 mg PO/IV/IM/SC
Pediatric Dose :1 mg IM as single dose
IV :rare anaphylactoid reactions and death