Coagulation factor disorders
Dr. Maji Jose
Coagulation factor disorders
• Inherited bleeding disorders
– Hemophilia A and B
– vonWillebrands disease
– Other factor deficiencies
• Acquired bleeding disorders
– Liver disease
– Vitamin K deficiency/warfarin overdose
– DIC
HAEMOPHILIA
• Also called as BLEEDER’S DISEASE,DISEASE OF
HAPSBURG,DISEASE OF KINGS.
• Disease has been known since ancient times but
SCHONLEIN in 1839 gave this ‘bleeders disease’
the name HAEMOPHILIA.
• Its 2nd most common hereditary coagulation
disorder.
THREE FORMS OF HAEMOPHILIA SEEN
• Haemophilia A(Classic haemophilia)
• Haemophilia B(Christmas disease)
• Haemophilia C
TYPE
Haemophilia A
CLOTTING FACTOR DEFICIENCY
Plasma thromboplastinogen
(AHG,antihaemophilicglobulin,
Factor VIII)
Haemophilia B
Plasmathromboplastin
component (PTC,Factor IX)
Haemophilia C
Plasmathromboplastin
antecedant(PTA,Factor XI)
• Its inherited as sex (X) linked recessive trait and
therefore manifested in males,while females are
carriers.
• Occassional women carriers of haemophilia may
produce factorVIII levels far below 50% and
become symptomatic carriers.
• True female haemophilis-due to consanguinity
within family-rare
• Transmitted through an unaffected daughter to a
grandson.
• Sons of haemophilic are normal and not
carriers of the trait.
• Heterogenous daughters carry the defect to
half of their sons and as recessive trait to half
of their daughters.
• Frequency of haemophilias varies in different
races,highest incidence being in population of
Britain,Northern Europe,Australia.
• Occurs in 1 in 10,000 male births
• Interesting factor-occurrence of this disorder
in royal blood of Great Britain and European
royal families.
HAEMOPHILIA A
• Most common type of haemophilia.
• Due to deficiency of factor VIII
ETIOLOGY
• Genes for factor VIII and factor IX located on long
arm of X-chromosome in bands q28 and q27.
• Haemophilia A result from inversion mutation45%
• Haemophilia A caused by quantitative reduction
of factor VIII in 90% cases,10% cases has normal
or increased levels of factor VIII with reduced
activity
• Normal haemostasis requires 25% of factor VIII
activity,symptomatic haemophilic patients have
factor VIII levels below 5%.
HAEMOPHILIA B
• Haemophilia B-several mutations like partial and total
deletions,missense mutations that result in decrease or
absence of factor IX .1 in 50,000 males
HAEMOPHILIA C
• Factor XI gene located on chromosome 4
• Mutation of factor XI gene cause failure ,reduced
production of active protein and rarely production of an
abnormal molecule result in factor XI deficiency.
CLASSIFICATION
CLASSIFICATION
FACTOR
ACTIVITY
CAUSE OF
HAEMORHAGE
MILD
>5
MAJOR TRAUMA
MODERATE
1-5
SEVERE
<1
MILD TO MODERA
TE TRAUMA
SPONTANEOUS
HAEMARTHROSIS,
SOFT TISSUE
BLEEDING
Clinical features
• Persistent bleeding after mild trauma.
• Haemorrhage into subcutaneous tissues internal organs
and joints is a common feature and result in haematomas.
• Its present from birth,but may not become clinically
apparent for years.
• 30-50% of patients with severe haemophilia present with
manifestations of neonatal bleeding such as prolonged
bleeding from umblical cord.
• Spontaneous cyclic remissions and
exacerbations of haemophilia are common
• Petechiae usually do not occur in patients
with haemophilia because they are
manifestations of capillary blood
leaking,which is result of vasculitis or
abnormalities in number or functions of
platelets.
• Haemophilia C – distinguished from A and B
by absence of bleeding into joints and
muscles and by its occurrence in individuals
of either gender
ORAL MANIFESTATIONS
• Gingival haemorrhage massive and prolonged
• Physiologic process of tooth eruption and
exfoliation maybe attended with severe
prolonged haemorrhage.
• Mandibular ‘pseudotumours’-a condition in
which there is subperiosteal bleeding ,with
reactive new bone formation causing tumour like
expansion of bone.-STONEMAN and BEIERL
• Dental extraction difficult-pre-medication
• Use of rubber bands-its placed around neck of
the tooth and allowed to migrate apically
causing exfoliation of tooth through pressure
necrosis of Periodontal ligament
LAB FINDINGS
• Coagulation time-prolonged
• Bleeding time –normal
• Prothrobin time and platelet aggregation-normal
• Activated partial thromboplastin time-prolonged
• Functional assay of factors useful in diagnosing
haemophilia caused due to dysfunction of coagulation
factors.
• Combination of low factorVIII and low Von
Willebrands factor indicate Von Willebrands
disease.
• In vitro,the deficiency of clot promoting
factors in the plasma of haemophilics impairs
clotting because it appears to retard
development of substance responsiblefor
conversion of prothrombin to thrombin
• A small percentage of haemophilics have
circulating anticoagulant,probably an
antibody,which specifically inactivates
antihaemophilic factor,negating effects of
transfusion
• Prognosis-variable and many affected person
die during chilhood.
TREATMENT
• No surgical cure.
• Tooth extraction in hospitals.
• Preoperative transfusion of whole blood and
administration of antihaemophilic factor
concentrate recommended.
VON WILLEBRANDS DISEASE
• PSUEDOHAEMOPHILIA,VASCULAR
HAEMOPHILIA,VASCULAR PURPURA
• It’s a disease characterised by the tendency to
excessive bleeding in patients who have normal
platelet count ,normal clotting time,normal
serum fibrinogen and prothrombin time.
• BT-prolonged
• It was 1st described by-Erik Adolf Von Willebrand
• 1st common hereditary disorder
• Inherited as AD trait transmitted by and manifested in
both males and females.
• More in females
• 1 in 1000 persons
ETIOLOGY
• vWdisease is due to an abnormality either
quantitative or qualitative of vWF ,which is large
multimeric glycoprotein that functions as the carrier
protein for factor VIII.
• A gene on chromosome 12p codes for the synthesis
of this macromolecule.
• A variety of point mutations,insertions and deletion
at vWF locus
• vWf –required for normal adhesion of platelet.
• It functions in both primary and secondary
haemostasis.
CLASSIFICATION :
• Type I :
characterised by partial quantitative decrease of
normal vWF and factor VIII
• Type II :
A variant of disease with primarily qualitative defects of
vWF. It can be either AD or AR
• Type III :
Severe and rarest form.
In homogenous patients type III vW disease is
charecterised by marked deficiencies of both vWFand
factor VIII in plasma .
Absence of vW F from both platelets and
endothelial cells and lack of secondary
transfusion response. This type is
characterised by severe clinical bleeding and is
inherited as AR trait. And common in case of
consanguinous marriage.
In heterozygous disease is less severe.
CLINICAL FEATURES.
•
Many children are asyptomatic – diagnosed as a
result of positive family history of during routine preoperative screening.
•
•
Excessive bleeding either spontaniously or following a
minor trauma.
Sites of bleeding- nose ,skin ,gingiva
•
Bleeding into GIT, severe menorrahagia, spontaneous
nose bleeds and cutaneous ecchymosis is seen.
•
Hemarthrosis is rare. Bleeding tendency- cyclic or
sporadic.
ORAL MANIFESTATIONS :
• Gingival bleeding- spontaneous or after brushing of teeth.
• Bleeding after dental extraction result in unmanagable
flow.
LABORATORY FINDINGS
• BT- range from several minutes to 1 hour.
• PT – Normal
• aPTT- Increased.
• CT – Normal but may be slightly prolonged.
• Capillary fragiliy – increased with +ve
torniquet test.
• Clot retraction --normal
• TREATMENT :
Transfusion of plasma and antihemophilic
factor and by local control of hemostasis.
THANK YOU