Inherited Bleeding Disorders Flashcards
what is the timescale of the coagulation cascade
Continuous process happens all the time in everyone
Fibrin lysis is happening at same rate of coagulation
what is the relationship between clot build up and break down in a coagulopathy pt
Clotting and clot breakdown are not matched
- Imbalance in ability to clot or not clot
what is the role of proteins in the coagulation cascade
Areas of problems if deficient
Breaks on coagulation system
- Missing not behave the way they should
- Defined control is upset
how should you treat a bleeding disorder pt in general
Treat as a normal person
- Depend on individual and disease level
Treatment planning
Be aware of potential problems
- Hygiene phase therapy
- Local anaesthetic
- Extractions and surgery
what is the main technique to employ for dental treatment of blood disorder pt
PREVENTION
Avoid having to do dentistry - then not a risk as problem cannot arise (manage with prevention)
- Oral Hygiene
- Regular dental care
- Fluoride supplements
- Fissure sealant
- Dietary advice
what are dental treatments that special care would be required for treating a bleeding disorder pt (4)
Extraction
Minor oral surgery
Periodontal surgery
Soft tissue Biopsies
what are dental treatments that no additional problems would be incurred for a bleeding disorder pt
Hygiene therapy
Removable prosthodontics
Restorative dentistry inc crowns and bridges
Endodontics
Orthodontic treatment
No blood being released from mouth or blood getting into mouth
No need for ID block
what do you and the pt haematologist need to do prior to dental extractions and surgery
Appropriate monitoring +/- treatment prior to the procedure
Preparation work is necessary to get pt properly ready so more likely to have successful treatment
Liaise with haematologist so they work out coagulation issue for the dental tx plan
- Communicate well
what are the 3 possible areas of defect for the inherited bleeding disorders
coagulation cascade
platelets
a combined deficiency
what could be a coagulation cascade issue
a reduction in one, or more, of the coagulation factors
what could be issues with the platelets
number or function
- both are key to platelet role
Factor VIII deficiency
haemophilia
haemophilia A
factor IX deficiency
Christmas disease
haemophilia B
Von Willebrand’s disease
Reduced factor VIII level
Reduced platelet aggregation
factor XI deficiency effects
common in Ashkenazy Jew population
what are examples of types of rare bleeding disorders
Inherited defects of other factors in the coagulation pathway
Inherited defect of either the number or function of the platelets
Numbers in each group are small
- Large number of different conditions registered in the UK (Over 50)
Management is complex as the bleeding does not always relate to the factor levels
what is the representation of bleeding disorders like in small gene pools
disproportionately represented
what are carriers of Haemophilia
More than enough
- Large amount of redundancy in clotting factors in normal life
Serious bleeding problem where coagulation severely tested then can be an issue
what type of inheritance is HA and HB
sex linked recessive gene
- One X chromosome that is defective
Rare for girls
Boy with will have
what is the CF that is effected in haemophilia
CF8
Make some but inadequate if slightly broken
Completely defective – no F8 made
spectrum of activity depending on how defective the gene is
what are haemophilia centres
Manages all coagulopathies
Few in Scotland
Practically - rural have distance to travel to get to major support
General plan of action with GP and local hospital and then large problems at centre
Have a special dental care team attached
who are more prone to get rare coagulation disorders
Autosomal recessive (?) inheritance - Bad luck – 2 recessive genes
More common in racial groups where cousin marriage frequent
- Factor XI common in Ashkenazy Jews
why are rare coagulation disorders difficult to manage
Generally, lack of clear correlation between bleeding and level of factor, so more difficult to manage
- Doesn’t always translate into bleeding problems
what are inhibitors to CFs
antibodies which develop to factor VIII and IX (clotting factor)
- Body doesn’t make them usually
- Binds to artificial clotting factor (not made in body) so removed from circulation so no clotting factor
- — Slightly different to body’s – matches the receptor and triggers the sequences but tail end can be subtly different so recognised as foreign
The amount of antibody developed varies between patients
when are inhibitors made
35-40% of patients develop an inhibitor when they first start treatment
Usually disappear shortly after treatment
- Use factor fast - fine as take a while for body to make response
But if give artificial clotting factor often then need to factor in part removed by inhibitor
- Give more to overcome the loss
how should pt be treated with artificial recombinant CFs to manage inhibitors
Need to have carefully Tx to allow inhibitors to drop most of the time so when given factors have a positive effect
what does a pt with a congenital bleeding disorder look like
Normal appearance, challenges with bleeding but tend to live a normal life
what sex is affected by haemophilia
males
what sex are the carriers of haemophilia
females
what is the severe level of haemophila
less than 0.02iu/ml
2%
what are the ranges of severe to moderate to mild to carriers of haemophilia
Severe <0.02iu/ml
Moderate 0.02-0.09 iu/ml
Mild 0.1 – 0.4 iu/ml
Carriers <0.5 iu/ml
why is there such a large decrease between normal CF8 level to severe haemophilia
Lots of reserved capacity for F8
- Take a while to see effect
- Excessive capacity in kidneys
what is the clinical effect of haemophilia A
small clotting problem, more bleeding when cut themselves
treatment of severe and moderate haemophilia A
Require the use of recombinant factor VIII
- No other option/ substitution
Made by bacteria
- Protein factor 8 purified and injected as needed
- Depend on activity
treatment of mild and carriers of haemophilia a
Majority respond to DDAVP
- Vasopressin, like ADH
- Release stuck F8 from endothelial cells (like glucose to haemoglobin)
- Released due to competitive binding
- Deals with mild bleeding problems
Very mild cases may only require oral tranexamic acid
- Inhibitor of fibrinolysis
- Slow down clot break down – important balance of 2 processes
- Returns pt to normal
- Slower and lower level of turnover of clots
Occasionally require F8
- E.g. Challenge to vascular system e.g. extraction
treatment of haemophilia B
Do not response to DDAVP
- F9 is not bound to endothelial cells unlike F8
Prophylactic cover requires recombinant factor IX
- Only way to manage is with recombinant
what type of inheritance is von WIllebrand disease
Autosomal dominant
- Both sexes equally affected
- Normal gene and spontaneous mutation or inherited
what causes von Willebrand disease
Deficiency of von Willebrand factor with a reduction in factor VIII levels
Platelet and coagulation F8 problem
what are the 3 types of von Willebrand disease
Type 1 - Dominant - Mild
Type 2 - Dominant - Mild
Type 3 - Recessive - Severe
- less likely - 2 parents pass on recessive gene
what is the treatment for von willebrand disease
Majority of patients responds to DDAVP
- F8 platelet aggregation
Interacts with F8 in blood
- Defective VW factor on platelet
- Role of platelet in starting coagulation is affected
- now ineffective
Very mild cases may only require oral tranexamic acid
how are coagulation disorders treated throughout the UK
Common standardised treatment regimes for all patients.
- National management of Tx
Depend on level of risk that they pose
Treatment should be available locally.
- Mild haemophilia – dentist can do all (sometime extractions in haemophilia centre)
- Hospital visits reduced.
- —-More convenient and simpler for pt to have locally managed
in general how do severe and moderate coagulation disorder pt get treated
Majority of the treatment in the hospital except for prosthodontics.
- Denture by local – small bleeding risk
Treatment by GDP/PDS by arrangement
in general how do mild and carriers of coagulation disorders get treated
Treatment shared with GDP/PDS.
- Extractions, LA
Patient reviewed at the hospital every 2 years.
- Check nothing needs changed, all fine
5 types of dental treatment where special care would be required no matter the severity of coagulation disorder
administration of LA (esp ID nerve block)
extractions
minor oral surgery
periodontal surgery
biopsies
risk of blood loss
safe LA injection sites for coagulopathy pt (3)
Buccal infiltration
Intraligamentary injections (space between tooth and gum)
Intra-papillary injections (space between the teeth)
dangerous LA injection sites for coagulopathy pt (3)
Inferior alveolar nerve block
Lingual infiltration
Posterior superior (maxilla) nerve block
can mild haemophiliac get LA injections by GDP
yes - if choice of LA and technique is correct
what is the concern with extractions and dental surgeries for haemophiliacs
stopping bleeding
how should a extraction/surgery be approached for a haemophiliac
Appropriate cover from Haemophilia Unit A
- Activity of F8 and 9 and inhibitors at basal and post injection level
- Work out the amount needed to be administered prior to extraction
- Haematologist prepare pt
traumatic treatment
Consider antibiotics
- Infection will disturb clit
- Routinely not used unless there is an infection
Observe for 2-3 hours after surgery (minimum requirement)
- Initially bleeding is stopped by platelets
- Takes a few hours for coagulation to build up fibrin clump over it
Comprehensive post-operative instructions
- If start to bleed again
- –Local treatment and potential more clotting factors needed
- –Communication between GDP and haematologist
how long should a severe and moderate coagulopathy pt be observed post surgery/extraction
Patients should be observed overnight following surgery
Risk of problem is higher with more they do
Take out of domestic environment to try and ensure low activity level
- Less BP and trauma to trigger bleeding
how long should a mild and carrier pt be observed post surgery/extraction
2-3 hours after surgery
what 9 possible parts of a coagulopathy pt comprehensive care team
Patient haematologist physiotherapist nurses dental surgeon psycho-social workers laboratory technicians orthopaedic surgeon
A lot involved in managing these pt
Manage well - should have good quality of life
what is thrombophilia
Increased risk of clots developing
- Opposite to haemophilia
Disproportionate clotting to fibrinolytic action
- Over producing clot or not enough fibrinolytic products
Can be relatively undetectable until make blood clot inappropriately
- E.g. DVT leads to pulmonary embolism
- Mild until certain set of circumstances causes them to become visible
Often an acquired condition superimposed on a genetic condition
Usually possible to find a cause for the clot
what are 4 inherited syndromes that can lead to thrombophilia
Protein C deficiency
Protein S deficiency
Factor V Leiden
Antithrombin III deficiency
what are 7 acquired syndromes that can lead to thrombophilia
Antiphospholipid syndrome
- Lupus anticoagulants (sub group of lupus)
Oral contraceptives
Surgery
Trauma
Cancer
Pregnancy
Immobilisation
risk of having high levels of clots
how are acquired syndromes causing thrombophilia managed
managed by medications that will reduce the level of clots
how are inherited syndromes of thrombophilia managed
broken down into individual groups and managed from there
thrombocytopenia
redcued platelet numbers
qualitative platelet disorders
normal platelet number but abnormal function
thrombocytopenia
increased platelet numbers
what are 3 platelet abnormalities
Thrombocytopenia
Qualitative disorders
Thrombocythemia
what are causes of thrombocytopenia
Idiopathic
Drug related - Alcohol - Penicillins - Heparin secondary to lymphoproliferative disorders
what is the effect on dental treatment of thrombocytopenia
dental treatment can proceed safely
providing the platelet count > 50 x10^9
how can qualitative platelet disorders arise
inherited
what are 3 rare qualitative platelet disorders
Bernard Soulier Syndrome
Hermansky Pudlak
Glanzmann’s thrombasthenia
what are 4 reasons for acquired qualitative platelet disorders
Cirrhosis
Drugs
Alcohol
Cardiopulmonary bypass
what is the treatment for thrombocythemia
Uncommon disease
Usually on aspirin to prevent clot formation
