Bleeding Disorders

Question 1

What is haemostasis?

Answer 1

Arresting the flow of blood
First stage of wound healing
Primary - platelet plug
Secondary - coagulation

Question 2

What are the causes of bleeding?

Answer 2

Aspirin/Warfarin/Methotrexate/VWD/Bone marrow disease/immune disorders/liver disease/renal disease

Question 3

What are vascular disorders?

Answer 3

Marfan
Ehlers-Danlos
Osler-Weber Rendu Syndromes

Question 4

What are platelet problems?

Answer 4

ITP
Glanzmann disease
VWD
Bernard Soulier Syndrome
Renal failure
Bone marrow disorders
Splenomegaly and liver disease
Systemic lupus erythematosus

Question 5

What are anti-platelet drugs?

Answer 5

Aspirin
Clopidrogel
Dipyridamole
Ticagrelor

Question 6

What is Idiopathic Thrombocytopenic purpura?

Answer 6

Antibody mediated platelet destruction
Features include petechiae; ecchymoses; post op bleeding
FBC indicated as platelet count expected to be low
Treatment includes corticosteroids; splenectomy; thrombopoietin(stimulate platelet production)

Question 7

What is VWD?

Answer 7

Most common inherited bleeding disorder
Deficiency of VW factor - causes abnormal platelet function and low factor VIII activity
Autosomal dominant
M:F
1:1000 of population
6% of women with menorrhagia
vWF promotes platelet adhesion to damaged endothelium and other platelets, and also stabilises and transports Factor VIII

Question 8

What are the clinical features of vWD?

Answer 8

Clinical severity depends on the amount and severity of the defect
3 types:
1. Type 1 (most common)
2. Type 2 (normal amount of vWF but dysfunctional)
3. Type 3 (most severe, no vWF) similar to haemophilia

Question 9

What is the management of vWD?

Answer 9

Haematologist consultation
Desmopressin can be used in Type 1 and Type 2A but is contra-indicated in Type 2B and type 3 (increases release of vWF)
Severe clotting factor needed
Factor VIII, cryoprecipitate and fresh frozen plasma are effective
In more severe cases vWF concentrate may be required
Avoid blocks
Avoid aspirin and NSAIDs

Question 10

What is Aspirin?

Answer 10

Irreversible cyclo-oxygenase (COX) enzyme inhibitor
COX Catalyses the production of thromboxane A2, which is important for platelet aggregation
Its effect lasts as long as the platelets (7-10 days)
Recovery can occur by day in 80% of cases
Low dose Aspirin is the first line of treatment for thrombosis and MI
Can cause GI bleeding and is best taken with food
Aspirin will only affect the function of platelets not the number

Question 11

What are Thienopyridines?

Answer 11

Irreversibly inhibit platelet adhesion by the ADP Dependent Pathway
Within 2 hours of ingestion
Clopidrogrel is used in conjunction with aspirin, in patients with aspirin allergy or intolerance, atherosclerotic events, percutaneous coronary intervention (PCI)
Prasugrel is a newer drug which is more potent and acts more rapidly.
Platelets recover after 2 days

It prevents platelets (a type of blood cell) from sticking together and forming a dangerous blood clot
Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent.

Question 12

What are phosphodiesterase inhibitors?

Answer 12

Inhibits phosphodiesterase with inhibits adenosine uptake and breakdown of cyclic adenosine and guanosine monophosphate
Dipyridamole (Persantin) also have a vasodilator effect

Phosphodiesterase inhibitors are medications that cause blood vessels to relax and widen, improving circulation and lowering blood pressure.

Question 13

What are P2Y12 receptor agonists?

Answer 13

Ticagrelor is a P2Y12 receptor agonist
It works by blocking the ADP P2Y12 receptor Its effects are reversible
It acts within 1.5 hours but has a shorter effect

Ticagrelor slows the blood’s clotting action by making platelets less sticky.
Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries

Question 14

What are the challenges to coagulation?

Answer 14

2 categories:
1) Coagulation disorders (haemophilia A/B/C, Liver disease, Vitamin K def, Factor VIII deficiency)
2) Anticoagulants (warfarin, NOAC, heparin)

Question 15

What is haemophilia A?

Answer 15

X linked recessive (males)
Caused by deficiency Factor 8
1 in 10000
10x more common than Haemophilia B
3% cases are due to spontaneous mutation
Female carriers rarely have bleeding tendency

Question 16

What are the clinical features of Haemophilia A?

Answer 16

Severity of the bleeding disorder correlates with the level of factor VIII:
1) Severe (<1%) - spontaneous bleeding into joints and muscles
2) Moderate (2.5%) - severe bleeding after trauma/surgery
3) Mild (5-50%) - prolonged bleeding after trauma/surgery

Haemophilia should be suspected in males with a history of:
- Easy bruising in childhood
- Spontaneous bleeding particularly in joints, muscles or soft tissues
- Excessive bleeding following trauma

Question 17

What is the management of Haemophilia A?

Answer 17

Non-surgical dentistry can be carried out with tranexamic acid and regional LA
Factor replacement required for IDB and lingual infiltration, but not for buccal infiltration, intrapapillary injections or intraligamentary injections
Surgical procedures will require at least desmopressin and tranexamic acid
factor 8 levels of 50-75% are required for minor surgery and dental extractions
local measures and tranexamic acid can be used post-operatively
for persistent or severe bleeding recombinant factor 8 can be administered
replacement factor 8 must be given for intubation
repeated administration can result in factor 8 antibodies
for maxillofacial procedures factor 8 levels should be 75-100%
lingual flaps should be avoided to prevent tracking to the mediastinum
NSAIDs and aspirin should be avoided
The patient should be warned to report swelling, dysphagia or hoarseness ASAP

Question 18

What are the clinical findings for Haemophilia A?

Answer 18

Severity of bleeding disorder correlates to level of factor VIII:
1. Severe <1% spontaneous bleeding into joints and muscles
2. Moderate 2-5% severe bleeding after trauma
3. Mild 5-50% prolonged bleeding after trauma/surgery

Question 19

When is haemophilia suspected in males?

Answer 19

Easy bruising in early childhood
Spontaneous bleeding particularly in joints, muscles or soft tissues
Excessive bleeding following trauma

Question 20

What is the management of haemophilia?

Answer 20

Non-surgical dentistry can be carried with tranexamic acid and regional LA
Factor replacement required for IDB and lingual infiltration, but not for buccal infiltration, intraligamentary injections
Surgical procedures will require at least desmopressin and tranexamic acid
Replacement factor VIII given for intubation

Question 21

What is liver disease?

Answer 21

The liver is important for the synthesis of Vitamin K dependent clotting factors I (fibrinogen), II (prothrombin), VII, IX and X
The liver also produces factor XI
Deficiencies lead to prolonged PT
It also produces thrombopoietin (MGDF) which regulates platelet production by bone marrow
Failure of normal liver function can lead to malabsorption of Vitamin K
Alcohol abuse is the most common cause of liver disease

Question 22

How is bleeding related to liver disease?

Answer 22

Reduced clotting factors
Bone marrow suppression and thrombocytopenia
Malnutrition leading to deficiency of Vitamin K due to heavy drinking

Question 23

What treatment is provided for bleeding associated with liver disease?

Answer 23

Frozen plasma may be needed
Vitamin K treatment in obstructive disease
Hepatitis is frequently undiagnosed and can result in cirrhosis

Question 24

What is the Warfarin?

Answer 24

Coumarin oral anticoagulant
Works by inhibiting biosynthesis of vitamin K dependent anticoagulants (II,VII,IX and X)
It prolongs PT and aPTT and is measured using INR
Normal target INRs are between 2-3
For patients with mechanical heart valves it may be between 2.5-3.5 but possibly as high as 4.5

Question 25

What is the management of patients with Warfarin?

Answer 25

The BNF states that an INR should be undertaken between up to 72 hours before the procedure
For patients with an unstable INR, the value should be checked less than 24hrs before the procedure
Hospital referral is indicated if the patient has an additional bleeding risk factors, an INR greater than 4 or complex procedures
NHS Tayside Guidelines states that INR as close to the time of extraction as possible should be checked.

Question 26

What are the NHS Tayside Guidelines?

Answer 26

No indication for routinely prescribing antibiotics for patients who take oral anticoagulants. (Where antibiotics are indicated, it should be noted that many antibiotics interact with coumarins and ideally the INR should be rechecked 4 days after starting a course of antibiotics)
Morning appointments
LA with vasoconstrictor should be used unless contraindicated.
Caution when scaling.
Extraction limited to a maximum of 3 teeth per visit with only a single tooth extracted at the first visit
Sockets should be gently packed with haemostat and sutured ideally with resorbable sutures
Paracetamol is safest option of post op pain control.

Question 27

What are the complications of warfarin?

Answer 27

Stopping warfarin outweighs the risk of bleeding
Risk of thrombolic event increases due to hypercoagulability and rebound thrombosis
Bleeding episodes can be treated with vitamin K, prothrombin complex concentrate and fresh frozen plasma

Question 28

What are the interactions with Warfarin?

Answer 28

Warfarin’s effect is altered by many drugs
NSAIDs and aspirin can displace warfarin from serum albumin and increase INR as well as inhibit platelet function
Broad spectrum antibiotics affect GI flora and the absorption of vitamin K
Metronidazole, macrolides and azoles inhibit metabolism of warfarin and increase INR
St John’s Wort induce enzymes that breakdown Warfarin reducing INR
If antimicrobials are required narrow spectrum Penicillin - V or clindamycin should be used.

Question 29

What are Novel Oral Anticoagulants?

Answer 29

Direct thrombin inhibitors (Dabigatran). Dabigatran is used for prevention of stroke.
Factor Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban)
Fewer interactions with warfarin
suffer fewer thrombotic events
reduce incidence of bleeding events
used for patients with atrial fibrillation and may be used in acute coronary syndromes

Question 30

What are the interactions with NAOCs?

Answer 30

Ketoconazole and itraconazole
NSAIDs
Rifampicin
St John’s Wort

Question 31

What does Dabigatran interact with?

Answer 31

Erythromycin and clarithromycin
Carbamazepine
Dexamthasone
Verapamil

Question 32

What does Rivaroxaban interact with?

Answer 32

Phenytoin

Question 33

What is the SDCEP guidelines for patients taking NAOCs?

Answer 33

Patients with a low risk of bleeding complications, treat without interrupting their anticoagulant medication
Pts with a high risk of bleeding complications, advise them to miss (apixaban, dabigatran) their morning dose or (rivaroxaban) delay for 4 hours their morning dose on the day of their dental treatment.