Bleeding disorders

Question 1

What are the components of the blood haemolytic system? (3)

Answer 1

Plasma coagulation factors
Platelets
Blood vessel wall

Question 2

What are the main 4 steps of the blood haemostatic system?

Answer 2

1. Trigger
2. Primary haemostasis
3. Thrombin generation
4. Thrombin consolidates clot formation

Question 3

Explain the steps of the blood haemolytic system (7)

Answer 3

STEP 1: TRIGGER

1. Collagen and tissue factor exposed
2. Von Willebrand Factor (vWF) binds to collagen

STEP2: Primary haemostasis

3. Platelets adhere to vWF-collagen
4. Platelets activate and aggregate.

STEP 3: Thrombin generation
5. TF initiates rapid thrombin generation on activated platelets

Step 4: Thrombin consolidates clot formation

6. Thrombin converts fibrinogen to fibrin and completes platelet activation.
7. Stable fibrin-platelet clot is formed.

END PRODUCT: Stable cross-linked clot

Question 4

What causes thrombin production?

Answer 4

Tissue factors exposed to coagulation factors

Question 5

What is primary haemostasis?

Answer 5

When platelets adhere to vWF-collagen and platelets activate and aggregate.

Question 6

What can go wrong with the coagulation pathway? (2)

Answer 6

1. Abnormal primary haemostasis
   > Reduced platelet number or function
   > Reduced Von Willebrand factor
2. Abnormal coagulation pathway?
   > Reduced clotting factors (e.g. factor VIII)

Question 7

Is abnormal skin bleeding a primary haemostasis or coagulation disorder?

Answer 7

Primary haemostasis

Question 8

Is deep tissues bleeding a primary haemostasis or a coagulation disorder?

Answer 8

Coagulation disorder

Question 9

What are the patterns of bleeding for primary haemostasis disorders? (5)

Answer 9

• Petechiae/bruising
• Epistaxis
• Gum bleeding
• Menorrhagia
• GI/CNS bleeds

Question 10

What are the patterns of bleeding for coagulation factor disorders? (3)

Answer 10

1. Bleeds into joints
2. Soft tissue bleeds
3. CNS/GI bleeds

Question 11

How do you identify people with abnormal haemostasis? (2)

Answer 11

1. Clinical Evaluation
   > Bleeding history is very sensitive to underlying bleeding disorders.
   
   • after previous dental procedures or surgery
   • after minor trauma
     > Family history of bleeding
     > General medical history
     > Drug history
2. Laboratory evaluation
3. Full blood count
   > platelet count (but not platelet function)
4. Clotting screen
   > ‘PT’ and ‘aPTT’ indicate whether coagulation factors are functioning.

Question 12

How does the full blood count check for bleeding disorders?

Answer 12

Looks at platelet count (not function)

Question 13

How does a clotting screen check for bleeding disorders?
What is PT?
What is aPTT?
What would be shown if there is abnormal function of coagulation factors?

Answer 13

PT = prothrombin time
aPTT = activated partial thromboplastin time

these indicate if coagulation factors are functioning

abnormal function usually gives increased PT and/or increased aPTT

Question 14

What is INR and what does it show?

Answer 14

INR = international normalised ratio

ratio of patient PT to ‘normal’ PT

Question 15

Why do you have to be careful with laboratory evaluation? (3)

Answer 15

> not all bleeding disorders cause abnormal FBC, PT or aPTT.

> abnormal FBC, PT or aPTT doesn’t necessarily mean bleeding

> further specialist tests are always required to make specific diagnosis
e.g. Factors assays. Factor VIII down so Factor VIII deficiency (Haemophilia A)

Question 16

What are the classifications of bleeding disorders (3)

Give examples for each

Answer 16

1. INHERITED DISEASES
   - Haemophilia A
   - Von Willebrand disease
2. ACQUIRED DISEASES
   - Thrombocytopenia (e.g. immune thrombocytopenia, chemotherapy)
   - Kidney disease
   - Liver disease
3. ANTI-THROMBOTIC DRUGS

Question 17

What is Von Willebrand disease?

Answer 17

It is reduced circulating levels of vWF resulting in abnormal bleeding.

most common genetic bleeding disorder.

Maybe no abnormalities in PT/aPTT/PLT

Question 18

What are the symptoms of Von Willebrand disease?

Answer 18

Abnormal primary haemostasis

Question 19

What are the symptoms of abnormal primary haemostasis? (4)

Answer 19

• Epistaxis
• Gum bleeding
• Heavy menstrual bleeding
• Skin bleeding - (don’t confuse with non-accidental injury)

Question 20

What are the treatments to prevent bleeding in mild Von Willebrand disease? (2)
explain how they work and their route of entry

Answer 20

1. Tranexamic acid
   - tablets or mouthwash
   - reduced clot break-down (antifibrinolytic)
   > tranexamic acid stabilises fibrin clot formed and prevents premature breakdown by fibrinolytic enzymes such as plasmin.
2. Desmopressin (DDAVP)
   - subcutaneous or intranasal
   - releases endogenous vWF

Question 21

What is immune thrombocytopenia?

Answer 21

Immune-mediated destruction and reduced platelet production due to autoantibody production.

Question 22

What causes immune thrombocytopenia?

Answer 22

Idiopathic or after viral infection, exposure to some drugs.

Question 23

How can you diagnose immune thrombocytopenia in a lab?

Answer 23

reduced platelet count (PLT) (<10x10^9/L)

Question 24

What are the symptoms of immune thrombocytopenia?

Answer 24

abnormal primary haemostasis

similar to vWD + skin purpura if PLT<10

Question 25

how do you treat immune thrombocytopenia? (2)

Answer 25

long term disease control --> immunosuppression with steroids or other agents ``` treatment of bleeding: --> tranexamic acid --> local measures --> intravenous immunoglobin platelet transfusion only in life threatening bleeding ```

Question 26

How does liver disease cause bleeding disorders?

Answer 26

The liver synthesises most clotting proteins and regulates platelet production. A decrease in clotting factor and fibrinogen levels because of reduced synthesis and vitamin K malabsorption. This causes a decreased PLT number because of reduced thrombopoietin synthesis There is a decreased PLT function bec of metabolic disturbances There is an increased clot breakdown (fibrinolysis

Question 27

What are the clinical features of liver disease?

Answer 27

skin, soft tissue and GI tract bleeding. subconjunctival haemorrhage and jaundice oesophageal varices form portal hypertension

Question 28

How can you detect liver disease in the laboratory?

Answer 28

increase PT increased aPTT decreased fibrinogen decreased PLT count

Question 29

Does chronic liver disease show stable abnormal clotting test results often without bleeding?

Answer 29

yes

Question 30

How do you treat bleeding in liver disease? (2)

Answer 30

NO TREATMENT NEEDED IF NOT BLEEDING AND STABLE IF BLEEDING: Tranexamic acid Vitamin K Consider fresh frozen plasma - contains all of the different coagulation factors and fibrinogen

Question 31

What are antithrombotic drugs?

Answer 31

drugs that affect haemostasis they're widely prescribed. all can cause bleeding

Question 32

What are the 2 categories of anti-thrombotic drugs?

Answer 32

1. Anti-platelet drugs | 2. Anti-coagulant drugs

Question 33

What do anti-platelet agents do? | what are they used to prevent/treat?

Answer 33

they inhibit platelet function. prevent or treat arterial thrombosis (acute coronary syndromes, stroke, peripheral arterial thrombosis)

Question 34

What do anti-coagulant drugs do? | What do they prevent/treat?

Answer 34

They inhibit the coagulation pathway. Prevent or treat venous thrombosis (deep vein thrombosis, pulmonary embolism, stroke in arterial fibrillation or in pts with mechanical heart valve).

Question 35

name some examples of antiplatelet drugs.

Answer 35

Aspirin Clopidogrel Drugs with 'unintentional' anti-platelet effects e.g. NSAIDs These drugs cause no abnormalities in standard lab tests as they affect platelet function.

Question 36

Name some examples of anti-coagulant drugs. (3)

Answer 36

1. Warfarin 2. Novel Oral Anti-Coagulants/Direct oral anti-coagulants (NOACs/DOACs) (rivaroxaban, apixaban, edoxaban, dabigatran) 3. Low molecular weight heparin others (except warfarin) don't cause major abnormalities in test results except in overdoes.

Question 37

How does warfarin work?

Answer 37

Warfarin acts by diminishing availability of vitamin K in liver and therefore reduces synthesis of several coagulation factors. It causes prolonged PT and is monitored using INR test. INR range for most warfarin indications is 2-3.

Question 38

How do you manage bleeding risk for dental procedures? | What are the general principles?

Answer 38

different procedures counter different risks of bleeding. different anti-thrombotic drug regimes confer different risks of bleeding. bleeding is undesirable..but in some cases stopping antithrombotic drugs may increase the risk of breakthrough thrombosis. FOR MOST PROCEDURES THE LIKELIHOOD OF BLEEDING IS LOW AND STOPPING ANTI-THROMBOTICS IS UNCOMMON it is reasonable to delay the plan for dental treatment if pt is on a short term course of antithrombotics.

Question 39

Explain how you would manage a pt with warfarin before surgery?

Answer 39

Check INR no more the 24 hours before procedure. If INR is below 4 treat without interrupting medication. actively consider suturing and packing If INR is above 4, delay treatment.