Abnormalities of Haemostasis

Question 1

What constitutes abnormal bleeding?

Answer 1

• Epistaxis not stopped by 10 mins compression or requiring medical attention/transfusion
• Bruising without apparent trauma (esp. multiple/large)
• Prolonged bleeding from trivial wounds, or in oral cavity or recurring spontaneously in 7 days after wound. Spontaneous GI bleeding leading to anaemia.
• Menorrhagia requiring treatment or leading to anaemia, not due to structural lesions of the uterus.
• Heavy, prolonged or recurrent post-operative bleeding

Question 2

Broadly speaking, what are the two causes of abnormal haemostasis?

Answer 2

Lack of a specific factor

Defective function of a specific factor

Question 3

What can cause thrombocytopenia?

Answer 3

• Bone marrow failure e.g. leukaemia, B12 deficiency
• Shortened half life of platelets
• Increased pooling of platelets in an enlarged spleen

Question 4

State one very common cause of thrombocytopenia. State some clinical features

Answer 4

Autoimmune thrombocytopenia

purpura
multiple bruises
ecchymoses

Question 5

What is a distinctive clinical feature of thrombocytopenia?

Answer 5

Petechiae = small spots of bleeding under the skin

Question 6

Name and describe three hereditary platelet defects.

Answer 6

1. Glanzmann’s Thrombasthenia – absence of GpIIb/IIIa prevents platelet aggregation
2. Bernard Soulier Syndrome – absence of GpIb prevents binding to VWF
3. Storage Pool Disease – storage granules in platelets aren’t able to be release adequately

Question 7

Give three examples of drugs which cause impaired platelet function (acquired platelet defects)

Answer 7

aspirin, NSAIDs, clopidogrel

Question 8

In addition to binding to collagen and trapping platelets, state another role of VWF

Answer 8

Stabilising factor 8 (if VWF is low, factor 8 may be low)

Question 9

Von Willebrand Disease is usually hereditary. What are the 3 types of von Willebrand disease? State the pattern of inheritance for each

Answer 9

Type 1 – deficiency of VWF but it functions normally (autosomal dominant)
Type 2 – VWF does not function normally (autosomal dominant)
Type 3 – VWF not made at all (autosomal recessive)

Question 10

State two inherited vessel wall conditions that cause defects in primary haemostasis.

Answer 10

1. Hereditary haemorrhagic telangiectasia (rare)

2. Ehlers-Danlos Syndrome (connective tissue disorder)

Question 11

State some acquired causes of vessel wall conditions that cause defects in primary haemostasis.

Answer 11

• Scurvy
• Steroid therapy
• Ageing (=> senile purpura)
• Vasculitis

Question 12

Describe the pattern of bleeding in disorders of primary haemostasis.

Answer 12

The primary platelet plug isn’t strong enough;

• Bleeding is immediate
• Prolonged bleeding from cuts
• Epistaxes
• Gum bleeding
• Menorrhagia
• Easy bruising
• Prolonged bleeding after trauma and surgery

Question 13

What is an important effect of severe von Willebrand disease? What does this result in symptomatically?

Answer 13

Reduced factor 8

This causes haemophilia type bleeding patterns

Question 14

What tests are done for disorders of primary haemostasis?

Answer 14

Platelet count and morphology
Bleeding time
Assays for VWF
Clinical observation

Question 15

What is haemophilia caused by?

Answer 15

Lack of Factor 8 (A) or Factor 9 (B) => impaired thrombin generation + failure to generate fibrin

Question 16

State 3 acquired causes of deficiency of coagulation factors (more common in hospital practice). Say why in each case

Answer 16

1. Liver disease - since most coagulation factors are synthesised in the liver
2. Dilution - low concentration of clotting factors
3. Anti-coagulant drugs (e.g. warfarin)

Question 17

State some disorders of coagulation that are due to increased consumption.

Answer 17

Disseminated intravascular coagulation (DIC)

Immune - autoantibodies

Question 18

What is disseminated intravascular coagulation (DIC)? What is it associated with, and what are some consequences?

Answer 18

Excessive activation of the whole coagulation process (including primary and secondary haemostasis, and fibrinolysis)
=> increased consumption and depletion of coagulation factors + platelets
=> activation of fibrinolysis depletes fibrinogen
=> deposition of fibrin in vessels causes organ failure

• It is associated with sepsis, inflammation and major tissue damage

Question 19

Describe the pattern of bleeding in coagulation disorders (i.e. disorders of secondary haemostasis)

Answer 19

• superficial cuts do not bleed
• bruising is common, but nosebleeds are rare
• spontaneous bleeding is deep, into muscles
  and joints
• bleeding after trauma may be delayed and is prolonged
• bleeding frequently restarts after stopping

Question 20

What is the hallmark of haemophilia?

Answer 20

Haemarthrosis (bleeding into joint spaces)

Question 21

What simple medical procedure must you avoid doing to patients with haemophilia? Why?

Answer 21

Intramuscular injection – it can cause deep bleeding patterns

Question 22

State some tests that are used for coagulation disorders.

Answer 22

Screening Tests:

• Prothrombin time (PT)
• Activated partial thromboplastin time (APTT)
• Platelet count

Factor Assays

Tests for inhibitors

Question 23

PT and APTT tests are used to assess which pathways within the coagulation cascade?

Answer 23

APTT - intrinsic

PT - extrinsic

Question 24

Describe the APTT and PT results for a patient with haemophilia.

Answer 24

Prolonged APTT but normal PT

This is because the defect lies in the intrinsic pathway (factor 8 or 9)

Question 25

List some bleeding disorders that are not detected by routine clotting tests.

Answer 25

• Mild factor deficiencies
• Von Willebrand Disease
• Factor 8 Deficiency (cross-linking)
• Platelet disorders
• Excessive fibrinolysis
• Vessel wall disorders
• Metabolic disorders (e.g. uraemia)
  NOTE: urea interferes with platelet function

Question 26

State a hereditary disorder of fibrinolysis.

Answer 26

Antiplasmin deficiency

Question 27

State two acquired disorders of fibrinolysis.

Answer 27

1. Drugs such as tissue plasminogen activator

2. Disseminated intravascular coagulation (DIC)

Question 28

What is the treatment that is considered for a patient whose abnormal haemostasis is caused by either production failure, immune destruction of platelets, or increased consumption?

Answer 28

For immune destruction:

• Immunosuppression (eg prednisolone)
• Splenectomy for ITP

Otherwise, you just replace the missing factors/platelets (i.e. factor or platelet replacement therapy)

Question 29

What are the four types of Factor replacement therapy, and what do they each contain?

Answer 29

1. Plasma:
   - Contains all coagulation factors
2. Cryoprecipitate:
   - Rich in Fibrinogen, FVIII, VWF, Factor XIII
3. Factor concentrates
   - Concentrates available for all factors except factor V.
   - Prothrombin complex concentrates (PCCs) contain factors II, VII, IX, X
4. Recombinant forms of FVIII and FIX are available.

Question 30

Describe the use of Desmopressin (DDAVP) in von Willebrand disease.

Answer 30

Desmopressin (vasopressin derivative) makes the endothelial cells release their stored VWF;
Only useful for mild von Willebrand disease

Question 31

State two other drugs that are used as haemostatic treatments.

Answer 31

1. Tranexemic acid (inhibits fibrinolysis)

2. Fibrin glue