Abnormalities of Haemostasis

Question 1

Broadly speaking, what are the 2 causes of abnormal haemostasis?

Answer 1

Lack of a specific factor (failure of production or increased clearance)
Defective function of a specific factor (genetic or acquired)

Question 2

What can cause a failure of production leading to thrombocytopenia?

Answer 2

Bone marrow failure

e.g. leukaemia, B12 deficiency

Question 3

What can cause increased clearance leading to thrombocytopenia?

Answer 3

Autoimmune thrombocytopenia (ITP) (common)
DIC

Question 4

What is a distinctive clinical feature of thrombocytopenia?

Answer 4

Petechiae

Question 5

State 3 hereditary platelet defects.

Answer 5

Glanzmann’s Thrombasthenia: absence of GpIIb/IIIa (prevents platelet aggregation)
Bernard Soulier Syndrome: absence of GpIb (prevents binding to vWF)
Storage Pool Disease: storage granules not able to release adequately

Question 6

State 3 mechanisms/ causes of thrombocytopenia.

Answer 6

Failure of platelet production by the megakaryocytes
Shortened half-life of platelets
Increased pooling of platelets in an enlarged spleen (hypersplenism) + destruction

Question 7

State a broad acquired cause of impaired platelet function.

Answer 7

Drugs e.g. Aspirin, NSAIDs, clopidogrel

Question 8

What are the 2 roles of von Willebrand factor in haemostasis?

Answer 8

Binding to collagen + trapping platelets

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 their pattern of inheritance.

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 2 inherited vessel wall conditions that cause defects in primary haemostasis.

Answer 10

Hereditary haemorrhagic telangiectasia

Ehlers-Danlos Syndrome

Question 11

State 4 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 defects of primary haemostasis.

Answer 12

Primary platelet plug isn’t strong enough to stop the bleeding  
Immediate
Prolonged from cuts  
Epistaxes  
Gum bleeding  
Menorrhagia  
Easy bruising  
Prolonged bleeding after trauma + surgery

Question 13

How are the clotting factors affected in severe von Willebrand disease?

Answer 13

Reduced factor 8 (because vWF stabilizes factor 8)

Causes haemophilia type bleeding patterns

Question 14

What tests can be done for disorders of primary haemostasis?

Answer 14

Platelet count
Bleeding time
Assays for vWF
Clinical observation

Question 15

What is haemophilia caused by?

What is its pattern of inheritance?

Answer 15

Lack of Factor 8 (A) or Factor 9 (B)
Leads to impaired thrombin generation
Failure to generate fibrin to stabilise the platelet plug
X-linked recessive

Question 16

Describe the difference in outcome for deficiencies of factors 2, 8 + 9, 11 and 12.

Answer 16

2: lethal
8 + 9 (haemophilia): severe but compatible with life, spontaneous joint + muscle bleeding
11: bleeding after trauma but not spontaneously
12: no excess bleeding

Question 17

State 3 acquired causes of deficiency of coagulation factors.

Answer 17

Liver disease
Dilution (need to replace plasma as well as RBC + platelets)
Anti-coagulant drugs (e.g. warfarin)

Question 18

State 2 disorders of coagulation that are due to increased consumption.

Answer 18

Disseminated intravascular coagulation (DIC)

Autoimmune thrombocytopenia

Question 19

What happens in Disseminated Intravascular Coagulation (DIC)?

Answer 19

Generalised activation of coagulation
It’s associated with sepsis, major tissue damage + inflammation
It consumes + depletes coagulation factors
Platelets are consumed
Activation of fibrinolysis depletes fibrinogen
Deposition of fibrin in vessels causes organ failure

Question 20

Describe the pattern of bleeding in coagulation disorders.

Answer 20

Superficial cuts DO NOT bleed (primary haemostasis is fine)
Bruising is common, nosebleeds rare
Spontaneous bleeding is DEEP, into muscles + joints
Bleeding after trauma may be delayed + prolonged
Frequently restarts after stopping

Question 21

What is the hallmark of haemophilia?

Answer 21

Haemarthrosis

Question 22

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

Answer 22

Intramuscular injection: can cause deep bleeding patterns

Question 23

State 3 tests that are used for coagulation disorders.

Answer 23

Screening Tests: APTT, PT + Platelet Count
Factor Assays
Tests for inhibitors

Question 24

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

Answer 24

Prolongs APTT but normal PT

Because the defect lies in the intrinsic pathway (factor 8 or 9)

Question 25

State 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) (Thrombotic disorders) ```

Question 26

State a hereditary disorder of fibrinolysis.

Answer 26

Antiplasmin deficiency

Question 27

State 2 acquired disorders of fibrinolysis.

Answer 27

Drugs such as tissue plasminogen activator (tPA) | Disseminated intravascular coagulation (DIC)– because everything has been used up

Question 28

What is the treatment that is considered for a patient whose abnormal haemostasis is caused by immune destruction of platelets?

Answer 28

Immunosuppression (e.g. prednisolone) | Splenectomy for ITP

Question 29

What clotting factors are found in cryoprecipitate?

Answer 29

Fibrinogen Factor VIII Factor XIII vWF

Question 30

Factor concentrates are available for all factors except which one?

Answer 30

Factor V

Question 31

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

Answer 31

Desmopressin makes the endothelial cells release their stored vWF Good for people with mild von Willebrand disease (causes release of endogenous stores of vWF)

Question 32

State 2 other drugs that are used as haemostatic treatments.

Answer 32

``` Tranexemic acid (inhibits fibrinolysis) Fibrin glue ```

Question 33

List 5 examples contributing to significant bleeding history

Answer 33

Epistaxis not stopped by 10 mins compression Cutaneous haemorrage/ bruising with no apparent trauma >15 mins bleeding from trivial wounds/ recurrence spontaneously in 7 days after Menorrhagia requiring treatment/ leading to anaemia Heavy, prolonged, recurrent bleeding after surgery

Question 34

What impaired function causes a disorder of primary haemostasis?

Answer 34

Hereditary absence of glycoproteins/ storage granules

Question 35

What is the role of the coagulation cascade?

Answer 35

To generate a burst of thrombin which will convert fibrinogen to fibrin

Question 36

What does deficiency of any coagulation factor result in?

Answer 36

Failure of thrombin generation + hence fibrin formation

Question 37

What is required to stop the platelet plug from falling apart in large vessels?

Answer 37

Fibrin formation (stabilises plug)

Question 38

Describe the inheritance pattern of common bleeding disorders

Answer 38

Haemophilia: Sex linked recessive Von Willebrand disease: Autosomal dominant T1+2, Autosomal recessive T3 The rest are autosomal recessive

Question 39

How is failure of production/ function treated?

Answer 39

Replace missing factors/ platelets

Question 40

How is increased consumption treated?

Answer 40

Treat cause | Replace as necessary in meanwhile

Question 41

What does plasma contain? (when given as replacement therapy)

Answer 41

All coagulation factors