Abnormalities of Homeostasis

Question 1

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

Answer 1

Lack of a specific factor

Defective function of a specific factor

Question 2

What can cause thrombocytopenia?

Answer 2

Failure of production – bone marrow failure e.g. leukaemia, B12 deficiency
Accelerated clearance - DIC (disseminated intravascular coagulation), auto-ITP (autoimmune thrombocytopenia purpura)

Question 3

State one very common cause of thrombocytopenia.

Answer 3

Autoimmune thrombocytopenia

Question 4

What is a distinctive clinical feature of thrombocytopenia?

Answer 4

Petechiae

Question 5

State three hereditary platelet defects and what causes them.

Answer 5

Glanzmann’s Thrombasthenia:
absence of GlpIIb/IIIa (aka integrin αIIbβ3)
prevents platelet aggregation

Bernard Soulier Syndrome:
absence of GlpIb
prevents binding to von Willebrand factor

Storage Pool Disease:
storage granules are not able to release adequately

Question 6

Broadly speaking, state three mechanisms 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)

Question 7

State a broad acquired cause of impaired platelet function.

Answer 7

Drugs e.g. Asprin, NSAIDs, clopidogrel

Question 8

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

Answer 8

Binding to collagen and 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 threetypes 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 two inherited vessel wall conditions that cause defects in primary haemostasis.

Answer 10

Hereditary haemorrhagic telangiectasia

Ehlers-Danlos Syndrome

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 defects of primary haemostasis.

Answer 12

The primary platelet plug isn’t strong enough to stop the bleeding  
Bleeding is immediate
Prolonged from cuts  
Epistaxes  
Gum bleeding  
Menorrhagia  
Easy bruising  
Prolonged bleeding after trauma and surgery

Question 13

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

Answer 13

Reduced factor 8 (because VWF stabilizes factor 8)

This 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)
This leads to impaired thrombin generation
In haemophilia you get failure to generate fibrin to stabilize the platelet plug
It is X-linked recessive

Question 16

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

Answer 16

II - lethal

VIII & IX (haemophilia) – severe but compatible with life
Spontaneous joint and muscle bleeding

XI – bleeding after trauma but not spontaneously

XII – no excess bleeding

Question 17

State some acquired causes of deficiency of coagulation factors.

Answer 17

Liver disease
Dilution - haemorrhage and only red cells (not plasma) replaced
Anti-coagulant drugs (e.g. warfarin)

Question 18

State some 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 – Tissue factor expressed inappropriately

Associated with sepsis, major tissue damage, inflammation

Consumes and depletes coagulation factors
Platelets 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 (because primary haemostasis is fine)

Bruising is common

Spontaneous bleeding is DEEP, into muscles and joints

Bleeding after trauma may be delayed and 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 – it can cause deep bleeding patterns

Question 23

State some 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

This is 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) 
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

Drugs such as tissue plasminogen activator

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)

Question 29

What clotting factors are found in cryoprecipitate?

Answer 29

Fibrinogen
Factor VIII
Factor XIII
Von Willebrand Factor

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
This is good for people with mild von Willebrand disease (as it releases endogenous stored of VWF)

Question 32

State two other drugs that are used as haemostatic treatments.

Answer 32

Tranexemic acid (inhibits fibrinolysis) 
Fibrin glue

Question 33

What is a sign specific to thrombocytopenia?

Answer 33

petechiae
same as purpura and ecchymoses but they differ in size

petechiae – < 5 mm

purpura – 5-9 mm

ecchymoses – > 9 mm

Question 34

What sign is characteristic of severe WVD?

Answer 34

Haemophillia like bleeding