Abnormalities of haemostasis

Question 1

What are the two main types of abnormal haemostasis?

Answer 1

Lack of a specific factor

Defective function of a specific factor

Question 2

What can cause you to lack a specific factor?

Answer 2

Failure of production- congenital or acquired

Increased consumption/clearance

Question 3

What can cause a defective function of a specific factor?

Answer 3

Genetic defect
Acquired defect (more common) e.g. drugs, synthetic defect and inhibition

Question 4

What is thrombocytopenia?

Answer 4

Low number of platelets

Question 5

What causes thrombocytopenia?

Answer 5

Failure of platelet production by megakaryocytes- Bone marrow failure e.g. leukaemia and B12 deficiency
Shortened half life of platelets- Accelerated clearance e.g. autoimmune thrombocytopenia, disseminated intravascular coagulation
Increased pooling of platelets in enlarged spleen

Question 6

What else could disorders of primary haemostasis be caused by except from thrombocytopenia?

Answer 6

Impaired function of platelets- absence of storage granules or glycoproteins

Question 7

What can cause impaired function of platelets?

Answer 7

Acquired due to drugs e.g. aspirin, NSAIDs, clopidogrel

Question 8

What hereditary platelet defects are there?

Answer 8

Glanzann’s thrombasthenia
Bernard Soulier syndrome
Storage pool disease

Question 9

What causes Glanzann’s thrombasthenia?

Answer 9

Absent glycoprotein 2b/3a

Question 10

What does the absence of glycoprotein 2b/3a cause?

Answer 10

Lack of platelet aggregation

Question 11

What causes Bernard Soulier syndrome?

Answer 11

Lack of glycoprotein 1b

Question 12

What does the lack of glycoprotein 1b cause?

Answer 12

Platelets can’t bind to von Willebrand factor

Question 13

What is storage pool disease?

Answer 13

Problem with storage granules so they can’t be released adequately

Question 14

What is Von Willebrand disease?

Answer 14

Hereditary decrease in quantity and/or function

It can be acquired due to an antibody

Question 15

What are the two functions of vWF in haemostasis?

Answer 15

Binding to collagen and capturing platelets

Stabilising factor 8

Question 16

What are the three types of VWD?

Answer 16

Type 1- Deficiency of VWF but functions normally
Type 2- VWF is made but doesn’t function normally
Type 3- VWF isn’t made at all

Question 17

What are some examples of inherited (rare) disorders of primary haemostasis that affect the vessel wall?

Answer 17

Hereditary haemorrhage telangiectasia
Ehlers-Dalos syndrome
Other connective tissue disorders

Question 18

What are some examples of acquired disorders of primary haemostasis that affect the vessel wall?

Answer 18

Scurvy
Steroid therapy
Atrophy of supporting tissues of blood vessels
Ageing (senile purpura)
Vasculitis

Question 19

What is typical primary haemophilia bleeding like?

Answer 19

Immediate
Prolonged bleeding from cuts
Epistaxes
Gum bleeding
Menorrhagia
Easy bruising
Prolonged bleeding after trauma
Thrombocytopenia gives rise to petechiae

Question 20

Why can you have haemophilia type bleeding in severe VWD?

Answer 20

VWF levels are very low so factor 8 will also be very low

Question 21

What is haemophilia?

Answer 21

Failure to generate fibrin to stabilise platelet plug- Lack of factor 8 or 9 resulting in impaired thrombin generation

Question 22

What is the genomics of haemophilia like?

Answer 22

It is an X linked condition

Question 23

How severe is deficiency of prothrombin (factor 2) compared to haemophilia?

Answer 23

Deficiency of prothrombin is lethal but haemophilia is severe but compatible with life

Question 24

How severe are deficiency of factor 11 and factor 12

Answer 24

Factor 11- Bleed after trauma but not spontaneously

Factor 12- No excess bleeding

Question 25

How can deficiency of coagulation factors be acquired?

Answer 25

Liver disease Dilution Anti-coagulant drugs e.g. warfarin

Question 26

What are two examples of increased consumption leading to disorders of coagulation?

Answer 26

Disseminated intravascular coagulation | Autoimmune antibodies

Question 27

What is disseminated intravascular coagulation?

Answer 27

Generalised activation of coagulation- tissue factor is exposed and causes activation of cascade

Question 28

What is DIC associated with?

Answer 28

Sepsis, major tissue damage and inflammation

Question 29

What does DIC do?

Answer 29

It consumes and depletes coagulation factors Platelets are consumed Activation of fibrinolysis depletes fibrinogen Deposition of fibrin in vessels causes organ failure

Question 30

What is typical bleeding in coagulation disorders?

Answer 30

Superficial cuts don't bleed Bruising is common Nosebleeds are rare Spontaneous bleeding is deep into muscles and joints Bleeding after trauma is delayed and prolonged

Question 31

In what condition should intramuscular injections be avoided and why?

Answer 31

Haemophilia because it can cause deep bleeding patterns

Question 32

What tests are there for coagulation disorders?

Answer 32

Screening tests Prothrombin time- extrinsic path disorders Activated partial thromboplastin time- intrinsic path disorders Platelet count Factor assays Tests for inhibitors

Question 33

What bleeding disorders are not detected by routine clotting tests?

Answer 33

``` Mild factor deficiencies Von Willebrand disease Factor 8 deficiency Platelet disorders Excessive fibrinolysis Vessel wall disorders Metabolic disorders ```

Question 34

What hereditary and acquired disorders of fibrinolysis are there?

Answer 34

Rare Hereditary- Antiplasmin deficiency Acquired- Drugs such as tap and disseminated intravascular coagulation

Question 35

How is abnormal homeostasis where production failure is responsible treated?

Answer 35

Replace missing factor/platelets Prophylactic Therapeutic Stop drugs

Question 36

How is abnormal haemostasis where immune destruction is responsible treated?

Answer 36

Immunosuppression | Splenectomy for autoimmune thrombocytopenia

Question 37

How is abnormal haemostasis where increased consumption is responsible treated?

Answer 37

Treat cause | Replace as necessary

Question 38

If you're give someone factor replacement therapy, what are the different sorts and what do they contain?

Answer 38

Plasma- contains all coagulation factors Cryoprecipitate- Fibrinogen, factor 8, vWF and factor 13 Factor concentrates- available for all factors except 5

Question 39

How is desmopressin (DDAVP) used to treat haemostasis?

Answer 39

Vasopressin analogue which makes the endothelial cells release their own VWF that is stored- good for mild VWD