8: Disorders of haemostasis

Question 1

2 main general reasons why abnormal haemostasis occurs

Answer 1

Lack of a specific factor (increased consumption, failure of production)
Defective function of a factor (genetic or acquired defect)

Question 2

What is primary haemostasis?

Answer 2

Formation of an unstable plug

Platelet adhesion + aggregation

Question 3

What are the 3 types of disorders of primary haemostasis?

Answer 3

Disorders of PLATELETS: Thrombocytopenia (low platelet) or impaired function

Disorders of VWF

Disorders of VESSEL WALL

Question 4

What is the autoimmune cause of thrombocytopenia?

Answer 4

Auto-immune (auto-ITP)

Anti-platelet autoantibodies sensitizes platelets, meaning they are cleared faster by macrophages

Question 5

What are mechanisms of thrombocytopenia?

Answer 5

Bone marrow failure (leukemia, B12 deficiency)
Accelerated clearance (ITP)
Pooling/destruction of platelets in enlarged spleen (hypersplenism)

Question 6

What are mechanisms of impaired function of platelets?

Answer 6

Hereditary absence of glycoproteins or storage granules

ACQUIRED due to drugs (aspirin, NSAIDs, clopidogrel)

Question 7

Example of a hereditary platelet defect?

Answer 7

Lack of glycoproteins Gp2b/3a = Glanzmann’s thrombasthenia (autosomal recessive)

Question 8

What is a disorder of VWF known as?

Answer 8

Von Willebrand Disease
Hereditary (COMMON) - less VWF or impaired function

Acquired (RARE) - due to anitbodies

Oral contraceptives can be used for menhorragia

Question 9

What are the 2 functions of VWF in haemostasis?

Answer 9

1. Binds to collagen and captures platelets

2. Stabilises F8

Question 10

What are the disorders of the vessel wall?

Answer 10

Acquired: scurvy, steroid therapy, age

Hereditary vascular disorders

Question 11

Bleeding in primary haemostasis disorders?

Answer 11

Immediate, prolonged bleeding from cuts
Epistaxis
Gum bleeding
Easy bruising
Menorrhagia

In thrombocytopenia: PETECHIAE
In severe VWD: Haemophilia-like bleeding

Question 12

How do you test for primary haemostasis

Answer 12

Clinical observation
Platelet count/morphology
Assays of VWF
Platelet function analyser in lab

Question 13

What is secondary haemostasis?

Answer 13

Stabilisation of plug with fibrin

- Blood COAGULATION stage

Question 14

What is the role of the coagulation cascade?

Answer 14

To generate a BURST OF THROMBIN which will convert fibrinogen to fibrin

Question 15

What is haemophilia?

Answer 15

Failure to generate fibrin to stabilise platelet plug

Question 16

What are the disorders of coagulation?

Answer 16

Deficiency of coagulation factor
(Hereditary/acquired)

Increased consumption of coagulation factor

Question 17

What are examples of hereditary coag. factor deficiency?

Answer 17

Haemophilia A (F8 deficiency)
Haemophilia B (F9 deficiency)

Question 18

What are the differences between haemophilia and other coag. factor deficiency diseases?

Answer 18

Haemophilia A/B = severe but compatible with life, spontaneous joint/muscle bleeding

Pro-thrombin deficiency = LETHAL

Factor 11 deficiency = bleed after trauma but NOT spontaneously

Factor 12 def. = No bleeding at all

Question 19

What are examples of acquired coag. factor deficiency?

Answer 19

Liver disease (most coag factors produced here)
Dilution of blood (red cell transfusions dont have plasma)
Anticoags (warfarin)

Question 20

What are examples of increased consumption of coag factor?

Answer 20

Disseminated Intravascular coagulation (DIC)

Autoimmune disease

Question 21

Explain DIC

Answer 21

Generalised activation of coagulation around the body
Depletes coag factors, platelets, fibrinogen, etc..

Associated with sepsis, inflammation, major tissue damage

Question 22

Bleeding in coagulation disorders?

Answer 22

Superficial cuts do not bleed since platelets are fine
More bruising, but nosebleeds rare
HAEMOARTHROSIS = SPONTANEOUS deep bleeding into JOINTS/muscles

Question 23

Major differences between haemostasis due to platelet and coagulation disorders

Answer 23

Platelet: SUPERFICIAL bleeding into skin + mucosal membranes
IMMEDIATE bleeding after injury

Coagulation: SPONTANEOUS bleeding DEEP into joints, muscles and tissue
DELAYED but SEVERE bleeding after injury

Question 24

How do you test for coag. disorders?

Answer 24

Screening test (APTT)
Factor assays (F8)
Test for inhibitors

Question 25

What happens to APTT in haemophilia?

Answer 25

PROLONGED

Question 26

Most of the common bleeding disorders not usually detected by routine clotting tests. What else can you do?

Answer 26

Look at bleeding history

Question 27

What are the disorders of fibrinolysis?

Answer 27

Hereditary: Antiplasmin deficiency
Acquired: drugs, DIC

Rare disorder

Question 28

Genetics of haemophilia?

Answer 28

X linked recessive

XY (males) with haemophilia gene will have haemophilia

XX (females) with one gene will be carriers

Question 29

Genetics of VWD?

Answer 29

Autosomal dominant

Question 30

Treatment of abnormal haemostasis?

Answer 30

Failure of production/function: Factor replacement therapy, gene therapy for haemophilia, stop drugs

Immune destruction: immunosuppressants, splenectomy for ITP

Increased consumption: Treat cause, replace if necessary

Question 31

What are the types of factor replacement?

Answer 31

Plasma (contains all factors)
Cryoprecipitate
Factor concentrates

Question 32

Additional treatments?

Answer 32

DDAVP (Vasopressin analogue) - increases release of VWF from endothelial cells. Endogenous VWF hence only for mild disorders

Tranexamic acid - inhibits fibrinolysis

Fibrin glue/spray

Question 33

Prolonged PT may result from..

Answer 33

Factor 7 deficiency

Question 34

Prolonged of APTT may result from..

Answer 34

Haemophilia A/B

Question 35

What can you used for management of patients of VWD?

Answer 35

Oral contraceptive pill - for menhorragia
VWF/F8 concentrates
DDAVP - increases VWF
Tranexamic acid