3: Bleeding disorders

Question 1

What are some causes of problems with secondary haemostasis?

Answer 1

Single factor deficiencies - Haemophilia A & B

Multiple factor deficiencies - Vitamin K deficiency, liver disease, DIC

note that DIC is a cause of problems with both primary and secondary haemostasis (because it drains platelets AND clotting factors)

Question 2

What are some causes of problems with primary haemostasis?

Answer 2

VASCULAR: less available collagen (ageing), Vit C deficiency, steroids, Henoch Schonlein purpura (vasculitis)

PLATELETS: bone marrow suppression, renal failure, autoimmune thrombocytic purpura, DIC, hypersplenism

VON WILLEBRAND DISEASE

Question 3

What is a

reduced

increased

number of platelets called?

Answer 3

Reduced platelets - thrombocytopaenia

Increased platelets - thrombocytosis

Question 4

Which drugs reduce the function of platelets?

Answer 4

Anti-platelets e.g aspirin, clopidogrel, ticagrelor

NSAIDs

Question 5

What is Von Willebrand’s disease?

Answer 5

vWF deficiency

Question 6

Von Willebrand’s disease is more commonly diagnosed in (men / women).

Why?

Answer 6

women

menorrhagia presents early

Question 7

Which vasculitis, seen in children, causes abnormal bleeding?

Answer 7

HSP

Question 8

Where should you look for a purpuric rash first?

Why?

Answer 8

Lower limbs

Oncotic pressure (gravity) pushes blood out of capillaries into compartments of lower limb

Question 9

Where should you look for haemorrhages in a patient with abnormal bleeding?

Answer 9

Skin

Mouth

Eyes

Question 10

What are some acquired causes of thrombocytopaenia?

Answer 10

Bone marrow pathology e.g malignancy

DIC (widespread clotting uses up all your platelets and clotting factors)

Autoimmune disease (autoimmune thrombocytopaenic purpura)

Renal failure (uraemia causes platelet destruction)

Question 11

What are autoimmune diseases causing

a) vessel dysfunction
b) platelet destruction

causing abnormal bleeding?

Answer 11

a) HSP (vasculitis)

b) ATP

Question 12

Why can hypersplenism cause platelet destruction?

Answer 12

Overactive haemolysis

Question 13

Which drugs are designed to cause platelet dysfunction?

How do they work?

Answer 13

Anti-platelets e.g aspirin, clopidogrel, ticagrelor

Block thromboxane A2

Question 14

Why does renal failure cause platelet dysfunction?

Answer 14

Build up of toxins e.g urea

Question 15

What is the mode of inheritance of Von Willebrand’s disease?

Answer 15

Autosomal dominant

Question 16

Apart from promoting platelet aggregation, what does vWF do?

Answer 16

Carries Factor XIII around

So deficiency also impacts coagulation

Question 17

Low levels of circulating ___ is the most common reason for failure of haemostasis.

Answer 17

platelets

i.e thrombocytopaenia

Question 18

What is prothrombin also known as?

Answer 18

Factor II

just to make things more confusing

Question 19

In which condition are clotting factors and platelets used up to the point that they are deficient?

Answer 19

DIC

Question 20

Where are clotting factors produced?

Answer 20

Liver

Question 21

Problems with which organ impact coagulation?

Answer 21

Liver

where clotting factors are produced

Question 22

Which vitamin is required to produce clotting factors?

Answer 22

Vitamin K

Question 23

Which clotting factors are deficient in

Haemophilia A

Haemophilia B?

Answer 23

Haemophilia A - VIII

Haemophilia B - IX

Question 24

Which clotting factors require Vitamin K to be activated?

Answer 24

II, VII, IX and X

Question 25

Which clotting factors are **inhibited** by **warfarin therapy?**

Answer 25

**II, VII, IX and X**

Question 26

Which **clotting time** is used to measure **warfarin response?** ## Footnote **Which clotting factors does warfarin inhibit?** **What is required to produce these factors in the liver?**

Answer 26

**PT** **II, VII, IX and X** **Vitamin K**

Question 27

**Clotting factors** are deficient in ___ failure.

Answer 27

**liver failure**

Question 28

\_\_\_ _ deficiency causes **abnormal bleeding.**

Answer 28

**Vitamin K** required for production of factors II, VII, IX and X in the liver

Question 29

Where is **Vitamin K** absorbed?

Answer 29

**Small intestine**

Question 30

What is required for **Vitamin K** to be absorbed in the small intestine?

Answer 30

**Bile salts**

Question 31

Given that **Vitamin K** is absorbed in the **small intestine** using **bile**, what GI conditions can cause **Vitamin K deficiency?**

Answer 31

**Malabsorption** - Crohn's disease, resection, bacterial overgrowth **Obstructive jaundice** - cholecystitis, pancreatic Ca

Question 32

Which **drug** acts against **Vitamin K?**

Answer 32

**Warfarin**

Question 33

**Vitamin K** can be used to reverse the effects of which drug?

Answer 33

**Warfarin**

Question 34

Why are **babies** given a **Vitamin K injection** at birth?

Answer 34

**To prevent bleeding caused by temporary Vit K deficiency, which is quite common** haemorrhagic disease of the newborn

Question 35

What is **DIC?**

Answer 35

**Disseminated intravascular coagulation** Massive, inappropriate activation of haemostasis and fibrinolysis Using up all your platelets and clotting factors Which causes deficiencies --\> tendency for abnormal bleeding

Question 36

Apart from **platelet / clotting factor** deficiency, what does massive thrombosis in DIC cause?

Answer 36

**End organ damage** because all your vessels are occluded

Question 37

Apart from **abnormal bleeding**, what does DIC cause?

Answer 37

**End organ damage** because thromboses occlude blood vessels

Question 38

Which enzyme breaks down **fibrin**?

Answer 38

**Plasmin**

Question 39

What are some **causes of DIC?**

Answer 39

**Massive trauma** **Sepsis** **Obstetric emergencies** e.g toxic shock syndrome, placental abruption **Malignancy** **Hypovolaemic shock**

Question 40

In which type of **sepsis** is **DIC** especially common?

Answer 40

**Meningococcal sepsis**

Question 41

How is **DIC treated?**

Answer 41

**Treat underlying cause** Replace deficencies **platelet transfusions** **plasma transfusions** (for clotting factors) **fibrinogen replacement**

Question 42

What is the **mode of inheritance** of **haemophilia**?

Answer 42

**X-linked recessive**

Question 43

**Haemophilia** is only expressed in **(males / females).**

Answer 43

**males** because it is X-linked recessive

Question 44

Where does bleeding occur in **haemophilia**?

Answer 44

**Skin** **Mouth** **Eyes** **Into joints** (haemarthrosis)

Question 45

Why does **haemarthrosis** recur in people with **haemophilia?**

Answer 45

**Blood in joint** **\> Iron in joint (irritant)** **\> Inflammation** **\> Recurrent bleeding**

Question 46

**Haemophilia** is a problem with **(primary / secondary) haemostasis**.

Answer 46

**secondary haemostasis**

Question 47

How is **haemophilia** treated?

Answer 47

**Factor VIII / IX injections**

Question 48

How regularly are **haemophiliacs** given **clotting factor injections?**

Answer 48

**Every 2 - 3 days**

Question 49

Which clotting time is abnormal in **haemophilia?**

Answer 49

**APTT** because it measures XIII/IXa action (which are deficient in haemophilia A/B)

Question 50

In which joints does **haemarthrosis** occur in haemophilia?

Answer 50

**Ankles** **Knees** **Elbows** (also: quads, iliopsoas)

Question 51

In **multiple factor deficiencies**, which **clotting times** are prolonged?

Answer 51

**PT** **APTT** i.e both of them

Question 52

Name **three reasons** for **multiple factor deficiency**.

Answer 52

**Liver disease** **Vitamin K deficiency** **DIC**

Question 53

Name a reason for **single factor deficiency**.

Answer 53

**Haemophilia**