Bleeding Disorders

Question 1

Inherited definition

Answer 1

traits present from birth and genetically derived from parents/ancestors

Question 2

Acquired definition

Answer 2

traits that develop during a person’s lifetime. Not passed from one generation ot another.

Question 3

Haemophilia/Bleeding Disorder definition

Answer 3

a problem with the blood clotting process, which can lead to abnormally heavy and prolonged bleeding. The bleeding can even be “spontaneous”

Question 4

Causes of abnormal bleeding

Answer 4

• blood vessel/vascular disorders
• platelet disorders
• coagulation pathway disorders

Question 5

Examples of inherited blood vessel/vascular disorders (2):

Answer 5

• hereditary haemorrhagic telangiectasia aka osler weber rendu syndrome
• collagen abnormalities: Ehlers-Danlos
  Syndrome

Question 6

Examples of acquired blood vessel/vascular disorders (3):

Answer 6

• Scurvy (vitamin C deficiency)
• Steroid Rx (Cushing’s syndrome)
• Old age

Question 7

• common?
• type of mutation
• is
• ## causes (3)
• effect on platelet count
• effect on coagulation screen

Answer 7

• aka Osler-Weber-Rendu syndrome
• uncommon
• autosomal dominant
• dilated microvascular swellings: skin,
  hands, fingertips, mucous membrane,
  internal organs
• nose bleeds, GI bleeds
• can cause iron deficiencies
• swellings bleed when traumatised (little
  capillaries near the skin are very sensitive)
• total platelet count normal
• coagulation screen will be normal

Question 8

Management of Hereditary Haemorrhagic Telangiectasia (5):

Answer 8

• iron replacement
• tranexanic acid (anti-fibrolytic prevents
  bleeds occurs)
• hormonal therapy eg norethisterone
• laser therapy on specific areas
• local measures: nasal packs

Question 9

Collagen/Connective Tissue Disorders: ehler’s-danlos syndrome:

• is
• clinical signs and blood tests
• management

Answer 9

• fragility of:
  - skin
  - ligaments
  - blood vessels*
  - perivascular connective tissue*
• easy bleeding and bruising because
  collagen is in vessel walls
• total platelet count normal
• coagulation screen will be normal
• no specific management but useful to
  know if in labour etc

Question 10

Scurvy:
- is
- clinical signs (3)
- history
- management

Answer 10

• acquired vitamin C deficiency
• bleeding gums
• peri-follicular haemorrhages
• bruises
• must ask: alcohol abuse and diet
• give vitamin C

Question 11

Thrombocytopenia:
- is
- numbers
- symptoms seen when
- symptoms are

Answer 11

• low platelet count
• normal range = 150-400 x10^9/L
• low = <105 x10^9/L
• symptoms <10 (ish)
• epistaxis, GI bleeds, menorrhagia, bruising,
  petechiae/purpura

Question 12

Disorders of platelet numbers can be

Answer 12

inherited which are rare
acquired which are common

Question 13

Disorders of platelet numbers: Acquired:

Answer 13

insert diagram

Question 14

ITP:

Answer 14

• immune thrombocytopenic purpura
• auto-antibodies against platelets
• leads to platelet removal by spleen

Question 15

ITP in children:

Answer 15

• acute condition in children
• often follows an infection
• self-limiting

Question 16

ITP in adults:

Answer 16

• acute/chronic condition in adults
• many potential triggers
• history is key

Question 17

Are males or females affected more by ITP?

Answer 17

Both are equally affected

Question 18

Treatment of ITP:

Answer 18

• treat if bleeding or platelets <30 with:
• steroids
• IV immunoglobulins
• TPO agonists (thrombopeotin hormone in
  bone marrow causes proliferation)
• monoclonal antibodies
• occasionally, splenectomy

Question 19

Disorders of platelet function:

Answer 19

insert table

Question 20

-
- clinical features (4)

Answer 20

• x linked recessive mutation
• Haemophilia A: Factors VIII deficiency
• Haemophilia B: Factor IX deficiency aka
  christmas disease
• Clinical Features:
• spontaneous bleeding into joints and
  muscle
• chronic debilitating joint disease
• unexpected post-operative bleeding
• family history in most cases (1 in 3 due to
  spontaneous mutations)

Question 21

Coagulation Cascade

Answer 21

insert diagram
- extrinsic: trauma damages blood vessels and exposes cells under the endothelial layer, exposing tissue factor embedded in membrane
F7 in blood binds to TF using calcium making a Via-TF complex

• intrinsic: Circulating factor XII contacts negatively charged phosphates on platelets/subendothelial collagen, activating it to XIIa
  Which cleaves XI to Xia
  IX to IX a (with Ca)
  Meanwhile FVIII starts being cleaved to VIIIa by thrombin

FXIa and VIIIa enter common pathway

Fxa is generated which turns prothrombin (II) into thrombin Iia

Thrombin works as a co enzyme to turn the stabilising factor XIII into XIIIa as well as helping F1 turn into its activated form- 1a aka fibrin

all this thrombin generation ultimately therefore helps form a stable fibrin clot around the platelet plug already formed in haemostasis

Question 22

X linked recessive inheritance

Answer 22

haemophilia

Carrier mums: have 50% haemophiliac sons
and 50% carrier daughters

All the daughters of affected men become carriers
very rare for a daughter to be affected only if X0

Question 23

Coagulation disorders on cascade page

Answer 23

insert

Question 24

Tests of coagulation

Answer 24

insert

Question 25

Blood results in haemophilia A+B

Answer 25

insert - intrinsic affected - extrinsic not affected - low factor 8 levels in haemophilia A - low factor 9 levels in haemophilia B

Question 26

Treatment of Haemophilia

Answer 26

insert prophylactic (preventive treatment)

Question 27

Von Willebrand's Factor:

Answer 27

- Von willebrand's factor = large multimeric glycoprotein - synthesised by endothelial cells and megakaryocytes - acts as a brdiging molecule between platelet and collagen at sites of vascular injury - promotes platelet aggregation

Question 28

Von Willebrand's Disease: - is - what % of population - dominant or recessive - in health does - in disease causes

Answer 28

- deficiency of Von Willebrand's Factor and factor VIII in plasma - most common inherited clotting abnormality (1% population) - autosomal dominant - the VW factor carries factor VIII in the blod and binds platelets to sub-endothelial collagen - deficiency leads to: - mucocutaneous bleeds, nose bleeds, menorrhagia - clot formation does not happen as it should in an injury

Question 29

Blood Results in Von willebrands Disease:

Answer 29

insert

Question 30

Treatment of vWD

Answer 30

- desmopressin = increases synthesis/release - anti-fibrinolytics = tranexamic acid, reduces thrombus breakdown - plasma products: replace VWF and Facto VIII

Question 31

Acquired Haemophilia: - is - hence - how common - causes - how to treat

Answer 31

- auto-antibodies act as inhibitors to clotting factors - effectively renders factor deficient - rare: acquired haemophilia A most common - look for underlying driver that has led to antibody formation: - malignancy - autoimmune - viral - pregnancy - complex to treat: - bypassing agents - immunosuppression

Question 32

Liver Disease

Answer 32

- defects in synthesis of clotting proteins - some degree of "auto-anticoagulation" - bleeding disorders and thrombotic disorders possible - impaired platelet number and function

Question 33

What are phagocytes that destroy pathogens like bacteria that enter the liver called?

Answer 33

Kupffer cells e

Question 34

Vitamin K deficiency

Answer 34

Dietary: - fat malabsorption - biliary obstruction (jaundice) - newborn state Warfarin: - PT time (INR) measures extrinsic pathway - Factors II,VII,X

Question 35

Vitamin K dependent Factors:

Answer 35

- X,IX, VII,II and proteins S and C - required for gamma carboxylation of VK dependent coag factors turning them from non-functional to functional forms - Mnemonic: 1972 was the diSCo era

Question 36

Disseminated Intravascular Coagulation:

Answer 36

- septicaemia: Mengingococcal, endotoxin in G-ve sepsis - acute promyelocytic leukaemia - cancer, trauma - pregnancy complication - release of tissue factor - breakdown balance of: coagulation, fibronolysis - clotting factors and platlets used up

Question 37

Blood Results in Disseminated Intravascular Coagulation

Answer 37

- prolonged PT, APTT - low fibrinogen - low platelets - raised D-dimer - raised fibrin degradation products (FDPs) - red cell fragments on blood film

Question 38

Treatment of Disseminated Intravascular Coagulation:

Answer 38

- ***treat underlying cause: eg antibiotics for sepsis - supportive Rx with blood products to try and correct coagulation abnormalities if bleeding - vitamin K - consider anti-coagulation

Question 39

What type of inheritance is seen with Hereditary Haemorrhagic Telangiectasia 1 = Autosomal Dominant 2 = Autosomal Recessive 3 = X-Linked Dominant 4 = X-Linked Recessive 5 = Y-Linked Recessive

Answer 39

1

Question 40

Bernard Soulier disease is due to a mutation in which molecule? 1 = GP0 2 = GP1b 3 = GP2b3a 4 = GP10a11b 5 = GP123

Answer 40

2

Question 41

In the absence of bleeding, when might you treat ITP? 1 = When platelets <10 2 = When platelets <20 3 = When platelets <30 4 = When platelets <50 5 = When platelets <150

Answer 41

3

Question 42

Haemophilia A is the deficiency of which factor 1 = Factor VII 2 = Factor VIII 3 = Factor IX 4 = Factor X 5 = Factor XI

Answer 42

2

Question 43

In addition to protein S and C, the Vitamin K dependent clotting factors are: 1 = Factors 1,3,5,7 2 = Factors 2,7,9,11 3 = Factors 2,3,5,10 4 = Factors 2,7,9,10 5 = Factors 7,9,11,12

Answer 43

2

Question 44

The APTT can be used as a screening test for the activity of which pathway? 1 = Common pathway 2 = Extrinsic pathway 3 = Intrinsic pathway 4 = Fibrin pathway 5 = Plasmin pathway

Answer 44

3