Bleeding Disorders

Question 1

Which factors does Heparin affect?

Answer 1

anti thrombin

prevents activation factors 2 and 10

Question 2

Which factors does Warfarin affect?

Answer 2

vitamin K antagonist

affects synthesis of factors 2, 7, 9, 10

Question 3

Which factors does DIC affect?

Answer 3

Factors 1,2,5,8,11

D I C

deux (2)
I - 11, 1
C - 8 and 5 (round numbers)

Question 4

Which factors does Liver Disease affect?

Answer 4

Factors 1,2,5,7,9,10,11

Question 5

Describe blood clotting results in Haemophilia?

Answer 5

APTT increased
PT normal
Bleeding Time normal

Question 6

Describe blood clotting results in von Willebrand’s disease?

Answer 6

APTT increased
PT normal
Bleeding Time increased

Question 7

Describe blood clotting results in Vitamin K deficiency?

Answer 7

APTT increased
PT increased
Bleeding Time normal

Question 8

What is Warfarin? How does it work?

Answer 8

indirect anticoagulant

organic compound 4-hydroxycoumarins

vitamin K antagonist

acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.

Question 9

Indications for Warfarin?

Answer 9

venous thromboembolism
- target INR = 2.5, if recurrent 3.5

atrial fibrillation
- target INR = 2.5

mechanical ♡ valves
- target INR depends on the valve type and location.
- mitral valves generally require a higher INR than aortic valves.

Question 10

warfarin monitoring

Answer 10

INR (international normalised ration)

ratio of the prothrombin time for the patient over the normal prothrombin time.

Question 11

Warfarin has a long half-life and achieving a stable INR may take several days.

Answer 11

true

Question 12

Factors that may potentiate warfarin

Answer 12

liver disease

P450 enzyme inhibitors: amiodarone, ciprofloxacin

cranberry juice

NSAIDs: displace warfarin from plasma albumin & inhibit platelet function

Question 13

warfarin side effects

Answer 13

haemorrhage

teratogenic: although can be used in breastfeeding mothers

skin necrosis: when first started

purple toes

reduced protein C biosynthesis
- temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration.

Question 14

what to do if the patient is on warfarin and having major bleeding?

Answer 14

stop warfarin

intravenous vitamin K 5mg

prothrombin complex concentrate
- if not available then FFP

Question 15

what to do with patients on Warfarin & INR > 8.0

Minor bleeding

Answer 15

stop warfarin

intravenous vitamin K 1-3mg
- 24 hrs later: repeat dose if INR still too high

restart warfarin when INR < 5.0

Question 16

What to do with patients on Warfarin & INR > 8.0

No bleeding

Answer 16

stop warfarin

oral vitamin K 1-5mg
- 24 hrs later: repeat dose if INR still too high

restart when INR < 5.0

Question 17

What to do with patients on Warfarin & INR 5.0-8.0

Minor bleeding

Answer 17

stop warfarin

intravenous vitamin K 1-3mg

restart when INR < 5.0

Question 18

What to do with patients on Warfarin & INR 5.0-8.0

No bleeding

Answer 18

withhold 1 or 2 doses of warfarin

reduce subsequent maintenance dose

Question 19

Drugs which either inhibit or induce the which system may affect the metabolism of warfarin and hence the INR

Answer 19

P450

Question 20

Inducers of the P450 system will affect INR how?

Answer 20

INR will decrease

Question 21

INHIBITORS of the P450 system will affect INR how?

Answer 21

INR will increase

Question 22

Inducers of the P450 system include

Answer 22

antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone
rifampicin
St John’s Wort
chronic alcohol intake
griseofulvin
smoking (affects CYP1A2, reason why smokers require more aminophylline)

Question 23

Inhibitors of the P450 system include

Answer 23

Acute alcohol intake
SSRIs: fluoxetine, sertraline
Antibiotics: ciprofloxacin, clarithromycine/erythromycin
Imidazoles: ketoconazole, fluconazole
Sodium Valproate
Amiodarone
Allopurinol
Cimetidine, Omeprazole
Isoniazid
ritonavir, quinupristin

Question 24

There are two main types of heparin, these are?

Answer 24

unfractionated, ‘standard’ heparin or low molecular weight heparin (LMWH)

Question 25

Heparins generally act by

Answer 25

activating antithrombin III

Question 26

Unfractionated heparin works by?

Answer 26

forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa

Question 27

LMWH works by?

Answer 27

increases the action of antithrombin III on factor Xa

Question 28

Adverse effects of heparins include:

Answer 28

bleeding thrombocytopenia osteoporosis and an increased risk of fractures hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion

Question 29

How do you administer standard heparin vs LMWH?

Answer 29

standard - Intravenous LMWH - Subcutaneous

Question 30

Duration standard heparin vs LMWH?

Answer 30

standard - short LMWH - long

Question 31

LMWH heparin has lower risks of what compared to standard heparin?

Answer 31

Heparin-induced thrombocytopaenia (HIT) | Osteoporosis

Question 32

How do you monitor standard heparin?

Answer 32

Activated partial thromboplastin time (APTT)

Question 33

How would you monitor LMWH?

Answer 33

Anti-Factor Xa (although routine monitoring is not required)

Question 34

When is standard heparin useful?

Answer 34

Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure

Question 35

When is LMWH indicated?

Answer 35

Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes

Question 36

Heparin-induced thrombocytopaenia (HIT) is a bleeding condition

Answer 36

false | despite being associated with low platelets HIT is actually a prothrombotic condition

Question 37

When does HIT usually develop?

Answer 37

5-10 days of treatment

Question 38

What is the pathophysiology of HIT?

Answer 38

immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin these antibodies bind to the PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors

Question 39

What are the features of HIT?

Answer 39

features include a greater than 50% reduction in platelets, thrombosis and skin allergy

Question 40

How would you address Heparin overdose?

Answer 40

Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH. In HIT address need for ongoing anticoagulation: direct thrombin inhibitor e.g. argatroban danaparoid

Question 41

How is Haemophilia inherited?

Answer 41

X-linked recessive disorder of coagulation | Up to 30% of patients have no family history of the condition.

Question 42

Haemophilia A is due to?

Answer 42

deficiency of factor VIII

Question 43

Haemophilia B is due to?

Answer 43

(Christmas disease) there is a lack of factor IX

Question 44

Symptoms of haemophilias?

Answer 44

haemoarthroses, haematomas | prolonged bleeding after surgery or trauma

Question 45

Blood tests in Haemophilias/

Answer 45

prolonged APTT | bleeding time, thrombin time, prothrombin time normal

Question 46

Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.

Answer 46

true

Question 47

What is the most common inherited bleeding disorder?

Answer 47

Von Willebrand's disease

Question 48

The majority of VWD cases are inherited in which pattern?

Answer 48

autosomal dominant

Question 49

Symptoms of VWFD?

Answer 49

characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare

Question 50

What is the role of VWF?

Answer 50

large glycoprotein which forms massive multimers up to 1,000,000 Da in size promotes platelet adhesion to damaged endothelium carrier molecule for factor VIII

Question 51

What are the 3 types of VWFD?

Answer 51

type 1: partial reduction in vWF (80% of patients) type 2*: abnormal form of vWF type 3**: total lack of vWF (autosomal recessive)

Question 52

What will investigations show in VWFD?

Answer 52

prolonged bleeding time APTT may be prolonged factor VIII levels may be moderately reduced defective platelet aggregation with ristocetin

Question 53

Management of VWFD?

Answer 53

tranexamic acid for mild bleeding desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells factor VIII concentrate

Question 54

type 3 von Willebrand's disease (most severe form) is inherited as an autosomal recessive trait

Answer 54

true

Question 55

What is the commonest type of VWFD?

Answer 55

80% of patients have type 1 disease

Question 56

What is Hereditary haemorrhagic telangiectasia?

Answer 56

autosomal dominant condition characterised by (as the name suggests) multiple telangiectasia over the skin and mucous membranes

Question 57

In HHT twenty percent of cases occur spontaneously without prior family history.

Answer 57

true

Question 58

How is HHT diagnosed?

Answer 58

There are 4 main diagnostic criteria. If the patient has 2 then they are said to have a possible diagnosis of HHT. If they meet 3 or more of the criteria they are said to have a definite diagnosis of HHT

Question 59

What are the diagnostic criteria of HHT?

Answer 59

Epistaxis : spontaneous, recurrent nosebleeds Telangiectases: multiple at characteristic sites (lips, oral cavity, fingers, nose) Visceral lesions: for example gastrointestinal telangiectasia (with or without bleeding), pulmonary arteriovenous malformations (AVM), hepatic AVM, cerebral AVM, spinal AVM Family history: a first-degree relative with HHT

Question 60

Epistaxis is split into what? How do these arise?

Answer 60

anterior and posterior bleeds, Anterior: visible source of bleeding and usually occurs due to an insult to the network of capillaries that form Kiesselbach’s Plexus Posterior haemorrhages, on the other hand, tend to be more profuse and originate from deeper structures.

Question 61

Which type of epistaxis is more common in elderly?

Answer 61

Posterior

Question 62

Posterior epistaxis has a higher risk of ?

Answer 62

aspiration and airway compromise

Question 63

most cases of epistaxis tend to be benign and self-limiting, they may be an indicator of serious pathology

Answer 63

true

Question 64

Most common cause of epistaxis?

Answer 64

trauma to the nose- this can range from the insertion of foreign bodies, nose picking and nose blowing

Question 65

Causes of epistaxis can include platelet function disorders such as

Answer 65

thrombocytopenia, splenomegaly, leukaemia, Waldenstrom’s macroglobulinaemia and ITP

Question 66

Epistaxis In adolescent males could be

Answer 66

juvenile angiofibroma is a benign tumour that may bleed as it is highly vascularised.

Question 67

If the nasal septum looks abraded or atrophied, inquire about

Answer 67

drug use | inhaled cocaine is a powerful vasoconstrictor and repeated use may result in obliteration of the septum

Question 68

In the elderly, what may cause prolonged nasal bleeding

Answer 68

hereditary haemorrhagic telangiectasia

Question 69

If the patient is haemodynamically stable in epistaxis, bleeding can be controlled with first aid measures. This involves:

Answer 69

Asking the patient to sit with their torso forward and their mouth open- avoid lying down unless they feel faint. This decreases blood flow to the nasopharynx and allows the patient to spit out any blood in their mouth. It also reduces the risk of aspirating blood. Pinch the cartilaginous (soft) area of the nose firmly and consistently for at least 20 minutes and ask the patient to breathe through their mouth. If first aid measures are successful, consider using a topical antiseptic such as Naseptin (chlorhexidine and neomycin) to reduce crusting and the risk of vestibulitis.

Question 70

Naseptin cautions and alternative?

Answer 70

peanut, soy or neomycin allergies, and Mupirocin is a viable alternative.

Question 71

In epistaxis Admission and follow up care may be considered in who?

Answer 71

patients who have a comorbidity (e.g. coronary artery disease, or severe hypertension) is present an underlying cause is suspected if they are aged under 2 years (as underlying causes such as haemophilia or leukaemia are more likely in this age group).

Question 72

If bleeding does not stop after 10-15 minutes of continuous pressure on the nose, consider?

Answer 72

cautery or packing

Question 73

When should cautery be used?

Answer 73

if the source of the bleed is visible and cautery is tolerated- it is not so well-tolerated in younger children

Question 74

When should packing be used?

Answer 74

if cautery is not viable or the bleeding point cannot be visualised. If the nose is packed in primary care, the patient should be admitted to hospital for review.

Question 75

How do you cauterise in nosebleed?

Answer 75

Ask the patient to blow their nose in order to remove any clots. Be wary that bleeding may resume. Use a topical local anaesthetic spray (e.g. Co-phenylcaine) and wait 3-4 minutes for it to take effect Identify the bleeding point and apply the silver nitrate stick for 3-10 seconds until it becomes grey-white. Avoid touching areas which do not require treatment, and only cauterise one side of the septum as there is a risk of perforation. Dab the area clean with a cotton bud and apply Naseptin or Muciprocin

Question 76

How do you pack in nosebleed?

Answer 76

Anaesthetise with topical local anaesthetic spray (e.g. Co-phenylcaine) and wait for 3-4 minutes Pack the patient’s nose while they are sitting with their head forward, following the manufacturer’s instructions Pressure on the cartilage around the nostril can cause cosmetic changes and this should be reviewed after inserting the pack. Examine the patient’s mouth and throat for any continuing bleeding, and consider packing the other nostril as this increases pressure on the septum and offending vessel. Patients should be admitted to hospital for observation and review, and to ENT if available

Question 77

Patients with a bleed from an unknown or posterior source (i.e. the bleeding site cannot be located on speculum, bleeding from both nostrils or profuse) should be admitted to hospital.

Answer 77

true

Question 78

(epistaxis) Patients that are haemodynamically unstable or compromised should be admitted to the emergency department

Answer 78

yes | Control bleeding with first aid measures in the interim.

Question 79

Self care advice for epistaxis?

Answer 79

Patients should be informed that blowing or picking the nose, heavy lifting, exercise, lying flat, drinking alcohol or hot drinks should be avoided. The same applies for patients who have just been cauterised, as any strain on the nostril may induce a re-bleed.

Question 80

Common causes of epistaxis in children include:

Answer 80

nose picking (most common cause) foreign body upper respiratory tract infection allergic rhinitis

Question 81

Who do kids with epistaxis who are <2yrs need referal?

Answer 81

may be secondary to trauma or bleeding disorders.