Bleeding Disorders Flashcards
Pack includes notes on Heparin & Warfarin, Epistaxis, HHT
Which factors does Heparin affect?
Prevents activation factors 2,9,10,11
Which factors does Warfarin affect?
Affects synthesis of factors 2,7,9,10
Which factors does DIC affect?
Factors 1,2,5,8,11
Which factors does Liver Disease affect?
Factors 1,2,5,7,9,10,11
Describe blood clotting results in Haemophilia?
APTT increased
PT normal
Bleeding Time normal
Describe blood clotting results in von Willebrand’s disease?
APTT increased
PT normal
Bleeding Time increased
Describe blood clotting results in Vitamin K deficiency?
APTT increased
PT increased
Bleeding Time normal
What is Warfarin? How does it work?
oral anticoagulant
inhibits epoxide reductase preventing the reduction of vitamin K to its active hydroquinone form
which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.
Indications for Warfarin?
venous thromboembolism: target INR = 2.5, if recurrent 3.5
atrial fibrillation, target INR = 2.5
mechanical heart valves, target INR depends on the valve type and location. Mitral valves generally require a higher INR than aortic valves.
Patients on warfarin are monitored using the
NR (international normalised ration), the ratio of the prothrombin time for the patient over the normal prothrombin time.
Warfarin has a long half-life and achieving a stable INR may take several days.
true
Factors that may potentiate warfarin
liver disease
P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
cranberry juice
NSAIDs because they displace warfarin from plasma albumin & inhibit platelet function
Side effects of Warfarin?
haemorrhage
teratogenic, although can be used in breastfeeding mothers
skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis
purple toes
What to do if the patient is on warfarin and having major bleeding?
Stop warfarin
Give intravenous vitamin K 5mg
Prothrombin complex concentrate - if not available then FFP*
What to do with patients on Warfarin & INR > 8.0
Minor bleeding
Stop warfarin
Give intravenous vitamin K 1-3mg
Repeat dose of vitamin K if INR still too high after 24 hours
Restart warfarin when INR < 5.0
What to do with patients on Warfarin & INR > 8.0
No bleeding
Stop warfarin
Give vitamin K 1-5mg by mouth, using the intravenous preparation orally
Repeat dose of vitamin K if INR still too high after 24 hours
Restart when INR < 5.0
What to do with patients on Warfarin & INR 5.0-8.0
Minor bleeding
Stop warfarin
Give intravenous vitamin K 1-3mg
Restart when INR < 5.0
What to do with patients on Warfarin & INR 5.0-8.0
No bleeding
Withhold 1 or 2 doses of warfarin
Reduce subsequent maintenance dose
Drugs which either inhibit or induce the which system may affect the metabolism of warfarin and hence the INR
P450
Inducers of the P450 system will affect INR how?
INR will decrease
INHIBITORS of the P450 system will affect INR how?
INR will increase
Inducers of the P450 system include
antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone
rifampicin
St John’s Wort
chronic alcohol intake
griseofulvin
smoking (affects CYP1A2, reason why smokers require more aminophylline)
Inhibitors of the P450 system include
Acute alcohol intake SSRIs: fluoxetine, sertraline Antibiotics: ciprofloxacin, clarithromycine/erythromycin Imidazoles: ketoconazole, fluconazole Sodium Valproate Amiodarone Allopurinol Cimetidine, Omeprazole Isoniazid ritonavir, quinupristin
There are two main types of heparin, these are?
unfractionated, ‘standard’ heparin or low molecular weight heparin (LMWH)
Heparins generally act by
activating antithrombin III
Unfractionated heparin works by?
forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa
LMWH works by?
increases the action of antithrombin III on factor Xa
Adverse effects of heparins include:
bleeding
thrombocytopenia
osteoporosis and an increased risk of fractures
hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion
How do you administer standard heparin vs LMWH?
standard - Intravenous LMWH - Subcutaneous
Duration standard heparin vs LMWH?
standard - short LMWH - long
LMWH heparin has lower risks of what compared to standard heparin?
Heparin-induced thrombocytopaenia (HIT)
Osteoporosis
How do you monitor standard heparin?
Activated partial thromboplastin time (APTT)
How would you monitor LMWH?
Anti-Factor Xa (although routine monitoring is not required)
When is standard heparin useful?
Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure
When is LMWH indicated?
Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes
Heparin-induced thrombocytopaenia (HIT) is a bleeding condition
false
despite being associated with low platelets HIT is actually a prothrombotic condition
When does HIT usually develop?
5-10 days of treatment
What is the pathophysiology of HIT?
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
What are the features of HIT?
features include a greater than 50% reduction in platelets, thrombosis and skin allergy
How would you address Heparin overdose?
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
How is Haemophilia inherited?
X-linked recessive disorder of coagulation
Up to 30% of patients have no family history of the condition.
Haemophilia A is due to?
deficiency of factor VIII
Haemophilia B is due to?
(Christmas disease) there is a lack of factor IX
Symptoms of haemophilias?
haemoarthroses, haematomas
prolonged bleeding after surgery or trauma
Blood tests in Haemophilias/
prolonged APTT
bleeding time, thrombin time, prothrombin time normal
Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.
true
What is the most common inherited bleeding disorder?
Von Willebrand’s disease
The majority of VWD cases are inherited in which pattern?
autosomal dominant
Symptoms of VWFD?
characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
What is the role of VWF?
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
What are the 3 types of VWFD?
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
What will investigations show in VWFD?
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Management of VWFD?
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
type 3 von Willebrand’s disease (most severe form) is inherited as an autosomal recessive trait
true
What is the commonest type of VWFD?
80% of patients have type 1 disease
What is Hereditary haemorrhagic telangiectasia?
autosomal dominant condition characterised by (as the name suggests) multiple telangiectasia over the skin and mucous membranes
In HHT twenty percent of cases occur spontaneously without prior family history.
true
How is HHT diagnosed?
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
What are the diagnostic criteria of HHT?
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
Epistaxis is split into what? How do these arise?
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.
Which type of epistaxis is more common in elderly?
Posterior
Posterior epistaxis has a higher risk of ?
aspiration and airway compromise
most cases of epistaxis tend to be benign and self-limiting, they may be an indicator of serious pathology
true
Most common cause of epistaxis?
trauma to the nose- this can range from the insertion of foreign bodies, nose picking and nose blowing
Causes of epistaxis can include platelet function disorders such as
thrombocytopenia, splenomegaly, leukaemia, Waldenstrom’s macroglobulinaemia and ITP
Epistaxis In adolescent males could be
juvenile angiofibroma is a benign tumour that may bleed as it is highly vascularised.
If the nasal septum looks abraded or atrophied, inquire about
drug use
inhaled cocaine is a powerful vasoconstrictor and repeated use may result in obliteration of the septum
In the elderly, what may cause prolonged nasal bleeding
hereditary haemorrhagic telangiectasia
If the patient is haemodynamically stable in epistaxis, bleeding can be controlled with first aid measures. This involves:
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.
Naseptin cautions and alternative?
peanut, soy or neomycin allergies, and Mupirocin is a viable alternative.
In epistaxis Admission and follow up care may be considered in who?
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).
If bleeding does not stop after 10-15 minutes of continuous pressure on the nose, consider?
cautery or packing
When should cautery be used?
if the source of the bleed is visible and cautery is tolerated- it is not so well-tolerated in younger children
When should packing be used?
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.
How do you cauterise in nosebleed?
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
How do you pack in nosebleed?
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
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.
true
(epistaxis) Patients that are haemodynamically unstable or compromised should be admitted to the emergency department
yes
Control bleeding with first aid measures in the interim.
Self care advice for epistaxis?
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.
Common causes of epistaxis in children include:
nose picking (most common cause)
foreign body
upper respiratory tract infection
allergic rhinitis
Who do kids with epistaxis who are <2yrs need referal?
may be secondary to trauma or bleeding disorders.
