Theme 7 Haematology: Acquired Bleeding Disorders Flashcards
Name the anticoagulants?
- heparin
- fondaparinux
- vitamin K antagonists: warfarin
- DOACs (direct oral anticoagulants) - rivaraoxaban, dabigatran
Why do we use anticoagulants?
- prevention of venous thromboembolism
- prevention of stroke in AF
- treatment of VTE
- mechanical valve patients
- arterial thrombosis/ limb ischaemia
What is the mode of action of heparin?
increases ability of antithrombin to bind to and irreversibly switch off thrombin (IIa), factor Xa and factor IXa and Xa
(prevents fibrinogen being converted by thrombin to fibrin)
What does unfractionated heparin mean?
heparin of different sizes
What are the differences in low molecular weight heparin and unfractionated heparin?
- low molecular weight heparin switches off factor Xa
- unfractionated heparin works against factor Xa and also switches off thrombin
- LMWH doesn’t inhibit platelet function whereas unfractionated heparin does
- LMWH is give subcutaneously, has a longer half life and is excreted by the kidneys
- unfractionated heparin is excreted by the kidneys and liver
What are 3 complications of heparin?
- Skin/ allergic reactions
- Osteoporosis
- Heparin induced thrombocytopenia (HIT)
- heparin interacts with platelets and causes a drop
What is the 4Ts pre test probability score?
- system for assessing heparin induced thrombocytopenia
1. Thrombocytopenia: extent of fall in platelet count
2. Timing: onset of fall in platelet count
3. Thrombosis or other sequelae
4. Other cause of thrombocytopenia
What happens if a patient starts bleeding on unfractionated heparin or fondaparinux?
stop treatment
give antidote if possible
Which clotting factors are vitamin K dependant?
II, VII, IX, X, protein C and S
What is INR?
-international normalised ratio
-to control dose of oral anticoagulants
INR = (prothrombin ratio)^ISI
ISI = correction factor to account for sensitivity of thromboplastin compared with the international reference preparation (IRP)
What is the prothrombin ratio?
prothrombin ratio = patients prothrombin time / mean normal prothrombin time
How do you treat excess warfarin if the patient is bleeding?
stop warfarin
give prothrombin complex concentrate
give vitamin K IV
What are the ideal characteristics of an anticoagulant?
- oral administration
- no requirement for routine coagulation monitoring and dose adjustment
- wide therapeutic window: high efficacy in preventing thrombosis, low bleeding risk
- rapid onset of action
- predictable pharmacokinetics and pharmacodynamics
- minimal interactions with food
- availability of an antidote
- acceptable costs
- no unexpected toxicities
Which DOACs inhibit Factor Xa
- rivaroXAban
- apiXAban
- edoXAban
Which DOACs inhibit thrombin?
dabigatran
Do DOACs have a predictable dose-response?
yes (compared to warfarin where the dose varies 40 fold)
- in DOACs, the dose is uniform for most patients
- no need for routine monitoring
- minimal interactions with drugs
Why can dabigatran not be given to a patient with renal impairment?
it is excreted by the kidneys
What are the specific contraindications and cautions for DOACs?
- renal impairment
- women of child bearing age
- extremes of body weight > 20kg
- management of bleeding
What are the general measures taken in patients on DOACs who start bleeding?
- assess severity of bleeding
- assess degree of anticoagulant effect
- discontinue drug unless bleeding is minor
Which drug is the antidote for dabigatran?
idarucizumab
antibody that binds to dabigatran with high affinity to prevent interaction with thrombin
How does aspirin work?
- inactivates platelet cyclooxygenase reducing thromboxane A2
- stops platelet activation
- irreversible events, no reversal agents
If you are vitamin K deficient, you are deficient in which factors?
Factors II, VII, IX, X
What are the causes and treatment of vitamin K deficiency?
Causes: obstructive jaundice, prolonged nutritional deficiency, broad spectrum antibiotics, neonates
Treatment: IV/ oral vitamin K
What impact would liver disease have on haemostasis?
- thrombocytopenia (production or hypersplenism)
- platelet dysfunction
- reduced plasma concentration of all coagulation factors
- excessive plasmin activity
- delayed fibrin
What are 3 causes of bleeding in renal disease?
- Anaemia
- decreased platelet interaction with vascular lining
- platelet function reduced - Drugs accumulating in renal failure can bind to platelets and block their receptors
- Uremia
- disrupt plt-plt and plt-vessel wall interaction
What defines a major haemorrhage
HR> 110 systolic BP < 90mmHg and/or transfusion of a volume equal to the patients total blood volume in less than 24 hours or 50% blood volume loss within 3 hours
How would LTHT handle a major haemorrage?
- take baseline blood samples prior to transfusion e.g FBC, U&E etc
- administer RBC: FFP in 1:1 ratio
- prevent hypothermia: keep patient warm
- consider administering tranexamic acid
What is DIC?
- disseminated intravascular coagulation
- characterised by systemic activation of pathways leading to and regulating coagulation, which can result in the generation of fibrin clots that may cause organ failure with consumption of platelets and coagulation factors that may result in clinical bleeding
Explain the pathogenesis of DIC
- excess thrombin generation
- reduced natural anticoagulant activity
- decreased fibrinolysis
What are the causes of acute DIC?
- sepsis
- obstetric complications
- trauma/tissue necrosis/fat embolism
- massive blood loss
- fulminant liver disease
What are the causes of chronic DIC/
malignancy
end stage liver disease
vascular abnormalities
What are the clinical features of DIC?
- mucosal oozing, bleeding from surgical wounds or indwelling canulae
- multi organ failure secondary to microthrombi
- skin necrosis
- thrombus
How do we treat DIC?
- treat underlying cause e.g chemotherapy
- maintain tissue perfusion
- folic acid and vitK
- platelet transfusion if platelets < 50
- fibrinogen
