T7-L7: Acquired Bleeding Disorders Flashcards
What is the mode of action of LMWH?
Binds to anti-thrombin to switch of FcXa. it works mainly by switching of FcX unlike unfractionated heparin which irreversibly switches of Fc IIa, Fc Xa and to a lesser extend Fc IX and XIa.
Give differences between unfractionated heparin and LMWH.
Unfractionated Heparin:
- Anti Xa and Anti-IIa action 1:1
- Hepatic and renal elimination
- APTT monitoring
- High frequency of HIT
- Half life of 2 house if s/c
- Inhibits platelet function
- Requires regular monitoring
LMWH:
- Has a greater anti-Xa effect compared to anti-II
- Eliminated through the kidneys
- Anti-Xa assay monitoring (if required)
- Low frequency of HIT
- s/c injection with a half life of 4 hours
- Has no effect on platelet function
- Requires less monitoring
What are the complications of Heparin treatment?
- Skin/allergic reactions
- Osteoporosis
- Heparin Induced Thrombocytopenia - Can be associated with thrombosis or even skin necrosis
What is the treatment of bleeding of LMWH or unfractionated heparin?
Unfractionated heparin - stop IV heparin and give Protamine Subpage as an antidote. If given too much, Protamine can over anticoagulate patients.
LMWH: Stop LMWH. Protamine reverses 60% of the effect.
Fondaparinux has no antidote. Instead you need to stop treatment and start general haemostat measures Can consider using tranexamic acid and FVIIa.
What is the method of action of Sinthrome?
Like Warfarin, Vitamin K antagonist like Warfarin. Fc II, VII, IX, X, Protein C and Protein S and Vitamin K dependent.
Protein C and S fall first so treatment of Warfarin needs to be overlapped with heparin (if not it can lead to Warfarin induce skin necrosis and protein C and S fall faster).
What is INR?
International Normalised Ratio. This is a corrected value for the patients prothrombin time/mean prothrombin time. It is a laboratory measurement of how long it takes blood to form a clot. It is therefore used to monitor Wafarin use.
Give examples of drugs that interact with Warfarin.
Many, to name a few:
- Cimetidine - Ampicillin (oral) - Amiodarone - NSAID’s - Sulphinpyrazone - Chlorpromazine - Cotrimoxazole - Sulphonylureas - Erythromycin - Corticosteroids - Cephalosporins
Also many food interactions - Vitamin K containing and also alcohol
How do we treat bleeding on Warfarin?
Stop Wafarin. Then give prothrombin complex concentrates- includes Fc II, Fc VII, Fc IX and FcX in larger concentrations. It is also imperative to give Vitamin K as if not the issue will not correct.
What are the disadvantages of DOACs?
Specific contraindications and causations
- Renal impairment
- Women of Child Bearing Age
- Extremes of Body Weight > 120Kg
Due to the drugs being relatively new other issues include:
- Difficult management fo bleeding as antidotes are expensive
- Some labs do not have the facility
- Adherence issues - they have a rapid onset and inaction and so if the drug is not taken, the patient is not protected for that period of time
What changes on Coagulation tests do we see with DOCAs?
Rivaroxiban and Apixiban - no effect on N/A. Mostly no effect in APTT and either no effect or increased PT. The test of choice is antiXa where we see increased levels.
Dabigatran - Fc IIa inhibitor leads to prolonged PT time, APTT and TT time. We see increased Haemoclot.
What is the method of action of Aspirin?
- Inactivates platelet cyclooxygenase reducing thromboxane A2
- Irreversible effect, lasts 4-5 days - need to wait for the bone marrow to make new platelets that do not have aspirin bound
- No reversal agents
- Give 2-3 adult doses of platelets in critical bleeding
What is the method of action of Clopidogrel?
P2Y12 antagonist.
What are causes of Vitamin K deficiency? What occurs as a result?
Causes:
- Obstructive jaundice
- Nutritional deficiency
- Broad spectrum antibodies (the gut no longer absorbed antibiotics)
- classically occurs in days 1-7 in neonates
Leads to deficiency in vitamin K dependent factors - II, VII, IX and X. Prolonges PT and APTT.
How can liver disease lead to bleeding?
The liver creates most clotting factors, components of the fibrinolytic system and naturally occurring anti-coagulants such as protein C, S and antithrombin. When patients develop cirrhosis they can develop coagulopathy - we seen Fc VIII and vWF levels raise and other factors drop. There is a risk of severe bleeding. You can also get a drop in the anticoagulant side and making it hard to gauge which way the haemostatic balance is tipping. If bleeding we normally give FFP and platelets. If patients cannot handle large volumes we tend to use Prothrombin complex concentrates.
How can renal disease lead to bleeding?
We can get bleeding in chronic renal failure. Bleeding can be caused by anaemia.
- When you have a healthy amount of RBC, the RBC push the platelets to the outer parts of the vessel lining. In anaemia platelets float in the middle of the vessel platelets so cannot do their job as well. RBC release ADP and thromboxane which enhance platelet function. Drugs accumulating in renal failure (penicillins) can bind to platelets and block their receptors.
- Uraemia can disrupt the way platelets interact with each other and the vessel wall leading to bleeding
Treatment is DDAVP, Tranexemic acid and cryoprecipitate.
