Anticoagulation for cardiopulmonary bypass Flashcards
Heparin…
- A glycosaminoglycan, derived from porcine tissue
- Unfractionated heparin is 3-30kDa
MOA- anionic and binds to the positive element of antithrombin, causing a conformational change activating the molecule. Activated antithrombin binds to factor Xa and IIa (thrombin) and irreversibly inactivates them. Also has direct effects on Xa and thrombin via other enzymes.
Adverse effects of heparin
- Bleeding
- Activation of immunoglobulins leading to heparin-induced thrombocytopaenia
- Hyperkalaemia- heparin inhibits aldosterone synthesis
- Hypotension- heparin releases NO and inhibits Ca
- Increased consumption of platelets
Heparin dosing for cardiopulmonary bypass
- 300-400 international units/kg
- Aiming for an ACT >480 secs
How do ACT machines work
- Blood sample is placed on a plate with a high level of surface activator (celite, silicate etc.)
- Endogenous phospholipids on platelets are activated and the clotting cascade begins
- The machine times how long it takes for the blood sample to clot
What methods can be used to assess heparin anticoagulation
- ACT
- activated partial thromboplastin time (aPTT)
- Anti-Xa levels
Causes of heparin resistance (Not achieving an ACT >480s after giving 300-400unit/kg of heparin)
Anti-thrombin deficiency
- Decreased production- liver failure
- Increased clearance- use of heparin pre-operatively, sepsis, nephrotic syndrome
- Congenital AT deficiency
Anti-thrombin independent mechanisms
- Heparin is a negatively charged molecule and will attach to positively charged ones reducing total free heparin, this occurs in sepsis, infective endocarditis, GTN use and oestrogen
Management of heparin resistance
- Redose heparin
- Give antithrombin via FFP to increase levels and potentiate heparin effect
- Give another anticoagulant e.g. bivalirudin
Protamine…
- Reverses the effects of heparin by being positively charged, binding to the negatively charged heparin and forming an ionic bond
- Heparin can therefore not bind to antithrombin and also helps dissociate heparin from antithrombin
- Protamine- heparin complex is cleared by the reticuloendothelial system, it has a half-life of 7.4mins
Adverse effects of protamine
- Hypotension: reduced risk if given slowly
- Pulmonary hypertension: through TXA2 activation
- Anaphylaxis
- Anaphylactoid reactions: Heparin-protamine complex activate the complement pathway and cause a vasogenic reaction
- Activate platelets causing consumption and a thrombocytopaenia
Heparin-induced thrombocytopenia
Type One- not immune mediated, direct effect of heparin on platelets, occurring within 72hours of starting heparin, does not complicate bypass
Type Two- heparin-platelet factor 4 complex activates IgG leading to platelet destruction and thrombocytopenia, occurs typically 5-14 days following heparin exposure. Release of microparticles from platelet activation leads to thrombi formation.
4T scoring system for HIT
- Decrease in platelet count
- Timing
- Thrombosis
- Other causes of thrombocytopenia
Diagnosis of HIT
- 4T score >5 = high
- ELISA screening
- Functional assays
Alternatives to heparin for cardiopulmonary bypass in HIT
Heparin with an antiplatelet agent
- tirofiban, prostacyclin or cangrelor
- allows for heparin effect and prevents platelet activation
Heparin after pre-operative plasma exchange
- Plasma exchange until function assay is negative for HIT antibodies
Bivalirudin
- Direct thrombin inhibitor
- Given as a bolus followed by an infusion. Aiming ACT >300
- Cleared renally, no reversal agent, can be filtered by bypass machine
Argatroban
- Direct thrombin inhibitor
- Undergoes hepatic clearance so is used instead of bivalirudin in renal failure patients
Antiphospholipid syndrome
An autoimmune condition, antibodies against phospholipid complexes. commonly anti-thrombin, anti-cardiolipin and anti-B2-glycoprotein.
Antibodies complex and activate endothelial cells and platelets, leading to venous and arterial clot formation.
2% of population, 30-40yrs, 5:1 female: male. Can progress to catastrophic antiphospholipid syndrome which is multiple emboli causing multi-organ failure
Anticoagulation for bypass in patients with anti-phospholipid syndrome
- Falsely prolonged aPTT and ACT times because the autoantibodies form complexes with the phospholipids in the test material
- Patients are usually on warfarin pre-op
- Thrombotic and bleeding risk because of this
- No set guidelines exist
Factor V Leiden
- Inherited autosomal dominant thrombophilia
- FV Leiden mutation are resistant to inactivation by protein C leading to increased risk of MI and CVA
Protein C and S Deficiency
- Inherited thrombophilias
- Protein C and S regulate factor VIII and V leading to clot lysis
- Increased risk of embolic events
Haemophilia
Haemophilia A- factor VIII deficiency
Haemophilia B- factor IX deficiency
Haemophilia C- factor XI deficiency
X-linked recessive conditions causing inherited coagulopathy
