Anticoagulants Flashcards
Write about warfarin
Used in the treatment of VTE and PE
Used for the prophylaxis and treatment of thromboembolic complications associated with rheumatic heart disease, atrial fibrillation and or prosthetic heart valve replacement
Reduction in the risk of death, recurrent myocardial infarction and thromboembolic events such as stroke after MI
Used to maintain a level of anticoagulation to minimise the risk of thrombosis and haemorrhagic complication
How does warfarin work
Interferes with the biochemistry of vitamin K dependent factors in the liver and interferes with the production of functional factors
Two isomers: R and S, S has a greater anticoagulant effect
Taken orally and easily absorbed from the GIT
Who should avoid warfarin
Severe hypertension
Peptic ulcer
Bacterial endocarditis
Pregnant
Biochemically how does warfarin affect coagulation
Vitamin K is necessary for the synthesis of gamma carboxyl glutamate residues on FII, VII, IX and X in the liver
Gla residues serve as high affinity binding sites for Ca++
Vit K converts the glutamyl residues of the protein to gamma-carboxyglutamyl residues by the liver enzyme carboxylase
These residues comprise the Gla domain which along with Ca++ is important for the anchoring of the protein to negatively charged phospholipids on the platelet surface
Warfarin blocks the reaction by inhibiting the enzyme and preventing the reduction of vitamin K epoxide
How is warfarin monitored
Test = International normalised ratio (INR) which is calculated from the prothrombin time
Laboratory testing or point of care self testing
What are some complications of warfarin therapy
(5)
There is a narrow therapeutic range: bleeding or thrombosis can occur
Too much warfarin can cause bleeding
Can induce necrosis if protein C level is reduced
Formation of micro-thrombi in the skin, oxygen insufficiency and cell death
Outside range can increase mortality, risk of stroke and rate of hospitalisation
Why can warfarin cause reduced levels o f protein C
Warfarin reduces levels of all vitamin K dependent factors
But protein C has the shortest half life
How can warfarin be reversed
Discontinue warfarin if not urgrent
Administer vitamin K orally or through IV
Administer prothrombin complex concentrates
What are prothrombin complex concentrates
Contain FII, FVII, FIX, FX, PC, PS
Given when there is an urgent requirement to reverse warfarin effect e.g. bleed or surgery
Write about heparin
Used when there is need for rapid anticoagulant effect
Prevents VTE, treats DVT and PE, early treatment of unstable angina and MI, cardiac surgery or bypass, vascular surgery and coronary angioplasty
Selected patients with DIC
How does heparin work
Mediated through antithrombin (AT) in the coagulation cascade
Binding to antithrombin is through a unique pentasaccharide sequence randomly distributed in the heparin molecule
Inhibits platelet function
Antithrombin prevents the work of FXa and thrombin thus preventing formation of fibrin
Write about unfractionated heparin
(4)
Mucopolysaccharide with alternating units of sulphated glucosamine and glucaronic acid
The negative charge allows the binding to and inactivation of FIIa and FXa
Produced from porcine intestinal mucosa or bovine lung
Administered by IV infusion either as a bolus dose or by continuous infusion
metabolised in liver and excreted in urine
Write about the mechanism of action of unfractionated heparin
Binding to FXa causes a conformational change in FXa and its inactivation
Binding to FIIa: UFH binds to AT and FIIa requiring longer chain of heparin
Write about low molecular weight heparin
Prevention and treatment of VTE (DVT and PE), early treatment of unstable angina and MI
Produced from UFH by chemical process resulting in a heparin that has a lower molecular weight
Contain the unique pentasaccharide unit required for binding to antithrombin and FXa (has less effect on FIIa and others)
Improved bioavailability, T1/2 = 4 hrs
Preductable response
Reduced side effects regarding osteopeonia and HIT
Limited requirement for monitoring
How is heparin administered
Unfractionated = continuous IV
LMW heparin = subcutaneous route
What are the complications of heparin therapy
Osteonpenia
Bleeding
HIT (heparin induced thrombocytopenia)
What increases your risk of heparin associated bleeding
Dose
Concomitant thrombolytic therapy or other drugs
Recent surgery
Trauma
Invasive procedures
Concomitant haemostatic defects
What are the symptoms of HIT
Thrombosis
Skin necrosis
Anaphylaxis
Adrenal haemorrhage necrosis
Can be life-threatening
How does heparin-induced thrombocytopenia occur
Caused by antibodies that bind to complexes of heparin and platelet factor 4, activating the platelets and promoting a prothrombotic state
HIT is more frequently encountered with unfractionated heparin than with low molecular weight heparin
How is heparin monitored
No laboratory monitoring of UFH
UFH monitored by the APTT
- APTT ratio is reported for UFH with a therapeutic range assigned
How is LMWH monitored
Monitored using a specific assay (anti Xa assay) due to the lack of sensitivity of the APTT
What is the anti Xa assay
Based on the incubation of the test plasma containing heparin with a reagent containing excess AT and FXa
The residual FXa is mixed with a chromogenic substrate and the colour change is inversely proportional to the concentration heparin in the test plasma
Compare heparin vs warfarin
(heparin)
Intravenous
Immediate onset of action
Short term use
Cheap
Needs careful monitoring
Compare heparin and warfarin (warfarin)
Oral
Slow onset and offset
Long term use
Cheap
needs careful monitoring
Give some examples of DOACs
Rivaroxaban and dabigatran
When would DOACs be used
Reduce risk of stroke in non-valvular atrial fibrillation
prevention of VTE following hip or knee replacement
Treatment and ongoing prevent of VTE
When would you not use DOACs
Renal impairment
Disorders of haemostasis
Clinically significant active bleeding
Prosthetic heart valve
Liver disease
Pregnant and breastfeeding women
Children under 18
What is dabigatran
A direct thrombin inhibitor
What is rivaroxaban
A factor Xa inhibitor
How is dabigatran monitor
Not typically monitored in haematology lab
Ecarin clotting time
Dilute thrombin time
How is rivaroxaban monitored
Not typically monitored in haematology lab
Anti-factor Xa
Why are anticoagulants used to treat VTE
Prevention of thrombus growth within blood vessels
Prevention of recurrence of thrombosis
Prevention of thrombosis in high risk situations
When would anticoagulants be used as a prophylaxis
Patients with high risk of thrombosis e.g. atrial fibrillation
Disrupted electrical activity to the atria
Irregular heartbeat with stasis of blood in the left atrium
Risk of stroke and VTE
What is VTE (DVT/PE)
(6)
Venous thrombo embolism
High rate of morbidity and mortality if not treated
Third most common cause of death from cardiovascular disease after heart attack and stroke
A multi-causal disease with important gene-environment interactions
Case fatality between 1 and 5%
Incidence and fatality dependent on age
Write about anticoagulants for arterial thrombosis
Little benefit because of the high platelet content of the clot
Artherosclerosis and the rupture of a plaque will cause arterial thrombisis
Treated with aspirin and other platelet antagonists not anticoagulants
How is VTE diagnosed
The presence of a blood clot is investigated using both a clinical and laboratory assessment and the probability of having a clot is determined by the clinician
Clinical assessment is conducted using a clinical
assessment score called the Wells DVT (or PE) pre-test probability score
A numerical value is assigned based on the presence of particular signs or symptoms and an overall score is obtained to determine the probability of the person having a clot
The higher the score – the more likely that a DVT or PE is present
This allows the clinician to make decisions regarding further testing
and treatment
What additional tests are done for VTE
D-dimer
Radiology
How is D-dimer used for VTE diagnosis
The D-Dimer assay should have a high negative predictive value i.e. a negative result will exclude VTE (beware of positive results)
May be negative if small clot or if clot is >10 days old
How is radiology used to diagnose VTE (DVT)
Venography, compression or ultrasonography is used for DVT
How is radiology used to diagnose VTE (PE)
Pulmonary angiography
Ventilation-perfusion (V/Q) scan
