Case 7: Venous Thromboembolism Flashcards
Describe the aetiology and risk factors for venous thromboembolism (VTE)
- i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE).
Aetiology of VTE
○ DVT - Deep vein thrombus
- Clot that forms in veins deep in the muscle
- Usually in lower limbs (above or below knee)
- Sometimes in upper limbs
○ PE - Pulmonary embolus
- Clot breaks off (mostly deep vein emboli) and travel through venous system - lodges in pulmonary arteries
○ Cause: Abnormality of:
- Vessel wall - atheroma, direct injury, inflammation
- Blood flow - stagnation, turbulence
- Blood components - smoking, post partum, post operation
○ Cause: Virchow’s triad (increase thrombus formation)
- Endothelial/vascular damage
- Hypercoagulability (tendency to form clot rather than bleed)
- Circulatory Stasis - (promotes clot formation)
Risk factors (see notes)
Describe pathophys of VTE
○ Thrombosis: when there is increase of procoagulants in body (clotting factors, phospholipids, platelets)
○ Virchow’s triad - cause VTE
○ The clotting cascade - forms stable fibrin clot
(see notes)
Describe signs and symptoms of VTE –> DVT and PE
see notes
How is VTE diagnosed and what are the differential diagnoses?
i) Blood tests
- Routine blood tests for all: FBC, U + E, INR, aPPT, LFTs
- Thrombophilia screen in some patients
- D-dimer: fibrin degradation product
> Low risk patients VTE: normal D-dimer level = certain no underlying thrombus
> High D-dimer - could be due to VTE = more likely clot forms
> High risk patients w High D-dimer level = imaging study
ii) Imaging
- DVT: ultrasound scan of vein
- CTPA: CT pulmonary angiogram
Differential Diagnosis
DVT
- Baker’s Cyst (knee injury, arthritis)
- Cellulitis
- Post-phlebitis syndrome/venous insufficiency
Pulmonary embolism (PE)
- Pneumonia
- ACS
- Rib fracture
- Asthma
- COPD
- Heart Failure
- Pericarditis (swelling and irritation of pericardium
- Pleurisy (pleura becomes inflamed)
Anticoagulants: parenteral
Heparins
- MOA : UFH, LMWH
- Advantages
- Disadvantages
see notes
Anticoagulants: oral
Vitamin K Antagonists (VKA) - Warfarin
- MOA
- Advantages
- Disadvantages
see notes
Anticoagulants: oral
Novel oral anticoagulants (NOACs) - Dabigatran, Rivaroxaban, Apixaban
- MOA
- Advantages
- Disadvantages
see notes
Describe the common laboratory tests used to monitor heparins, VKA and NOACs.
aPTT (UFH) - activated partial thromboplastin time
- Blood coagulation test
- How long it takes for blood to clot
- High aPTT - more time for blood to clot
- Low aPTT - blood clotting faster than normal - increase risk of developing clot
INR (warfarin-VKA)
- Measures time for blood to clot, prothrombin time (PT)
- High INR = blood clots too slowly
- Low INR = risk of developing blood clot
Anti-factor Xa test (UFH and LMWH)
- Measures activity of heparins
- Measures plasma heparin levels
- High levels: person may be getting excessive dose and/or not clearing drug at expected rate –> increased risk of excessive bleeding
What factors (e.g. co-morbidities, medication) would place a patient at a higher risk of bleeding when receiving anticoagulant drugs?
Risk factors for bleeding
○ > 75 years old
○ Moderate renal impairment (CrCl 30-50mL/min)
○ Being female
○ Diabetes Mellitus
○ Elevated BP or history of hypertension
○ History of bleeding
○ History of myocardial infarction or ischaemic heart disease
○ History of cerebrovascular disease or thromboembolism
○ Active Cancer
○ Previous stroke
○ Antiplatelet therapy
○ Renal or liver failure
○ Anaemia
○ active or recent (< 30 days) bleeding, which usually contraindicates anticoagulant therapy.
○ prior history of bleeding (especially while receiving anticoagulation),
○ a potential bleeding lesion (eg, peptic ulceration),
○ recent surgery (within 14 days),
○ severe kidney disease
Discuss what determines the duration of anticoagulation therapy post VTE?
Proximal deep vein thrombosis + PE
○ All patients should receive anticoagulant therapy for at least 3 months
○ Patient’s whose proximal DVT or PE were caused by major surgery or trauma –> can stop anticoagulation at 3 months
Distal deep vein thrombosis
○ Treat for 6-12 weeks
Extended anticoagulation for deep vein thrombosis + PE (beyond 3-6 months)
○ Non-surgical cause of PE or DVT
○ Decide whether to stop or continue w extended anticoagulant therapy after 3 months of anticoagulation
○ Continuing for longer = reduce risk of VTE recurrence during therapy by at least 80%
- Associated w major bleeding risk of <1% per year
- Once anticoagulant therapy stopped - risk of recurrence = same as those who cease treatment after 3-6 months
- Decision: balance btwn risks of bleeding and VTE recurrence
Explain the mechanisms of the main clinically significant drug-drug and drug-food interactions involving warfarin and the NOACs.
- How could these be managed to minimise harm?
Warfarin
○ Many drugs and food interact w warfarin + affect prothrombin time
○ Concomitant use of drugs used to treat prophylaxis of thrombosis or other drugs w adverse effects on haemostasis –> increase effect of warfarin = increase risk of bleeding
○ C/I: fibrinolytic drugs such as alteplase, azole antifungals, macrolide antibiotics
○ Metabolic interactions: warfarin metabolised by CYP2C9, CYP1A2, CYP3A4 - so inhibitors or competitors of these = increase warfarin plasma concentration and INR —> warfarin dosage may need to be reduced + increased monitoring
- Increase risk of bleeding
- Drugs that induce these metabolic pathways = decrease plasma conc + INR = reduced efficacy - warfarin dosage needs to be increased + monitoring
NOACs
○ Rivaroxaban: Metabolised by CYP3A4, CYP2J2 and CYP independent mechanisms, substrate of P-gp - BCRP
- Using w substances that strongly inhibit CYP3A4 and P-gp = reduced hepatic and renal clearance = increase plasma conc of rivaroxaban
- C/I - Azole- antimycotics - e.g. ketoconazole or HIV protease inhibitors - e.g. ritonavir
○ Apixaban
- Metabolised by CYP3A4/5 (major)
- Substrate of P-gp, BCRP
- C/I - Azole antifungals, HIV protease inhibitors, anticoagulants (unless transitioning)
○ Dabigatran
- Not metabolised by CYP system
- Substrate of P-gp (dabigatran etexilate)
- C/I - Azole antifungals, Dronedarone, Immunosuppressants: Calcineurin inhibitors, anticoagulants (unless transitioning)
Develop an education plan for a patient who is receiving an anticoagulant i.e. enoxaparin, warfarin or a NOAC for VTE
Reason for treatment - pros and cons
Monitoring, red flags
Factors affecting RX/prophylaxis
Interactions of ACs - drug-drug, drug-health/disease, drug-herb, drug-food
