Venous Thrombosis: Aetiology and Management Flashcards
Thrombophlebitic syndrome: occurs when someone has had a ____
3 features
DVT: From disruption to circulation of the veins in the leg
recurrent pain, swelling and ulcers
2 Consequenes of thromboembolism
Thrombophlebitis sydnrome
Pulmonary HT –> causes HF and can be fatal
What is Virchow’s Triad?
3 contributory factors to thrombosis:
Blood composition:
- viscosity = hct, protein/paraprotein
- platelet count
- coagulation system
Vessel wall
Blood flow (stasis)
Coagulation cascade
Procoagulant and anti-coagulant factors
Pro-coagulant = XII, XI, IX, VIII, X, V, II
Anti-coagulant = TFPI, Protein C/S, thrombomodulin, EPCR, Antithrombin, fibrinolysis
Coagulation definition = balance of htomrbotic and anti-thrombotic factors
Give an example of a condition where someone can be predisposed to thrombosis which can precipitate a thromboembolic event
pregnancy
What is thrombophilia?
Increased tendency to form blood clots
- tendency towards procoagulant state (excess coag factors/platelets, or deficiency in anti-coags)
- 50% of thrombophilic events are precipitate (e.g. pregnancy, surgery)
Is vessel wall pro/antithrombotic
Antithrombotic
anticoagulant moleculex expressed:
- thrombomodulin
- EPCR
- TFPI
- Heparans
it does NOT secrete TF
it secretes anti-platelet factors:
- prostacyclin
- NO
What is immunothrombosis?
change of vessel well from antithrombotic to prothrombotic during inflammation
Stimuli for vessel wall to be prothrombotic
Infection
Malignancy
Vasculitis
Trauma
Effects of prothrombotic vessel wall
Anticoagulant molecules downregulated, adhesion molecules upregulated
TF expressed, prostacyclin production decreased
VWF released from endothelial cells (makes endothelial cells sticky)
- platelets captured on these sticky cells and are activated
- neutrophils are captured when platelets activated
- neutrophils then produce NETS (neutrophil extrudes on DNA) aka NETosis
- DNA is procoagulant
- neutrophils also release neutrophil elastase - breakdown TFPI
Blood flow and thrombosis
Causes of stasis
Stasis -> thrombosis
- activated factors accumulated -> platelet/leukocyte adhesion and transmigation
- hypoxia promotion -> inflammatory effects on endothelium
Causes of stasis:
- Immobility (surgery, travel)
- Compression (tumour, pregnancy)
- Viscosity (polycythaemia, paraprotein)
- Congenital (vascular abnormalities)
OCP + FV Leiden ineratction
how do we go about VTE
2 types of anticoagulant therapy
therapeutic = high dose
prophylactic = low dose
Heparin: anti-coagulant immediate
Unfractionated (IV infusion: monitored) or LMWH (SC: no monitoring)
- Pentasaccharide (SC) – the key sugar sequence in heparins that mediate its effects
- Works by increasing anticoagulant activity (potentiating anti-thrombin)
LT cons: require injections, increased risk of osteoporosis, variable renal dependence
DOACs: anti-coagulant immediate
Anti-Xa: Rivaroxaban, Apixaban, Edoxaban
Anti-IIa: Dabigatran
Properties = PO, short 1/2 life, no monitoring required (unlike warfarin )
immediate acting (peak in 3-4 hours)
useful LT, but NOT useful for prosthetic heart valve patients
LMWH vs unfractioned heparin
Low molecular weight heparin
- Reliable pharmacokinetics (so does NOT usually need monitoring – unless renal concerns)
- LMWHs are smaller and do not bind to inflammatory molecules – less need for monitoring
- Anti-Xa assays can be used to monitor renal failure and extremes of weight or risk
Unfractionated Heparin
- Variable kinetics
- Variable dose-response
How do we monitor anticoagulants
ALWAYS monitor therapeutic levels with APTT or anti-Xa
Amount of anticoagulant effect you get from unfractionated heparin can be unpredictable, so monitoring is important here
Warfarin: anti-coagulant delayed
mechanism for action and on which factors
favoured drug for what condition
how do we reverse its effects
Vitamin K antagonist
Reduces 2, 7, 9 and 10 + Protein C/S indirectly by antagonising vitamin K -> delayted onset of action
reverse effects:
- Immediate reverse: give factors 2, 7, 9 and 10
- Reverse in 12 hours: give vitamin K
Monitoring warfarin therapy
contraindications
Measure INR (drived from PT)
Difficult because there are lots of variables at play:
- Dietary vitamin K intake
- Variable absorption
- Interactions with other drugs
- Teratogenic – warfarin is very rarely given to women who are pregnant
Warfarin is teratogenic:
- Major teratogenic effects occur in the first trimester (on bone, heart)
- Warfarin also causes problems in the second trimester (neurological)
- The key organs that warfarin affects don’t develop for the first 6 weeks
- If a woman detects her pregnancy within these 6 weeks, warfarin can be stopped
Heparin, DOAC and warfarin summary
INR diagram
Patients who are at increased risk of thrombosis
what do we call intervening with anticoag therapies to reduce risk of a thromboembolic event
Medical inpatients (infection/inflammation, age, immobility)
Patients with cancer (procoagulant molecules, inflammation, flow obstruction)
Surgical patients (immobility, trauma, inflammation)
Previous VTE, family history, genetic traits
Obese patients
Elderly patients
Term is = preventative intervention thromboprophylaxis
features of thromboprophylaxis (4)
Low molecular weight heparin (LMWH)
- E.g. Tinzaparin 4500 u/Enoxaparin 40 mg OD
- Not monitored
TED stockings (for surgery, or if heparin is contraindicated)
Intermittent pneumatic compression (increases flow – reduces stasis)
Sometimes DOAC +/- aspirin (orthopaedics)
NICE guidelines thromboprophylaxis
all admissions to hospital should be assessed for thrombotic risk and, unless contraindication exists, receive heparin prophylaxis (2010).
Risk assessment for VTE
Risk assessment for bleeding
Treating thrombosis
Thrombolysis ONLY in life-threating PE or limb threatening DVT
- as thrombi associated with increased risk of intracranial haemorrhage
- reduces subsequent post-phlebitic syndrome
Thrombosis
- higher doses of same drugs used in prophylaxis
- need immediate results (so heparin over warfarin)
- start on LMWH (e.g. tinzaparin) AND warfarin, as well as starting a DOAC
- stop LMWH when INR >2 for 2 days
Preventing recurrence
High risk pts may require LT anticoag
Does the risk of thrombosis if untreated outweigh the risk of bleeding if treated?
Asses recurrence risk (morb and mort of recurrence)
- depends on factors that triggered initial episode
- if after surgery = low risk of recurrence -> NO NEED for LT anti-coag
- idiopathic = high risk of recurrence
Assess risk of therapy (morb and mort of bleeding)
- variation of risks with different therapies
- men have a higher risk of recurrence than women
- proximal thrombosis (popliteal and above) higher recurrence rate than distal
- PEs have a similar recurrence rate to proximal thrombosis
what increases with age
fatal bleeding (nearly always intracerebral bleeding)
major bleeding
recurrence rate
DOACs > warfarin
immediate effects
half the risk of intracranial bleeding
much lower fatality
When to LT coag?
Idiopathic precipitant
minor precipitant (3 months coag)
- COCP, trauma, flights
- longer duration if presence of other thrombotic/haemorrhagic risk factors
SBAs part 1
SBAs part 2
