Thrombotic disorders Flashcards
Virchows Triad: Things that could potentially explain underlying reason of thrombosis
Vascular injury: Surgery, atherosclerosis, trauma
Stasis (main cause of : Immobility: post op; coma; planes, pressure: catheter, tumour obstruction; increased viscosity: polycythaemia, dehydration, epo.
Hypercoagulability: Increased procoagulants, decrease in inhibitors,
ALSO cancer
Signs and symptoms of DVT and PE
DVT: Leg swelling, leg pain, oedema
PE: Shortness of breath, chest pain, tachycardia, tachypnoea
Diagnosis of DVT
Undertake risk factor test (oedema, cancer, immobilisation etc etc)
Low risk: Undertake D-dimer test. If high/+ve U/S. If D-dimer low, discharge
High risk: Ultrasound
D-dimer test
Breakdown products of fibrin.
+ve in 83-98% of DVT and PE (low risk?)
Also positive in patients without VTE e.g after surgery, or inflammation.
High NPV, low PPV
PE signs and diagnosis
Rule out infectious disease
Symp: Pleuritic pain, shortness of breath and haemoptysis.
Sign: tachycardia, tachypnoea, hypoxia
+ve D-dimer often, Pulmonary CT angiogram, sometimes V/Q scan
Thrombophilia
Either acquired, hereditary or both
Tendency to clot
Manifests as VTE
Causes of VTE ** exam??
note VTE is a disease that encompasess DVT and PE
30-40% spontaneous: of these, likely thrombophilia
Remainder are provoked events (see virchows triad): surgery/trauma, immobility, hospitalisation, malignancy (up to 20%), HRT/pregnancy, OCP, myeloproliferative disease, antiphospholipid
remember multi hit
Inherited thrombophilia causes
Abnormal inhibitor function: resistance to activated protein C (factor V Leiden)*
Increased factor levels: Prothrombin gene mutation 20210A*, increased f8
Deficiency of inhibitors: antithrombin, proteins C and S. Rare REMEMBER DO NOT AFFECT APTT
*most common, and are what are tested
Factor V Leiden what i it how does it affect coagulation
Single point mutation in f5
Most common hereditary thrombophilia
4% of Northern Europeans *
Normal:Factor Va cofactor of X, Activated protein C cleaves Va to slow Xa production (@ arginine 506).
So mutation means aprotein C cannot cleave, Xa lasts longer. Va layers will be higher.
Why test for APCr?
Heterozygote 3-7 times increased risk of thrombosis.
Homozygotes: 50-100 fold risk
TREATMENT for PE and DVT
Heparin
-Initially Heparin, (inhibits through increased antithrombin affect. Prolonged APTT 1+1, long TCT, reversed with protamine)
We use LMWH: Smaller GAGs of heparin.
Accelerates inhibition of Xa more so than thrombin due to smaller chains doing this versus longer chains with thrombin.
Does not affect APTT
Subcutaneous?
twice daily, 1mg/kg. Enoxaparin or clexane
TREATMENT for PE and DVT. Venous thrombosis
LMWH
Warfarin at same time, minimum 5 day overlap
Alternatively a novel oral agent.
Inhibits coagulation to allow self fibrinlytic mechanisms to operate
TREATMENT for PE and DVT
Warfarin
- Monitored with INR: High INR- more likely to bleed
- Risk of many drug interactions (antibiotics, anticonvulsants, diltiazem, amiodarone, rifampicin)
- Takes time for reduced vitamin K to reduce production of active clotting factors (5-7 days for therapeutic level)
How to reverse bleeding on warfarin
Vitamin K- IV
If immediately needed, prothrombinex containing 2, 9, 10
New oral anticoagulants (DOAC’s)
Rivaroxaban: Inhibits Xa
Dabigatran: Inhibits thrombin/IIa
Same use as warfarin for VTE
Dabigatran superior to warfarin for A fib
Advantages: No monitoring needed, fixed dose, less intracranial haemorrhage.
Disadvantages: Renal excretion, so in renal impairment, retained
