Deep Vein Thrombosis (DVT) - Venous Thromboembolism

Venous Thromboembolism

Deep Vein Thrombosis (DVT)

Risk Factors

·        Key risk factors:

o   Age

o   Obesity

o   Immobility

o   Co-morbidity

·        These can present as:

o   Post-operatively (immobile + hypercoagulable)

o   Stasis (long period of immobility)

o   Pregnancy & immediately post-partum

o   Thrombophilia

o   Smokers on the pill.

o   Obesity, Cancer, Polycythaemia

o   PMHx or FHx of DVT

Presentation

·        May be rapidly offset by collateral bypass

·        Less than 1/3 present with classic syndrome of calf discomfort, distal oedema, venous distension & pain on forced dorsiflexion of foot

·        Homen's sign: pull big toe up ® stretch calf ® pain. Of little diagnostic value and theoretically could dislodge a clot

·        Exclude Baker‟s cyst: herniation from joint space into popliteal space – wouldn‟t cause leg swelling

·        Approx. 50% are asymptomatic

Investigations

Possible Investigations

·         Imaging:

o   CXR: most are normal

o   Doppler US for DVT

o   Ventilation-Perfusion Scan

o   Pulmonary arteriogram: gold standard but not often done

o   CT Pulmonary Angiogram: pretty good and getting better

·         ECG: 

o   Small-medium PE: usually normal except for tachycardia. May be signs of AF or right ventricular strain 

o   Massive PE: S1Q3T3 pattern: S wave in lead I, Q wave in lead III, inverted T wave in lead III. Tall peaked T waves in lead II.

·         Bloods:

o   ABGs: Aa gradient

o   FBC - check Hb, WBCs, platelets (eg ­ ® hypercoagulable)

o   Clotting times: likely to be normal – these test bleeding disorders, not clotting disorders

·         D-dimmer test for fibrin degradation products ® digested clot (cheap and easy):

o   +ive for cancer, trauma, post surgery, sepsis ® lots of false positives

o   Don‟t use as first line test – only in the context of a complete algorithm

·         Decision analysis:

o   If > 6% risk of a PE then test

o   If > 48% risk of a PE then treat

o   If risk > 6% but < 48% then further testing

o   Test sequence: 

§  Chest X-ray and D-dimmer: if d-dimmer negative then no DVT/PE. Positive test doesn‟t change pre-test odds. If Chest X-ray normal then V/Q scan. If abnormal go straight to CT angiogram 

§  V/Q Scan: if positive then treat.  If negative, doesn‟t change pre-test odds

§  CT angiogram 

Treatment

Aims:

o   Prevent PE

o   Restore venous patency

Options:

o   Anticoagulant:  See below

·        IV or subcutaneous heparin for 5 days: aim for APTT 1.5 – 2.5 times normal

§  Oral warfarin for 3 months: 5mg daily then dose adjust to aim for INR 2.0 – 3.0. Can continue longer – haemorrhages, if they occur, are usually early on

o  Surgery: really only if limb at risk.  Veins often re-occlude

o  Thrombolytic Treatment: better clearance of occlusion, no change to PE risk, ­risk of bleed or intra-cranial haemorrhage Þ little evidence of net benefit

·        Prophylaxis:

o  Cost effective if risk high. Base assessment on clinical risk – lab results not good predictor. If low risk after surgery – early ambulation and stockings may be sufficient

o  2/3rds decrease in risk with Low molecular weight Heparin (inject daily for duration of risk)

o  Mechanical: intermittent external compression with inflatable cuffs as effective as drugs in moderate risk people – but frequently misused

o   Antiplatelet: aspirin not as effective as anticoagulant but good in the community as LMM Heparin not funded (ie can be prescribed by GP for a temporarily bed-bound elderly or obese person)

Anticoagulant Treatment

·        Standard (unfractionated) Heparin:

o  Potentiates antithrombin III at all sites of coagulation activation (cf Low Molecular weight Heparin which only acts at Factor 10)

o  Dosing: 

§  10 fold variability in individual dose response ® individual titration required

§  T½ = 100 minutes

§  Monitor APTT and aim for 1.5 – 2.5. (If goes above 3 then 8 * risk of bleed)

§  Monitor after 10 hours (4 – 5 half lives)

o  Emboli doses:

§  IV dose: Loading 5000 IU, maintenance 1400 IU/j (20 IU/kg/hr)

§  Subcutaneous: 17,5000 IU 12 hourly, duration of action 9 – 10 hours 

§  T½ ¯ in large PE Þ need infusion not bolus

o  Standard Heparin Prophylaxis: 

§  Medical view (surgeons disagree!): 5% DVTs in general surgical operations, 20% in orthopaedics

§  Pre-op Prophylaxis:

·        ¯Non-fatal PE by 40% and fatal by 65% 

·        ­Risk of excess bleeding from 3.7% to 6%

§  Low dose heparin (never warfarin):

·        5000 IU standard heparin 12 hourly start 2 hourly pre-op

·        LMW Heparin single dose: more costly and no advantage in most cases

·        Continue for 2 weeks for patients at high risk (biggest mistake is to stop too soon)

o  Heparin induced bleeding:

§  Uncommon for 1^st 2 days, then common for days 3 – 10

§  Retroperitoneal is a common occult site of bleeding

§  Thrombocytopenia after 5 days

§  Antidote: Protamine sulphate + FPP (clotting factors)

·        Low Molecular Weight Heparin:

o  Lots of different types, all with different T½s and doses 

o  Longer T½ (can have once daily dosing), better bioavailability, less platelet inactivation, and potentially less bleeding 

o  Elimination is not dose dependent (heparin approaches this at high dose)

o  Need to adjust for obesity

o  Protamine reversal less efficient

·        Warfarin:

o  Competitive inhibition of Vitamin K dependent clotting factors (II, VII, IX, X) and inhibits proteins C and S

o  Pharmacokinetics:

§  Very narrow therapeutic index

§  10 fold variability from dose to plasma concentration, and further 10 fold variability from plasma concentration to effect

§  99% albumin bound Þ Vd = intravascular space

§  T ½ = 25 – 60 hours, biological effect lasts 2 – 5 days

o   Contraindications:

§  Teratogenic, but not in breast milk

§  Risks of bleeding, eg peptic ulcer, haemorrhagic stroke

§  On NSAIDs (® GI bleed)

o   Consider:

§  Can the patient cope with therapy and monitoring (infirm, alcoholic, etc)

§  ­Warfarin sensitivity if > 65 years due to ¯liver metabolism

§  Patient education important – lots of different sized/coloured pills

o   Dose:

§  Do pre-test INR

§  Start low, monitor on day 3

§  Dose range approx 3 – 9 mg daily (contrary to New Ethicals)

o   Target range for INR:

§  Venous thromboembolism: INR of 2 – 3 for 3 months for 1^st VTE

§  Non-rheumatic atrial fibrillation:

·        > 60 with no risk factors: INR 1.5 – 2.7

·        Risk factors: hypertension, previous VTE, recent heart failure

·        Don‟t anticoagulate patients < 60 years if no risk factors

§  MI: 20% ¯ in mortality and reinfarction but no advantage of warfarin over aspirin except with added fibrillation (in which case aim for INR 2 – 3)

o   Bleeding:

§  Risk factors: age, haemostatic disorder, malignancy, uraemia, GI ulceration, recent surgery, haemorrhagic strokes, low protein states (ie ¯clotting factors)

§  Management:

·        If INR < 7 withhold doses until INR in normal range (unless severe bleed)

·        INR > 7 and no prosthetic heart valve: 0.5 mg iv vitamin K (never IM)

·        If INR > 7 and prosthetic heart valve, don‟t use vitamin K unless evidence of an inter-cranial haemorrhage

·        If overt bleeding: stop warfarin, give FFP or Prothrombin complex concentrates

o   Drug interactions:

§  Inducers: take 10 days to ¯warfarin concentration, and warfarin toxicity when stopped. Phenytoin, carbamazepine, phenobarbitone, rifampicin

§  Inhibitors: immediate effect ® warfarin toxicity. ¯INR when these are stopped: macrolides, metronidazole, fluoxetine, quinolones (eg ciprofloxacin), chloramphenicol, cimitidine, disulphram

·        If massive PE, consider thrombolysis. Echocardiogram to determine RV function useful in assessing risks and benefits