Prevention

 

High risk patients

 

Total hip and total knee arthroplasty

Hip fractures

Major trauma

Elective spinal patients

 

Options

 

Mechanical prophylaxis

Chemoprophylaxis

 

Mechanical prophylaxis

 

Graduated Compression Stockings

 

GCD

 

Mechanism - graded compression highest at ankle and lowest above knee

 

Precautions - peripheral vascular disease / recent skin graft / severe leg edema

 

Results

 

Sachdeva et al Cochrane Database Review 2018

- 20 RCTs and 1700 patients

- GCS reduces incidence of DVT and PE compared to control groups

 

Pneumatic Compression Devices (PCD)

 

Pneumatic compression devices

 

Results

 

Kakkos et al Cochrane Database Review 2022

- 34 RCTs and 15,000 orthopedic patients

- PCD alone: DVT 4%, symptomatic PE 1%, major bleeding 0.3%

- PCD + pharmocology: DVT 2%, symptomatic PE 0.7%, major bleeding 2%

 

Wong et al Hip Pelvis 2024

- 540 THA treated only with graduated stockings and pneumatic compression

- routine ultrasound day 4 and 7

- incidence proximal DVT 1%

 

Chemoprophylaxis

 

Contraindications to chemoprophylaxis

 

Active bleeding

High risk bleeding

- hemophilia

- thrombocytopenia - platelets < 50

- history GI bleeding

Severe hepatic disease (INR < 1.3)

Renal impairment

- must adjust LMWH and oral factor Xa inhibitor doses

History of HITT (heparin induced thrombocytopenia)

Recent neurosurgery or eye surgery

 

Spinal anesthesia

 

Queensland Health Guidelines for Prevention of DVT

 

LMWH

- prophylaxis 12 hours after insertion

- typically withhold for 4 - 6 hours after removal

 

Oral Factor Xa inhibitors

- 24 hours minimum after insertion

- 6 hours after withdrawal

 

Timing

 

Queensland Health Guidelines for Prevention of DVT

 

Onset

 

Hemostasis obtained

 

Heparin / LMWH - 12 hours post op

 

Oral factor Xa inhibitors

- Rivaroxaban 6 - 10 hours post op

- Dabigatran 4 hours postop

- Apixaban 12 - 24 hours post op

 

Duration

 

TKA - 10 - 14 days

THA - 4 - 5 weeks

 

Options

 

Aspirin

Heparin

Low molecular weight heparin (LMWH)

Oral factor Xa inhibitors - Rivaroxaban, Apixaban

Warfarin - usually used for treatment

 

Heparin

 

Definition Dose Mechanism Advantage Disadvantage

Naturally occurring anticoagulant

Mixture of sulphated mucopolysaccharide chains

Heterogenous molecular weights ~ 15 000 daltons

Bolus 5000 units IV

Maintenance 1000 u /hr

Check APTT 6 hours after change

Check APTT daily

Maintain APTT 70-120

Binds to Anti-thrombin III

Short half life 2 hours

Good for bridging anticoagulation

Antidote: protamine

Infusion

Requires monitoring

Inhibits platelets

Affected by renal function

HITT

 

 

Action

 

Binds to Anti-Thrombin III 

- causes conformational change causing increased affinity for thrombin (x 1000) & Xa

- also inhibits aggregation of platelets

 

Indication in orthopedics

 

Patient requires surgery and on maintenance warfarin

Used to bridge anticoagulation

 

Heparin Induced Thrombocytopenias / HITT

 

Paradoxical thrombosis

- due to drug-antibody binding to platelets

- causes arterial and venous thrombosis, and skin necrosis

- resolves promptly with ceasing heparin

- 80% cross-reactivity with LMWHs

- patients should have regular platelet checks in first week of heparin / LMWH

 

Low Molecular Weight Heparin (LMWH)

 

Definition Types Mechanism Advantage Disadvantage

Fractionated heparin

Molecular weight < 5000

Enoxeparin / Clexane

- 0.5 mg/kg od

- 40 mg od

 

Dalteparin / Fragmin

- 5000IU od

Antifactor Xa

Longer half life than heparin

Decreased bleeding due to reduced platelet effect

No monitoring required

Antidote: Protamine sulfate

Given by injection

Reduce dose with low GFR

Increase dose BMI > 40

Difficult to reverse

HITT

 

Action

 

Pure Anti Xa 

- to inactivate thrombin the chain has to attach to antithrombin III & heparin simultaneously

- because LMWH are too short to do this

- only inhibit Xa

- less platelet interaction

 

Decreased bleeding because no anti-thrombin action / platelet interaction

 

Results

 

Hull et al Arch Int Med 2000

- RCT of 1000 THA of warfarin v dalteparin

- warfarin: DVT 24%, proximal DVT 1%, symptomatic DVT 4.5%

- dalteparin: DVT 13%, proximal DVT 1%, symptomatic DVT 1.5%

 

Direct oral Factor Xa inhibitors

 

Definition Types Mechanism Advantage Disadvantage
Act directly on Factor X

Rivaroxaban 10 mg od

Apixaban 2.5 mg bid

Dabigatran 220 mg od

Factor Xa inhibitor

Oral dosing

No monitoring required

Antidotes available for each

Interact with statins

 

Mechanism

 

Act directly on Factor X - do not use ATIII as an intermediate

 

Aspirin

 

Definition Types Mechanism Advantage Disadvantage
Acetylsalicyclic acid

Aspirin 80 - 300mg

COX inhibitor Oral form

GI bleeding

Stomach upset

Not indicated in high risk patients

 

Mechanism

- irreversibly inhibits cyclo-oxygenase in platelets

- blocks thromboxane A2 formation

 

Results

 

PEP trial Lancet 2000

- 17,000 hip fracture and arthroplasty patients

- aspirin v placebo

- aspirin: DVT/PE 1.6%

- placebo: DVT/PE 2.5%

 

Warfarin

 

Definition Types Mechanism Advantage Disadvantage
Vitamin K antagonist

 

Structural analog of Vitamin K

Limit factors II,VII,IX,X

Oral form

Antidote - FFP / Vitamin K

Delayed effect for first 3 days

Requires monitoring

Multiple interactions

 

Mechanism

 

Structural analogue of vitamin K 

- blocks the activation of vitamin K

- factors II, VII, IX, X & Protein C + S are vitamin K dependent 

 

Disadvantage

 

1.  Paradoxical procoagulant effect in initial period

- needs cover with another anticoagulant

2.  Delayed Effect

- half-life of factors ranges between 6 and 60 hours

- there is a window period of 3 days with increased PT but no true anticoagulation exists

3.  Teratogenic - contraindicated in pregnancy

4.  Requires monitoring - goal is INR 2.0

 

Metabolism

 

Oral warfarin is readily absorbed & almost entirely albumin-bound

 

Metabolised in liver

 

Potentiators

- Cimetidine

- Phenytoin

- Trimethoprim

- Cephalosporins 

- Tramadol 

 

Inhibitors

- Rifampicin

- Phenobarbitone

 

Reversed with parenteral Vit K or FFP

 

Dosing

 

Starts simultaneously

- 5 mg nocte for 2 days

- then daily dose as per INR 

- usually 3 - 5 mg

 

Treatment INR

- 1.5-2.5 DVT

- 2.5-4.0 PE

 

Prophylaxis INR

- 1.5 - 2

 

Results

Mismetti et al J Thromb Hemost 2004

- meta-analysis

- vitamin K antagonists less effective than LMWH in preventing total or proximal DVT

- no significant difference in rates of major bleeding or haematoma

 

Results

 

Oral Factor Xa inhibitors v LMWH

 

Kakkar et al Lancet 2008

- RCT of 2500 THA patients

- 30 days of rivaroxaban v 14 days enoxeparin

- rivaroxaban: DVT 2%, PE 0.1%, bleeding 7%

- enoxeparin: DVT 8%, PE 0.5%, bleeding 6%

 

Turpie et al Lancet 2009

- RCT of 3100 TKA patients

- rivaroxaban v enoxeparin 10 - 14 days

- enoxeparin: DVT/PE 10%, symptomatic DVT/PE 1.2, PE 0.5%

- rivaroxaban: DVT/PE 7%, symptomatic DVT/PE 0.7%, PE 0.3%

 

 

 

 

 

IVC Filter

 

Indications

- complications of anticoagulation therapy

- recurrence of PE whist fully anticoagulation

- high rate of death if subsequent event / further embolic load on right ventricle

 

Disadvantage

 

Surgical procedure

- inserted through groin

- need to be removed

 

Results

 

Bicalo et al J Arthroplasty

- filter vs IV heparin

- 3 of 28 complications for heparin

- 1 of 26 for filter