Prophylaxis of venous thromboembolism Flashcards
% of deaths in hospital attributable to PE?
10% - largely preventable as well
When is graduated compression stockings contraindicated?
Graduated compression stockings may be contraindicated in patients with the following conditions: peripheral arterial disease, peripheral neuropathy, recent skin graft, inflammatory conditions of the lower leg, severe oedema of the leg, severe lower limb deformity or morbid obesity where correct fitting or stocking cannot be achieved. Intermittent pneumatic compression or foot pumps can exacerbate ischemic disease and therefore may be contraindicated in patients with peripheral arterial disease or arterial ulcers.
Mechanical (non-drug) methods of DVT prevention:
Mechanical methods of prophylaxis, which include graduated compression stockings, and the use of intermittent pneumatic compression devices and the venous foot pump, increase venous outflow and/or reduce stasis within the leg veins. The primary attraction of mechanical prophylaxis is the lack of bleeding potential.
Non-drug, non mechanical methods of DVT prevention:
Adequate hydration and early mobilisation are simple measures that should be applied as standard practice to prevent VTE.
Use of anti platelet drugs in DVT:
Efficacy issues
Less efficacious than other agents
Safety issues
Associated with an increased risk of bleeding
Comments
Aspirin or other antiplatelet therapy (e.g. clopidogrel) is not recommended for VTE prevention as more effective medicines are available.
Use of Vitamin K antagonists in DVT prevention:
Efficacy issues
Less effective than heparins.
Safety issues
Associated with major bleeding.
Comments
Although Vitamin K antagonists have an established role in the treatment of venous thromboembolism, they have a lesser role in prevention in hospital inpatients. This is because they are not as effective (possibly because of the number of days required to get to effective anticoagulation), and are still associated with a bleeding risk.
They also require regular monitoring with INRs, which makes them more inconvenient in a busy ward situation. Their role is really in selected situations e.g. in Australian guidelines warfarin is not recommended for thromboprophylaxis for total hip replacement except where warfarin is used for therapeutic reasons other than thromboprophylaxis. In these cases, adjusted therapeutic doses are more likely to be effective in preventing VTE than fixed low-dose warfarin.
Heparin in DVT prophylaxis
Efficacy issues
Effective for VTE prevention.
Safety issues
Acceptable increase in bleeding risk.
Comments
Heparin is also known as standard or unfractionated heparin. Dalteparin and enoxaparin are low molecular weight heparins (LMWHs). Danaparoid is a low molecular weight heparinoid.
In general surgery heparin and LMWHs have similar efficacy in preventing VTE. LMWHs require only once daily administration.
LMWH is more effective than low-dose heparin in high-risk orthopaedic surgery (e.g. elective hip surgery, hip fracture, knee replacement).
Danaparoid is an option for patients with heparin-induced thrombocytopenia.
Factor Xa inhibitors in DVT prophylaxis
Efficacy issues
Fondaparinux is an injectable direct Factor Xa inhibitor. Apixaban and rivaroxaban are newer oral anticoagulants that appears to have similar efficacy to enoxaparin 40 mg once daily subcutaneously, after total hip or knee replacement
Safety issues
Fondaparinux is associated with higher risk of bleeding, especially in the older patient. Apixaban and rivaroxaban are newer medicines with limited post-marketing surveillance. Appear to have similar bleeding rates to enoxaparin. Currently no readily available antidote. Adherence important due to short half-life.
Comments
Apixaban and rivaroxaban are orally active direct Factor Xa inhibitors and fondaparinux is given subcutaneously. All three medicines are currently indicated for VTE prophylaxis for short-term use after hip or knee replacement. All were more effective than LMWHs in preventing VTE following after hip or knee replacement surgery, however fondaparinux was associated with higher rates of major bleeding than LMWHs.
Direct thrombin inhibitors in DVT prophylaxis
Efficacy issues
Dabigatran is a new oral agent that appears to have similar efficacy to enoxaparin 40 mg once daily subcutaneously, after total hip or knee replacement.
Safety issues
New drug with limited post-marketing surveillance. Appears to have similar bleeding rates to enoxaparin. Currently no readily available antidote. Some clinically important drug interactions – dose modifications are needed if dabigatran used with amiodarone or verapamil. Requires dose reduction in renal impairment and older patients. Adherence important due to short half-life.
Comments
Direct thrombin inhibitors include bivalirudin, dabigatran, or lepirudin.
The only direct thrombin inhibitor which is currently indicated for VTE prophylaxis for short-term use after hip or knee replacement is dabigatran. It is orally administered and appears to have similar efficacy to enoxaparin 40 mg daily after hip or knee replacement surgery, however a clinically important difference cannot be ruled out.
Side-effects of heparin:
A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT), caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets, which causes thrombocytopenia. This condition is usually reversed on discontinuation, and in general can be avoided with the use of synthetic heparins. Also, a benign form of thrombocytopenia is associated with early heparin use, which resolves without stopping heparin.
Two nonhemorrhagic side-effects of heparin treatment are known. The first is elevation of serum aminotransferase levels, which has been reported in as many as 80% of patients receiving heparin. This abnormality is not associated with liver dysfunction, and it disappears after the drug is discontinued. The other complication is hyperkalemia, which occurs in 5 to 10% of patients receiving heparin, and is the result of heparin-induced aldosterone suppression. The hyperkalemia can appear within a few days after the onset of heparin therapy. More rarely, the side-effects alopecia and osteoporosis can occur with chronic use.
Antidote of heparin:
Protamine sulfate (1 mg per 100 units of heparin that had been given over the past four hours) has been given to counteract the anticoagulant effect of heparin
Experts’ choice of VTE prophylaxis
Enoxaparin, Subcut, 40mg mornings, VTE prophylaxis
Appropriate monitoring for Enoxaparin
Platelets (count should be monitored on days 0, 3, 5 and then on alternate days if treatment is continued), Hb, Wound site, clinical manifestations of bleeding, renal function
HIT monitoring
Platelet count should be monitored on days 0, 3, 5 and then on alternate days if treatment is continued. If the platelet count drops 30–50% below baseline, heparin or LMWH should be withheld and an alternate anticoagulant substituted. Severe HIT usually occurs between days five to ten but may occur earlier if a patient has been exposed to heparin recently (
Assessment of bleeding and actions to be taken
Bleeding assessment should include: assessment of vital signs, clinical review of the operative site (where appropriate) and review of surgical drains and urinary, intravenous or epidural catheters. Easy bruising or petechial haemorrhages may precede obvious bleeding, while nose bleeding, haematuria, or melena may be the first sign of bleeding. Minor bleeding is usually controlled by withholding VTE prophylaxis. If severe bleeding occurs, protamine sulfate reverses unfractionated heparin and partially reverses LMWH.
