The antithrombotics are used in blood surgery restorative for the prevention of thrombotic complications arterial and venous and mortality reduction cardio and cerebro-vascular partner.
If the medical community agrees on the importance of antiplatelet agents for the reduction of mortality cardio and cerebro-vascular, there is currently no consensus on treatment modalities based on the nature of the surgery performed.
What antithrombotic use?
Not fractionated heparin (UFH) used in perioperative (and per – operative) (iv or sc.) is monitored by active thromboplastin time (or the heparinemie).
The low molecular weight heparins (LMWH) administered in the peri-operative period could have a preventive effect on the proliferation of smooth muscle cells and so on Restenosis, but current data are fragmentary and insufficient. Haemorrhagic accidents under LMWH are more often the result of a non respect of the recommended therapeutic modalities (disrespect of the regimens, overdoses, off-label use) for treatments extended beyond of the usual duration of 10 days, or prescriptions in case of kidney failure or in the elderly with renal function impaired. In case of significant bleeding risk it is desirable to prefer a UFH usage to that of a LMWH, due to a greater possibility of adaptation of the doses.
The recommendations of the HAS regarding the use of LMWH are:
Severe contraindication to LMWH in curative treatment in renal insufficiency (creatinine clearance < 30 ml/min); in this case the HNF can be used. This measure does not apply to the special situation of the dialysis which is an indication to some specialties.
The prescription of LMWH is deprecated:
- curative dose in moderate renal failure (between 30 and 60 ml/min creatinine clearance),-in severe preventive treatment in case of renal failure (creatinine clearance < 30 ml/min). Warnings for the LMWH in preventive and curative treatment:
- caveat on the hemorrhagic risk inherent in certain situations at risk (elderly, renal failure, no respect of the recommended therapeutic modalities, long-term treatment).
-the need to systematically assess renal function of patients older than 75 years using the Cockroft formula before starting treatment with LMWH,
-split or not heparins can induce immuno-allergic thrombocytopenia, a biweekly monitoring is essential.
Oral anticoagulants it is preferable to use the AVK to long half-life Previscan®' or Coumadin®. Warfarin (Coumadin®, 2 and 10mg tablets) is preferred in the elderly, the latter having a special sensitivity to the AVK with result a dosage lower to have the same effectiveness. The use of the AVK remains controversial however, as increasing the risk of bleeding including after 75 years. The target is a TP expressed as INR (between 2 and 3). A low INR may be offered (less risk of bleeding), but the effectiveness of such a dosage is not demonstrated in vascular surgery. The association to aspirin increases the risk of bleeding. The hemorrhagic risk of a treatment by AVK is overall 0.1% of serious hemorrhagic accidents (deaths, bleeding of sequelae or requiring a surgical, hospitalization or a transfusion) and 0.5% of bleeding incidents per month of treatment.
The antiplatelet agents (PAA)
-Acetylsalicylic acid (ASA). Aspirin exerts its antiplatelet action by an inhibition of the production of thromboxane A2 in platelets, through the blocking of the cyclo-oxygenase platelet (COX1), which is irreversible by lack of possibility of synthesis of cyclo-oxygenase novo. It comes to the dosages of aspirin between 50 and 325 mg/d. If the antiplatelet effect is independent of the dose of aspirin used, the speed of the effect is dose-dependent. Indeed have an immediate effect, to use a route of intravenous administration, while to have action in the hour following oral administration a greater than or equal to 360mg starting dose should be prescribed. Finally in the case of dosage less than 150 mg orally, the full antiplatelet effect will be obtained in 48 h. On the other hand, low (< 160mg) doses are as effective in treatment long term with a reduced risk of hemorrhagic accidents.
-Ticlopidine and clopidogrel. Ticlopidine induced an inhibition of platelet aggregation induced by adenosine diphosphate (ADP), collagen, arachidonic acid, the Thrombin and the Platelet aggregating Factor (PAF). Furthermore she lowers plasma Fibrinogen and thereby the blood viscosity, and it increases the deformability of red blood cells. We still don't know the exact mechanism of action well, but it is suggested that the ticlopidine inhibit exposure induced by ADP of the binding site at the complex of membrane glycoproteins IIb and IIIa Fibrinogen. Its action is dose-dependent and beyond 500 mg day, there is a clear risk of bleeding. Clopidogrel has a mechanism of action similar to ticlopidine, but at lower dosages with for corollary a significant reduction in the number of complications and clinical tolerance.
-Anti-inflammatory non steroidal. NSAIDS also inhibit the cyclo-oxygenase but reversibly. The duration of the action is temporary and directly dependent on the half-life of the molecule. Flurbiprofen (cebutid®) alone has an AMM like PAA. It has shown its effectiveness to reduce the risk of rethrombose after a successful recanalization coronary post-myocardial. It is reserved for the relay of the other PAA, but its effectiveness remains to be seen.
The therapeutic modalities proposed by the VIIth conference consensus, do not meet all clinical situations. The following proposals will have to be confirmed or otherwise set aside by other studies.
Prevention of complications General established a treatment long term by PAA is recommended (aspirin 75 to 325 mg/day) in patients with a PAD and a coronary or cerebro-vascular insufficiency symptomatic (1 A), but also asymptomatic. The authors recommend in these patients compared to the absence of PAA (+ 1 c) clopidogrel, but suggest that aspirin is preferred over clopidogrel with however a low level of recommendation (2A).
Prevention of focal thrombotic complications – Introduction of the PAA even in the absence of formal proof, there is sufficient scientific data to begin the PAA treatment before any sous-inguinal, prosthetic or venous bypass. In 2 trials randomised in 3 or aspirin was started in preoperative, the permeability of the bypasses had improved. In other cases, the PAA treatment is started two to three days after surgery to minimize the risk of haematoma.
A heparin is recommended for the duration of the clamping for all major blood reconstruction (1's).
The thrombogenicity of the venous bypass is maximum in the course of the operation because of the high endothelial avulsion to picking, justifying the treatment with aspirin. The subsequent permeability depends on the development of strictures on the conduit or its anastomoses, and to a lesser degree of degradation of the network of upstream or downstream. In these patients, it is recommended to continue aspirin long term, if they have a coronary or cerebro-vascular insufficiency symptomatic (1's) but also asymptomatic (1 c +). HAS also indicates that patients who received a sous-inguinal bypass, a PAA long term treatment is recommended (off-label prescription) because of the high cardiovascular risk, but also because of its effectiveness in the prevention of occlusion of bypass surgery (A). Responsible for myointimale hyperplasia of the development of the graft or the anastomoses stenosis is little or not affected by PAA treatment.
AVK treatment is not justified in routine patients bearers of popliteal venous bypasses or leg (2A), the low improvement of permeability to long-term not compensating for the major increase in the risk of bleeding.
The association of AVK (INR 2 to 3 target) and low-dose aspirin is suggested (2B) for sous-inguinaux bypass surgery high risk of occlusion and amputation, considering that in this situation it is permissible to accept a higher risk of bleeding. HAS added this requirement (off-label) should be restricted to a limited time, usually less than 1 year (B).
Prosthetic bypass occlusions of prosthetic bypass surgery are all secondary to the thrombogenicity of the persistent platelet membership source material and more rarely the development of anastomotic stenosis. Aspirin is recommended for sous-inguinaux prosthetic bypass surgery (1's).
-Sus-inguinal surgery, visceral and renal arteries and proximal supra-aortiques trunks blood occlusion risk is low in the restorations of vessels of superior to 6mm and high throughput. The PAA treatment is indicated for the 1ermois. In the past, the continuation of the treatment depends primarily the presence or not of the spread of the disease atheromateuse and atherogenic risk factors.
-Surgery of the carotid bifurcation
PAA (75-160mg aspirin) treatment started at best before the intervention should be continued indefinitely to prevent further neurological event risk (+ 1 c). The occurrence of a Restenosis is not influenced by the PAA treatment.
The consensus of TASC II extends to surgery endoluminale PAA usage during a revascularization. Whatever the site of angioplasty, the procedure must be framed by the PAA treatment started in preoperative. Heparin injected during the procedure can be relayed:
– either by the only treatment PAA in the case of simple expansion, uncomplicated, on ships of diameter 6 mm and throughput high,
-extended electric syringe or relayed by a LMWH for 12 to 24 hours. The pursuit of heparin (or LMWH) beyond this period could be justified only by a persistent major thrombotic risk.
Particular case of the carotid dilation and supra-aortiques trunks
In the absence of scientific evidence, there is nevertheless a consensus to start the PAA treatment at least 48 h before the intervention, combining clopidogrel (1cp/J) and aspirin 75 or 160mg. This treatment is extended for at least 1 month, then relayed by a single PAA. If the clopidogrel has not prescribed 48 hours before the procedure, it can be so prescribed dose double or triple on the eve of the procedure (by analogy to the coronary dilatation).
In all cases the prescription of antithrombotics must subject to a careful assessment of the hemorrhagic risk-benefit balance.
Peculiarity of the patient with Coronary Stent (EC) in case of intervention, maintaining or not double PAA treatment must take into account the time elapsed since the laying of the EC, the type and the type of intervention proposed:
-intervention at low risk of bleeding (type carotid surgery) may be considered as appropriate under double PAA, at the cost of post-operative monitoring of the operating site.
-intervention at medium or high risk (type aortic surgery) required discontinuation of clopidogrel (5 days) and the pursuit of low-dose aspirin. Clopidogrel will be resumed as soon as possible after the operation given its time for action (3 days).
-complete the treatment stop PAA and its replacement by an NSAID or a LMWH should be considered for interventions at major risk of bleeding (e.g. Prostate Surgery). The patient should be warned of the high risk of thrombosis of the EC in this case.
How to manage the antithrombotic treatment in perioperative?
Management depends on whether the thrombotic risk at the end of the treatment is major or medium.
Patient under AVK – is a major thromboembolic risk in case of:
-mechanical valve (all mitrales prostheses and prosthetics all aortic first-generation prostheses), second generation aortic valves if there is a risk of embolisms associated factor,
-atrial fibrillation associated with other factors of VTE risk (valvular).
In these cases, the relay of the AVK is essential and must be done using a UFH as follows:
–stop of the AVK 3 to 5 days before the procedure, depending on the used molecule,
-early the next day from the stop of the AVK, heparin anticoagulant dose (control by heparinemie and/or TCA).
-control of INR the night before the procedure,
-stop the continuous infusion of heparin 4 to 6 hours before the move operation or last injection of heparin calcium 8 h before (3 injections per day) or 12 h before (2 injections per day); resumption of heparin 6 to 8 hours after,
-recovery of AVK as soon as possible and stop of heparin as soon as 2 INR 2 days apart are satisfactory.
-Thromboembolic risk is average in the case of:
-prevention and treatment of venous thromboembolic disease or,
-FA in patients over 65 years of age or those with VTE risk factors associated with: history of STROKE, Cardiac decompensation, dating less than 2 months, or left ventricular dilatation (telediastolique diameter of the VG > 60 mm).
-some cases of insufficiency or mitral shrinkage (dilatation of the left atrium),
-mechanical bioprostheses valvular aortic in the absence of cofactor of embolisms risk,
-valve bioprostheses in postoperative of implantation (months).
The relay of antithrombotic treatment is generally warranted. In this case the arrangements proposed are the following:
- judgment of the AVK 3 to 5 days prior to surgery.
- is relay by HNF: identical to the major thromboembolic risk,.
- or relay by LMWH in curative doses (if it has a legal authority in the indication of the current condition) with stop the LMWH to J-1 and balance of hemostasis (INR, platelets). LMWH is taken over 12 to 36 hours after surgery;
- resumption of the AVK as soon as possible and stop of heparin as soon as two INR 2 days apart are satisfactory.
Patient under AAP
-The thrombotic risk is major in the following situations:
-acute coronary syndromes from less than a month,
-the implementation of a naked EC dating from less than a month,
-the implementation of a CBS dating back less than 2 months for stents, less than 6 months for stents with paclitaxel (taxus) and sirolimus (cypher)
-the implementation of a CBS covered less than one year,
-radiation endocoronaire less than a year. In these cases, the relay 1 or 2 AAP, if it is necessary in view of the work carried out, should be done after expert advice (only UFH, LMWH in curative doses, alone or in combination with the cebutid®).
-The thrombotic risk is medium in the following situations:
-acute coronary syndromes dating back over one month and stable angina, – secondary prevention of IDM and the AOMI -, secondary prevention of STROKE – patients without heart disease Embolic,
-the FA in a matter of less than 65 years without risk of thrombo – embolisms factor and heart disease Embolic. The relay of antithrombotic treatment is generally warranted.
-Thrombotic risk is minor in the following situation:
-primary prevention by PAA for the risk of death and of IDM at about more of 50 years with at least a vascular risk factor. A discontinuation of treatment may be considered.
Relay for the PAA? the relay of the PAA is possible using molecules with antithrombotic action reversible in the short term. No treatment has however been validated. Flurbiprofen (cebutid®), which has a reversible PAA activity in 24 hours is sometimes used without formal proof of its effectiveness. LMWH are an alternative. They are used according to the same pattern as for the AVK relay.
-In the case of major thromboembolic risk
Given the importance of the risk of thrombosis at the stop of the PAA, it is desirable to delay surgery. If this gesture seems indispensable, the relay will be after an opinion by only UFH, LMWH in curative doses, or LMWH in curative doses associated with the cebutid®).
-In the case of thromboembolic risk: relay by cebutid® as follows:-judgment of the PAA based on the half-life of the product (7 to 10 days) or the time needed to find a sufficient agregante function (either 50 G/l of functional platelets, renewal being made at the rate of 10% of the initial number of platelets per day).
-beginning of the cebutid® (50mg morning and evening) after the stop of the PAA – stop of the cebutid® 24 hours before the gesture -, resumption of the PAA at the waning, preceded or associated with a preventive treatment depending on the context.
|MAJOR RISK||LOWER RISK|
|Installation of a bare stent||< 6 weeks||> 6 weeks|
|Installation of an active stent||< 6-12 months||> 6-12 months|
|SCA: STEMI and NSTEMI||< 6 weeks||> 6 weeks|
|REQUIRED PLATELET BIANTIAGREGATION||ANTIAGGREGATING MONOTHERAPY HAS LIFE|
|Treatment antiaggregatory||STOP HAS TO CONSIDER||DELAY BETWEEN THE STOP AND THE GESTURE|
|Aspirin||Aspirin||3-5 days only if risk bleeding majeursinon: NO NEED to STOP|
|Clopidogrel + aspirin||Clopidogrel||5 days|
|Aspirin + Prasugrel||Prasugrel||7 days|
|Aspirin + Ticagrenol||Ticagrenol||5 days|