Prophylaxis

Prophylaxis is as important as therapy itself. Epidemiological studies, which have demonstrated the high incidence of the disease, and the fact that the disease is silent in the early stages represent the rationale for prophylactic measures in patients at risk.

In orthopaedic surgery prophylaxis consists of early mobilization, use of elastic stockings with graduated compression, and intermittent pneumatic compression. Such measures can represent the only prophylaxis in some kinds of surgery, but more invasive orthopaedic surgery requires drug therapy [6,15].

LMWHs are very effective in reducing the risk of DVT, with a lower risk of major bleeding than UH [16].A major bleeding is clinically evident and associated with a decrease of at least 2g/dl of hemoglobin and requires blood transfusion. It may be subperitoneal or intracranial or located in critical organs, or it causes death of the patient.

A minor bleeding such as epistaxis or macrohematuria is not associated with the features mentioned above.

Various LMWH belong to a homogeneous drug group, but differ from each other in molecular weight, bioavailability, and antiXa-IIa rate. These differences determine their differing efficacy and safety profiles.

Studies conducted on the use of LMWHs in orthopaedic surgery have shown them to be superior to UH in reducing both thromboembolic events and major bleedings; however, definitive data to help distinguish between the different LMWHs are lacking. Some clinical randomized trials defining symptomatic DVT relapse as an endpoint compared safety and efficacy of subcu-taneously administered enoxaparin and nadroparin with intravenous UH in patients affected by proximal DVT. In both cases LMWHs were demonstrated to be as effective and safe as UH. Reviparin sodium and parnaparin also showed good efficacy and clinical tolerance. The dosages are different according to the molecule and (in some cases) to the weight.

Among the new anti-thrombotic drugs, those that were most highly developed in clinical phase III trials are fondaparinux (synthetic pentasaccharide, which specifically links anti-thrombin, improving its Xa factor inhibition capacity) [17], and the oral thrombin inhibitors (synthetic molecules, among which the most studied is melagatran, a direct inhibitor of thrombin active site, can be administered orally every 12 h at fixed dosages) [18].

Fondaparinux can be administered subcutaneously; it has a plasmatic half-life of about 17 h and thus can be given daily. Specifically, among the drugs commonly used, fondaparinux can be given for prophylaxis but does not seem to be indicated for DVT long-term therapy. Here, melagatran seems to be more promising [19].

A discussed problem is the duration of administration, particularly in patients who have undergone subarachnoidal anaesthesia. The American College of Chest Physicians (ACCP) recommendations [2] call for particular attention to patients whose history reveals coagulation alterations or bleeding risk factors. In these patients, in case of spinal anesthesia, anti-thrombot-ic administration may cause hematoma and bleeding that may lead to neurological deficits (sometimes permanent).

Since the risk seems to be related mainly to the procedures of placing and removing the catheter, regional anesthesia should be considered for both pre-

and postoperative prophylaxis, provided that the time of drug administration is far enough from such manuevers.

As for the duration of prophylaxis, it is necessary to remember that some patients may develop a DVT after discharge. Therefore, it is useful to continue the prophylaxis for a sufficient time and corresponding to the kind of surgery [19].

According to the most recent recommendations of the American College of Chest Physicians [2], in patients who are candidates for a total hip replacement or total knee replacement, prophylaxis must be started with LMWHs at full dosage 12 h before surgery or 12-24 h after surgery, or 4-6 h after surgery at half dosage and at full dosage from the day after.

An alternative may be to start the administration of fondaparinux 6-8 h after surgery or the administration of vitamin K antagonists, whose dosage must maintain the INR at 2.0-3.0, in the preoperative period or on the evening of the day of surgery.

As for the prophylaxis duration, there is near consensus that it must be continued until the patient can move by himself, i.e., for a period of about 4-6 weeks.

For the so-called minor orthopaedic surgical procedures, which involve patient immobilization, guidelines are not as accurate; in any case, there are sufficient indications to suggest the use of LMWHs for at least 2 or 3 weeks or until the patient can move by himself [2].

Finally, even respecting the guidelines, it would be useful for all clinics to develop personal multisubject operative procedures, based on wise preopera-tive study of the patient and in consideration of all the possible human and technical resources to optimize the diagnostic-therapeutic course.

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