Page 2366 - Hematology_ Basic Principles and Practice ( PDFDrive )

2108 Part XII Hemostasis and Thrombosis

thrombosis and requires that additional testing with serial ultraso- effective in patients undergoing elective hip surgery and reduces the
nography be performed if this is suspected. If the lack of compress- incidence of venous thrombosis by approximately 40%, it is less
ibility of the veins or an intraluminal filling defect with flow seen on effective than other current prophylactic strategies and thus should
Doppler ultrasound studies is visualized in the venous segment previ- be reserved for patients with renal failure in whom LMWH and
ously affected, these tests are not sufficiently reliable to either confirm fondaparinux are contraindicated. Low-dose UFH has not been
or rule out acute thrombosis. In these cases, serial testing to detect shown to be effective in patients undergoing surgery for hip fracture
extension may be useful. Alternately, if the patient had a follow-up or hip or knee arthroplasty. In addition, use of subcutaneous heparin
ultrasound examination, comparison with previous imaging may be may be associated with heparin-induced thrombocytopenia, particu-
useful. larly in the postoperative period.

Acute Recurrent Pulmonary Embolism Vitamin K Antagonists (Warfarin)

Patients presenting with clinical symptomatology consistent with an When administered in doses that increase the INR to 2.0–3.0,
acute recurrent PE should be assessed urgently. Empiric anticoagulant vitamin K antagonists (VKAs) effectively prevent postoperative VTE
therapy should be provided if diagnostic testing is delayed. A signifi- in patients in all risk categories. VKAs can be given preoperatively,
cant proportion of patients have persistent residual defects on CTPA at the time of surgery, or in the early postoperative period. The
or V/Q scanning even up to 11 months after the acute PE. Therefore antithrombotic effect of VKAs is not achieved until the fourth or fifth
baseline imaging (e.g., at the completion of anticoagulant treatment) day of administration. Nevertheless, when used in this fashion, VKAs
can facilitate diagnosis of recurrence by evaluating differences between are effective in very high-risk patient groups. Prophylaxis with VKAs
tests. It is important to use the same imaging modality as baseline if is relatively inconvenient, however, because frequent INR monitoring
possible because of poor agreement between CTPA and V/Q scan- and dose adjustments are necessary.
ning for detecting residual defects. However, cost, availability, and
clinical considerations (e.g., renal failure, radiation exposure, young
age, pregnancy, underlying lung disease) also influence the choice of Direct Oral Anticoagulants for Orthopedic
test. Thromboprophylaxis
Similar to the diagnosis of initial PE, recurrent PE can be diag-
nosed on CTPA in the presence of a new central filling defect or Rivaroxaban and apixaban are oral direct factor Xa inhibitors with
occlusion of segmental or more proximal branches of the pulmonary excellent bioavailability that have been studied in patients undergoing
arteries. total knee- or hip-replacement surgery. In a pooled analysis of ran-
domized trials, 10 mg/day of rivaroxaban was superior to enoxaparin
(40 mg once daily or 30 mg every 12 hours) for prevention of
PROPHYLAXIS OF VENOUS THROMBOEMBOLISM symptomatic VTE and all-cause mortality with similar major bleed-
ing rates. Apixaban is also associated with a similar risk of symptomatic
PE is a common preventable cause of death in hospitalized patients. VTE and major bleeding, and reduced risk of clinically relevant
Hospitalized patients can be classified as having a low, moderate, or bleeding compared with enoxaparin. Overall, the net clinical benefit
high risk for developing VTE. Effective prophylaxis is cost effective with rivaroxaban and apixaban is similar to that with enoxaparin.
and is available for high-risk groups. However, rivaroxaban and apixaban simplify extended out-of-hospital
thromboprophylaxis compared with enoxaparin because they obviate
the need for daily subcutaneous injections.
Low-Molecular-Weight Heparins and Fondaparinux Although rivaroxaban and apixaban have also been evaluated for
extended thromboprophylaxis in medically ill patients, the benefit-
Low-molecular-weight heparins (LMWHs) exert their anticoagulant risk profile in this setting is less certain because of an increased risk
effect by preferentially catalyzing the inactivation of factor Xa by of bleeding compared with shorter courses of prophylactic dose
antithrombin. When used in prophylactic doses once or twice daily, enoxaparin.
LMWH is an effective and safe agent for VTE prophylaxis in medical Dabigatran etexilate is an oral direct thrombin inhibitor that also
and surgical patients. Anticoagulant monitoring is not required when has been evaluated in patients undergoing total knee- or hip-
used in prophylactic doses. It is at least as effective as standard low- replacement surgery. Dabigatran etexilate is a prodrug that is con-
dose UFH and warfarin in most patient populations. verted to the active agent dabigatran, which binds both free and
The anticoagulant effect of LMWH is mediated by a unique clot-bound thrombin. In large clinical trials, once-daily dabigatran
pentasaccharide sequence in the heparin molecule that binds anti- (150 mg or 220 mg once daily) was noninferior to enoxaparin 40 mg
thrombin. The pentasaccharide moiety has been synthesized chemi- once daily but was inferior when enoxaparin was dosed at 30 mg
cally as fondaparinux. Extended use of fondaparinux following hip twice daily.
fracture surgery significantly reduces the risk of symptomatic VTE. The efficacy and safety of oral direct factor Xa inhibitors and
In patients with acute coronary syndromes, fondaparinux given at direct thrombin inhibitors for thromboprophylaxis following knee-
prophylactic doses was associated with decreased bleeding complica- or hip-replacement surgery have not been directly compared in clini-
tions compared with therapeutic doses of enoxaparin. cal trials.

Low-Dose Unfractionated Heparin Intermittent Pneumatic Compression

Low doses of UFH prevent thrombosis by antithrombin-mediated Intermittent pneumatic compression of the legs enhances blood flow
inhibition of thrombin, factor Xa, and other serine proteases. For in the deep veins and increases systemic fibrinolytic activity. Although
prophylaxis, UFH is usually given subcutaneously at a dose of 5000 few methodologically rigorous studies support the effectiveness of
units every 8–12 hours. Low-dose UFH prophylaxis does not require intermittent pneumatic compression for VTE prophylaxis, this
laboratory monitoring and is simple and convenient to administer. It modality has few clinically important side effects and is particularly
is an acceptable option for moderate-risk general surgical and medical useful in patients who have a high risk of bleeding. It also is frequently
patients, and it reduces the risk of VTE by 50%–70%. When used used, albeit with little supporting evidence, during the operative
in these doses, UFH is both highly effective and associated with only procedure in patients undergoing extended-duration surgery and in
a small increase in the risk of bleeding. Although low-dose UFH is patients after trauma. Intermittent compression is the prophylactic