Page 2367 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 142 Venous Thromboembolism 2109

measure of choice in selected patients undergoing neurosurgical dosing schedule. LMWH and fondaparinux do not have predict-
procedures; however, most of these patients should eventually receive able effects on the aPTT and therefore cannot be monitored using
pharmacologic thromboprophylaxis as well. this test.

Low-Molecular-Weight Heparin is the Treatment of
Graduated Compression Stockings
Choice for Venous Thromboembolism Associated
Graduated compression stockings also reduce venous stasis in the legs With Pregnancy and Cancer
and are effective for preventing postoperative VTE in low- and
moderate-risk general surgical patients and in medical or surgical VKAs, DOACs, and fondaparinux are contraindicated in pregnancy.
patients with neurologic disorders, including paralysis of the lower In patients with cancer, use of LMWH is associated with a reduced
limbs. However, graduated compression stockings may increase the risk of VTE recurrence and bleeding compared with VKA. Further,
risk of skin ulcers when used in hospitalized patients with stroke. In the anticoagulant effect of VKAs can be affected by reduced oral
surgical patients, the combination of graduated compression stock- intake and concomitant medications which can lead to suboptimal
ings and low-dose UFH is significantly more effective than low-dose anticoagulant therapy in cancer patients receiving chemotherapy.
UFH alone. Use of graduated compression stockings alone, however,
constitutes inadequate prophylaxis in patients undergoing surgery
associated with a very high risk of thromboembolism. Graduated Unfractionated Heparin
compression stockings are inexpensive and should be considered for
use in all high-risk surgical patients even if other forms of prophylaxis Although increasingly less common, selected patients may be admit-
are used. ted to the hospital for intravenous UFH therapy. There is no evidence
that UFH therapy is superior to LMWH in any clinical setting.
Practical considerations include the need for reliable intravenous
TREATMENT OF VENOUS THROMBOEMBOLISM access, frequent blood work, and infusion adjustment. Hence, intra-
venous UFH is typically reserved for patients at high risk of bleeding
The goals of treatment for VTE are to prevent death from PE, reduce in whom rapid anticoagulant reversal may be necessary. Patients with
morbidity from the acute event, decrease the risk of postthrombotic significant renal impairment are also treated with UFH because
symptoms, and prevent CTEPH. All of these goals can be achieved LMWH is eliminated by the kidneys, leading to a risk of anticoagu-
with adequate anticoagulant therapy. Use of thrombolytic therapy or lant accumulation. UFH therapy can be monitored using the activated
surgical thrombectomy is reserved for patients with severe disease or clotting time, the aPTT, or by heparin assays that measure the ability
severe complications. of heparin to accelerate the inactivation of factor Xa. It is important
to give adequate doses of UFH at initial presentation because the risk
Anticoagulant Therapy for Treatment of Acute Venous of recurrent VTE is increased if there is failure to achieve a therapeutic
level of anticoagulation. Accordingly, the aPTT ratio of 1.5 to 2.5
Thromboembolism times the control should be maintained above a level equivalent to a
heparin level of 0.3 to 0.7 units/mL, as determined by measuring
The treatment of acute VTE currently involves administration of anti-Xa activity. For most currently used aPTT reagents, this is
effective doses of anticoagulants as soon as the diagnosis is confirmed equivalent to an aPTT ratio of 1.8–2.5 times the control value. To
(or if testing is delayed and the clinical likelihood of disease is moder- monitor UFH given by continuous intravenous infusion, the aPTT
ate or high, before confirmation of the diagnosis).Traditionally should be measured 6 hours after the bolus dose so that it reflects the
patients with acute VTE were admitted to hospital and given intra- anticoagulant effects of the infusion. If twice-daily subcutaneous
venous UFH, to achieve a therapeutic activated partial thromboplastin UFH is given, a mid-interval aPTT is typically measured 6 hours
time (aPTT). A VKA, typically warfarin, was then started and the after the injection. UFH can also be given in fixed doses without
heparin continued until the INR was more than 2.0 on two consecu- laboratory monitoring; in a study of more than 700 VTE patients,
tive measurements. Although this treatment strategy remains a UFH was administered using a fixed, weight-adjusted dose without
practice standard, the vast majority of patients with acute DVT and/ aPTT monitoring. The risks of bleeding and recurrent thrombosis
or PE can be managed in the outpatient setting because of the were similar to those in patients treated with twice-daily LMWH.
availability of safe and effective treatment options such as direct oral
anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxa-
ban), LMWH, and fondaparinux. Patients who are hemodynamically Vitamin K Antagonists (Warfarin)
stable, lack contraindications to treatment (e.g., severe thrombocyto-
penia, recent bleeding, severe renal or liver disease), have manageable Because rapid anticoagulant effect is desired in the setting of acute
symptoms, and are likely to be compliant with treatment are good VTE, initiation of warfarin therapy requires concomitant adminis-
candidates for outpatient therapy. tration with a parenteral agent (UFH, LMWH), which should be
continued for at least 5 days and until the INR has been between
2.0 and 3.0 on 2 consecutive days. An initial dose of 5–10 mg
Low-Molecular-Weight Heparin and Fondaparinux daily for 2 days can be given to most individuals, with doses less
than 5 mg reserved for elderly patients. Subsequent dosing should
Treatment with LMWH or fondaparinux involves administration of be based on results of INR testing. The required maintenance dose
weight-adjusted, once- or twice-daily subcutaneous injections that of warfarin may be influenced by age, gender, race, nutritional
do not require routine monitoring of anticoagulant effect. However, status, organ function, and concomitant medications, and should
the anticoagulant effect can be measured using anti–factor Xa activ- be determined based on the results of routine INR monitoring.
ity assays calibrated for the specific drug for selected patients with Women generally require lower warfarin doses than men. The
anticoagulant-related complications such as bleeding or need for warfarin dose variability is also affected by variation in the geno-
urgent surgery/procedure, those at the extremes of weight (<40 kg types of the cytochrome P450 CYP2C9 and the vitamin K epoxide
or >100 kg), or renal insufficiency. LMWH and fondaparinux should reductase complex, VKORC1. These enzymes influence the rate
generally be avoided in patients with significant renal impairment of warfarin metabolism and sensitivity, respectively. Studies using
(creatinine clearance <30 mL/min). For LMWH, typically one warfarin genotyping to optimize warfarin dosing have yielded con-
would target a peak anti-Xa level of 0.5–1.0 unit/mL measured 4 flicting results, and further study along with economic evaluation is
hours after a subcutaneous injection of LMWH using a twice-daily ongoing.