Chapter 80 Anticoagulants and Neuraxial and Peripheral Nerve Blocks Flashcards
KEY POINTS 1. Some 50% of DVTs after total joint surgery begin intraoperatively; the highest incidence occurs during surgery and the first postoperative day. Almost 75% of DVTs develop within the first 48 hr after surgery. 2. Case reports of intraspinal hematoma after aspirin and NSAIDs had complicating factors such as concomitant administration of other anticoagulant, epidural vascular abnormalities, and technical difficulties. The intake of different antiplatelet medications has been identif
The predisposing factors to the development of DVTs
during surgery
stasis, intimal injury, and hypercoagulability
Some of the risk factors for the development of DVTs are
previous history of DVT or pulmonary embolism,
major surgery, age over 60, obesity, malignancy,
increased duration of surgery, prolonged immobilization,
presence of varicose veins, and the use of estrogen. The
problem is pronounced in total joint operations where
intraoperative factors predispose to the development of DVTs.
The increased coagulability of the
blood is aggravated by
decreases in antithrombin III and tissue plasminogen activator (t-PA).
the most reliable diagnostic test for DVT
Ascending venous contrast venography. It is invasive, requires a radiology suite,
the first-line modality for confirming diagnosis of DVT in
symptomatic patients.
B-mode compression ultrasonography with and without Doppler. It is portable and the most accurate
noninvasive study of DVTs. Failure of the vein to compress
is indirect evidence that a thrombus is present
The prevention of DVT after total joint surgery includes
intraoperative, mechanical, and pharmacologic measures
The use of epidural hypotensive anesthesia is associated with improved
visualization of the operative field, less intraoperative
blood loss, and shorter duration of surgery
Mechanical devices decrease stasis by
augmenting venous flow in the lower legs, and appear to have a fibrinolytic effect through a reduction in plasminogen activator inhibitor. Various types of mechanical devices include calf-length sleeve, thigh-length stockings, and foot pump devices
the most efficacious way of preventing DVT
A combination of mechanical
and pharmacologic measures
The pharmacologic management of DVTs includes
the use of aspirin, warfarin, LMWH, thrombin inhibitors, and the newer drugs including rivaroxaban
For aspirin, most regimens use doses of
325 to 650 mg twice a day. The risks
of aspirin use are gastritis and gastric erosions or ulcers
For warfarin, the usual dosing
regimen is
mg given the night of surgery, followed by adjustment of the dose to maintain an international normalized
ratio (INR) of 2.0 to 2.5. Higher INRs may result in hemarthromas. The therapy is maintained for 1 month after
surgery
ecause of warfarin’s delayed effect and the early
development of postoperative thrombus
add an LMWH as a “bridge therapy” while
the effect of warfarin is commencing
Heparin is not widely used for postoperative prophylaxis
after total joint surgery probably because
of the better bioavailability and predictability of LMWH.
The LMWH therapy
continued for 1 to 2 weeks after the surgery.
Fondaparinux
a specific Xa inhibitor, is given for 5 to 9 days after surgery
at a daily dose of 2.5 mg. The drug reduces the incidence
of venous thromboembolism by 57%, comparable
to enoxaparin.
Ximelagatran
an oral thrombin inhibitor. However, its use resulted in severe liver toxicity and this led
to the Food and Drug Administration (FDA) recommending against its approval.
The medication recommendations of
the group for patients at standard risk of both pulmonary
embolism and bleeding, and for patients at elevated risk for
pulmonary embolism and standard risk of major bleeding,
include the following (in alphabetical order):
aspirin; LWMH, pentassacharides, and warfarin (INR goal of
For patients at standard risk of pulmonary embolism
and elevated risk of bleeding, and for patients at elevated
risk of both pulmonary embolism and major bleeding, the group recommended the following medications
aspirin and warfarin (INR goal of
In patients with STEMI regardless of whether they undergo reperfusion or fibrinolytic therapy
With regards to anticoagulants, the task force recommended the addition of clopidogrel to aspirin
The ACA/AHA guidelines
recommended that clopidogrel should be discontinued
or
at least 5 days and preferably 7 days unless the urgency for
revascularization outweighs the risks of excess bleeding.
For
STEMI patients who do not undergo reperfusion therapy,
the ACA/AHA guidelines stated that
it is reasonable to give
IV or subcutaneous unfractionated heparin (UFH) or subcutaneous
LMWH for at least 48 hr.
For patients who
undergo invasive management, anticoagulant therapy with
unfractionated heparin or LMWH is recommended
After stent placement, it has been recommended that
aspirin be continued for
1 month after a bare-metal stent, 3 months after a sirolimus-eluting stent, and 6 months after a paclitaxel-eluting stent
For clopidogrel, it has been
recommended that the drug be continued for
at least 1 month and ideally up to a year, and for at least 1 year after both sirolimus- and paclitaxel-eluting stent
Problems with warfarin include its
narrow therapeutic range (INR 2–3), unpredictable and patientspecific dose response, delayed onset and offset of action, need for anticoagulation monitoring, slow reversibility,
and many drug–drug and drug–food interactions.
Antiplatelet therapy is highly effective in reducing
the risk of recurrent ischemic stroke or TIA and is recommended over oral anticoagulant for noncardioembolic stroke
Aspirin MAO
irreversibly binds to the platelet COX enzyme inhibiting the formation of thromboxane A2 that causes platelet aggregation, resulting in the formation of an
adequate but fragile clot.
Aspirin Dosing and Effects
Most regimens use doses of 325 to 650 mg twice a day. Lower doses of aspirin are more effective in preventing clot formation, as the platelet COX enzyme is blocked, decreasing the formation of thromboxane A2, which causes platelet aggregation. Higher doses of aspirin inhibit the COX enzyme in the platelets and in the vascular endothelium; this inhibition also results in decreased levels of PGI2, which inhibits platelet aggregation. The ultimate effect of higher dosages is therefore a reflection of the antagonistic effects of reduced levels of
thromboxane A2 and PGI2.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
bind to the platelet COX enzyme but the binding is
reversible; their effect on platelet function usually normalizes within 3 days
platelet function analyzer (PFA).
a test
of in vitro platelet function, as well as a good screening
test for von Willebrand disease, monitoring the effect of
DDAVP administration, and is prolonged after antiplatelet
therapy. The test measures the ability of platelets to occlude a microscopic aperture in a membrane coated with
collagen and epinephrine (C-EPI or PFA-I) or collagen
and adenosine diphosphate (C-ADP or PFA II) under controlled high shear rates. The time required to obtain a
complete platelet plug is the closure time in seconds. The
normal closure times are 60 to 160 s for C-EPI and 50 to
124 s for C-ADP. Aspirin and NSAIDs prolong the closure
time of C-EPI, while clopidogrel, von Willebrand disease, low platelet count, low hematocrit, and renal failure prolong the closure time for C-ADP.
COX-2 inhibitors
have analgesic effects. They have less gastrointestinal
toxicity and compared to aspirin or NSAIDS,
thienopyridine drugs ticlopidine and clopidogrel
inhibit platelet aggregation by inhibiting ADP receptor mediated platelet activation. These drugs also modulate
vascular smooth muscle reducing vascular contraction.
Clopidogrel is 40 to 100 times more potent than ticlopidine.
ticlopidine and clopidogrel dose
The doses employed are 75 mg daily for clopidogrel and 250 mg twice a day for ticlopidine
Ticlopidine is rarely
used because it causes
hypercholesterolemia, neutropenia, and thrombocytopenic purpura. There is also a possible
delayed antithrombotic effect of ticlopidine and may not
offer protection in the cardiac patient for the first 2 weeks of ticlopidine therapy.
Clopidogrel is preferred because
it has a better safety profile and appears to have a better effect
than aspirin in patients with peripheral vascular disease and
is increasingly used in these patients.
The maximal inhibition of ADP-induced platelet aggregation with clopidogrel
occurs
3 to 5 days after initiation of a standard dose (75 mg),
but within 4 to 6 hr after the administration of a large loading dose (300–600 mg). The large loading dose is given to patients before they undergo percutaneous coronary intervention.
neuraxial blocks may be performed in patients on
aspirin or NSAIDs
Neuraxial blocks in patients on COX-2 inhibitors are
safe, although the concomitant use of COX-2
inhibitors and warfarin may increase the risk of bleeding.
For clopidogrel, it is recommended that the drug be discontinued for
7 days before a neuraxial injection. In contrast, a delay of 10 to 14 days is recommended with ticlopidine. This is because the half-life of ticlopidine increases from
12 hr after a single dose to 4 to 5 days after a steady state is reached
Aspirin and NSAIDs alone
do not significantly increase
the risk of spinal hematoma. The combination of these
drugs, however, increases the risk of spontaneous hemorrhagic complications, bleeding at puncture sites, and spinal hematoma. The society cautioned the performance of intraspinal injections in patients who are on combined antiplatelet medications.
For patients on clopidogrel and aspirin, it is recommended
that the clopidogrel be stopped for
7 days and the
patient placed on aspirin therapy. The aspirin is then continued up to the time of injection, after which the patient is switched back on clopidogrel after the block. If the indication for the anticoagulation is very strong then LMWH can be given during the 7 days that the clopidogrel is stopped.
Warfarin
an oral anticoagulant that interferes with the synthesis of the vitamin K–dependent clotting factors II, VII, IX, and X. It also inhibits the anticoagulant protein C. Both factor VII and protein C have short halflives
(6–7 hr) and increase in the INR is the result of the
competing effects of reduced factor VII and protein C
and the washout of existing clotting factors.
after the initial dose of Warfarin Prophylactic anticoagulation (INRs of 2.0–2.5) is
reached
48 to 72 hr after the initial dose
The anticoagulant
effect of warfarin is primarily dependent on
the levels of factor II that has a half-life of 50 hr. Maximal anticoagulation is reached in 4 to 5 days when factor II is sufficiently reduced
The risks of warfarin usage are
bleeding and the rare occurrence of skin necrosis. Its drawbacks
include the necessity of monitoring its effect with serial INR monitoring, its interaction with a host of other drugs,
and the fact that it has to be stopped a few days before
surgery.