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Low-molecular-weight heparins (LMWHs) exert their anticoagulant effects by

binding to antithrombin, thereby enhancing its capacity to inhibit thrombin and factor

Xa.

This inhibition of factor Xa is mediated by a unique pentasaccharide sequence found

on about one-fifth of LMWH chains. most of the LMWH chains are insufficient in

length to bridge antithrombin to thrombin. Thus, LMWH catalyzes the inhibition offactor Xa to a greater extent than thrombin.

LMWH has a more predictable anticoagulant effect than heparin because of less

plasma protein binding. The half-life of LMWH ranges from 2 to 5 hours depending

on the specific LMWH used. Bioavailability after subcutaneous (SQ) injection is

approximately 90%, and peak concentrations are reached at 1 to 5 hours. LMWH does

not reliably alter the activated partial thromboplastin time (aPTT) or prothrombin time

(PT) at therapeutic concentrations. Because the clearance of LMWHs is primarily

through the kidney,

Protamine sulfate only partially reverses the anticoagulant effect of LMWH. Becauselonger chains bind protamine with higher affinity, protamine reverses all of the anti-

IIa (antithrombin) activity of LMWH but only 60% of LMWHs anti-Xa activity.The

dose of protamine varies based on LMWH subtype (1 mg protamine per 100 mg

enoxaparin or 1 mg protamine per 100 U of dalteparin or tinzaparin)

a decreased incidence of heparin-induced thrombocytopenia (HIT) due to less binding

to platelet factor 4. Furthermore, the risk of osteoporosis with long-term LMWH use

is thought to be less than UFH because of reduced binding to osteoblasts.

the use of LMWHs in the ICU setting may be more problematic, because these

patients often have comorbidities (obesity, renal insufficiency/failure, anasarca, or

hypotension requiring inotrope therapy), which can lead to unpredictable dose effects.

If levels fall outside the usual therapeutic range as a result of these abnormalities,

patients may be placed at risk for underdosing (causing avoidable thrombosis) or

overdosing (causing avoidable bleeding). Because of their long half-lives compared

with UFH, especially in patients with renal impairment, LMWH to produce

therapeutic anticoagulation

PROTECT study, which compared 5000 units of dalteparin once daily to UFH 5000

units twice daily for VTE prophylaxis in critically ill patients, there was no difference

in the rates of major bleeding (5.5% vs 5.6 %, respectively) despite the inclusion ofpatients with a range of renal insufficiency, including patients with end-stage renal

disease requiring hemodialysis.

Metaanalysis of12 studies involving approximately 5000 patients revealed that

therapeutic enoxa- parin dosing was associated with increase in major bleeding in

patients with a CrCl of 30 mL/min or less compared with UFH.

with renal failure, the authors suggest clinicians consider monitoring the anticoagulant

effect with anti-Xa heparin levels 4 hours after the third dose (when steady state has

been achieved) to assess for potential increased drug accumulation. Furthermore,

repeat anti-Xa levels are warranted after any dose adjustments or changes in renal

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function. The target therapeutic range (in anti-Xa units) is .5 to 1.0 U/mL for patients

on twice-daily LMWH and 1.0 to 2.0 U/mL for patients on once-daily LMWH.

clinical trials have generally excluded ICU patients. Therefore, the efficacy and safety

of LMWHs in the treatment of acute VTE in critically ill patients remains unclear.

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