PRACTICAL THERAPEUTICS
`
`Low-Molecular-Weight Heparin
`in Outpatient Treatment of DVT
`
`BRYAN F. YEAGER, PHARM.D. , and SAMUEL C. MATHENY, M.D., M.P.H.
`University of Kentucky College of Medicine, Lexington, Kentucky
`
`Patients with a diagnosis of acute deep venous thrombosis have traditionally been
`hospitalized and treated with unfractionated heparin followed by oral anticoagulation
`therapy. Several clinical trials have shown that low-molecular-weight heparin is at
`least as safe and effective as unfractionated heparin in the treatment of uncompli(cid:173)
`cated deep venous thrombosis. The use of low-molecular-weight heparin in an outpa(cid:173)
`tient program for the management of deep venous thrombosis provides a treatment
`alternative to hospitalization in selected patients. Use of low-molecular-weight
`heparin on an outpatient basis requires coordination of care, laboratory monitoring,
`and patient education and participation in treatment. Overlapping the initiation of
`warfarin permits long-term anticoagulation. Advantages include a decreased inci(cid:173)
`dence of heparin-induced thrombocytopenia and fewer episodes of bleeding compli(cid:173)
`cations. Future clinical trials evaluating the safety and efficacy of low-molecular(cid:173)
`weight heparin in the treatment of complicated deep venous thrombosis will further
`define appropriate indications for use and strategies for outpatient management.
`
`Each year, members
`of two different med(cid:173)
`ical fa culties develop
`articles for "Practical
`Therapeutics. " This arti(cid:173)
`cle is one in a series
`coordinated by the
`Department of Family
`Practice at the Univer(cid:173)
`sity of Kentucky College
`of Medicine, Lexington.
`Guest editors of the
`series are Bryan F.
`Yeager, Pharm.D.,
`Thomas Armsey, MD.,
`and Samuel C. Math(cid:173)
`eny, MD., MPH
`
`D eep venous thrombosis (DVT)
`
`is associated with more than
`600,000 hospitalizations annu(cid:173)
`ally in the United States and
`results in more than 200,000
`deaths caused by pulmonary embolism. 1
`Patients with a diagnosis of acute DVT have
`traditionally been hospitalized and treated
`with a continuous infusion of unfractionated
`heparin for five to 10 days, followed by oral
`anticoagulation therapy for at least three
`months. Hospitalization has traditionally
`been considered necessary because of con(cid:173)
`cerns about fatal pulmonary embolism (and
`the need for careful laboratory monitoring),
`but this risk is now known to be low during
`the initial treatment of DVT. 2 Because of the
`wide variability in anticoagulant response
`among patients treated with unfractionated
`heparin, frequent monitoring of the activated
`partial thromboplastin time (aPTT) and
`dosage adjustments are required to keep anti(cid:173)
`coagulation in the therapeutic range. In most
`
`The risk of fatal pulmonary embolism during the initial treat(cid:173)
`ment of DVT is lower than was previously believed.
`
`patients who have no major risk factors for
`bleeding or subsequent pulmonary embolism,
`such as protein C or S deficiency, history of
`previous pulmonary embolism or more prox(cid:173)
`imal DVT, hospitalization is necessary only
`for monitoring aPTT and adjusting unfrac(cid:173)
`tionated heparin therapy.
`Several clinical trials have shown that low(cid:173)
`molecular-weight heparins are at least as safe
`and effective as unfractionated heparin in the
`treatment of DVT.3-6 These agents have a
`longer half-life and a more predictable antico(cid:173)
`agulant response than unfractionated heparin,
`which allows for subcutaneous administration
`without laboratory monitoring.7 The use of
`low-molecular-weight heparins in the treat(cid:173)
`ment of DVT provides an opportunity to real(cid:173)
`ize significant cost savings by preventing or
`shortening hospitalization and by increasing
`patient comfort and satisfaction with health
`care. 8 Shifting the management of DVT to the
`ambulatory setting presents several clinical
`and logistical challenges for clinicians, admin(cid:173)
`istrators and patients. The success of an out(cid:173)
`patient program for the management of DVT
`depends on familiarity with currently avail(cid:173)
`able low-molecular-weight heparins, patient
`selection, protocol development and outcome
`evaluation.
`
`FEBRUARY 15, 1999 / VOLUME 59, NUMBER 4
`
`AMERICAN FAMILY PHYSICIAN
`
`945
`
`MYLAN - EXHIBIT 1028
`
`

`

`(7SX v,,._--:-C,,.', · •~
`Unfractionated heparin
`
`~>CJ?
`
`-~~
`Binds to plasma proteins,
`endothel ium and
`macrophages
`
`•
`Activated
`factor Xa
`
`Antithrombin
`
`Activated factor
`Ila (thrombin)
`
`Inactivated
`factor Xa
`
`\;t,~ .. _,
`
`Inactivated
`factor Ila
`
`aPTT measures anti-factor Ila activity
`
`FIGURE 1A. Effect of low-molecular-weight heparin (LMWH) and unfractionated heparin on fac(cid:173)
`tor Ila and factor Xa. Both types of heparin inactivate factor Xa by interacting with antithrom(cid:173)
`bin. Longer chain, unfractionated heparin (UFH) is able to inactivate factor Ila through forma(cid:173)
`tion of a tertiary complex, unlike LMWH. Compared with LMWH, UFH binds more to plasma
`proteins, endothelium and macrophages, resulting in reduced bioavailability and greater
`patient variability to a given dose. UFH inactivates factors Ila and Xa and affects the aPTT, a mea(cid:173)
`sure of anti-factor Ila activity. (aPTT = activated partial thromboplastin time)
`
`Low-molecular(cid:173)
`weight heparin
`
`Antithrombin
`
`Activated
`factor Xa
`
`Activated
`factor Ila
`
`Inactivated
`factor Xa
`
`Factor Ila still
`activated
`
`Minimal anti-factor Ila activity
`
`FIGURE 1 B. Low-molecular-weight heparin inhibits factor Xa and min(cid:173)
`imally affects factor Ila; thus activated partial thromboplastin time is
`not used to measure its anticoagulant activity.
`
`Low-Molecular-Weight Heparins
`Low-molecular-weight heparins are derived
`from depolymerization of standard heparin,
`which yields fragments approximately one
`third the size of the parent compound. These
`lower-molecular-weight fractions have several
`properties that differentiate them from
`unfractionated heparin. Low-molecular(cid:173)
`weight heparins exert their anticoagulant
`effect by inhibiting factor Xa and augmenting
`tissue-f<!_ctor-pathway inhibitor but minimally
`affect thrombin, or factor Ila (Figure la and
`lb). Thus, the aPTT, a measure of antithrom(cid:173)
`bin (anti-factor Ila) activity, is not used to
`measure the activity of low-molecular-weight
`heparins, which requires instead a specific
`anti-Xa assay.
`In addition to having lower antithrombin
`activity than unfractionated heparin, low(cid:173)
`molecular-weight heparins bind less
`to
`plasma proteins, endothelium and macro(cid:173)
`phages, permitting greater bioavailability and
`little inter-patient and intra-patient variability
`in response to a given dosage. 9 Clinical trials
`have confirmed that effective antithrombotic
`
`946 AMERICAN FAMILY PHYSICIAN
`
`VOLUME 59, NUMBER 4 / FEBRUARY 15, 1999
`
`

`

`LMW Heparin in DVT
`
`activity can be consistently achieved by calcu(cid:173)
`lating dosages based on body weight without
`the need for laboratory monitoring. 10
`Since these agents are eliminated primarily
`through the kidneys, accumulation of anti(cid:173)
`factor Xa activity may occur in patients with
`chronic renal insufficiency. Plasma anti-factor
`Xa concentrations should be monitored in
`patients with renal dysfunction and possibly
`in those weighing less than 50 kg (ll0 lb) or
`more than 80 kg (176 lb). 10 Low-molecular(cid:173)
`weight heparins also appear to be associated
`with less bleeding and a decreased frequency
`of heparin-induced thrombocytopenia, as a
`result of their lower affinity for platelets and
`von Willebrand factor.10 Danaparoid (Orga(cid:173)
`ran) and lepirudin (Refludan) are indicated in
`the treatment of heparin-induced thrombo(cid:173)
`cytopenia type II. Lepirudin is a recombinant
`form of hirudin, an anticoagulant derived
`from the saliva of leeches. Danaparoid is a
`low-molecular-weight heparin composed of a
`mixture of heparan, dermatan and chondroi(cid:173)
`tin sulfates.
`Low-molecular-weight heparins currently
`available in the United States include enoxa(cid:173)
`parin (Lovenox), dalteparin (Fragmin) and
`ardeparin
`(Normiflo), while nadroparin
`(Fraxiparine), tinzaparin (Logiparin, Inno(cid:173)
`hep) and reviparin ( Clivarine) are marketed
`elsewhere (Table 1). Enoxaparin was recently
`labeled by the U.S. Food and Drug Adminis(cid:173)
`tration for outpatient treatment of DVT and
`may also be used in the inpatient setting to
`manage DVT with or without pulmonary
`embolism. Each of these agents is prepared
`with a different method of depolymerization,
`resulting in distinct molecular weights (4,000
`to 5,500 Da) and relative effects on factor Xa
`and thrombin. For this reason, low-molecular(cid:173)
`weight heparins are unique and not necessarily
`therapeutically interchangeable, although their
`-pharmacologic and clinical characteristics are
`similar. 10
`Several meta-analyses have indicated that
`low-molecular-weight heparins are superior
`to unfractionated heparin in the treatment of
`
`Low-molecular-weight heparin is associated with less bleed(cid:173)
`ing and fewer episodes of heparin-induced thrombocytope(cid:173)
`nia than unfractionated heparin.
`
`patients with established DVT. One analysis
`did not indicate a significant difference in
`symptomatic recurrence rates or adverse
`events but did note trends favoring low-mole-
`cular-weight heparins. 11 The safety and effec-
`
`TABLE 1
`Comparison of Low-Molecular-Weight Heparins
`
`Average
`Clinical trial
`treatment doses molecular
`weight (Da)
`(anti-Xa units)
`
`Intravenous
`half-life
`(minutes)
`
`Cost*
`
`Not evaluated
`
`6,000
`
`200
`
`$154.50+
`
`Agent
`
`Ardeparin
`(Normiflo)t
`
`Dalteparin
`(Fragmin)t
`
`100 U per kg
`tw ice daily
`
`Enoxaparin
`(Lovenox)t
`
`100 U per kg
`tw ice daily
`
`Nadroparin
`(Fraxiparine)
`
`225 U per kg
`tw ice daily
`
`Reviparin
`(Clivarine)
`
`100 U per kg
`twice dai ly
`
`Tinzaparin
`(Logiparin,
`lnnohep)
`
`175Uperkg
`once daily
`
`Danaparoid II
`(Orgaran)
`
`750 U tw ice
`daily
`
`5,000
`
`119 to 139
`
`63.00§
`
`4,500
`
`129 to 180
`
`78 .50
`
`4,500
`
`132 to 162
`
`NA
`
`4,300
`
`4,900
`
`NA
`
`111
`
`NA
`
`NA
`
`5,500
`
`24 hours
`
`237 00§
`
`Anti-Xa = plasma anti-factor Xa; Da = dalton (atomic mass unit); NA = not available.
`*-Unless otherwise noted, estimated cost to the pharmacist for one day's ther(cid:173)
`apy, rounded to the nearest half dollar, based on average wholesale prices in Red
`book. Montvale, N.J. : Medical Economics Data, 1998. Cost to the patient will be
`higher, depending on prescription filling fee.
`t-Available in the United States.
`+-Price given is for 10 vials of medication (5,000 units per 0.5 ml). No dosing
`recommendation is given.
`§-Price given is for treatment of a 70-kg (154-lb) adult.
`II- Indicated for heparin-induced thrombocytopenia only
`
`Information from references 9 and 10.
`
`FEBRUARY 15, 1999 / VOLUME 59, NUMBER 4
`
`AMERICAN FAMILY PHYSICIAN 947
`
`

`

`tiveness of these agents were significantly bet(cid:173)
`ter than that of unfractionated heparin in two
`other analyses. 12,13 Collectively, the results
`reveal a statistically significant reduction in
`thrombus size, recurrent venous thromboem(cid:173)
`bolism, major bleeding events and pooled
`long-term mortality rate. Although the lower
`mortality rates observed in these trials were
`mostly attributable to a subgroup of patients
`with cancer, the data may indicate greater effi(cid:173)
`cacy oflow-molecular-weight heparins in this
`high-risk population.14
`Two recent studies of patients with DVT
`have also been conducted to compare the effect
`of low-molecular-weight heparins given on an
`outpatient basis subcutaneously twice daily
`with that of unfractionated heparin given by
`continuous intravenous infusion in the hospi(cid:173)
`tal.15·16 No significant difference was found in
`rates of recurrent venous thromboembolism,
`hemorrhagic complications, development of
`thrombocytopenia or mortality. Low-molecu(cid:173)
`lar-weight heparins were as safe and effective
`as unfractionated heparin, and most patients
`were managed at home immediately after
`diagnosis or a brief hospitalization.
`In addition to comparable efficacy in the
`treatment of DVT, patients receiving low(cid:173)
`molecular-weight heparin reported a higher
`quality of life in terms of physical and social
`function and sense of well-being. Treatment
`of DVT with low-molecular-weight heparin
`
`The Authors
`
`BRYAN F. YEAGER, PHARM.D., is assistant professor in the Department of Family Prac(cid:173)
`tice, Division of Pharmacy Practice and Science, at the University of Kentucky College
`of Medicine, Lexington . Dr. Yeager obtained a doctorate in pharmacy from the Uni(cid:173)
`versity of Texas at Austin. He completed a postdoctoral residency in primary care and
`geriatrics at the University of Texas at Austin. Dr. Yeager is a board-certified pharma(cid:173)
`cotherapy specialist.
`
`SAMUEL C. MATHENY, M.D., M.P.H., is professor and chair of the Department of Fam(cid:173)
`ily Practice at the University of Kentucky College of Medicine. Dr. Matheny graduated
`from the University of Kentucky College of Medicine. He also holds a master of pub(cid:173)
`lic health degree from the University of California, Los Angeles, School of Medicine.
`
`Address correspondence to Bryan F Yeager, Pharm. 0., Department of Family Practice,
`K302 Kentucky Clinic, Lexington, KY 40536-0284. Reprints are not available from the
`authors.
`
`TABLE 2
`Exclusion Criteria for Outpatient Therapy
`with Low-Molecular-Weight Heparin
`
`Clinical evidence of pulmonary embolism or
`suspected embolism
`
`Conditions that increase the risk of bleeding:
`Recent surgery
`Peptic ulcer disease
`Malignant hypertension
`Increased risk of falling
`
`High risk of recurrent thrombosis:
`Extensive proximal deep venous thrombosis
`Recurrent deep venous thrombosis
`Preg nancy
`Protein C or S deficiency
`
`Likelihood of noncompliance
`
`Unavailable for follow-up
`
`Inadequate home support system
`
`Information from references 14 and 15.
`
`was more cost-effective than therapy with
`unfractionated heparin because the length of
`the hospital stay was reduced by 60 to 70 per(cid:173)
`cent without an increase in the cost of home
`health care.
`
`Patient Selection
`Criteria are needed for the selection of
`patients_who may be candidates for low-mol(cid:173)
`ecular-weight heparin therapy on an ambula(cid:173)
`tory basis. The studies15·16 evaluating the effec(cid:173)
`tiveness of low-molecular-weight heparins in
`the treatment of DVT excluded certain patient
`populations (Table 2). Based on selection cri(cid:173)
`teria from these clinical trials, approximately
`40 percent of all patients diagnosed with DVT
`would be eligible for home-based treatment
`with low-molecular-weight heparin.15·16
`While the safety and efficacy of low-molec(cid:173)
`ular-weight heparin in the treatment of
`patients with DVT alone is clear, controversy
`surrounds its use in the hospital and at home
`in patients with documented or suspected pul-
`
`948 AMERICAN FAMILY PHYSICIAN
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`VOLUME 59, NUMBER 4 / FEBRUARY 15, 1999
`
`

`

`LMW Heparin in DVT
`
`evidence indicates that any one low-molecu(cid:173)
`lar-weight heparin is more effective or safer
`than another in the treatment of DVT on an
`outpatient basis. Drug selection is often dic(cid:173)
`tated by ease and frequency of administra(cid:173)
`tion, cost and evaluation of the safety and
`efficacy of each agent based on the results of
`clinical trials.
`All low-molecular-weight heparins are pack(cid:173)
`aged in syringes containing smaller, prophylac(cid:173)
`tic doses, so repackaging is necessary to provide
`the appropriate treatment dosage as a single
`injection. New unit-dose syringes for several
`agents used for the treatment of DVT have just
`been approved or are awaiting FDA approval.
`Information about the stability and compati(cid:173)
`bility oflow-molecular-weight heparins should
`be obtained from the manufacturer or other
`sources to ensure proper preparation and stor(cid:173)
`age of these agents. These agents may be dis(cid:173)
`pensed by outpatient pharmacies to patients
`for self-administration at home or prepared by
`home health care professionals delivering care
`directly to the patient.
`
`Patient selection
`
`Confirmed diagnosis of DVT
`
`!
`
`Uncomplicated DVT?
`(See Table 2)
`
`l No
`
`No
`Hospitalize and treat
`Competent caregiver or - - - - •
`ability for self-care?
`
`l Yes
`
`Start LMWH treatment protocol
`on an outpatient basis
`
`FIGURE 2. Algorithm for the selection of patients for low-molecular(cid:173)
`weight heparin therapy of deep venous thrombosis. (DVT = deep
`venous thrombosis; LMWH = low-molecular-weight heparin)
`
`monary embolism. A recent study' 7 evaluating
`once-daily administration of tinzaparin com(cid:173)
`pared with unfractionated heparin in the treat(cid:173)
`ment of acute pulmonary embolism found no
`difference in rates of combined recurrent
`thromboembolism, major bleeding or death.
`However, low-molecular-weight heparin was
`not given on an outpatient basis in that study,
`and the results cannot be extrapolated to
`patients who take these agents at home.
`The Columbus study18 compared low-mo(cid:173)
`lecular-weight heparin, given twice daily, with
`unfractionated heparin in patients with DVT,
`with or without pulmonary embolism or his(cid:173)
`tory of venous thromboembolism. Twenty(cid:173)
`seven percent of the patients who were ran(cid:173)
`domized to the low-molecular-weight heparin
`arm of this trial were managed outside the
`hospital. Both treatment groups were similar
`in the incidence of recurrent thromboembolic
`events, episodes of major bleeding and mor(cid:173)
`tality. While further study is warranted to
`determine if patients with DVT and suspected
`pulmonary embolism may be safely and effec(cid:173)
`tively treated with low-molecular-weight
`heparin in the ambulatory setting, the evi(cid:173)
`dence in favor of this therapy is mounting
`rapidly. 19 At present, outpatient low-molecu(cid:173)
`lar-weight therapy is best reserved for use in
`patients with uncomplicated DVT, a compe(cid:173)
`tent caregiver at home or the ability for self(cid:173)
`care, and ·an appropriate mechanism for fol(cid:173)
`low-up with their family physician (Figure 2).
`
`Development of Protocol
`A multidisciplinary approach is necessary
`to develop the specific details of an outpatient
`management protocol for DVT. Physicians,
`nurses, pharmacists and other health care pro(cid:173)
`fessionals each contribute a unique perspec(cid:173)
`tive in planning and implementing a program
`protocol for managing patients with low-mo(cid:173)
`lecular-weight heparin therapy on an outpa(cid:173)
`tient basis.
`In addition to cost, drug selection and
`other pharmaceutical factors should be dis(cid:173)
`cussed before protocol implementation. 20 No
`
`F EBRUARY 15, 1999 / VOLUME 59, NUMBER 4
`
`AMERICAN FAMILY PHYSICIAN
`
`949
`
`

`

`Warfarin therapy should overlap with administration of low(cid:173)
`molecular-weight heparin, and warfarin therapy alone
`should be continued for at least three months.
`
`An outpatient management protocol for
`DVT should include information on anti(cid:173)
`thrombotic therapy, laboratory monitoring,
`patient activity, nonpharmacologic manage(cid:173)
`ment and patient education.21 After the diag(cid:173)
`nosis of DVT is confirmed, many patients
`may be treated on an ambulatory basis. If the
`patient or a family member is unable to
`administer low-molecular-weight heparin, the
`physician should arrange for home health care
`if the patient is eligible. Antithrombotic ther(cid:173)
`apy should be started on the first day of ther-
`
`apy and should include at least five days of
`treatment with low-molecular-weight heparin
`overlapping from the first day of treatment
`with warfarin (Coumadin). The average start(cid:173)
`ing dosage of warfarin is 5 mg daily in most
`patients, except the elderly and those with
`hepatic disease, who require a lower dosage.
`Determination of activated partial throm(cid:173)
`boplastin time (aPTT) to rule out clotting
`abnormalities and prothrombin time/Inter(cid:173)
`national Normalized Ratio (PT/INR), and a
`complete blood cell count with platelets
`should be obtained at baseline, as well as a
`platelet count on the fifth day of therapy. An
`INR should be obtained on the third day and
`again daily until low-molecular-weight heparin
`therapy is discontinued. Therapy with low(cid:173)
`molecular-weight heparin may be discontin(cid:173)
`ued after at least five days of therapy once the
`
`TABLE 3
`Clinical Monitoring and Patient Education for Therapy
`with Low-Molecular-Weight Heparin
`
`Clinical monitoring
`Baseline:
`Hemoglobin
`Hematocrit
`Platelet count
`aPTT
`PT/INR
`DVT symptoms
`
`During low-molecular-weight heparin treatment:
`PT/INR-goal 2.0 to 3.0
`Warfarin (Coumadin)- initial dosage:
`2.5 to 5.0 mg daily
`Platelet count
`DVT symptoms
`Medication administration problems
`Bleeding
`PE symptoms (chest pain, shortness of breath)
`Noncompliance
`
`Patient education
`Drug description and use
`Treatment duration (5 to 7 days)
`Side effects
`Dosing (Table 1)
`Injection site selection
`Injection technique
`Injection sitt. monitoring
`Drug interactions
`Handling of missed doses and overdoses
`Storage requirements
`Syringe disposal
`First-dose demonstration
`
`aPTT = activated partial thromboplastin time; PT = prothrombin time; INR = International Normalized Ratio;
`DVT = deep venous thrombosis; PE = pulmonary embolism.
`Information from Dedden P, Chang B, Nagel D. Pharmacy-managed program for home treatment of deep vein
`thrombosis with enoxaparin. Am J Health Syst Pharm 1997;54: 1968-72.
`
`950 AMERICAN FAMILY PHYSICIAN
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`VOLUME 59, NUMBER 4 / FEBRUARY 15, 1999
`
`

`

`LMW Heparin in DVT
`
`INR is between 2.0 and 3.0. In the majority of
`patients whose risks for recurrent throm(cid:173)
`boembolism are low, three months of war(cid:173)
`farin therapy usually suffice. In patients with
`an ongoing risk of thrombosis ( e.g., cancer,
`hereditary clotting diathesis), longer or even
`life-long therapy may be indicated.9
`Patients should reduce their level of activity
`as long as pain persists and elevate the extrem(cid:173)
`ities when possible during the first two days of
`therapy. 21 Local therapy should be instituted
`on the first day and include application of
`local heat and range-of-motion exercises. The
`treatment protocol should also include an
`inpatient option for initiation of therapy.
`Patients admitted to the hospital with a new
`diagnosis of DVT may receive one to four days
`of therapy with unfractionated heparin plus
`oral warfarin before starting treatment with
`low-molecular-weight heparin. Therapy with
`low-molecular-weight heparin should be ini(cid:173)
`tiated within one hour of discontinuing intra(cid:173)
`venous administration of unfractionated
`heparin. Whether DVT is managed with low(cid:173)
`molecular-weight heparin in an outpatient or
`inpatient setting, intensive patient education
`is required to ensure a positive therapeutic
`outcome.
`Physicians involved with the DVT program
`are responsible for providing education to pa(cid:173)
`tients who receive outpatient therapy (Table 3 ).
`Patients should be taught the proper technique
`for administering low-molecular-weight hep(cid:173)
`arin, indications for heparin and warfarin
`therapy, medication side effects and potential
`drug interactions. The first dose oflow-molec(cid:173)
`ular-weight heparin should be given in the
`clinic to ensure patient tolerance and demon(cid:173)
`strate appropriate injection technique.
`Kits with a sharps container, alcohol pads
`and instructions for administration may be
`useful. Physicians should instruct patients
`about the necessary monitoring of the drug,
`the injection site and DVT, give guidelines for
`seeking additional medical assistance and out(cid:173)
`line necessary follow-up appointments. If
`possible, written materials, information pack-
`
`ets and audiovisual aids should be given to
`patients to reinforce the learning process.
`Patient education materials are available from
`manufacturers of some low-molecular-weight
`heparins. The extent of program education
`should be documented in the patient's med(cid:173)
`ical record.
`
`Outcome Evaluation
`Patients should be closely monitored dur(cid:173)
`ing and after completion of the treatment pro(cid:173)
`tocol. Significant bleeding events, episodes of
`recurrent thrombosis (e.g., DVT, pulmonary
`embolism), other symptoms and any prob(cid:173)
`lems with medication administration should
`be documented.
`As
`for cost considerations, economic
`appraisals of DVT therapy with low-molecu(cid:173)
`lar-weight heparins compared with unfraction(cid:173)
`ated heparin have shown a 20 percent reduc(cid:173)
`tion in disease management costs attributable
`to decreased length of hospital stay and an aver(cid:173)
`age cost savings of over $900 per patient.8
`22
`•
`
`REFERENCES
`
`1. Howard PA. Dalteparin: a low-molecular-weight
`heparin. Ann Pharmacother 1997;31 : 192-203 .
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