Health Care Guideline:
Deep Vein Thrombosis
General Implementation June 1998
Copyright © 1998 by Institute for Clinical Systems Integration
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Guideline Leader
Vic Kelmenson, MD, HealthPartners
Family Practice
Elizabeth Brackett, MD, HealthPartners
Internal Medicine
Jeff Larsen, MD, River Falls
Denise Dupras, MD, Mayo Clinic
Bruce Burnett, MD, HealthSystem Minnesota
Nursing
Kay Dickison, RN, HealthPartners
Laurie Ritz, RN, HealthSystem Minnesota
Pharmacy
Peter Marshall, PharmD, HealthPartners
Pulmonology
Vic Kelmenson, MD, HealthPartners
Surgery
David Borgstrom, MD, HealthPartners
Health Education
Jane Rodriguez, HealthPartners
Buyers Health Care Action Group
Diane Davies, MD, Pfizer
Measurement Advisor
Jane Gendron, ICSI
Facilitator
Jane Erickson, RN
Adult non pregnant patients age 18 and over with deep vein thrombosis (DVT) in the lower extremities in both the inpatient and outpatient settings.
Potential Aims for Medical Groups When Using This Guideline
1. Prevent progression or recurrence of thrombolytic disease.
Potential measures of accomplishing this aim:
a. Percentage of patients who develop pulmonary embolism after a diagnosis of DVT.
b. Percentage of patients treated for DVT who have a recurrence of DVT.
2. Reduce the risk of complications from anticoagulation therapy.
Potential measures of accomplishing this aim:
a. Percentage of patients for whom platelet count is monitored before and during treatment with heparin.
b. Percentage of patients with major bleeding complications.
c. Percentage of patients with minor bleeding complications.
d. Number of patients with DVT treated with LMWH.
3. Reduce resources and costs used in the diagnosis and treatment of DVT.
Potential measures of accomplishing this aim:
a. Percentage of patients who receive therapy in a setting other than acute inpatient.
b. Average inpatient length-of-stay for patients with a primary diagnosis of DVT.
c. Percentage of inpatients who receive warfarin on day 1 of heparin therapy.
d. Percent of patients who require hospital readmission within 30 days for condition related to DVT (including complications).
Clinical Algorithm & Annotations
Symptoms of DVT include unilateral pain and/or swelling above or below the knee of recent onset. Erythema, warmth and superficial thrombophlebitis with a palpable tender cord over a superficial vein may be present.It is well known that the clinical findings are poor predictors of the presence or severity of thrombosis.In the most severe form, phlegmasia cerulea dolens, the venous drainage of the lower extremity is acutely and severely obstructed resulting in induration, swelling, and threatened limb viability.This may require other treatment.(See Annotation #13.)
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2. Clinical Suspicion of DVT? (Pretest Probability)
Determining the pretest probability of DVT based on Wells criteria will aid the clinician in planning the follow-up of a negative ultrasound (further testing for high risk patients or elimination of DVT from consideration in low risk patients).(See Appendix A.)
Increased risk of DVT occurs with intimal injury, venous stasis, or hypercoagulability.Determine the patient's history of previous thromboembolic disease, family history of thromboembolic disease (one or more first degree relatives), presence of active cancer, recent trauma or surgery, immobilization, presence of varicosities and current estrogen use.
The present history should include the character, location, onset and duration of the patient's leg pain as well as the same characterization of any swelling.Recent unilateral swelling and pain without any explanatory bone or joint trauma is suspicious for DVT.Although the likelihood of DVT is less in a patient without risk factors or frank physical finding, the serious risk of untreated DVT leading to pulmonary embolism makes prompt objective testing necessary.(See Annotation Appendix A and Annotation and Discussion #8.)
Strength of the evidence for this recommendation:B.
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Although treatment for these patients may be similar to that found in the algorithm, the work group felt that these patients should be treated individually and not by the guideline.Recent evidence suggests that LMWH may be appropriate for treatment of pulmonary embolism and recurrent thromboembolism.
Include:
A. Suspected pulmonary embolism (PE)
1. shortness of breath
2. chest pain
3. hemoptysis
B. Familial bleeding or clotting disorders
C. Pregnancy
D. Phlegmasia
E. Renal dysfunction requiring dialysis
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Ultrasound should be the initial test done to confirm the diagnosis of DVT.The ability to diagnose DVT may vary depending on whether the site of the DVT is the calf or more proximal.
The interpretation of ultrasound can be difficult in patients with previous DVT.Consider consulting with the interpreting physician.
See the Discussion and References section under #9, Other Studies.
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8. Continued Suspicion of DVT?
Clinical Pre-Test Probability (see Appendix A) and Duplex ultrasound are adequate to rule-in or rule-out DVT in the majority of cases.If you strongly suspect a DVT and the ultrasound is negative, consider venography or repeat ultrasound in 3-7 days.
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A. Contrast venography
B. Serial ultrasonography
Serial ultrasonography for suspected calf vein thrombosis and anticoagulation when proximal extension is discovered is an acceptable alternative to venography.
C. Impedance plethysmography may be less effective than ultrasonography.
D. D-Dimer testing
E. Spiral contrast CT and MRI (experimental)
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A. Proximal Thrombosis - DVT above the calf
B. Calf Thrombosis
Once a DVT limited to the calf veins is identified there are two possible courses of action:
1. Treatment with anticoagulation as for proximal DVT
2. Serial ultrasonography or IPG and treatment for proximal extension of the thrombus.
Note that this is still an area of controversy.
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12. Contraindication to Anticoagulation
A. Absolute contraindications to anticoagulation therapy are active hemorrhage or recent intracranial hemorrhage.
B. Relative contraindications include factors associated with increased bleeding complications.These have been identified in prospective and retrospective studies for unfractionated heparin and warfarin and are listed below.
1. Comorbidities:
a. recent surgery
b. trauma
c. cancer
d. anemia (hematocrit <30)
e. renal disease (serum creatinine >1.6 mg/dl or creatinine clearance less than 30 ml/mn)
f. liver disease (hyperbilirubinemia/macrocytosis)
g. cardiac disease (hypertension, acute myocardial infarction, intra-aortic balloon pump)
2. History of gastrointestinal bleed
3. Age - subsequently shown to be important with warfarin only for patients over 80 years of age
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Other therapies for the management of simple DVT include:
I. Prevention of Pulmonary Embolism (PE)
A. Proximal DVT
1. Treatment is required due to the risk of mortality.
2. Vena caval interruption is the procedure of choice in patients with acute symptomatic DVT in whom anticoagulation is contraindicated, in whom anticoagulation fails, or in whom a bleeding complication requires termination of anticoagulation.
3. The addition of vena caval interruption, in addition to therapeutic anticoagulation, has not been shown to decrease the incidence of pulmonary embolism complicating DVT.
B. Calf thrombosis
1. Observation without anticoagulant can be considered for calf thrombosis.
II. Prevention of Post Phlebitic Syndrome
A.Surgical thromboembolectomy
B. Lytic therapy (unless anticoagulation is contraindicated)
Strength of the evidence for these recommendations:
Vena caval interruption: B.
Surgical thromboembolectomy: C.
Lytic Therapy: C.
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The guideline work group feels that low molecular weight heparin (LMWH) is the preferred treatment for DVT when available.
A. Low Molecular Weight Heparin
Low molecular weight heparins provide reliable anticoagulation levels when given subcutaneously on a weight determined dosing schedule.No laboratory monitoring of the intensity of anticoagulation is required for LMWH.
Currently available formulations include enoxaparin (Lovenox®) and dalteparin (Fragmin®) dosed as follows (may need adjustment for patients with renal failure):
1. enoxaparin 1 mg/kg SQ BID
2. dalteparin 100 units/kg SQ BID
3. dalteparin 200 units/kg SQ qd (effectiveness of once daily dosing is still controversial)
LMWH should be continued for at least 5 days and until warfarin is therapeutic for 2 days.
The decision for hospital or home therapy is not mutually exclusive.Medically a patient could be started on LMWH in the hospital and discharged to continued therapy at home at any time during the course of therapy.
Pharmacodynamic studies have shown persisting anticoagulant activity of LMWH at therapeutic doses for up to 24 hours.LMWH may be relatively contraindicated for patients likely to undergo an invasive procedure or study within 24 hours.Unfractionated heparin can be used in this situation.
B. Unfractionated Heparin (UH)
1. Unfractionated heparin is administered by continuous IV infusion following a bolus dose.
2. Heparin nomograms can more rapidly achieve therapeutic aPTT levels, and their use is recommended.(See Appendix B)
3. Heparin should be continued for at least 5 days after the initiation of warfarin therapy and until international normalized ratio (INR) is above 2.0 for two consecutive days.
4. Monitoring of UH therapy requires the determination of serial aPTTs.These should be conducted by the same laboratory using uniform reagents.
C. Both UH and LMWH are associated with heparin-induced thrombocytopenia (HIT).Monitoring should include a baseline platelet count and periodic platelet counts during heparin therapy.Heparin therapy should be discontinued if the platelet count drops by more than 30% or below 100,000 mm3.
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A. Warfarin therapy should be started at the same time as initiation of heparin unless thrombophilia is suspected, or the patient is pregnant (out of guideline).
1. The patient's medical history, medications and diet should be reviewed to be sure that they do not influence the patient's sensitivity to warfarin.Dosing adjustments should be made if they do.(See Appendix C)
2. The work group strongly recommends the reporting of protime ratio as INR with the use of a sensitive thromboplastin.
3. Heparin should be continued for at least 5 days after the initiation of warfarin therapy and until international normalized ratio (INR) is above 2.0 for two consecutive days.
4. INR should be checked daily until in the therapeutic range for two days, then two or three times weekly for two weeks, then less often depending on the stability of INR results.
B. It is recommended that warfarin therapy be initiated with a dose of 5 mg (less in patients with risks for increased sensitivity to warfarin) with dosage adjustments based on results of INR testing.
1. A high loading dose of warfarin (greater than 10 mg) is of no clinical use and should be discouraged.
2. A "rapid" method for initiating warfarin therapy using 10 mg with subsequent dosing based on daily INR results has been used but has been associated with early over-anticoagulation.
C. A therapeutic range of anticoagulation to keep the INR between 2.0-3.0 is recommended for patients with DVT.
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16. Okay for outpatient treatment?
Outpatient therapy with LMWH requires an organized support system to deal with the following issues:
· LMWH heparin is not currently packaged in a convenient commercial dose form.Therefore, it must be repackaged or multiple injections must be given for each dose.Multi-dose vials and pre-filled syringes are expected in the near future.
· Patients need to be taught how to administer the drug.
· Daily INR's will be needed to guide the institution of warfarin therapy and the dose of warfarin will need to be adjusted to the INR.
· Patients will need resources to answer questions and deal with problems.
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Because of the need for an organized support system and time of day considerations for home care agencies many patients will need hospitalization during the first 24 hours to start therapy promptly.
A. To be treatable at home the patient or a caregiver must be able to administer subcutaneous injections.This can be done by the patient or home caregiver or by returning to the clinic for injections.The patient will need to be geographically accessible to have INR's drawn and receive care for problems which arise.
B. Medical exclusions in studies of the therapeutic use of LMWH have included chronic renal failure, and significant cardiopulmonary instability.The clinician should weigh this evidence when considering outpatient treatment.
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Patient education materials are available.
The patient should be instructed on the use of anticoagulation.
Both handouts and video tapes are available to patients to review low molecular weight heparin and warfarin.Instruction on appropriate techniques for self-injection or injection of the patient by a caregiver should be carried out by hospital, clinic or home health nurses.
The patient should be instructed on the use and follow-up needed for warfarin therapy.This includes instructions on medication interactions with warfarin and communication issues with regard to INR PT testing and symptoms.
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20. Complications During Therapy?
A. Heparin (Unfractionated and Low Molecular Weight Heparin)
1. Bleeding
2.Thrombocytopenia (a drop of 30% or more in platelet count or a count of less than 100,000 mm3 should raise concerns)
3. Osteoporosis
B. Warfarin
1. Bleeding
2. Skin Necrosis
3. Fetal malformation
The development of a complication attributable to anticoagulation requires action by the health care team.Sometimes, as with heparin-induced thrombocytopenia, the drug must be discontinued.The most common complication, bleeding, may require a dosage adjustment, discontinuation of the drug, orfurther evaluation in the setting of gastrointestinal or genitourinary bleeding.Specific actions are best determined in each case by the clinician, who can appropriately weigh the risks and benefits of continued anticoagulation therapy and who can take into account the timing of the complication.
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Recurrent symptomatic DVT or pulmonary embolism during adequate heparin or warfarin treatment represents failure of treatment and needs objective documentation, especially as a new DVT may be difficult to distinguish from postphlebitic syndrome.Alternate treatment such as an inferior vena cava filter is indicated; or if a warfarin failure, subcutaneous heparin may be substituted.
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22. Continued Anticoagulation With Follow-Up and Secondary Prevention
General Follow-up Considerations
A. Duration of anticoagulation varies:
1. Transient risk (e.g., surgery):6 weeks-3 months after risk factor ceases to be present
2. Idiopathic or medical > 6 months
3. Recurrent or continued risk factors:indefinite
B. A coordinated effort for follow-up of patients started on warfarin is required to minimize risks of both hemorrhagic and thrombotic complications while on treatment.In the first several weeks of anticoagulation, INR's need to be checked at least weekly.After stabilization, the interval between INR checks can be increased from weekly to biweekly, up to but not beyond 4 weeks.
C. Long term complications for patients treated for DVT include recurrent venous thromboembolism, postphlebitic syndrome, and bleeding while on anticoagulation therapy.
D. Custom fitted, graded compression stockings help alleviate symptoms of edema and pain in patients who have postphlebitic syndrome.One report showed that graded compression stockings reduced the incidence of postphlebitic syndrome by 50%.
E. Some patients who present with idiopathic DVT may have occult malignancy.However, extensive work-ups in asymptomatic patients beyond appropriate cancer screening have not shown benefit.
F. Thrombophilia
Certain patients should be tested for thrombophilia.This testing should be done 2 weeks after discontinuation of anticoagulation.The work group recommends consideration be given to discussion with a thrombophilia expert.
1. Patients who have recurrent thromboembolic disease.
2. Patients with first idiopathic DVT who:
a. Are young (< 50 years)
b. Have a family history of venous thromboembolism (one or more first degree relatives)
c. Have an unusual site of spontaneous thrombosis
d. Have massive venous thrombosis
G. Activity Level
There is no evidence that restricting activity is of benefit nor is there evidence to determine the activity level.In the absence of literature, the physician needs to be guided by individual patient circumstance including pain and swelling.
Lab Tests for Thrombophilia
Lab tests for thrombophilia should be done at least 2 weeks after discontinuation of anticoagulation.If levels are found to be low during anticoagulation, they should be confirmed off anticoagulation.The following are listed in decreasing order of prevalence among unselected DVT patients.
A. 21% Factor V Leiden (resistance to activated protein C)
B. 14% Lupus anticoagulant (in non-SLE patients)
C. 10% Hyperhomocysteinemia (diagnostic studies may be unreliable)
D. 2.8% Antithrombin III deficiency
E. 2.5% Protein C deficiency
F. 1.3% Protein S deficiency
Strength of the evidence for these recommendations:
A. Duration of anticoagulation:A.
B. Coordinated effort for follow-up:B.
C. Long-term complications:B.
D. Graduated compression stockings:B.
E. Occult malignancy:B.
F. Thrombophilia:B.
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Appendix A
A Clinical Model of the Pretest Probability of Deep-Vein Thrombosis*
Major points
Active cancer (ongoing treatment, treatment within previous 6 months, or palliative therapy)
Paralysis, paresis, or recent plaster immobilization of the leg or foot
Recent bed rest for > 3 days, major surgery within 4 weeks, or both
Localized tenderness along the distribution of the deep venous system
Swelling of the thigh and calf (should be measured)
Swelling of the calf to 3 cm greater than on symptomless side (measured 10 cm below tibial tuberosity)
Strong family history of deep vein thrombosis ( > 2 first-degree relatives with a history of deep vein thrombosis)
Minor points
History of recent trauma (within 60 days) to the symptomatic leg
Pitting edema (symptomatic leg only)
Dilated superficial veins (non-varicose) in symptomatic leg only
Hospitalization within previous 6 months
Erythema
Clinical probability of deep vein thrombosis
High probability
> 3 major points and no alternative diagnosis
> 2 major points, > 2 minor points, and no alternative diagnosis
Low probability
1 major point, > 2 minor points, and no alternative diagnosis
1 major point, > 1 minor point, and no alternative diagnosis
0 major points, > 3 minor points, and no alternative diagnosis
0 major points, > 2 minor points, and no alternative diagnosis
Intermediate probability
All other combinations
* Table adapted from Wells PS, et al."Accuracy of Clinical Assessment of Deep-Vein Thrombosis."Lancet 345:1326-30, May 1995.(Evidence grade B)
Appendix B
Heparin Nomogram
Several protocols for managing heparin therapy have been shown to more rapidly achieve therapeutic anticoagulation (as measured by aPTT levels) versus historical controls.This work group favors the protocol developed by Raschke et al, summarized as follows:
Loading dose:80 units/kg
Initial maintenance dose:18 units/kg/hour
Dosage adjustments:
aPTT levelDosage adjustment
< 35 seconds 80 units/kg bolus, then increase infusion rate by 4 units/kg/hour
35-45 seconds 40 units/kg bolus, then increase infusion rate by 2 units/kg/hour
46-75 seconds no change
71-90 seconds decrease infusion rate by 2 units/kg/hour
> 90 seconds hold infusion 1 hour, then decrease infusion rate by 3 units/kg/hour
aPTT levels are drawn 6 hours after any dosage change.aPTT levels should be ordered every 24 hours until 2 consecutive aPTTs are therapeutic.
Raschke RA, Reilly BM, Guidry JR, et al."The Weight-based Heparin Dosing Nomogram Compared with a 'Standard Care' Nomogram."Ann Intern Med 119:874-81, Nov 1 1993.(Evidence grade A)
Appendix C
Grade A: Conclusion based on a randomized, controlled trial that has been published in a peer-reviewed journal.
Grade B: Conclusion based on one of the following study types published in a peer-reviewed journal (but not on a randomized, controlled trial):
Grade C: Conclusion based on one of the following (but not on any studies of the types mentioned above):
Guidelines obtained from the Agency for Health Care Policy and Research
(AHCPR) or other sources, position statements, panel consensus statements
from the National Institutes of Health (NIH) or elsewhere, review articles,
and textbook chapters that cite primary evidence are not assigned a grade
because they are not primary evidence.The individual studies cited in such
secondary sources can be graded according to the categories presented above.
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