Practice Guidelines

AAFP and ACP Publish Recommendations on Diagnosis and Management of VTE

SHERRI DAMLO

There are 600,000 cases of venous thromboembolism (VTE) in the United States every year. Of all persons with undetected or untreated pulmonary embolism, 26 percent will have a fatal embolic event, and another 26 percent will have a recurrent embolic event that could become fatal. Therefore, an early diagnosis of VTE is important to prevent mortality and morbidity in this population.

Diagnosis

clinical prediction rules

The current evidence supports using a clinical prediction rule to establish the pretest probability of VTE. Physicians should use the Wells prediction rule to estimate the probability of deep venous thrombosis (DVT; Table 1) and pulmonary embolism (Table 2) before performing and interpreting other diagnostic testing. However, the Wells prediction rule performs best in younger patients without comorbidities or a history of VTE.

Table 1. Wells Prediction Rule for Diagnosing DVT*
Clinical characteristic	Score
Alternative diagnosis at least as likely as DVT Active cancer (treatment ongoing, within previous six months, or palliative)	-2 1
Calf swelling 3 cm larger than asymptomatic side (measured 10 cm below tibial tuberosity)	1
Collateral superficial veins (nonvaricose)	1
Paralysis, paresis, or recent plaster immobilization of the lower extremities	1
Pitting edema confined to the symptomatic leg	1
Recently bedridden for more than three days or major surgery within 12 weeks that required general or regional anesthesia	1
Swollen leg	1
DVT = deep venous thrombosis. note: Clinical probability of DVT is low if score is 0 or less; intermediate if 1 or 2; and high if 3 or more. *-In patients with symptoms in both legs, the more symptomatic leg is used. Adapted with permission from Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 2002;350:1796.

Table 2. Wells Prediction Rule for Diagnosing Pulmonary Embolism
Clinical characteristic	Score
Cancer	1
Hemoptysis	1
Heart rate more than 100 bpm	1.5
Previous pulmonary embolism or DVT	1.5
Recent surgery or immobilization	1.5
Alternative diagnosis less likely than pulmonary embolism	3
Clinical signs of DVT	3
bpm = beats per minute; DVT = deep venous thrombosis. note: Clinical probability of pulmonary embolism is low if score is 0 to 1; intermediate if 2 to 6; and high if 7 or more. Adapted with permission from Chagnon I, Bounameaux H, Aujesky D, Roy PM, Gourdier AL, Cornuz J, et al. Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism. Am J Med 2002;113:270.

Patients with low pretest probability of the disease and a negative D-dimer assay have a very low likelihood of VTE that reduces the need for further imaging.

d-dimer assay

Enzyme-linked immunosorbent assay (ELISA), quantitative rapid ELISA, and advanced turbidimetric D-dimer determinations are highly sensitive tests helpful in the diagnosis of VTE. A negative highly sensitive D-dimer test largely excludes the diagnosis of proximal DVT and pulmonary embolism in younger patients whose symptoms are of short duration and whose pretest probability of VTE is low, based on the Wells prediction rule. In older patients, those with associated comorbidities, and those with a long duration of symptoms, a D-dimer assay alone may not be sufficient to rule out VTE, even in an otherwise low-risk patient.

The sensitivity of D-dimer assays varies, so physicians should be informed of the type of d-dimer assay being used.

ultrasonography

For patients who are symptomatic, there is strong evidence that ultrasonography has a high specificity and sensitivity for diagnosing proximal DVT of the lower extremities. Sensitivity, however, is decreased in patients who have DVT in the calf or who are asymptomatic, so negative ultrasonography cannot rule out DVT in these patients. Therefore, ultrasonography is recommended for patients who are at intermediate or high risk of DVT according to the Wells prediction rule.

Ultrasonography or venography should be repeated in patients with suspected calf-vein DVT whose ultrasonography results are negative, as well as in patients with suspected proximal DVT but whose ultrasonography results are inadequate or equivocal. Therefore, contrast venography should still be considered the definitive test to rule out DVT.

helical computed tomography

Recent evidence suggests that helical computed tomography (CT) may have higher specificity and sensitivity compared with conventional pulmonary0 arteriography for the diagnosis of pulmonary embolism, and it is likely that technology will improve the accuracy of CT in the future. However, in patients who have a high pretest probability of pulmonary embolism and a negative CT scan, further imaging studies (e.g., ventilation-perfusion scan, multidetector helical computed axial tomography) are needed. For those patients, evidence suggests that CT alone may not be sensitive enough to exclude pulmonary embolism. Therefore, a single or sequential ultrasonography assessment of the lower extremities or pulmonary angiography may be warranted.

Management of VTE

inpatient treatment

Low-molecular-weight heparin (LMWH) is superior to unfractionated heparin for the initial treatment of DVT because it reduces mortality rates and the risk of major bleeding during initial therapy. Therefore, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommend that LMWH be used for the initial inpatient treatment of DVT. Unfractionated heparin or LMWH is appropriate for the initial treatment of patients with pulmonary embolism.

outpatient treatment

In stable patients for whom the required support services are in place, outpatient treatment of VTE with LMWH is as safe as inpatient treatment and is cost-effective.

prevention of post-thrombotic syndrome

There is a marked reduction in the severity and incidence of post-thrombotic syndrome among patients who wear over-the-counter or custom-fit compression stockings if their use is initiated within one month of the diagnosis of proximal DVT. Therefore, compression stockings should be routinely used within one month of proximal DVT diagnosis; use should be continued for at least one year to prevent post-thrombotic syndrome in these patients.

treatment during pregnancy

Pregnant women have a fivefold increased risk of VTE compared with women who are not pregnant. Vitamin K antagonists should be avoided in pregnant women because they can cross the placenta, and they are associated with embryopathy between six and 12 weeks' gestation and fetal bleeding at delivery. Although there is no association between embryopathy or fetal bleeding and the use of LMWH or unfractionated heparin, there is not enough evidence to make recommendations for anticoagulation treatment in pregnant patients with VTE.

anticoagulation therapy

The ACP and AAFP recommend that anticoagulation therapy be maintained for three to six months in patients with VTE secondary to transient risk factors. For patients with recurrent VTE, anticoagulation therapy should be continued for more than 12 months. The exact duration of anticoagulation therapy is not fully understood in patients with idiopathic or recurrent VTE, but extended-duration therapy can provide substantial benefit to these patients. Physicians should weigh the harms, benefits, and patient preferences when deciding the duration of anticoagulation therapy.

long-term management of vte

LMWH is comparable with oral anticoagulation therapy in select patients with VTE, and it may be useful in treating patients whose International Normalized Ratio is difficult to control. Therefore, the ACP and the AAFP recommend the use of LMWH as a safe and effective therapy for the long-term treatment of VTE. In addition, LMWH may be more effective than oral anticoagulation therapy in patients with cancer.

Practice Guideline Briefs

ACOG Publishes Guidelines on Hemoglobinopathies in Pregnancy

The American College of Obstetricians and Gynecologists (ACOG) estimates that more than 270 million persons worldwide are heterozygous carriers of hereditary disorders of hemoglobin (Hb), and at least 300,000 affected homozygotes or compound heterozygotes are born every year. To address this, ACOG has released recommendations for screening and clinical management of hemoglobinopathies during pregnancy.

Genetic screening can help physicians identify couples at risk of having children with hemoglobinopathies and counsel them about reproduction and prenatal diagnosis. DNA analysis of cultured amniocytes or chorionic villi is preferred for prenatal diagnosis of hemoglobinopathies. Persons of northern European, Japanese, Native American, Inuit, or Korean descent are considered to be at low risk of hemoglobinopathies. Those of southeast Asian, African, or Mediterranean descent are at higher risk of being carriers of hemoglobinopathies, and ACOG recommends that physicians offer these patients carrier screening. However, ethnicity is not always a good predictor of risk because patients from high-risk groups may marry outside of their ethnic group.

A complete blood count should be obtained to ensure that Hb is accurately identified for patients of non-African descent. For patients of African descent, ACOG recommends performing Hb electrophoresis in addition to obtaining a complete blood count (Figure 1). Solubility testing for Hb S (Sickledex), high-performance liquid chromatography, and isoelectric focusing have been used for primary screening; however, solubility tests alone often fail to identify transmissible Hb gene abnormalities that could affect fetal outcomes. Additionally, many persons with these genotypes (e.g., Hb C, beta thalassemia, Hb E, Hb B, Hb D) are asymptomatic. If their partners have the sickle cell trait or another hemoglobinopathy, they could have offspring with more serious hemoglobinopathies. Therefore, solubility testing could be valuable for rapid screening for sickling when the information is crucial to immediate patient care.

Women with sickle cell disease who are pregnant are at increased risk of morbidity and mortality because of the combination of underlying hemolytic anemia and multiorgan dysfunction associated with this disorder. These patients need increased prenatal folic acid supplementation. However, the standard of 1 mg of folate in prenatal vitamins is not adequate for patients with hemoglobinopathies; instead, 4 mg per day of folic acid is recommended.

Women with sickle cell disease who are pregnant also are at increased risk of spontaneous abortion, stillbirth, and preterm labor. Therefore, ACOG recommends that serial ultrasonography and antepartum fetal testing be performed. Most of these patients require narcotics for pain control, so physicians should interpret the results of abnormal antepartum testing with caution. Cesarean delivery is not recommended in women with sickle cell disease, and it should be performed only for obstetric indications. Epidural analgesia is usually well tolerated as long as hypotension and hypoxemia are avoided. Ideally, however, pregnant women with sickle cell disease should receive care at institutions that can manage complications of the disease and high-risk pregnancies.

SHERRI DAMLO

AAP Releases Guidelines on Treatment of Anaphylaxis

Epinephrine is an effective treatment option for anaphylaxis if it is injected into the lateral leg immediately. Delayed injection is associated with poor outcomes and may cause death. Persons who require additional care after the administration of epinephrine should seek immediate medical attention.

The American Academy of Pediatrics (AAP) recommends a lateral thigh epinephrine injection of 0.01 mg per kg, but no more than 0.30 mg, for children with anaphylaxis.[corrected] Administering the epinephrine intravenously increases the risk of dosing and dilution errors, and it also can increase the patient's risk of cardiac dysrhythmia.

Compared with other methods (e.g., syringe/needle/ampule), autoinjectors of epinephrine are preferred because they are easier to use. However, autoinjectors are available in only two doses (0.15 mg and 0.30 mg). Despite this potential problem, the AAP recommends that physicians prescribe an adequate autoinjector dose for children at risk of anaphylaxis. On the basis of limited data, children who are healthy and weigh 22 to 55 lb (10 to 25 kg) can be given 0.15 mg of epinephrine, and those who weigh 55 lb or more can receive 0.30 mg of epinephrine. For healthy children who weigh less than 22 lb, physicians should consider the health needs of the child and the risks of delaying the dose when a syringe/ampule/needle is used instead of an autoinjector.

The AAP recommends that children who have had a previous episode of anaphylaxis be given epinephrine because anaphylaxis is likely to occur again. In some instances, self-injection of epinephrine should be prescribed for patients who are at an increased risk of anaphylaxis (e.g., patients with asthma) but who have not yet had an episode.

Physicians should always prescribe epinephrine if there is an emergency involving an individual at risk of anaphylaxis. A comprehensive management approach should be used for children at risk of anaphylaxis, and patients and their families should be shown how to use epinephrine autoinjectors. Physicians also should explain the warning signs and symptoms of anaphylaxis and instruct patients to call for emergency help if anaphylaxis occurs.

It is also important to instruct patients and their families to avoid allergens. If possible, a subspecialist should evaluate children at increased risk to confirm allergic triggers, educate the patient on how to avoid them, and provide specific preventive treatment.

To provide a safe and secure environment for children at risk of anaphylaxis, the AAP recommends that patients and their families construct emergency action plans and give them to other persons responsible for the child's care at home as well as outside of the home.

SHERRI DAMLO

Answers to This Issue's Clinical Quiz Q1. C Q2. D Q3. B Q4. A Q5. A Q6. D Q7. A, D Q8. A, B, C, D Q9. A, B, C Q10. A, B, C, D Q11. A, C, D

This is a corrected version of the article that appeared in print.

Copyright © 2007 by the American Academy of Family Physicians. This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.