Correspondence
Acute Pulmonary Embolism
N Engl J Med 2008; 358:2744-2746June 19, 2008
- Article
To the Editor:
We were surprised that the nephrotic syndrome was omitted from the list of underlying prothrombotic conditions in the review of acute pulmonary embolism by Tapson (March 6 issue).1 The nephrotic syndrome is relatively common in comparison with some of the prothrombotic conditions listed by the author.2 Thrombotic events, including pulmonary embolism, may be the first presentation of the nephrotic syndrome. In our experience, diagnosis of the nephrotic syndrome is often delayed despite the presence of peripheral edema and abundant proteinuria and hypoalbuminemia at the time of hospital admission. This delay may result in further thrombotic events or a deterioration in kidney function, both of which could have been avoided.3 Timely diagnosis of the nephrotic syndrome can help in the identification of underlying glomerular disease and, where appropriate, the initiation of immunotherapy to induce remission of the nephrotic syndrome and the accompanying prothrombotic state.
3 ReferencesEmily P. Fraser, M.B., Ch.B.
Colin C. Geddes, M.B., Ch.B.
Western Infirmary, Glasgow G11 6NT, United Kingdom
emilypf@hotmail.com 1
Tapson VF . Acute pulmonary embolism. N Engl J Med 2008;358:1037-1052
Full Text | Web of Science | Medline2
Ritz E . The nephrotic syndrome. N Engl J Med 1998;338:1202-1211
Full Text | Web of Science | Medline3
Nandish SS ,Khardori R ,Elamin EM . Transient ischemic attack and nephrotic syndrome: case report and review of literature. Am J Med Sci 2006;332:32-35
CrossRef | Web of Science | Medline
To the Editor:
Tapson does not mention concern about deep venous thromboembolism during pregnancy and does not discuss certain specifics concerning this disorder in women who become pregnant with the use of assisted reproductive techniques. Although Tapson cites causes of false positive D-dimer tests, the presence of D-dimer during pregnancy indicates coagulation activation that is actually present throughout normal pregnancy.1 Therefore, during pregnancy and in the postpartum period, D-dimer testing may be unhelpful and should not be used as a preliminary laboratory measure for the presence of deep venous thromboembolism.
Women who become pregnant with the use of assisted reproductive techniques have an increased thrombophilic risk, especially if the ovarian hyperstimulation syndrome occurs. Deep venous thromboembolism involving upper-arm veins is a well-recognized complication.2 In such women, monitoring the level of activity against activated factor X is warranted during the second and third trimesters.
Finally, Tapson cautions against the use of warfarin for long-term anticoagulation during pregnancy, since it is a teratogen. Spanish doctors almost never use warfarin. There is occasional use of acenocumarol, except during weeks 6 to 12 of gestation, when it should not be used.3,4
4 ReferencesJaume Alijotas-Reig, M.D., Ph.D.
Vall d'Hebron University Hospital, 08035 Barcelona, Spain
jalijotas@vhebron.net 1
Hoke M ,Kyrle PA ,Philipp K , et al. Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin. Thromb Haemost 2004;91:935-940
Web of Science | Medline2
Chan WS ,Ginsberg JS . A review of upper extremity deep vein thrombosis in pregnancy: unmasking the `ART' behind the clot. J Thromb Haemost 2006;4:1673-1677
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Santamaria A ,Fontcuberta J . Anticoagulación y embarazo. Med Clin (Barc) 2008;130:57-59
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Jilma B ,Kamath S ,Lip GYH . Antithrombotic therapy in special circumstances. I. Pregnancy and cancer. BMJ 2003;326:37-40
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To the Editor:
Would Tapson comment on the use of low-dose warfarin during and after elective joint replacement, a common preventive practice used by orthopedists? I have yet to find any evidence-based guidelines to support this prophylactic regimen. My concern is that the perioperative use of warfarin in the absence of heparin or enoxaparin for use in the prevention of deep venous thrombosis and pulmonary embolism may result in a hypercoagulable state through the initial reduction of proteins C and S and result in a higher incidence of venous thromboembolism.
Thomas F. Castiglione, M.D.
South Shore Medical Center, Kingston, MA 02364
thomas_castiglione@ssmedcenter.com To the Editor:
Tapson does not mention the role of subcutaneous heparin in the treatment of pulmonary embolism. Heparin that is given subcutaneously in a fixed dose adjusted according to weight appears to be as effective and safe as low-molecular-weight heparin for the treatment of venous thromboembolism, and monitoring of the activated partial thromboplastin time may not be an important therapeutic goal.1
The author encourages prophylaxis for venous thromboembolism, but data supporting this practice for pulmonary embolism in medical patients are controversial at best. Although a recent meta-analysis of studies of prophylaxis for venous thromboembolism showed decreases in both the frequency of pulmonary embolism and associated mortality, 400 patients would need to be treated to prevent one death.2 Which medical patient should receive prophylaxis for venous thromboembolism: an asymptomatic and ambulatory young man who is hospitalized to undergo chemotherapy for testicular cancer or a malnourished and bedridden patient with metastatic pancreatic cancer? The challenge is to identify patients who are at high risk rather than provide general recommendations.
2 ReferencesHarris V. Naina, M.B., B.S.
Fernando J. Quevedo, M.D.
Mayo Clinic College of Medicine, Rochester, MN 55905
naina.harris@mayo. edu 1
Kearon C ,Ginsberg JS ,Julian JA , et al. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 2006;296:935-942
CrossRef | Web of Science | Medline2
Dentali F ,Douketis JD ,Gianni M ,Lim W ,Crowther MA . Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007;146:278-288
Web of Science | Medline
Author/Editor Response
As Fraser and Geddes suggest, the nephrotic syndrome is prothrombotic. It increases the risk of venous thromboembolism through loss of anticoagulant proteins, increased synthesis of thrombogenic factors, or local activation of the hemostasis system within the glomerulus. Although the nephrotic syndrome is an uncommon cause of thrombosis,1 the frequency of the association is sufficient for venous thromboembolism to be considered in patients with this condition, and vice versa.
Alijotas-Reig emphasizes several issues involving pregnancy. During pregnancy and the postpartum period, there is ongoing coagulation activation, so a positive D-dimer test result may be expected. As is the case in trauma, surgery, and cancer, this result often does not represent pathologic thromboembolism (i.e., it is a false positive result). It has been estimated that venous thrombosis in the upper arm occurs in about 1 in 1000 women who have become pregnant with the use of assisted reproductive techniques, and this event is not always preceded by the ovarian hyperstimulation syndrome.2 Although its occurrence is uncommon, recognition of the association is important. I agree that warfarin should be avoided during pregnancy. Low-molecular-weight heparin preparations do not cross the placenta, but levels of antifactor Xa should be monitored when such agents are used during pregnancy. Recommendations that focus on anticoagulation in pregnancy are offered by the American College of Chest Physicians.3
Castiglione notes the potential for detrimental prothrombotic effects with the use of low-dose warfarin in elective joint replacement. Hypercoagulability may result because the anticoagulant protein C has a half-life similar to that of factor VII (6 to 8 hours). Without the use of concomitant heparin or low-molecular-weight heparin, warfarin may decrease protein C levels before factors II and X reach desired levels, resulting in a transient prothrombotic state.4 This is of most concern in patients with established thrombosis and those at high risk. Evidence-based recommendations strongly support the use of low-molecular-weight heparin in joint replacement (grade 1A).5 The use of warfarin to achieve a target international normalized ratio of 2.0 to 3.0 is also recommended (grade 1A), rather than the use of “low-dose warfarin.” Adherence to current recommendations would appear to be prudent. Newer oral anticoagulants that include antithrombin and anti–factor Xa inhibitors may soon replace this drug.
Naina and Quevedo remind us that subcutaneous standard heparin can be used to treat acute venous thromboembolism. They cite a randomized trial with compelling data, although that trial took a number of years to recruit patients. Substantially more data (and specific advantages) support the use of low-molecular-weight heparin, as compared with standard heparin by the subcutaneous route. The criteria for prophylaxis in the medically ill are clearly outlined in reports of clinical trials.5 One must consider risk factors and then individualize treatment for affected patients, realizing that venous thromboembolism may have devastating consequences and that prophylaxis is generally safe.5
5 ReferencesVictor F. Tapson, M.D.
Duke University Medical Center, Durham, NC 27710
tapso001@mc.duke. edu 1
Samama MM . An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000;160:3415-3420
CrossRef | Web of Science | Medline2
Bates SM ,Greer IA ,Hirsh J ,Ginsberg JS . Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:3 Suppl:627S-644S
CrossRef | Web of Science | Medline3
Vigano S ,Mannucci PM ,Solinas S ,Bottasso B ,Mariani G . Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 1984;57:213-220
CrossRef | Web of Science | Medline4
Geerts WH ,Pineo GF ,Heit JA , et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:3 Suppl:338S-400S
CrossRef | Web of Science | Medline5
Francis CW . Prophylaxis for thromboembolism in hospitalized medical patients. N Engl J Med 2007;356:1438-1444[Erratum, N Engl J Med 2007;357:203.]
Full Text | Web of Science | Medline
- Citing Articles (2)
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1
Naing Htike, Keith Superdock, Sampath Thiruveedi, William Surkis, Geoffrey Teehan. (2011) Evaluating Proteinuria and Nephrotic Syndrome in Patients With Venous Thromboembolism. The American Journal of the Medical Sciences1
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Jacyntha A. Sterling. (2008) Hospital Pharmacy Pulse - Recent Publications on Medications and Pharmacy. Hospital Pharmacy 43:8, 676-683
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