Correspondence
Clinical Problem-Solving: Decision Making by Analogy
N Engl J Med 1995; 333:127-129July 13, 1995
- Article
To the Editor:
The patient with possible systemic lupus erythematosus described in the March 2 Clinical Problem-Solving article1 most likely had primary or secondary antiphospholipid-antibody syndrome.2,3 She had documented thrombi in both legs, along with an unexplained elevation in partial-thromboplastin time and a positive test for lupus anticoagulant. These serologic abnormalities, and occasionally a decrease in platelet count, are characteristic of antiphospholipid-antibody syndrome. A test for anticardiolipin antibodies was apparently not done.
The antiphospholipid-antibody syndrome occurs in up to one third of patients with systemic lupus.3 The presence of anticardiolipin antibodies would be consistent with this patient's clinical picture and, given her history of a serious clotting event, would mandate consideration of the need for long-term, and possibly lifelong, anticoagulation.3,4
4 ReferencesCatherine Meyer, M.D.
Mercy Hospital and Medical Center, Chicago, IL 606161
Greenberg DL ,Root RK . Decision making by analogy. N Engl J Med 1995;332:592-596
Full Text | Web of Science | Medline2
Love PE ,Santoro SA . Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders: prevalence and clinical significance. Ann Intern Med 1990;112:682-698
Web of Science | Medline3
Hughes GR . The antiphospholipid syndrome: ten years on. Lancet 1993;342:341-344
CrossRef | Web of Science | Medline4
Vianna JL ,Khamashta MA ,Ordi-Ros J , et al. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients. Am J Med 1994;96:3-9
CrossRef | Web of Science | Medline
To the Editor:
In the Clinical Problem-Solving article of March 2, in which systemic lupus erythematosus was the ultimate diagnosis, the clinician and the authors did not discuss an important clue. The patient had an initial bilirubin level of 3 mg per deciliter. Although we are told neither how much of the bilirubin was indirect nor the reticulocyte count, haptoglobin value, or lactate dehydrogenase level, it is reasonable, under the circumstances, to consider a diagnosis of hemolysis in the presence of an already low hematocrit, which ultimately dropped even further.
If the patient did indeed have hemolytic anemia, this finding could have oriented the clinician in an entirely different direction.
Peter H. Berczeller, M.D.
Le Mas de la Faye, 24600 St. Pardoux de Drone, FranceTo the Editor:
Lupus erythematosus should be considered early on in the case of any patient who has epilepsy in childhood and then a systemic process.
Carl F. Needles, M.D.
1955 Merrick Rd., Merrick, NY 11566To the Editor:
I believe the discussant and the managing team were misled by the results of the Doppler study, which were described as revealing bilateral mural thrombi. Only occlusive thrombi can be diagnosed with confidence by this technique. Given the equivocal results of the ventilation-perfusion scan, a d-dimer assay might have been helpful. This test is highly sensitive to the presence of thrombi1,2; a negative result would have provided reassurance that symptoms were not due to thromboemboli. Were the test positive, the managing team could have performed venography to confirm the venous thrombosis of the legs and provide justification for anticoagulant therapy.
The discussant states that since the patient's clots ``were in the distal superficial femoral system, I would be inclined to withhold anticoagulation and repeat the Doppler studies in two or three days, looking for extension of the clots.'' Clots in this location are considered proximal thrombi with the capability of embolizing to the lungs. Were clots indeed present, immediate anticoagulation would be indicated.
2 ReferencesDavid Green, M.D., Ph.D.
Northwestern University Medical School, Chicago, IL 60611-44961
Bounameaux H ,de Moerloose P ,Perrier A ,Reber G . Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994;71:1-6
Web of Science | Medline2
Ginsberg JS ,Wells PS ,Brill-Edwards P , et al. Application of a novel and rapid whole blood assay for D-dimer in patients with clinically suspected pulmonary embolism. Thromb Haemost 1995;73:35-38
Web of Science | Medline
To the Editor:
The comments about the young woman with suspected pulmonary embolism raise certain issues. We think that the course of treatment suggested by the discussant -- ``I would be inclined to withhold anticoagulation and repeat the Doppler studies in two or three days, looking for extension of the clots. I would treat only if there was evidence of extension into the proximal venous system'' -- is not correct and may cause confusion about the care of patients with proved proximal deep venous thrombosis. Deep venous thrombosis involving vein segments proximal to the popliteal bifurcation carry a high risk of pulmonary embolism and should be treated with full anticoagulation with heparin to prevent growth of the thrombus and pulmonary embolism.1 In the presence of contraindications to the anticoagulant treatment, the insertion of a vena caval filter should be considered, as was correctly pointed out in the Commentary. The proposed strategy of watchful waiting should be used only in patients with infrapopliteal (calf) venous thrombosis, which involves proximal extension in only 20 to 30 percent of cases.2 Even in the latter situation, however, the need for therapeutic anticoagulation is a matter of debate.3
3 ReferencesPasquale Parise, M.D.
Mauro Berrettini, M.D.
University of Perugia, 06126 Perugia, Italy1
Hirsh J, Salzman EW, Marder VJ. Treatment of venous thromboembolism. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and thrombosis: basic principles and clinical practice. 3rd ed. Philadelphia: J.B. Lippincott, 1994:1346-66.
2
Huisman MV ,Buller HR ,ten Cate JW ,Vreeken J . Serial impedance plethysmography for suspected deep venous thrombosis in outpatients: the Amsterdam General Practitioner Study. N Engl J Med 1986;314:823-828
Full Text | Web of Science | Medline3
Lagerstedt CI ,Olsson CG ,Fagher BO ,Oqvist BW ,Albrechtsson U . Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet 1985;2:515-518
CrossRef | Web of Science | Medline
To the Editor:
The Clinical Problem-Solving article was, as always, very enlightening, but I believe that Greenberg and Root could have taken their reasoning a bit further and made the risks of anticoagulation more explicit.
According to data cited by Greenberg and Root, the risk of death from a pulmonary embolus in a patient such as theirs could be calculated as follows: 0.90 × 0.50 × 0.30 = 0.14. The risk of death from pulmonary embolus after anticoagulation could be calculated in a similar fashion: 0.90 × 0.50 × 0.08 = 0.04. This means that 10 patients like the one described must receive anticoagulation to prevent one death.1 Using the data published by Malouf et al.,2 one can assume that 55 percent of patients would receive excessive anticoagulation and would have a 27 percent risk of cardiac tamponade and that 45 percent would not receive excessive anticoagulation and would thus have a 3 percent risk of cardiac tamponade. This means that cardiac tamponade could be expected to develop in 1.6 patients (10 × 0.55 × 0.27+10 × 0.45 × 0.03 = 1.6). Thus, the trade-off in preventing one death from a pulmonary embolus in patients like the one described is the development of cardiac tamponade in one or two patients. None of the patients in the series of Malouf et al. died of cardiac tamponade, and as Greenberg and Root state, cardiac tamponade is a potentially treatable condition, so this may be a reasonable trade-off.
Reasoning by analogy is a perilous undertaking,3 and it may be that I have taken it too far, but I feel that quantifying the risks and benefits whenever possible can facilitate decision making.
3 ReferencesRobert E. Kettler, M.D.
Medical College of Wisconsin, Milwaukee, WI 532261
Laupacis A ,Sackett DL ,Roberts RS . An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988;318:1728-1733
Full Text | Web of Science | Medline2
Malouf JF ,Alam S ,Gharzeddine W ,Stefadouros MA . The role of anticoagulation in the development of pericardial effusion and late tamponade after cardiac surgery. Eur Heart J 1993;14:1451-1457
CrossRef | Web of Science | Medline3
How to read clinical journalsIV. To determine etiology or causation. Can Med Assoc J 1981;124:985-990
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: The letter writers' comments clarify some potentially confusing issues and elucidate additional points regarding our patient that we did not address. Dr. Meyer raises the question whether our patient had the antiphospholipid-antibody syndrome. Although the patient had a positive test for lupus anticoagulant, her initial partial-thromboplastin time (35 seconds), platelet count (228,000 per cubic millimeter), rapid-plasma-reagin results, and anticardiolipin-antibody results were all normal. Nonetheless, the point is well taken, and the patient may well have a form of the syndrome that could have implications for long-term care.1 With respect to Dr. Berczeller's comments, hemolysis was considered as a possible cause of the patient's anemia and the appropriate studies were ordered. Shift cells were present on the initial peripheral smear, but no other red-cell abnormalities were found. Additional studies revealed the following laboratory values: corrected reticulocyte index, 0.5 percent; normal haptoglobin levels; and lactate dehydrogenase, 362 U per liter with mild elevations of LD2 through LD5.
Dr. Green and Drs. Parise and Berrettini raise two important issues not clearly covered in our case description. The diagnosis of bilateral superficial femoral-vein thrombosis was based on a venous duplex imaging examination of the legs including B-mode ultrasonography. This technique is highly sensitive and specific for proximal-vein thrombosis as compared with the gold standard, contrast venography.2 The d-dimer measurement, although also highly sensitive in patients with suspected deep venous thrombosis,3 would not have added to the diagnostic certainty in this case. The discussant either misheard or misinterpreted the duplex imaging results. His recommendation of watchful waiting was based on the diagnosis for distal- rather than proximal-vein thrombosis.
We thank Dr. Kettler for calculating and directly comparing the risks and benefits of therapeutic intervention with heparin in this patient. The therapeutic threshold, or point at which the risk is worth taking, is still a matter of clinical judgment. But the direct comparison of one death from pulmonary embolism with one to two episodes of tamponade clarifies the trade-offs and emphasizes the critical importance of avoiding excessive anticoagulation once the decision to treat is made.
3 ReferencesDeborah L. Greenberg, M.D.
Richard K. Root, M.D.
University of Washington School of Medicine, Seattle, WA 981051
Ghirardello A ,Doria A ,Ruffatti A , et al. Antiphospholipid antibodies (aPL) in systemic lupus erythematosus: are they specific tools for the diagnosis of aPL syndrome? Ann Rheum Dis 1994;52:140-142
CrossRef | Web of Science2
Lensing AWA ,Prandoni P ,Brandjes D , et al. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989;320:342-345
Full Text | Web of Science | Medline3
Bounameaux H ,de Moerloose P ,Perrier A ,Reber G . Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994;71:1-6
Web of Science | Medline
