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Multiple arterial occlusions in a young woman
CLINICOPATHOLOGIC
CONFERENCE
Multiple Arterial Occlusions in a Young Woman
Stenographic reports, edited by Philip E. Cryer, M.D. and John Kissane, M.D., of weekly clinkopathoiogic conferences held in Barnes and Wohl Hospitals, are published in each issue of the Journal. These conferences are participated in jointly by members of the Departments of Internal Medicine and Pathology of the Washington University School of Medicine. A 25 year old woman was transferred to Barnes Hospital on January 25, 1975. She had been in apparent good health until early December 1974 when she first noted episodic shortness of breath and pleuritic chest pain. The former recurred and progressed despite therapy with ephedrine. In early January she also noted numbness of her left leg and then her right leg. She was hospitalized elsewhere from January 9 through January 16, 1975. No diagnosis was established. Three days after discharge, pain in the right lower abdomen and a nonproductive cough developed and she was again hospitalized on January 20, 1975. Additional history included the fact that the patient had taken oral contraceptive tablets for several years: these were discontinued in mid-December of 1974. The patient was obese and had lost 60 pounds on a diet. She worked as a telephone operator. Physical findings on admission included a blood pressure of 1 lo/70 mm Hg, a pulse rate of 124/min and a temperature of 100.4’F. Lower abdominal tenderness was noted. Thewhite blood cell count was 14,900/mm3. A urinalysis was normal aside from 3 to 5 white blood ceils/high power field. An electrocardiogram was normal as were films of the chest and abdomen. On January 2 1, a cardiologic consultant described mild peripheral cyanosis, a blood pressure of 96160 mm Hg in the upper right arm and absent left radial, brachial and carotid pulses. He also noted a left parasternal heave and a prominent fourth heart sound. Two days later the patient complained of pain in both legs and feet, and prominent cyanosis of the toes was noted. The femoral, dorsal pedal and posterior tibia1 pulses were no longer palpable. A lung scan was technically unsatisfactory. On January 24, a right brachial arteriogram demonstrated partial obstruction of the left subclavian and carotid arteries, and of the abdominal aorta just below
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TABLE I*
II
III
IV.
Thrombotic Causes of Acute Arterial Occlusion
Degenerative 1. Atherosclerosis 2. Cystic medial necrosis 3. Fibromuscular dysplasia 4. Aneurysm Vasculitis 1. Polyarteritis 2. Systemic lupus erythematous 3. Arteritis Traumatic 1. Thoracic outlet compression syndrome 2. After diagnostic procedures such as arteriography 3. After intra-arterial injections Hematologic disorders 1. Myeloproliferative disease 2. Thrombotic thrombocytopenia purpura 3. Dysproteinemias 4. Disseminated intravascular coagulation
*Modified from Fairbairn JF, Juergens JL, Spittell JA: Peripheral Vascular Disease, 4th ed. W. B. Saunders, Philadelphia, 1972.
the origin of the renal arteries. The patient was then transferred to Barnes Hospital. On examination the patient appeared to be dyspneic but she was able to lie flat. The blood pressure was 108178 mm Hg in the right arm, the pulse rate 140/min, the respiratory rate 32/min and the temperature 35.9’C. The lips and digits were cyanotic. A loud first heart sound, an audible fourth heart sound and a soft, early systolic murmur radiating from the left sternal border toward the cardiac apex were noted as was a left supraclavicular bruit. Only right brachial and carotid, and weak left brachial and carotid pulses were palpable. Routine serum chemistry studies were normal aside from an albumin concentration of 2.6 g/100 ml and a lactic dehydrogenase (LDH) level of 377 mlU/ TABLE II*
Embolic Causes of Acute Arterial Occlusion
I. Cardiac 1. Auricular fibrillation-other dysrhythmias 2. Cardioversion 3. Myocardial infarcts with mural thrombus 4. Acute and subacute endocarditis 5. Atrial myxoma 6. Cardiomyopathies 7. Valve prosthesis I I. Arterial 1. Mural thrombus 2. Atheromatous I I I. Venous origin via patent foramen ovale *Modified from Fairbairn JF, Juergens JL, Spittell JA: Peripheral Vascular Disease, 4th ed. W. B. Saunders, Philadelphia, 1972.
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ml. The white blood cell count was 9,400/mm3, the platelet count 275,000/mm3, the prothrombin time 71 per cent and the partial thromboplastin time 41 seconds. The stool guaiac was negative. An electrocardiogram and chest roentgenograms were normal. Left and right femoral, and left brachial embolectomies were performed with a Fogarty catheter under local anesthesia. Femoral and brachial pulses, but not the more distal pulses, were palpable after the procedure. Intravenous heparin therapy was initiated. Later in the day a roentgenologic procedure was performed, and the patient was subsequently taken to surgery. CLINICAL DISCUSSION Dr. Michael Karl: I would like to depart from the usual procedure at these conferences by developing early in the hour the sequence of events that took place in this patient as I visualize them. I would then like to turn to the panel and ask them to either support this interpretation or destroy it. Let us first consider the problem of acute arterial occlusion with which the patient presented when she arrived at Barnes Hospital. Tables I and II are abridged from the text by Fairbairn, Juergens and Spittell, and list some of the causes of arterial occlusion. Table I lists those that are thrombotic in nature. Of this group, the only one that needs consideration in a 25 year old woman such as our patient, is cystic medial necrosis which is sometimes seen in Marfan’s syndrome in young women. From the history and information available, there is certainly nothing to suggest that this patient presented with Marfan’s syndrome. Similarly, there is little in her history, in her laboratory findings or in her clinical course to suggest that she had disseminated vasculitis, polyarteritis or systemic lupus erythematosus. The only type of arteritis that is worthy of comment in a 25 year old woman is Takayasu’s arteritis or pulseless disease, or the arteritis of young women, as it is sometimes referred to. This is a very unusual entity. The arteritis primarily involves the arch of the aorta. As a result, such a patient presents with many cerebral symptoms such as dizziness, headache, syncope, convulsions, blurred vision and characteristic eye signs, none of which were present in this young woman. I do not think we need to concern ourselves with thrombosis associated with trauma, since there is no history of trauma, nor do we need to concern ourselves with any of the hematologic disorders that are associated with thrombosis, since there is nothing in our laboratory data to suggest such a disorder. In this age group and in the absence of trauma, it is reasonable to assume that acute occlusion of the
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arteries usually
is embolic originates
in 90 per cent of the cases and from the heart. Some of the
causes of embolic occlusions are listed in Table II. There is little to suggest that in this patient the arterial emboli originated in the heart. We have no information that she was fibrillating. Neither clinically nor by electrocardiogram is there evidence of myocardial infarction. One must certainly seriously consider atrial myxoma in the differential diagnosis. On the other hand, there is little in the clinical course or the laboratory data to suggest the possibility of endocarditis, nor does the size or configuration of the heart suggest cardiomyopathy. Similarly, embolic phenomena originating in the arteries themselves usually do not occur in this age group. Finally, one must consider arterial emboli of venous origin which pass to the arterial side via a patent foramen ovale. In this 25 year old woman, I believe there are only two diagnoses that have to be considered: (1) The possibility that she might have a myxoma in the left atrium. (2) The possibility that she might have paradoxic emboli originating on the venous side of her circulation. I believe the latter is the correct diagnosis. I would suggest that the shortness of breath, the pleuritic pain and the cough that developed early in December 1974, leading to her first hospitalization on January 9, 1975, represented, in fact, multiple pulmonary emboli. Perhaps the very significantly elevated LDH level might support this. These emboli produced pulmonary hypertension and a right to left shunt through a previously hemodynamically insignificant foramen ovale. I suggest this rather than some other type of atrial septal defect because her chest film showed no unusual cardiac configuration and because none of the characteristic murmurs of an important atrial septal defect were noted. These venous emboli became arterial emboli via a now-patent foramen ovale. Before considering this sequence of events, one should consider the possibility of a myxoma. since this certainly can occur in a 25 year old woman and can present with multiple arterial emboli. Of 86 cases of myxoma of the heart described by Husten, 71 were located in the left atrium, nine in the right atrium, three in the left ventricle and three in the right ventricle. Thus, the vast majority occur in the left atrium. Dr. Weldon, would you comment on atria1 myxomas and would you also tell us whether it might not be reasonable to expect that based on an examination of the clot material that you secured at embolectomy the diagnosis of atrial myxoma could be made? Dr. Clarence Weldon: Cardiac myxoma is a disease that is talked about a great deal and not seen very often. But, it is a disease that excites a lot of interest because it has protean manifestations and simulates
other diseases. Usually, it produces either arterial embolization or obstruction, usually on the left side, as 75 per cent of these tumors arise in the left atrium. On the left side, it usually simulates mitral stenosis or sometimes pericarditis interfering with pulmonary venous return: on the right side, it simulates pericarditis or sometimes Epstein’s malformation of the tricuspid valve, or tricuspid stenosis. Not infrequently the diagnosis is first made from an arterial embolus. These arterial emboli have been reported in the coronary circulation, in the systemic circulation and in the pulmonary circulation. It has become more and more frequent, as this disease has been better understood, to make the initial diagnosis from a recovered embolus. The only thing that remains very much a mystery about cardiac myxoma, other than what remains a mystery about all neoplasms, is a very peculiar syndrome of malaise, anemia, fever, weight loss, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. This has been reported enough times to be a real part of the syndrome of cardiac myxoma. Dr. Karl: Dr. Sherman, would you comment on the relationship of contraceptive pills to both arterial and venous clots? You will recall that this young lady had been taking birth control pills until the time of her present illness. Dr. Lawrence Sherman: There is a host of literature about possible relationships between thromboembolism and birth control pills. One of the things which led to a search for causes was an increase in mortality due to thromboembolism in younger women during the mid 1960’s. Some of the best data were the early data from England by Vessey and Doll and their co-workers [ 1,2], wherein they showed that in patients who had thromboembolism the use of oral contraceptives was higher, and this was unrelated to other predisposing causes. Studies in this country have yielded similar results [3,4]. One of the problems with the data is the fact that virtually all the studies that have been done well have looked at idiopathic thromboembolism. In the larger studies in this country, they are apt to start with perhaps, 2,000 cases in which thromboembolism occurred, discard 90 per cent because there was “associated disease” and end up with a couple of hundred cases of idiopathic thromboembolism. Thus, it is difficult to evaluate the significance of these data for the 90 per cent with associated diseases [3]. However, I think most investigators would say that there is a relationship between oral contraceptives and thromboembolism (the degree of risk is about eightto tenfold in terms of strokes based upon a study which included this institution). The risk relative to ve-
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nous disease is about the same order of magnitude as that of pregnancy [6]. However, what is important is that there is a paucity of data to suggest an increased risk in people who have had thromboembolism. Most physicians are loathe to give the pill to patients who have had previous thromboembolism. Unfortunately, there are also little data relative to how oral contraceptives inter-relate to other predisposing factors which may chronically predispose to thromboembolism. At this point in time, one is inclined to give patients agents that contain small amounts of estrogens or agents that contain progestins rather than estrogens. It is almost a coin flip, at times in a given patient, between the hazards of pregnancy versus those of oral contraceptives. There is, however, a definite albeit small risk associated with the drugs. Dr. Karl: Thank you. The occurrence of paradoxic emboli presupposes certain events. First, there must be pulmonary emboli. Second, there must be some type of an abnormal communication between the right and left sides of the heart. Third, there must be some reversal of the normal pressure gradients in order to create a right to left shunt. These suppositions are borne out by the experience of others. For example, in 83 of 101 cases of paradoxic emboli, there was evidence of pulmonary emboli [6]. In 113 cases of paradoxic emboli, all but four were associated with a patent foramen ovale. In three, there were ventricular septal defects; and in one there was a patent ductus arteriosus [7]. Dr. Fiance, would you discuss the likelihood that this patient might have had pulmonary emboli and tell us a little bit about some of the difficulties encountered in making that diagnosis? Dr. I. Jerome Fiance: Dr. Karl, the greatest difficulty in making the diagnosis is not being aware of the possibility. In our Division, we are sensitive to this diagnosis because we see a fair number of people with pulmonary embolization. We have been particularly impressed, in recent years, with the number of young women who have been admitted to this hospital with so-called idiopathic pulmonary emboli. Faced with a twenty-five year old, obese, telephone operator who sat quite a bit, who took birth control pills and who had the sudden onset of shortness of breath and “asthma,” meaning, I assume, that she was wheezing, and who also had pleuritic chest pain, we would have made a flat footed diagnosis of pulmonary embolization. Of course, it is helpful to have confirmatory laboratory evidence. An abnormal chest roentgenogram, electrocardiogram and the triad of a normal serum glutamic oxaloacetic transaminase level with elevated bilirubin and lactic dehydrogenase levels are frequently not present. It would make the di-
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agnosis easier if we could have demonstrated peripheral thrombophlebitis, but the fact remains that her clinical presentation would certainly have led us to believe that she had pulmonary emboli, even though these studies were within normal limits. We could have had definitive confirmation, of course, with more sophisticated studies, which would include a ventilation-perfusion lung scan and pulmonary arteriography. Pulmonary emboli have multiple effects; not only do they mechanically block the pulmonary outflow tract and decrease pulmonary blood flow, but they also call forth a whole battery of humoral agents which cause bronchial constriction and vasoconstriction. In addition to the mechanical effects of blockage in the pulmonary arterial system, lung parenchymatous changes develop through the seepage of blood or infarction so that there is a loss of surfactant and consequent atelectasis, in addition to the effects of chemical agents. As the mechanical blockage of the pulmonary circulation persists, venous shunting takes place and later bronchial pulmonary collaterals develop. All this adds up to ventilation-perfusion abnormalities, hypoxemia, decreased compliance and bleeding leading to increased pulmonary arterial pressure and pulmonary hypertension. Dr. Karl: Dr. Fiance, it was noted that the patient was tachypneic. Despite her tachypnea, she was reported to have a negative chest film, both at the other hospital and at this hospital, and there was really very little noted on physical examination of the lungs. Would this increase your clinical suspicion of pulmonary embolization? Dr. Fiance: If a clot lodges in a major pulmonary artery, then one may see an increase in the hilar artery shadow, oligemia of the ipsilateral lung or increased blood supply to the contralateral lung, but it is not surprising to us that in many instances we see no changes on roentgenograms at all. In answer to your specific question, the answer is yes, it would have heightened our clinical suspicion of pulmonary embolkation. Dr. Karl: Dr. Sobel, could you tell us about interatrial defects of various types and how one makes the diagnosis. Would you also comment on the help that one might have derived from an echocardiogram in this particular patient, particularly in regard to the possibility of atrial myxoma? Dr. Burton Sobel: Perhaps it would be worthwhile first to back off just a little from the diagnosis you have supported so well and emphasize that one must consider arterial embolization whenever a patient presents with a cerebrovascular accident at a young age. Under such conditions, it is essential to consider release of embolic material from the heart. For ex-
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ample, the presentation may represent subacute bacterial endocarditis, previously occult. As you
12 reported cases in which patients with paradoxic emboli survived. The Brigham group subsequently
noted, many other cardiac problems can account for “paradoxic” arterial emboli including congenital lesions such as tetralogy of Fallot or Ebstein’s anomaly, pulmonary atresia accompanied by intracardiac shunt (and otherwise incompatible with life). Under these conditions, the cardiac disease is very obvious and the possibility of paradoxic emboli is usually not overlooked. However, when the cardiac disease is more subtle the diagnosis may be missed. For example, mitral stenosis may be quite a masquerader. It can mimick an atrial septal defect with the predominant murmur, a systolic murmur of tricuspid regurgitation. Even with severe mitral stenosis no audible diastolic rumble may be detectable if the cardiac output is low. Thus, the initial presentation may be arterial embolization. Usually embolization with mitral stenosis occurs when atrial fibrillation or bacterial or fungal endocar-
added five cases in which the diagnosis was made during life. Two of the patients died shortly after procedures of various types. These patients had evidence of venous thrombosis, emboli on the venous side of the circulation and arterial emboli. There was documentation of the arterial emboli by various means and intracardiac defects were demonstrated. The right to left shunt was also documented either by angiography or by an indicator dilution curve.
ditis is present. A common setting for arterial embolization appears to be present in this case in which the emboli are probably coming from the systemic venous circulation to the arterial circulation via an intracardiac shunt, namely, a patent foramen ovale. The incidence of probe-patent foramen ovale in adults is approximately 14 per cent. These otherwise insignificant defects are capable of developing a large enough orifice to allow right to left shunting when the atrium becomes dilated and the septum becomes stretched. This provides a setting for paradoxic arterial embolization. The diagnosis requires demonstration of peripheral venous disease, right atrial exceeding left atrial pressure, and pulmonary emboli. The difference in atrial pressures may be modest. Thus, profound right ventricular failure and severe right atrial hypertension are not necessary. The electrocardiogram in this case exhibits tachycardia, by far the most common electrocardiographic sign of pulmonary embolic disease. QRS complexes are often normal despite recurrent emboli. An echocardiogram is useful when either a myxoma or left atrial clot is considered as a possible cause for arterial embolization. Diagnosis of pulmonary emboli per se may be facilitated with the whole body EMI scanner, avoiding the need for an injection of contrast medium, but of course this device is still in a developmental phase. In this case, a pulmonary angiogram would have been a very appropriate diagnostic procedure and one we would have performed with alacrity. Dr. Karl: A report by Meister and colleagues [8] was published in 1972. At that time, there were only
December
Let us consider for a moment what roentgenologic procedure was performed prior to this patient’s trip to the operating room. Dr. Sobel has already indicated that he thinks the procedure that was done was a pulmonary artery angiogram. I certainly would concur that the procedure of choice at this stage would probably be a pulmonary angiogram. If there was some doubt in the minds of the attending physicians as to what events were going on, perhaps they might have done a right heart catheterization to demonstrate a right to left shunt. If Dr. Weldon had secured clot material that suggested he was dealing with emboli from an atrial myxoma, I would guess that he would then have done a left heart catheterization to demonstrate the tumor and would have evacuated the tumor. I would agree that the procedure that was probably done was a pulmonary artery angiogram. What operative procedure was performed on this patient? I would guess that Dr. Weldon did a right heart angiogram that demonstrated clot in the pulmonary artery and promptly took this patient up to the operating room to evacuate that embolus. Some surgeons at this point might have deemed it proper to interrupt the vena cava. I think that I might have relied on heparinization. Dr. Ludbrook, would you describe the roentgenologic findings? Dr. Philip Ludbrook: The initial chest film revealed mild cardiomegaly, with significant enlargement of the proximal pulmonary arteries, and some sparsity of the peripheral pulmonary vasculature, especially of the right lung. The initial contrast procedure was a left subclavian arteriogram, performed via the right subclavian artery. No opacification of the left subclavian artery was present in the antegrade phase, indicating proximal obstruction of that vessel. A later phase of the brachial arteriogram, demonstrated retrograde filling of the distal segment of the artery beyond the level of the obstruction. A large filling defect, constituting an arterial embolus, was well demarcated. The procedure performed at this hospital comprised right heart catheterization, with limited left
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heart catheterization. The investigation was performed on this extremely ill patient as an emergency procedure. She was extremely hypoxemic, with an arterial oxygen tension of 43 mm Hg, and marked arterial desaturation of 78 per cent. Arteriovenous oxygen extraction was markedly increased to 7.2 volumes per cent, with a correspondingly severe decrease in cardiac output. The calculated pulmonary vascular resistance was markedly increased to 800 units. Moderately severe pulmonary arterial and right ventricular systolic hypertension, with systolic pressures of 70 mm Hg were documented. Right ventricular end diastolic, and right atrial pressures were at the upper limit of normal, with a prominent atrial “a” wave. The patient was fluid depleted at the time of the investigation, and it is probable that right atrial pressures were relatively higher previously. The left atrium was easily entered via a dilated patent foramen ovale. Left atrial pressures were low, with a mean of 1 mm Hg. An oxygen saturation series was withdrawn, revealing severe desaturation at all levels of the right heart. No step up in oxygen saturation was present, hence no left to right shunting could be documented. Severe left atrial desaturation (75.6 per cent) and systemic arterial desaturation (78 per cent) were also present, evidencing a significant “step down” in oxygen saturation in the left atrium, as compared with a pulmonary vein specimen which was 86 per cent saturated. Thus right to left shunting of desaturated venous blood across the dilated patent foramen ovale into the left atrium was documented. Systemic arterial pressures were initially normal (105/65 mm Hg), with moderate hypotension (70150 mm Hg) following angiography. Selective pulmonary arteriograms were performed, revealing multiple large filling defects, indicating severe thromboembolic obstruction of both proximal pulmonary arteries. Severe generalized reduction of peripheral perfusion was also demonstrated. The right upper and mid-veins were almost devoid of perfusion, and multiple smaller areas of loss of vascularity were evident, indicating thromboembolic obstruction of multiple segmental and subsegmental pulmonary arteries. Left heart angiography was performed with the catheter advanced through the patent foramen ovale. Apart from the open foramen, normal left atrial and left ventricular anatomy and function were demonstrated angiographically-in particular there was no evidence of filling defects which might signify thromboembolic material in the left atrium or ventricle at time of the study. Moderate right atrial dilatation was present, with streaming of the contrast agent from the left to the
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right atrium, across the dilated patent foramen ovale. Left to right flow was directed superiorly, in characteristic fashion, by the flap-like margins of the foramen, thus differentiating this communication from a true atrial septal defect. Dr. Karl: Dr. Weldon, what operative procedure was performed and what about the clinical course of the patient? Dr. Weldon: This patient’s story was not reasoned out quite as elegantly when she was in the hospital as it has been here. When I first saw this young lady, her extremities were cyanotic and the viability of them was in jeopardy. We immediately took her to the operating room and did an embolectomy using a Fogarty catheter. We removed clot from the distal parts of the legs, the aorta and the brachial artery. At the end of the procedure, her extremities looked all right. We started her on some heparin. However, the next morning when I came back to the hospital, she looked dismal and although she had pretty good looking extremities, the rest of her looked very bad. She was profoundly cyanotic. I think we measured an oxygen tension, at one point, of 30 mm Hg in arterial blood. I would like to emphasize one point that has been made two or three times here already. Arterial embolism is not a disease. It is a manifestation of disease and it must not be regarded as a disease. You have to look for the cause. I think that is always true with the possible exception that contraceptive pills may cause arterial thrombosis in situ. I do not know whether they do or not. However, if I am not mistaken, Dr. Alan Weiss came to see this patient, and he listened to her chest a bit better than I did and detected loud sounds at the pulmonary valve region. He recognized her as a pulmonary hypertensive and made the bedside diagnosis of a paradoxic embolus from thromboembolic disease. The patient was then studied with an emergency procedure. You really have not had any indication here, except from arterial saturation data, about how sick this young lady was. She looked as though she might die. We operated on her directly from the cardiac catheterization laboratory and, Dr. Karl, we did an extensive procedure. We closed the foramen ovale as the first procedure. It was sprung widely patent. The closure was made to prevent further emboli. To my knowledge, this is the first time that this has been done. While we were there, we did a procedure which has fallen into some disrepute. We opened the pulmonary artery and removed the clots. There were massive clots in the pulmonary circulation and we could not remove all of them. However, she had a most dramatic improvement in her ventilation and in
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her
ability
to oxygenate
blood
also put a clip on the inferior ed both
ovarian
veins,
which
postoperatively. were
of normal
She had, as I recall it, a relatively uncomplicated benign postoperative course, and she was charged
from
the hospital
We
vena cava and we ligat-
about
10 or 12 days
size. and disafter
this operation. Dr. Sherman: The comment that was just made about arterial disease re-emphasizes the fact that arterial disease must also be considered. There are hard data to support the notion of an increased incidence of cerebral arterial disease in patients taking oral contraceptives. Although early reports did not show an increased incidence of coronary disease, more recently such a correlation has been described,
particularly There are
when other risk factors are present more phenomenologic but probably
[9]. real
reports of an increased incidence of thrombi in unusual areas such as mesenteric arteries [ 101, etc. There have been at least three cases in this medical center of women in the 20 to 40 year old age group having mesenteric artery thrombosis and infarction of the bowel while taking the pill. Dr. Karl: I think that the physicians who took care of this patient certainly ought to be congratulated. First, as I indicated earlier, such an antemortem diagnosis had been made only rarely in the past and, of these, only a few of the patients survived. Second, all these extensive procedures were carried out within 24 hours after the patient arrived at Barnes Hospital.
REFERENCES 1.
2.
3.
4.
5.
lnman WHW, Vessey MP: Investigation of deaths from pulmonary, coronary and cerebral thrombosis and embolism in women of childbearing age. Br Med J 2: 193, 1968. Vessey MP, Doll R: Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. Br Med J 2: 651, 1969. Sartwell PE. Masi AT, Arthes FG. Greene GR, Smith HE: Thromboembolism and oral contraceptiies: An epidemiological case-control study. Am J Epidemiol 90: 365, 1969. Greene GR. Sartwell PE: Oral contraceptive use in patients with thromboembolism following surgery, trauma, or infection. Am J Pub Health 62: 680, 1972. Collaborative group for the study of stroke in young
6. 7. 8. 9.
10.
December 1975
women. Oral contraception and increased risk of cerebral ischemia or thrombosis. N Engl J Med 288: 871, 1973. Corrin B: Paradoxical embolism. Br Heart J 26: 549, 1964. Padula RT, Camishion RC: Paradoxical emboliration. Ann Surg 167: 598. 1968. Meister SG. Grossman W, Dexter L. Dalen JS: Paradoxical embolism. Am J Med 53: 292. 1972. Mann JI, Vessey MP, Thorogocd M, et al.: Myocardial infarction in young women with special reference to oral contraceptive practice. Br Med J 2: 241, 1975. Ellis DL. Heifetz CJ: Mesenteric venous thrombosis in two women taking oral contraceptives. Am J Surg 125: 641, 1973.
The Amerkan
Journal of Medklne
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CONFERENCE
Multiple Arterial Occlusions in a Young Woman
Stenographic reports, edited by Philip E. Cryer, M.D. and John Kissane, M.D., of weekly clinkopathoiogic conferences held in Barnes and Wohl Hospitals, are published in each issue of the Journal. These conferences are participated in jointly by members of the Departments of Internal Medicine and Pathology of the Washington University School of Medicine. A 25 year old woman was transferred to Barnes Hospital on January 25, 1975. She had been in apparent good health until early December 1974 when she first noted episodic shortness of breath and pleuritic chest pain. The former recurred and progressed despite therapy with ephedrine. In early January she also noted numbness of her left leg and then her right leg. She was hospitalized elsewhere from January 9 through January 16, 1975. No diagnosis was established. Three days after discharge, pain in the right lower abdomen and a nonproductive cough developed and she was again hospitalized on January 20, 1975. Additional history included the fact that the patient had taken oral contraceptive tablets for several years: these were discontinued in mid-December of 1974. The patient was obese and had lost 60 pounds on a diet. She worked as a telephone operator. Physical findings on admission included a blood pressure of 1 lo/70 mm Hg, a pulse rate of 124/min and a temperature of 100.4’F. Lower abdominal tenderness was noted. Thewhite blood cell count was 14,900/mm3. A urinalysis was normal aside from 3 to 5 white blood ceils/high power field. An electrocardiogram was normal as were films of the chest and abdomen. On January 2 1, a cardiologic consultant described mild peripheral cyanosis, a blood pressure of 96160 mm Hg in the upper right arm and absent left radial, brachial and carotid pulses. He also noted a left parasternal heave and a prominent fourth heart sound. Two days later the patient complained of pain in both legs and feet, and prominent cyanosis of the toes was noted. The femoral, dorsal pedal and posterior tibia1 pulses were no longer palpable. A lung scan was technically unsatisfactory. On January 24, a right brachial arteriogram demonstrated partial obstruction of the left subclavian and carotid arteries, and of the abdominal aorta just below
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TABLE I*
II
III
IV.
Thrombotic Causes of Acute Arterial Occlusion
Degenerative 1. Atherosclerosis 2. Cystic medial necrosis 3. Fibromuscular dysplasia 4. Aneurysm Vasculitis 1. Polyarteritis 2. Systemic lupus erythematous 3. Arteritis Traumatic 1. Thoracic outlet compression syndrome 2. After diagnostic procedures such as arteriography 3. After intra-arterial injections Hematologic disorders 1. Myeloproliferative disease 2. Thrombotic thrombocytopenia purpura 3. Dysproteinemias 4. Disseminated intravascular coagulation
*Modified from Fairbairn JF, Juergens JL, Spittell JA: Peripheral Vascular Disease, 4th ed. W. B. Saunders, Philadelphia, 1972.
the origin of the renal arteries. The patient was then transferred to Barnes Hospital. On examination the patient appeared to be dyspneic but she was able to lie flat. The blood pressure was 108178 mm Hg in the right arm, the pulse rate 140/min, the respiratory rate 32/min and the temperature 35.9’C. The lips and digits were cyanotic. A loud first heart sound, an audible fourth heart sound and a soft, early systolic murmur radiating from the left sternal border toward the cardiac apex were noted as was a left supraclavicular bruit. Only right brachial and carotid, and weak left brachial and carotid pulses were palpable. Routine serum chemistry studies were normal aside from an albumin concentration of 2.6 g/100 ml and a lactic dehydrogenase (LDH) level of 377 mlU/ TABLE II*
Embolic Causes of Acute Arterial Occlusion
I. Cardiac 1. Auricular fibrillation-other dysrhythmias 2. Cardioversion 3. Myocardial infarcts with mural thrombus 4. Acute and subacute endocarditis 5. Atrial myxoma 6. Cardiomyopathies 7. Valve prosthesis I I. Arterial 1. Mural thrombus 2. Atheromatous I I I. Venous origin via patent foramen ovale *Modified from Fairbairn JF, Juergens JL, Spittell JA: Peripheral Vascular Disease, 4th ed. W. B. Saunders, Philadelphia, 1972.
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ml. The white blood cell count was 9,400/mm3, the platelet count 275,000/mm3, the prothrombin time 71 per cent and the partial thromboplastin time 41 seconds. The stool guaiac was negative. An electrocardiogram and chest roentgenograms were normal. Left and right femoral, and left brachial embolectomies were performed with a Fogarty catheter under local anesthesia. Femoral and brachial pulses, but not the more distal pulses, were palpable after the procedure. Intravenous heparin therapy was initiated. Later in the day a roentgenologic procedure was performed, and the patient was subsequently taken to surgery. CLINICAL DISCUSSION Dr. Michael Karl: I would like to depart from the usual procedure at these conferences by developing early in the hour the sequence of events that took place in this patient as I visualize them. I would then like to turn to the panel and ask them to either support this interpretation or destroy it. Let us first consider the problem of acute arterial occlusion with which the patient presented when she arrived at Barnes Hospital. Tables I and II are abridged from the text by Fairbairn, Juergens and Spittell, and list some of the causes of arterial occlusion. Table I lists those that are thrombotic in nature. Of this group, the only one that needs consideration in a 25 year old woman such as our patient, is cystic medial necrosis which is sometimes seen in Marfan’s syndrome in young women. From the history and information available, there is certainly nothing to suggest that this patient presented with Marfan’s syndrome. Similarly, there is little in her history, in her laboratory findings or in her clinical course to suggest that she had disseminated vasculitis, polyarteritis or systemic lupus erythematosus. The only type of arteritis that is worthy of comment in a 25 year old woman is Takayasu’s arteritis or pulseless disease, or the arteritis of young women, as it is sometimes referred to. This is a very unusual entity. The arteritis primarily involves the arch of the aorta. As a result, such a patient presents with many cerebral symptoms such as dizziness, headache, syncope, convulsions, blurred vision and characteristic eye signs, none of which were present in this young woman. I do not think we need to concern ourselves with thrombosis associated with trauma, since there is no history of trauma, nor do we need to concern ourselves with any of the hematologic disorders that are associated with thrombosis, since there is nothing in our laboratory data to suggest such a disorder. In this age group and in the absence of trauma, it is reasonable to assume that acute occlusion of the
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MULTIPLE ARTERIAL OCCLUSIONS IN A YOUNG WOMAN
arteries usually
is embolic originates
in 90 per cent of the cases and from the heart. Some of the
causes of embolic occlusions are listed in Table II. There is little to suggest that in this patient the arterial emboli originated in the heart. We have no information that she was fibrillating. Neither clinically nor by electrocardiogram is there evidence of myocardial infarction. One must certainly seriously consider atrial myxoma in the differential diagnosis. On the other hand, there is little in the clinical course or the laboratory data to suggest the possibility of endocarditis, nor does the size or configuration of the heart suggest cardiomyopathy. Similarly, embolic phenomena originating in the arteries themselves usually do not occur in this age group. Finally, one must consider arterial emboli of venous origin which pass to the arterial side via a patent foramen ovale. In this 25 year old woman, I believe there are only two diagnoses that have to be considered: (1) The possibility that she might have a myxoma in the left atrium. (2) The possibility that she might have paradoxic emboli originating on the venous side of her circulation. I believe the latter is the correct diagnosis. I would suggest that the shortness of breath, the pleuritic pain and the cough that developed early in December 1974, leading to her first hospitalization on January 9, 1975, represented, in fact, multiple pulmonary emboli. Perhaps the very significantly elevated LDH level might support this. These emboli produced pulmonary hypertension and a right to left shunt through a previously hemodynamically insignificant foramen ovale. I suggest this rather than some other type of atrial septal defect because her chest film showed no unusual cardiac configuration and because none of the characteristic murmurs of an important atrial septal defect were noted. These venous emboli became arterial emboli via a now-patent foramen ovale. Before considering this sequence of events, one should consider the possibility of a myxoma. since this certainly can occur in a 25 year old woman and can present with multiple arterial emboli. Of 86 cases of myxoma of the heart described by Husten, 71 were located in the left atrium, nine in the right atrium, three in the left ventricle and three in the right ventricle. Thus, the vast majority occur in the left atrium. Dr. Weldon, would you comment on atria1 myxomas and would you also tell us whether it might not be reasonable to expect that based on an examination of the clot material that you secured at embolectomy the diagnosis of atrial myxoma could be made? Dr. Clarence Weldon: Cardiac myxoma is a disease that is talked about a great deal and not seen very often. But, it is a disease that excites a lot of interest because it has protean manifestations and simulates
other diseases. Usually, it produces either arterial embolization or obstruction, usually on the left side, as 75 per cent of these tumors arise in the left atrium. On the left side, it usually simulates mitral stenosis or sometimes pericarditis interfering with pulmonary venous return: on the right side, it simulates pericarditis or sometimes Epstein’s malformation of the tricuspid valve, or tricuspid stenosis. Not infrequently the diagnosis is first made from an arterial embolus. These arterial emboli have been reported in the coronary circulation, in the systemic circulation and in the pulmonary circulation. It has become more and more frequent, as this disease has been better understood, to make the initial diagnosis from a recovered embolus. The only thing that remains very much a mystery about cardiac myxoma, other than what remains a mystery about all neoplasms, is a very peculiar syndrome of malaise, anemia, fever, weight loss, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. This has been reported enough times to be a real part of the syndrome of cardiac myxoma. Dr. Karl: Dr. Sherman, would you comment on the relationship of contraceptive pills to both arterial and venous clots? You will recall that this young lady had been taking birth control pills until the time of her present illness. Dr. Lawrence Sherman: There is a host of literature about possible relationships between thromboembolism and birth control pills. One of the things which led to a search for causes was an increase in mortality due to thromboembolism in younger women during the mid 1960’s. Some of the best data were the early data from England by Vessey and Doll and their co-workers [ 1,2], wherein they showed that in patients who had thromboembolism the use of oral contraceptives was higher, and this was unrelated to other predisposing causes. Studies in this country have yielded similar results [3,4]. One of the problems with the data is the fact that virtually all the studies that have been done well have looked at idiopathic thromboembolism. In the larger studies in this country, they are apt to start with perhaps, 2,000 cases in which thromboembolism occurred, discard 90 per cent because there was “associated disease” and end up with a couple of hundred cases of idiopathic thromboembolism. Thus, it is difficult to evaluate the significance of these data for the 90 per cent with associated diseases [3]. However, I think most investigators would say that there is a relationship between oral contraceptives and thromboembolism (the degree of risk is about eightto tenfold in terms of strokes based upon a study which included this institution). The risk relative to ve-
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CLINICOPATHOLOGIC CONFERENCE
nous disease is about the same order of magnitude as that of pregnancy [6]. However, what is important is that there is a paucity of data to suggest an increased risk in people who have had thromboembolism. Most physicians are loathe to give the pill to patients who have had previous thromboembolism. Unfortunately, there are also little data relative to how oral contraceptives inter-relate to other predisposing factors which may chronically predispose to thromboembolism. At this point in time, one is inclined to give patients agents that contain small amounts of estrogens or agents that contain progestins rather than estrogens. It is almost a coin flip, at times in a given patient, between the hazards of pregnancy versus those of oral contraceptives. There is, however, a definite albeit small risk associated with the drugs. Dr. Karl: Thank you. The occurrence of paradoxic emboli presupposes certain events. First, there must be pulmonary emboli. Second, there must be some type of an abnormal communication between the right and left sides of the heart. Third, there must be some reversal of the normal pressure gradients in order to create a right to left shunt. These suppositions are borne out by the experience of others. For example, in 83 of 101 cases of paradoxic emboli, there was evidence of pulmonary emboli [6]. In 113 cases of paradoxic emboli, all but four were associated with a patent foramen ovale. In three, there were ventricular septal defects; and in one there was a patent ductus arteriosus [7]. Dr. Fiance, would you discuss the likelihood that this patient might have had pulmonary emboli and tell us a little bit about some of the difficulties encountered in making that diagnosis? Dr. I. Jerome Fiance: Dr. Karl, the greatest difficulty in making the diagnosis is not being aware of the possibility. In our Division, we are sensitive to this diagnosis because we see a fair number of people with pulmonary embolization. We have been particularly impressed, in recent years, with the number of young women who have been admitted to this hospital with so-called idiopathic pulmonary emboli. Faced with a twenty-five year old, obese, telephone operator who sat quite a bit, who took birth control pills and who had the sudden onset of shortness of breath and “asthma,” meaning, I assume, that she was wheezing, and who also had pleuritic chest pain, we would have made a flat footed diagnosis of pulmonary embolization. Of course, it is helpful to have confirmatory laboratory evidence. An abnormal chest roentgenogram, electrocardiogram and the triad of a normal serum glutamic oxaloacetic transaminase level with elevated bilirubin and lactic dehydrogenase levels are frequently not present. It would make the di-
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agnosis easier if we could have demonstrated peripheral thrombophlebitis, but the fact remains that her clinical presentation would certainly have led us to believe that she had pulmonary emboli, even though these studies were within normal limits. We could have had definitive confirmation, of course, with more sophisticated studies, which would include a ventilation-perfusion lung scan and pulmonary arteriography. Pulmonary emboli have multiple effects; not only do they mechanically block the pulmonary outflow tract and decrease pulmonary blood flow, but they also call forth a whole battery of humoral agents which cause bronchial constriction and vasoconstriction. In addition to the mechanical effects of blockage in the pulmonary arterial system, lung parenchymatous changes develop through the seepage of blood or infarction so that there is a loss of surfactant and consequent atelectasis, in addition to the effects of chemical agents. As the mechanical blockage of the pulmonary circulation persists, venous shunting takes place and later bronchial pulmonary collaterals develop. All this adds up to ventilation-perfusion abnormalities, hypoxemia, decreased compliance and bleeding leading to increased pulmonary arterial pressure and pulmonary hypertension. Dr. Karl: Dr. Fiance, it was noted that the patient was tachypneic. Despite her tachypnea, she was reported to have a negative chest film, both at the other hospital and at this hospital, and there was really very little noted on physical examination of the lungs. Would this increase your clinical suspicion of pulmonary embolization? Dr. Fiance: If a clot lodges in a major pulmonary artery, then one may see an increase in the hilar artery shadow, oligemia of the ipsilateral lung or increased blood supply to the contralateral lung, but it is not surprising to us that in many instances we see no changes on roentgenograms at all. In answer to your specific question, the answer is yes, it would have heightened our clinical suspicion of pulmonary embolkation. Dr. Karl: Dr. Sobel, could you tell us about interatrial defects of various types and how one makes the diagnosis. Would you also comment on the help that one might have derived from an echocardiogram in this particular patient, particularly in regard to the possibility of atrial myxoma? Dr. Burton Sobel: Perhaps it would be worthwhile first to back off just a little from the diagnosis you have supported so well and emphasize that one must consider arterial embolization whenever a patient presents with a cerebrovascular accident at a young age. Under such conditions, it is essential to consider release of embolic material from the heart. For ex-
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MULTIPLE ARTERIAL OCCLUSIONS IN A YOUNG WOMAN
ample, the presentation may represent subacute bacterial endocarditis, previously occult. As you
12 reported cases in which patients with paradoxic emboli survived. The Brigham group subsequently
noted, many other cardiac problems can account for “paradoxic” arterial emboli including congenital lesions such as tetralogy of Fallot or Ebstein’s anomaly, pulmonary atresia accompanied by intracardiac shunt (and otherwise incompatible with life). Under these conditions, the cardiac disease is very obvious and the possibility of paradoxic emboli is usually not overlooked. However, when the cardiac disease is more subtle the diagnosis may be missed. For example, mitral stenosis may be quite a masquerader. It can mimick an atrial septal defect with the predominant murmur, a systolic murmur of tricuspid regurgitation. Even with severe mitral stenosis no audible diastolic rumble may be detectable if the cardiac output is low. Thus, the initial presentation may be arterial embolization. Usually embolization with mitral stenosis occurs when atrial fibrillation or bacterial or fungal endocar-
added five cases in which the diagnosis was made during life. Two of the patients died shortly after procedures of various types. These patients had evidence of venous thrombosis, emboli on the venous side of the circulation and arterial emboli. There was documentation of the arterial emboli by various means and intracardiac defects were demonstrated. The right to left shunt was also documented either by angiography or by an indicator dilution curve.
ditis is present. A common setting for arterial embolization appears to be present in this case in which the emboli are probably coming from the systemic venous circulation to the arterial circulation via an intracardiac shunt, namely, a patent foramen ovale. The incidence of probe-patent foramen ovale in adults is approximately 14 per cent. These otherwise insignificant defects are capable of developing a large enough orifice to allow right to left shunting when the atrium becomes dilated and the septum becomes stretched. This provides a setting for paradoxic arterial embolization. The diagnosis requires demonstration of peripheral venous disease, right atrial exceeding left atrial pressure, and pulmonary emboli. The difference in atrial pressures may be modest. Thus, profound right ventricular failure and severe right atrial hypertension are not necessary. The electrocardiogram in this case exhibits tachycardia, by far the most common electrocardiographic sign of pulmonary embolic disease. QRS complexes are often normal despite recurrent emboli. An echocardiogram is useful when either a myxoma or left atrial clot is considered as a possible cause for arterial embolization. Diagnosis of pulmonary emboli per se may be facilitated with the whole body EMI scanner, avoiding the need for an injection of contrast medium, but of course this device is still in a developmental phase. In this case, a pulmonary angiogram would have been a very appropriate diagnostic procedure and one we would have performed with alacrity. Dr. Karl: A report by Meister and colleagues [8] was published in 1972. At that time, there were only
December
Let us consider for a moment what roentgenologic procedure was performed prior to this patient’s trip to the operating room. Dr. Sobel has already indicated that he thinks the procedure that was done was a pulmonary artery angiogram. I certainly would concur that the procedure of choice at this stage would probably be a pulmonary angiogram. If there was some doubt in the minds of the attending physicians as to what events were going on, perhaps they might have done a right heart catheterization to demonstrate a right to left shunt. If Dr. Weldon had secured clot material that suggested he was dealing with emboli from an atrial myxoma, I would guess that he would then have done a left heart catheterization to demonstrate the tumor and would have evacuated the tumor. I would agree that the procedure that was probably done was a pulmonary artery angiogram. What operative procedure was performed on this patient? I would guess that Dr. Weldon did a right heart angiogram that demonstrated clot in the pulmonary artery and promptly took this patient up to the operating room to evacuate that embolus. Some surgeons at this point might have deemed it proper to interrupt the vena cava. I think that I might have relied on heparinization. Dr. Ludbrook, would you describe the roentgenologic findings? Dr. Philip Ludbrook: The initial chest film revealed mild cardiomegaly, with significant enlargement of the proximal pulmonary arteries, and some sparsity of the peripheral pulmonary vasculature, especially of the right lung. The initial contrast procedure was a left subclavian arteriogram, performed via the right subclavian artery. No opacification of the left subclavian artery was present in the antegrade phase, indicating proximal obstruction of that vessel. A later phase of the brachial arteriogram, demonstrated retrograde filling of the distal segment of the artery beyond the level of the obstruction. A large filling defect, constituting an arterial embolus, was well demarcated. The procedure performed at this hospital comprised right heart catheterization, with limited left
1975
The
American Journalof Medlclne Volume 59
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CLINICOPATHOLO@CCONFERENCE
heart catheterization. The investigation was performed on this extremely ill patient as an emergency procedure. She was extremely hypoxemic, with an arterial oxygen tension of 43 mm Hg, and marked arterial desaturation of 78 per cent. Arteriovenous oxygen extraction was markedly increased to 7.2 volumes per cent, with a correspondingly severe decrease in cardiac output. The calculated pulmonary vascular resistance was markedly increased to 800 units. Moderately severe pulmonary arterial and right ventricular systolic hypertension, with systolic pressures of 70 mm Hg were documented. Right ventricular end diastolic, and right atrial pressures were at the upper limit of normal, with a prominent atrial “a” wave. The patient was fluid depleted at the time of the investigation, and it is probable that right atrial pressures were relatively higher previously. The left atrium was easily entered via a dilated patent foramen ovale. Left atrial pressures were low, with a mean of 1 mm Hg. An oxygen saturation series was withdrawn, revealing severe desaturation at all levels of the right heart. No step up in oxygen saturation was present, hence no left to right shunting could be documented. Severe left atrial desaturation (75.6 per cent) and systemic arterial desaturation (78 per cent) were also present, evidencing a significant “step down” in oxygen saturation in the left atrium, as compared with a pulmonary vein specimen which was 86 per cent saturated. Thus right to left shunting of desaturated venous blood across the dilated patent foramen ovale into the left atrium was documented. Systemic arterial pressures were initially normal (105/65 mm Hg), with moderate hypotension (70150 mm Hg) following angiography. Selective pulmonary arteriograms were performed, revealing multiple large filling defects, indicating severe thromboembolic obstruction of both proximal pulmonary arteries. Severe generalized reduction of peripheral perfusion was also demonstrated. The right upper and mid-veins were almost devoid of perfusion, and multiple smaller areas of loss of vascularity were evident, indicating thromboembolic obstruction of multiple segmental and subsegmental pulmonary arteries. Left heart angiography was performed with the catheter advanced through the patent foramen ovale. Apart from the open foramen, normal left atrial and left ventricular anatomy and function were demonstrated angiographically-in particular there was no evidence of filling defects which might signify thromboembolic material in the left atrium or ventricle at time of the study. Moderate right atrial dilatation was present, with streaming of the contrast agent from the left to the
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right atrium, across the dilated patent foramen ovale. Left to right flow was directed superiorly, in characteristic fashion, by the flap-like margins of the foramen, thus differentiating this communication from a true atrial septal defect. Dr. Karl: Dr. Weldon, what operative procedure was performed and what about the clinical course of the patient? Dr. Weldon: This patient’s story was not reasoned out quite as elegantly when she was in the hospital as it has been here. When I first saw this young lady, her extremities were cyanotic and the viability of them was in jeopardy. We immediately took her to the operating room and did an embolectomy using a Fogarty catheter. We removed clot from the distal parts of the legs, the aorta and the brachial artery. At the end of the procedure, her extremities looked all right. We started her on some heparin. However, the next morning when I came back to the hospital, she looked dismal and although she had pretty good looking extremities, the rest of her looked very bad. She was profoundly cyanotic. I think we measured an oxygen tension, at one point, of 30 mm Hg in arterial blood. I would like to emphasize one point that has been made two or three times here already. Arterial embolism is not a disease. It is a manifestation of disease and it must not be regarded as a disease. You have to look for the cause. I think that is always true with the possible exception that contraceptive pills may cause arterial thrombosis in situ. I do not know whether they do or not. However, if I am not mistaken, Dr. Alan Weiss came to see this patient, and he listened to her chest a bit better than I did and detected loud sounds at the pulmonary valve region. He recognized her as a pulmonary hypertensive and made the bedside diagnosis of a paradoxic embolus from thromboembolic disease. The patient was then studied with an emergency procedure. You really have not had any indication here, except from arterial saturation data, about how sick this young lady was. She looked as though she might die. We operated on her directly from the cardiac catheterization laboratory and, Dr. Karl, we did an extensive procedure. We closed the foramen ovale as the first procedure. It was sprung widely patent. The closure was made to prevent further emboli. To my knowledge, this is the first time that this has been done. While we were there, we did a procedure which has fallen into some disrepute. We opened the pulmonary artery and removed the clots. There were massive clots in the pulmonary circulation and we could not remove all of them. However, she had a most dramatic improvement in her ventilation and in
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MULTIPLE ARTERIAL OCCLUSIONS IN A YOUNG WOMAN
her
ability
to oxygenate
blood
also put a clip on the inferior ed both
ovarian
veins,
which
postoperatively. were
of normal
She had, as I recall it, a relatively uncomplicated benign postoperative course, and she was charged
from
the hospital
We
vena cava and we ligat-
about
10 or 12 days
size. and disafter
this operation. Dr. Sherman: The comment that was just made about arterial disease re-emphasizes the fact that arterial disease must also be considered. There are hard data to support the notion of an increased incidence of cerebral arterial disease in patients taking oral contraceptives. Although early reports did not show an increased incidence of coronary disease, more recently such a correlation has been described,
particularly There are
when other risk factors are present more phenomenologic but probably
[9]. real
reports of an increased incidence of thrombi in unusual areas such as mesenteric arteries [ 101, etc. There have been at least three cases in this medical center of women in the 20 to 40 year old age group having mesenteric artery thrombosis and infarction of the bowel while taking the pill. Dr. Karl: I think that the physicians who took care of this patient certainly ought to be congratulated. First, as I indicated earlier, such an antemortem diagnosis had been made only rarely in the past and, of these, only a few of the patients survived. Second, all these extensive procedures were carried out within 24 hours after the patient arrived at Barnes Hospital.
REFERENCES 1.
2.
3.
4.
5.
lnman WHW, Vessey MP: Investigation of deaths from pulmonary, coronary and cerebral thrombosis and embolism in women of childbearing age. Br Med J 2: 193, 1968. Vessey MP, Doll R: Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. Br Med J 2: 651, 1969. Sartwell PE. Masi AT, Arthes FG. Greene GR, Smith HE: Thromboembolism and oral contraceptiies: An epidemiological case-control study. Am J Epidemiol 90: 365, 1969. Greene GR. Sartwell PE: Oral contraceptive use in patients with thromboembolism following surgery, trauma, or infection. Am J Pub Health 62: 680, 1972. Collaborative group for the study of stroke in young
6. 7. 8. 9.
10.
December 1975
women. Oral contraception and increased risk of cerebral ischemia or thrombosis. N Engl J Med 288: 871, 1973. Corrin B: Paradoxical embolism. Br Heart J 26: 549, 1964. Padula RT, Camishion RC: Paradoxical emboliration. Ann Surg 167: 598. 1968. Meister SG. Grossman W, Dexter L. Dalen JS: Paradoxical embolism. Am J Med 53: 292. 1972. Mann JI, Vessey MP, Thorogocd M, et al.: Myocardial infarction in young women with special reference to oral contraceptive practice. Br Med J 2: 241, 1975. Ellis DL. Heifetz CJ: Mesenteric venous thrombosis in two women taking oral contraceptives. Am J Surg 125: 641, 1973.
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