Immediate
for Intracardiac Thrombus in Acute Cardioembolic Stroke
Anticoagulation
Masahiro Yasaka, M.D. and Takenori
Yamaguchi,
M.D.
OSAKA, JAPAN
Abstract To assess the efficacy of immediate anticoagulation therapy on intracardiac thrombus formation in acute cardioembolic stroke, serial two-dimensional echocardiographic examinations were performed in 25 patients with acute cardioembolic stroke. Anticoagulation therapy was commenced within two days of onset in 7 patients (group A) but not in 18 patients (group B). Appearance or enlargement of intracardiac thrombi were not detected in group A but were noted in 7 patients (39%) of group B. Recurrence of systemic embolism was demonstrated in 3 patients (17%) of group B. There were no serious hemorrhagic complications in either group. Immediate anticoagulation could, therefore, be effective in preventing intracardiac thrombus formation and the consequent recurrence of systemic embolization in acute cardioembolic stroke. Because the study was preliminary and not randomized, further randomized study is desirable to establish the efficacy of immediate anticoagulation therapy.
Introduction Recurrence of embolization is a serious problem in patients with cardioembolic stroke.’-8 It has been established that anticoagulation in the chronic stage of embolization is effective in preventing recurrent attacks. 3-5 Most attacks usually occur, however, within two weeks of the initial event,5-8 and immediate anticoagulation in this period has been under dispute- 9-15 There have been few reports documenting the effect of immediate anticoagulation on the prevention of the formation of an intracardiac thrombus as a direct embolic source in patients with acute cardiogenic embolism. To address this question, we preliminarily performed serial two-dimensional echocardiographic examinations in patients with acute cardiogenic embolic stroke receiving immediate anticoagulation and in an untreated control group. From the Cerebrovascular Division,
Department
of Medicine, National Cardiovascular Center, Osaka,
886
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
Japan
887
Subjects and Methods Thirty consecutive patients were admitted to the Stroke Care Unit of the National Cardiovascular Center within forty-eight hours of cerebral embolism between June 1, 1986, and January 31, 1987. Good echocardiograms were obtained in 25 of the 30 patients, and these were entered into the study. There were 7 men and 18 women, ranging in age from thirty-eight to eighty-one years, with a mean of sixty-three years. The diagnosis of cerebral embolism was performed according to the criteria reported by Yamaguchi et al.’ Two-dimensional echocardiograms were obtained with a commercially available real-time, phased-array system with 3.75 MHz transducer. Echocardiographic examinations were performed at the time of admission and at days 4, 7, 10, 14, 21, and 28 after the onset of cerebral embolism. When an intracardiac thrombus was detected, echocardiographic examinations were repeated daily until the twenty-eighth day or until the intracardiac thrombus disappeared. Patients were examined in a left recumbent or supine position. The cardiac chambers, especially the left atrial and ventricular cavities, were examined extensively by shifting, rotating, and tilting the transducer and by adjusting the gain control of the equipment if necessary. The echocardiographic diagnosis of an intracardiac thrombus was made when a mass echo with a clearly defined contour was observed inside the cardiac chamber, when the echo of endocardial surface was identified, and when the echo of the mass was visualized from several positions on the chest wall.’6 A thrombus was considered to have enlarged when it had become 1.5 times larger than its previous size on the view where the thrombus was best visualized. A I
considered to be mobile if it showed motion independent of the adjacent endocardium, either opposite in direction or freely erratic. None of the 25 patients had previously received an anticoagulant. After admission, anticoagulant therapy was selective and varied according to the discretion of the patient’s primary
thrombus
was
physician. Immediate anticoagulation was started in 7 patients (group A) within two days of the onset. None of them had had infective endocarditis or hypertension. The infarct was located only in a part of the region supplied by the middle cerebral artery or the posterior cerebral artery and was not hemorrhagic on computed tomographic (CT) scan before anticoagulation commenced. Brain CT examinations were performed on the first hospital day in all patients and were TABLE I Cardiac
Underlying
Etiologies
~----
*Mitral valve replacements (a Mitrofro valve and a **The patient had calcification of the aortic valve.
Bjork-Shiley valve).
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
888
repeated at least every ten hospital days during the observation period. Heparin and warfarin potassium were used as the anticoagulant drugs. Heparin treatment was initiated with a bolus injection of 70 units X body weight (kg) intravenously followed by a constant infusion regulated to maintain the activated partial thromboplastin time between 2 and 3 times control values. Within fourteen days of commencement of heparin treatment, its administration was changed to oral. Oral anticoagulation was aimed at maintaining a prothrombic time (international normalized ratio) between 2.5 and 3.5. The remaining 18 patients (group B) did not receive any anticoagulant unless a newly formed intracardiac thrombus
was
noted.
Results All 25 patients had heart disease that was considered to be a source of emboli (Table I). Patients with rheumatic heart disease were all found to have mitral stenosis on echocardiog-
raphy. In group A, all but 1 patient (eighty-one years old) were under the age of seventy years. In the oldest patient, immediate anticoagulation was begun to avoid recurrent attacks, since she had already suffered her third attack. In 6 patients of group A, hemorrhagic transformation was noted on CT scans from the fourth to nineteenth day of anticoagulation. Two of them were petechial hemorrhages. The other four were small hematomas, less than 2 cm in diameter in the ischemic area, showing no mass effect. Neurologic deterioration due to these minor hemorrhagic transformations was not noted. An intracardiac thrombus was found in only 1 patient of group A at admission. After commencement of anticoagulant therapy, this thrombus gradually decreased in size and had disappeared by the fifteenth day (Figure 1). In the other 6 patients of this group, no intracardiac thrombus was detected during the observation period. Moreover, no recurrent attacks occurred during the anticoagulation period.
FIG. 1. Left
parasternal short-axis view. A thrombus was detected at disappeared after anticoagulation (middle and right).
decreased in size and
the left atrial appendage at admission AO: aortic valve. LA: left atrium.
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
(left).
It
889 TABLE II Intracardiac Thrombus and Recurrent Attacks in
Group
B
RHD: rheumatic heart disease; AF: atrial fibrillation, APP: left atrial appendage, HHD: hypertensive heart disease, AMI: infarction, Apex: left ventricular apex, HCM: hypertrophic cardiomyopathy, AoV: aortic valve. *The right upper extremity, **the left lower extremity, ***cerebral embolism, #calcification of the aortic valve.
myocardial
confirmed in 3 patients at admission (Table II). All these thrombi were seen to enlarge generally within fourteen days of admission. In 4 of the remaining 15 patients, newly formed intracardiac thrombi appeared in the first fourteen days of the observation period. In total, growth of the intracardiac thrombus was seen in 7 of the 18 patients (39 % ) during observation. Systemic embolization recurred in 3 of the 7 group B patients with intracardiac thrombi. All these patients had mitral stenosis, with a mobile thrombus at the left atrial appendage. The first of these was a fifty-five-year-old woman in whom an intracardiac thrombus was not detected on admission nor on days 4 or 7. On day 10, a mobile intracardiac thrombus was observed and anticoagulant therapy was initiated (Figure 2). Embolization to the right upper extremity occurred on day 14, and immediately after embolization, the intracardiac thrombus was no longer detectable by echocardiography. The second patient was a thirty-eight-year-old woman without an intracardiac thrombus at admission or on day 4. On day 7, she had a recurrent stroke, and a mobile thrombus was detected at the left atrial appendage. Anticoagulation with warfarin was initiated on the same day to prevent an additional recurrence. The third patient was a sixty-five-year-old woman, in whom no intracardiac thrombus was detectable either at admission or on day 4. On day 6 she suddenly developed an embolization to the left lower extremity. A mobile thrombus was detected at the left atrial appendage on day 7. In 11 patients of group B, hemorrhagic transformation of the infarct was demonstrated on CT scans from two to twenty-one days after onset. Nine were petechial hemorrhages and 2 were small hematomas, which did not cause neurologic deterioration. In 2 of these patients, anticoagulation was commenced after the detection of an intracardiac thrombus, in one on day 7 and the other on day 10. They developed petechial hemorrhage and small hemorrhage, In group
B,
an
intracardiac thrombus
acute
was
respectively. Two patients
in group B died during the observation period: 1 on day 4 of panperitonitis due to mesenteric arterial embolism complicated at admission and the other on day 5 owing to brain herniation. Discussion We have
already reported that dehydration accelerates intracardiac thrombus formation in
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
890
an
Ftc. 2. Left parasternal short-axis view. No thrombi were noted at admission, on day 4 or on day 7 (left). But on day 10, intracardiac thrombus appeared at the left atrial appendage (right). AO: aortic valve. LA: left atrium.
patients with acute cardioembolic stroke.&dquo; Avoidance of dehydration during the acute phase of cardioembolic stroke may thus be useful in the prevention of the recurrence of embolism. However, heart failure is so often noted in these patients that dehydration therapy, using diuretics, is sometimes inevitable. We consider that in these patients at least immediate anticoagulation should be considered. Several authors have reported a reduction in the incidence of recurrent attacks with anticoagulant treatment without the associated morbidity from brain hemorrhage or other hemorrhagic complications.9,18,19 There are no reports, however, on the value of immediate anticoagulation in the reduction of the incidence of intracardiac thrombus formation as a direct recurrent embolic source. The appearance or enlargement of thrombi were observed in 7 patients of group B. Most of the growth was detected within fourteen days of the onset of the embolic stroke. These observations are consistent with the fact that systemic embolism tends to recur most frequently during this period. 5-8 A 39 % incidence of intracardiac thrombus growth (4 newly formed; 3 enlarged) was seen in the control group B but none in group A. Moreover, recurrent attacks were noted in 3 patients of group B and none in group A. These data suggest that acute anticoagulation could prevent the formation of intracardiac thrombus as a direct source of emboli and consequent recurrent embolization. Serious hemorrhagic transformation of an infarct or other hemorrhagic complications were
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
891
apparent in patients receiving anticoagulant therapy. The reasons may be that all but 1 were under seventy, they . were all normotensive, and their hypodense areas were relatively small. Hemorrhagic transformation in patients with acute embolic stroke has been linked to advanced age or size of the infarct area.2° Some reports have linked hemorrhagic transformation to hypertension.2’.22 Particular care should, therefore, be taken in performing immediate antinot
coagulation in patients of advanced age or with large infarction or hypertension. In the patients in group A with an intracardiac thrombus detected at admission, the intracardiac thrombus regressed gradually on anticoagulant therapy. We suggest this is due to the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin
activity.23 Conclusion The results of this study indicate that immediate anticoagulation could be useful in preventing intracardiac thrombus formation itself and consequent recurrent embolization in patients suffering an acute cardiogenic cerebral embolism. Because our study was preliminary and not randomized, further randomized study is desirable to establish the efficacy of immediate anti-
coagulation therapy. Masahiro Yasaka, M. D. Cerebrovascular Division Department of Medicine National Cardiovascular Center 5-7-1, Fujishirodai , Suita City
Osaka, Japan
References 1.
Minematsu K, Choki J, et al: Clinical and neuroradiological analysis of thrombotic and embolic cerebral infarction. Jpn Circ J 48:50-58, 1984. 2. Darling RC, Austen WG, Linton RR: Arterial embo-
Yamaguchi T,
lism. Surg Gynecol Obstet 124:106-114, 1967. 3. Carter AB: Prognosis of cerebral embolism. Lancet 2:514-519, 1965. 4. McDevitt E, Carter SA, Gatje BE, et al: Use of anticoagulant in treatment of cerebrovascular disease. JAMA 166:592-597, 1958. 5. Cerebral Embolism Task Force: Cardiogenic brain embolism. The second report of the Cerebral Embolism Task Force. Arch Neurol 46:727-743, 1989. 6. Yamaguchi T, Minematsu K, Choki J, et al: Recurrent cerebral embolism and factors related to early recurrence. Analysis of 186 consecutive cases. In: Central Nervous System Control of the Heart, ed. by Stober T, Schimrigk K, Ganten D, et al. Boston: Martinus Nijhoff, 1986, pp 237-243. 7. Sherman DG, Goldman L, Whiting RB, et al: Thromboembolism in patients with atrial fibrillation. Arch Neurol 41:708-710, 1984.
8. Hart RG, Coull BM, Hart D: Early recurrent embolism associated with nonvalvular atrial fibrillation. A retrospective study. Stroke 14:688-693, 1983. 9. Cerebral Embolism Study Group: Immediate anticoagulation of embolic stroke. A randomized trial. Stroke 14:668-676, 1983. 10. Shields RW, Laureno R, Lachman T, et al: Anticoagulant-related hemorrhage in acute cerebral embolism. Stroke 15:426-437, 1984. 11. Miller VT, Hart RG: Heparin anticoagulation in acute brain ischemia. Stroke 19:403-406, 1988. 12. Sheinberg P: Heparin anticoagulation. Stroke 20 :173174, 1989. 13. Phillips SJ: An alternative view of heparin anticoagulation in acute focal brain ischemia. Stroke 20:295-298, 1989. 14. Yatsu FM, Hart RG, Mohr JP, et al: Anticoagulation of embolic strokes of cardiac origin. An update. Neurology 38:730-734, 1988. 15. Rothrock JF, Dittrich HC, McAllen S, et al: Acute anticoagulation following cardioembolic stroke. Stroke 20:730-734, 1989.
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
892 16.
17.
18.
19. 20.
Park YD, Sakakibara H, et al: Clinical feaof intracardiac thrombosis based on echocardiographic observation. Jpn Circ J 48:75-82, 1984. Yasaka M, Yamaguchi T, Miyashita T, et al: Predisposing factors of recurrent embolization in cardiogenic cerebral embolism. Stroke 21:1000-1007, 1990. Furlan AJ, Cavalier SJ, Hobbes RE, et al: Hemorrhage and anticoagulation after nonseptic brain infarction. Neurology 32:280-282, 1982. Martin GJ, Biller J: Nonseptic cerebral emboli of cardiac origin. Arch Intern Med 144:1997-1999, 1984. Okada Y, Yamaguchi T, Minematsu K, et al: Hemor-
transformation in cerebral embolism. Stroke
Beppu S,
rhagic
tures
20:598-603, 1989. 21. Laurent JP, Molinari GF, Oakley JC: Primate model of cerebral hematoma. J Neuropathol Exp Neurol 35:560-568, 1976. 22. Faris AA, Hardin CA, Poser CM: Pathogenesis of hemorrhagic infarction of the brain. I. Experimental investigations of role of hypertension and of collateral circulation. Arch Neurol 9:468-472, 1963. 23. Yasaka M, Yamaguchi T, Miyashita T, et al: Regression of intracardiac thrombus after embolic stroke. Stroke 21:1540-1544, 1990.
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
for Intracardiac Thrombus in Acute Cardioembolic Stroke
Anticoagulation
Masahiro Yasaka, M.D. and Takenori
Yamaguchi,
M.D.
OSAKA, JAPAN
Abstract To assess the efficacy of immediate anticoagulation therapy on intracardiac thrombus formation in acute cardioembolic stroke, serial two-dimensional echocardiographic examinations were performed in 25 patients with acute cardioembolic stroke. Anticoagulation therapy was commenced within two days of onset in 7 patients (group A) but not in 18 patients (group B). Appearance or enlargement of intracardiac thrombi were not detected in group A but were noted in 7 patients (39%) of group B. Recurrence of systemic embolism was demonstrated in 3 patients (17%) of group B. There were no serious hemorrhagic complications in either group. Immediate anticoagulation could, therefore, be effective in preventing intracardiac thrombus formation and the consequent recurrence of systemic embolization in acute cardioembolic stroke. Because the study was preliminary and not randomized, further randomized study is desirable to establish the efficacy of immediate anticoagulation therapy.
Introduction Recurrence of embolization is a serious problem in patients with cardioembolic stroke.’-8 It has been established that anticoagulation in the chronic stage of embolization is effective in preventing recurrent attacks. 3-5 Most attacks usually occur, however, within two weeks of the initial event,5-8 and immediate anticoagulation in this period has been under dispute- 9-15 There have been few reports documenting the effect of immediate anticoagulation on the prevention of the formation of an intracardiac thrombus as a direct embolic source in patients with acute cardiogenic embolism. To address this question, we preliminarily performed serial two-dimensional echocardiographic examinations in patients with acute cardiogenic embolic stroke receiving immediate anticoagulation and in an untreated control group. From the Cerebrovascular Division,
Department
of Medicine, National Cardiovascular Center, Osaka,
886
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
Japan
887
Subjects and Methods Thirty consecutive patients were admitted to the Stroke Care Unit of the National Cardiovascular Center within forty-eight hours of cerebral embolism between June 1, 1986, and January 31, 1987. Good echocardiograms were obtained in 25 of the 30 patients, and these were entered into the study. There were 7 men and 18 women, ranging in age from thirty-eight to eighty-one years, with a mean of sixty-three years. The diagnosis of cerebral embolism was performed according to the criteria reported by Yamaguchi et al.’ Two-dimensional echocardiograms were obtained with a commercially available real-time, phased-array system with 3.75 MHz transducer. Echocardiographic examinations were performed at the time of admission and at days 4, 7, 10, 14, 21, and 28 after the onset of cerebral embolism. When an intracardiac thrombus was detected, echocardiographic examinations were repeated daily until the twenty-eighth day or until the intracardiac thrombus disappeared. Patients were examined in a left recumbent or supine position. The cardiac chambers, especially the left atrial and ventricular cavities, were examined extensively by shifting, rotating, and tilting the transducer and by adjusting the gain control of the equipment if necessary. The echocardiographic diagnosis of an intracardiac thrombus was made when a mass echo with a clearly defined contour was observed inside the cardiac chamber, when the echo of endocardial surface was identified, and when the echo of the mass was visualized from several positions on the chest wall.’6 A thrombus was considered to have enlarged when it had become 1.5 times larger than its previous size on the view where the thrombus was best visualized. A I
considered to be mobile if it showed motion independent of the adjacent endocardium, either opposite in direction or freely erratic. None of the 25 patients had previously received an anticoagulant. After admission, anticoagulant therapy was selective and varied according to the discretion of the patient’s primary
thrombus
was
physician. Immediate anticoagulation was started in 7 patients (group A) within two days of the onset. None of them had had infective endocarditis or hypertension. The infarct was located only in a part of the region supplied by the middle cerebral artery or the posterior cerebral artery and was not hemorrhagic on computed tomographic (CT) scan before anticoagulation commenced. Brain CT examinations were performed on the first hospital day in all patients and were TABLE I Cardiac
Underlying
Etiologies
~----
*Mitral valve replacements (a Mitrofro valve and a **The patient had calcification of the aortic valve.
Bjork-Shiley valve).
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
888
repeated at least every ten hospital days during the observation period. Heparin and warfarin potassium were used as the anticoagulant drugs. Heparin treatment was initiated with a bolus injection of 70 units X body weight (kg) intravenously followed by a constant infusion regulated to maintain the activated partial thromboplastin time between 2 and 3 times control values. Within fourteen days of commencement of heparin treatment, its administration was changed to oral. Oral anticoagulation was aimed at maintaining a prothrombic time (international normalized ratio) between 2.5 and 3.5. The remaining 18 patients (group B) did not receive any anticoagulant unless a newly formed intracardiac thrombus
was
noted.
Results All 25 patients had heart disease that was considered to be a source of emboli (Table I). Patients with rheumatic heart disease were all found to have mitral stenosis on echocardiog-
raphy. In group A, all but 1 patient (eighty-one years old) were under the age of seventy years. In the oldest patient, immediate anticoagulation was begun to avoid recurrent attacks, since she had already suffered her third attack. In 6 patients of group A, hemorrhagic transformation was noted on CT scans from the fourth to nineteenth day of anticoagulation. Two of them were petechial hemorrhages. The other four were small hematomas, less than 2 cm in diameter in the ischemic area, showing no mass effect. Neurologic deterioration due to these minor hemorrhagic transformations was not noted. An intracardiac thrombus was found in only 1 patient of group A at admission. After commencement of anticoagulant therapy, this thrombus gradually decreased in size and had disappeared by the fifteenth day (Figure 1). In the other 6 patients of this group, no intracardiac thrombus was detected during the observation period. Moreover, no recurrent attacks occurred during the anticoagulation period.
FIG. 1. Left
parasternal short-axis view. A thrombus was detected at disappeared after anticoagulation (middle and right).
decreased in size and
the left atrial appendage at admission AO: aortic valve. LA: left atrium.
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
(left).
It
889 TABLE II Intracardiac Thrombus and Recurrent Attacks in
Group
B
RHD: rheumatic heart disease; AF: atrial fibrillation, APP: left atrial appendage, HHD: hypertensive heart disease, AMI: infarction, Apex: left ventricular apex, HCM: hypertrophic cardiomyopathy, AoV: aortic valve. *The right upper extremity, **the left lower extremity, ***cerebral embolism, #calcification of the aortic valve.
myocardial
confirmed in 3 patients at admission (Table II). All these thrombi were seen to enlarge generally within fourteen days of admission. In 4 of the remaining 15 patients, newly formed intracardiac thrombi appeared in the first fourteen days of the observation period. In total, growth of the intracardiac thrombus was seen in 7 of the 18 patients (39 % ) during observation. Systemic embolization recurred in 3 of the 7 group B patients with intracardiac thrombi. All these patients had mitral stenosis, with a mobile thrombus at the left atrial appendage. The first of these was a fifty-five-year-old woman in whom an intracardiac thrombus was not detected on admission nor on days 4 or 7. On day 10, a mobile intracardiac thrombus was observed and anticoagulant therapy was initiated (Figure 2). Embolization to the right upper extremity occurred on day 14, and immediately after embolization, the intracardiac thrombus was no longer detectable by echocardiography. The second patient was a thirty-eight-year-old woman without an intracardiac thrombus at admission or on day 4. On day 7, she had a recurrent stroke, and a mobile thrombus was detected at the left atrial appendage. Anticoagulation with warfarin was initiated on the same day to prevent an additional recurrence. The third patient was a sixty-five-year-old woman, in whom no intracardiac thrombus was detectable either at admission or on day 4. On day 6 she suddenly developed an embolization to the left lower extremity. A mobile thrombus was detected at the left atrial appendage on day 7. In 11 patients of group B, hemorrhagic transformation of the infarct was demonstrated on CT scans from two to twenty-one days after onset. Nine were petechial hemorrhages and 2 were small hematomas, which did not cause neurologic deterioration. In 2 of these patients, anticoagulation was commenced after the detection of an intracardiac thrombus, in one on day 7 and the other on day 10. They developed petechial hemorrhage and small hemorrhage, In group
B,
an
intracardiac thrombus
acute
was
respectively. Two patients
in group B died during the observation period: 1 on day 4 of panperitonitis due to mesenteric arterial embolism complicated at admission and the other on day 5 owing to brain herniation. Discussion We have
already reported that dehydration accelerates intracardiac thrombus formation in
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
890
an
Ftc. 2. Left parasternal short-axis view. No thrombi were noted at admission, on day 4 or on day 7 (left). But on day 10, intracardiac thrombus appeared at the left atrial appendage (right). AO: aortic valve. LA: left atrium.
patients with acute cardioembolic stroke.&dquo; Avoidance of dehydration during the acute phase of cardioembolic stroke may thus be useful in the prevention of the recurrence of embolism. However, heart failure is so often noted in these patients that dehydration therapy, using diuretics, is sometimes inevitable. We consider that in these patients at least immediate anticoagulation should be considered. Several authors have reported a reduction in the incidence of recurrent attacks with anticoagulant treatment without the associated morbidity from brain hemorrhage or other hemorrhagic complications.9,18,19 There are no reports, however, on the value of immediate anticoagulation in the reduction of the incidence of intracardiac thrombus formation as a direct recurrent embolic source. The appearance or enlargement of thrombi were observed in 7 patients of group B. Most of the growth was detected within fourteen days of the onset of the embolic stroke. These observations are consistent with the fact that systemic embolism tends to recur most frequently during this period. 5-8 A 39 % incidence of intracardiac thrombus growth (4 newly formed; 3 enlarged) was seen in the control group B but none in group A. Moreover, recurrent attacks were noted in 3 patients of group B and none in group A. These data suggest that acute anticoagulation could prevent the formation of intracardiac thrombus as a direct source of emboli and consequent recurrent embolization. Serious hemorrhagic transformation of an infarct or other hemorrhagic complications were
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
891
apparent in patients receiving anticoagulant therapy. The reasons may be that all but 1 were under seventy, they . were all normotensive, and their hypodense areas were relatively small. Hemorrhagic transformation in patients with acute embolic stroke has been linked to advanced age or size of the infarct area.2° Some reports have linked hemorrhagic transformation to hypertension.2’.22 Particular care should, therefore, be taken in performing immediate antinot
coagulation in patients of advanced age or with large infarction or hypertension. In the patients in group A with an intracardiac thrombus detected at admission, the intracardiac thrombus regressed gradually on anticoagulant therapy. We suggest this is due to the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin
activity.23 Conclusion The results of this study indicate that immediate anticoagulation could be useful in preventing intracardiac thrombus formation itself and consequent recurrent embolization in patients suffering an acute cardiogenic cerebral embolism. Because our study was preliminary and not randomized, further randomized study is desirable to establish the efficacy of immediate anti-
coagulation therapy. Masahiro Yasaka, M. D. Cerebrovascular Division Department of Medicine National Cardiovascular Center 5-7-1, Fujishirodai , Suita City
Osaka, Japan
References 1.
Minematsu K, Choki J, et al: Clinical and neuroradiological analysis of thrombotic and embolic cerebral infarction. Jpn Circ J 48:50-58, 1984. 2. Darling RC, Austen WG, Linton RR: Arterial embo-
Yamaguchi T,
lism. Surg Gynecol Obstet 124:106-114, 1967. 3. Carter AB: Prognosis of cerebral embolism. Lancet 2:514-519, 1965. 4. McDevitt E, Carter SA, Gatje BE, et al: Use of anticoagulant in treatment of cerebrovascular disease. JAMA 166:592-597, 1958. 5. Cerebral Embolism Task Force: Cardiogenic brain embolism. The second report of the Cerebral Embolism Task Force. Arch Neurol 46:727-743, 1989. 6. Yamaguchi T, Minematsu K, Choki J, et al: Recurrent cerebral embolism and factors related to early recurrence. Analysis of 186 consecutive cases. In: Central Nervous System Control of the Heart, ed. by Stober T, Schimrigk K, Ganten D, et al. Boston: Martinus Nijhoff, 1986, pp 237-243. 7. Sherman DG, Goldman L, Whiting RB, et al: Thromboembolism in patients with atrial fibrillation. Arch Neurol 41:708-710, 1984.
8. Hart RG, Coull BM, Hart D: Early recurrent embolism associated with nonvalvular atrial fibrillation. A retrospective study. Stroke 14:688-693, 1983. 9. Cerebral Embolism Study Group: Immediate anticoagulation of embolic stroke. A randomized trial. Stroke 14:668-676, 1983. 10. Shields RW, Laureno R, Lachman T, et al: Anticoagulant-related hemorrhage in acute cerebral embolism. Stroke 15:426-437, 1984. 11. Miller VT, Hart RG: Heparin anticoagulation in acute brain ischemia. Stroke 19:403-406, 1988. 12. Sheinberg P: Heparin anticoagulation. Stroke 20 :173174, 1989. 13. Phillips SJ: An alternative view of heparin anticoagulation in acute focal brain ischemia. Stroke 20:295-298, 1989. 14. Yatsu FM, Hart RG, Mohr JP, et al: Anticoagulation of embolic strokes of cardiac origin. An update. Neurology 38:730-734, 1988. 15. Rothrock JF, Dittrich HC, McAllen S, et al: Acute anticoagulation following cardioembolic stroke. Stroke 20:730-734, 1989.
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
892 16.
17.
18.
19. 20.
Park YD, Sakakibara H, et al: Clinical feaof intracardiac thrombosis based on echocardiographic observation. Jpn Circ J 48:75-82, 1984. Yasaka M, Yamaguchi T, Miyashita T, et al: Predisposing factors of recurrent embolization in cardiogenic cerebral embolism. Stroke 21:1000-1007, 1990. Furlan AJ, Cavalier SJ, Hobbes RE, et al: Hemorrhage and anticoagulation after nonseptic brain infarction. Neurology 32:280-282, 1982. Martin GJ, Biller J: Nonseptic cerebral emboli of cardiac origin. Arch Intern Med 144:1997-1999, 1984. Okada Y, Yamaguchi T, Minematsu K, et al: Hemor-
transformation in cerebral embolism. Stroke
Beppu S,
rhagic
tures
20:598-603, 1989. 21. Laurent JP, Molinari GF, Oakley JC: Primate model of cerebral hematoma. J Neuropathol Exp Neurol 35:560-568, 1976. 22. Faris AA, Hardin CA, Poser CM: Pathogenesis of hemorrhagic infarction of the brain. I. Experimental investigations of role of hypertension and of collateral circulation. Arch Neurol 9:468-472, 1963. 23. Yasaka M, Yamaguchi T, Miyashita T, et al: Regression of intracardiac thrombus after embolic stroke. Stroke 21:1540-1544, 1990.
Downloaded from ang.sagepub.com at UNIV CALGARY LIBRARY on April 13, 2015
