Spontaneous Peripheral Arterial Microembolization Steven G. Katz, MD, Roy D. Kohl, MD, Pasadena, California
Over a seven year period 52 patients having a clinical diagnosis of spontaneous peripheral arterial microembolization were identified. Sixty-one percent of patients were female, 15% were diabetic, and 73% used tobacco chronically. A striking finding was the very high incidence of associated systemic disorders such as thrombocytosis (8), polycythemia vera (3), metastatic adenocarcinoma (3), or collagen disease requiring steroid therapy (4). Forty-nine patients had significant proximal arterial lesions as the origin of their emboli. Three patients had digital ischemia as a result of increased platelet aggregation without arterial obstruction. Forty-eight patients underwent surgical therapy. Operative mortality was 4% and overall limb salvage in survivors was 96%. The clinical syndrome of arterial microembolization may result from several pathophysiologic mechanisms including cholesterol embolization from ulcerated plaques, fibrino-platelet aggregation in patients with hematologic disorders, or dislodgement of mural thrombus in those with aneurysmal disease. We observed aortoiliac disease to be more frequent than femoral-popliteal disease, and both were amenable to surgical correction. We conclude that the genesis of arterial microembolization is multifactorial and that a variety of systemic diseases may work in concert with atherosclerotic arterial disease to produce this clinical syndrome. Prompt recognition and appropriate treatment of this disorder can yield high rates of limb salvage. (Ann Vasc Surg 1992;6:334-337). KEY WORDS: Peripheral vascular disease; arterial microembolization; embolism; digital ischemia; "blue toe" syndrome.
Acute digital ischemia may result from a number of causes. Absent peripheral pulses and poorly perfused extremities will account for the majority. There remains a group of patients who present with the sudden onset of painful, cyanotic digits yet well perfused limbs, unrelated to macroembolization or thrombosis. In the past, these people have often been mistakenly diagnosed as suffering from a variety of diseases including gout, vasculitis, vasoFrom the Department of Vascular Surgery, Huntington Memorial Hospital, Pasadena, California. Presented at the Tenth Annual Meeting of the Southern California Vascular Surgical Society, September 27-29, 1991, Marina Del Rey, California. Reprint requests: Steven G. Katz, MD, 10 Congress Street, Suite 504, Pasadena, California 91105.
spasm, or small vessel disease. At present, the most likely diagnosis is ischemia due to arterial microembolization [I-3]. In 1945, Florey theorized that emboli of cholesterol crystals could produce distal gangrene. Fourteen years passed until Hoye validated this hypothesis [4,5]. Crane later reported the successful treatment of this syndrome by resecting the offending proximal ulcerative artherosclerotic plaque in three patients [6]. In the early 1970s Kwaan, Connelley, and Karmody further popularized the notion that arterial microembolization accounts for the majority of cases of digital ischemia in the face of patent proximal vessels [1,7,8]. The "blue toe" syndrome has aptly described this condition. The primary investigative focus has centered on its
334
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clinical presentation and its association with cholesterol microemboli. Few reports have described the associated systemic disorders that may play a role in the pathogenesis of this clinical syndrome. Over the last seven years we have encountered 52 patients who presented with digital cyanosis in otherwise well perfused extremities. This article will describe the clinical features, risk factors, associated systemic diseases, treatment, and outcomes in this group of patients. From this experience we have observed that the genesis of spontaneous arterial microembolization is multifactorial, and that cholesterol emboli from ulcerative plaques represent only one of several possible etiologies of this syndrome.
MATERIALS AND METHODS The records of all patients treated by us between January of 1984 and January of 1991 were reviewed. Fifty-two patients with the clinical diagnosis of spontaneous peripheral arterial microembolization were identified. Aortography with runoff was performed in all cases. The records of all patients were analyzed with regard to age, sex, associated risk factors, location of emboli, arterial pathology, treatment, clinical outcome, and associated disease. The diagnosis was based on the findings of digital ischemia and cyanosis in an otherwise well perfused extremity. All patients had ankle-brachial indices greater than 0.50 with arteriographically patent proximal vessels.
RESULTS The study was comprised of 32 women and 20 men. They ranged in age from 49 to 94 years, with the average being 69. Seventy-three percent of patients smoked 20 or more cigarettes per day. Sixty-one percent had hypertension, 32% had symptomatic heart disease, 17% had chronic obstructive lung disease requiring therapy, and 11% had hyperlipidemias. Only 15% were diabetic. The upper extremity was involved in six of the 52 patients. Five had unilateral, left-sided involvement, and one patient with thrombocytosis had bilateral disease. Digital cyanosis and palpable wrist pulses were present in all patients, none of whom had lower extremity involvement. Forty-six patients had emboli to the lower extremities. Fourteen patients had bilateral symptoms, and 32 patients had only one extremity affected. Palpable pulses at the ankle were present in 60% of patients with emboli to the lower extremities. Of the six patients with upper extremity involvement, five had stenotic or ulcerated atherosclerotic lesions involving the left subclavian artery. A single
335
patient with thrombocytosis had no arteriographically demonstrable large vessel pathology. All 14 patients with bilateral emboli of the lower extremity had arterial disease involving the infrarenal aorta and its abdominal branches; of these, five patients had aortic aneurysms. The remaining nine had significant atherosclerotic disease of their aorta and iliac vessels. Unilateral involvement of the lower extremities was observed in 32 patients; of these, two had aortic aneurysms. Aortoiliac occlusive disease was found in 15 patients, one of whom had mild disease (47%), and a similar number of patients (14) had disease confined to the femoral-popliteal vessels. A single patient had thrombocytosis with no demonstrable arterial pathology seen on biplanar views of the aorta, iliac, and femoral arteries. Associated systemic disease was seen in a relatively high number of patients. Twenty-one percent of patients were found to have myeloproliferative disorders (eight with essential thrombocytosis and two with polycythemia vera). Three patients had metastatic adenocarcinoma, four had collagen vascular disease requiring corticosteroid therapy, and histiocytic lymphoma and chronic lymphocytic leukemia were seen in one patient each. All but three had significant arterial pathology in addition to their associated disease.
TREATMENT Ninety-two percent of the patients in this study underwent arterial reconstruction. Four patients with emboli to the left had undergone carotidsubclavian bypass with ligation of the proximal subclavian artery. The one patient with bilateral upper extremity involvement and no large vessel disease was successfully treated with antiplatelet therapy. The remaining patient with disseminated carcinoma received supportive therapy, although a significant atherosclerotic lesion in the left subclavian artery was present; she died two months later. The seven patients with aortoiliac aneurysmal disease had aneurysm resection. Five patients with aortoiliac occlusive disease had an endarterectomy performed; 14 patients were treated with end-to-end aortobifemoral bypass; three patients had axillobifemoral bypass and femoral artery ligation; and one patient had an iliac balloon angioplasty. Of the 14 patients with femoropopliteal artery involvement, two with short segment disease were treated with endarterectomy and patch angioplasty. The 12 patients with more diffuse disease underwent femoral-popliteal bypass grafting with proximal artery ligation. Two patients received medical treatment only. The overall operative mortality was 4%. In follow-up ranging from nine months to seven years (mean 38 months), five patients required toe
336
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amputations and one patient required below-knee amputation. The below-knee amputation was performed despite a patent reconstruction. This patient had emboli from a large aortic aneurysm and had his amputation for gangrene before aneurysm resection. In addition to operative intervention, patients with myeloproliferative disorders or carcinoma were treated with appropriate antineoplastic chemotherapy. This included aikylating agents, radioactive phosphorus, and hydroxyurea. Patients with platelet counts of 400,000 or greater were treated with 300 mg of aspirin twice daily. The remainder received no adjunctive therapy.
DISCUSSION Arterial microembolization is now recognized as a significant cause of digital ischemia [%20]. The clinical syndrome results from embolic occlusion of vessels in the 100-600 micron range, leading to pain, lividity, cyanosis, and occasional gangrene of the affected digits [2]. Embolic material may include plaque with cholesterol crystals, laminated thrombus, or fibrin-platelet aggregates [1]. The clinical presentation is sometimes variable, and symptoms may be evanescent. Nevertheless, the appearance of a cyanotic, painful digit in an otherwise viable, well-perfused extremity should suggest the diagnosis and lead to a thorough vascular and hematologic evaluation. The clinical appearance of the extremity does help not differentiate between the various etiologic factors which may be operational in any individual patient. The demographics and risk factors in our group of patients were somewhat unusual. The ratio of female-to-male patients was unusually high, while the number of diabetic patients was low. A most striking finding was the high proportion of patients with myeloproliferative disorders, metastatic adenocarcinoma, or collagen vascular disease requiring corticosteroids. Patients with polycythemia vera or essential thrombocytosis have long been known to have increased platelet clumping. Recent studies have demonstrated that 50% of patients with carcinoma and 95% of patients with metastasis will show some laboratory evidence of increased platelet aggregability [21-23]. Thirty to 60% of cancer patients will also have some elevation of their platelet count. In addition, malignant cells have been shown to increase the response of platelets to adenosine diphosphate and thrombin [21]. Various rheumatologic disorders have been associated with an increase in platelet activity and episodes of arterial thrombosis; a recent report has also linked corticosteroid administration to occurrences of the "blue toe" syndrome in a patient with systemic lupus erythematosis [24,25]. Any disorder that increases
ANNALS OF VASCULAR SURGERY
the activity of platelets may predispose one to experience episodes of arterial microembolization with an atherosclerotic plaque often serving as the nidus for platelet aggregate formation. Ninety-four percent of our patients with arterial microembolization had significant proximal arterial disease. There were three exceptions and all had essential thrombocytosis and platelet counts in excess of 1,000,000. Karmody, who coined the term "blue toe syndrome," reported that 80% of his patients had occlusive disease predominantly involving the femoral and popliteal arteries [1]. In contrast, roughly half of our patients with unilateral symptomatology had disease primarily located in the aorta and iliac arteries, while all patients with bilateral emboli had disease located above the aortic bifurcation. The absence of pedal pulses does not eliminate the possibility of microemboli; 40% of our patients had no palpable ankle pulses and were found to have tightly stenotic but patent vessels by arteriography. Management of this disorder most often requires appropriate operative management coupled with treatment of any associated systemic disease. Medical therapy alone has met with only limited success [26,27]. Heparin and warfarin anticoagulants, which are essential to the treatment of cardiac origin emboli, have been of little value in the treatment of microemboli [28]. Some investigators have postulated that anticoagulants may in fact promote microemboli by interfering with the healing of plaque ulcerations [27,30,31]. Drugs that affect platetet aggregation may be of value in treating microemboli caused by fibrin-platelet emboli but would reasonably be expected to be of little benefit in those patients with cholesterol embolization. The modest success of medical therapy alone may be contrasted with the results of several surgical series which report 90% limb salvage rates [1-3,7,9,32]. This is only to be expected since the vast majority of patients will have significant segmental arterial disease serving as a nidus for embolization. Several recent reports have suggested that percutaneous angioplasty and atherectomy may be an alternative to surgical intervention. However, the series are anecdotal and follow-up has been too brief to allow judgment of its place in the treatment of this syndrome [33,34]. When the syndrome of arterial microembolization is suspected, a search for both a proximal embolic source as well as an underlying systemic disease should be made. Although noninvasive testing may suggest the presence of arterial pathology, only arteriography selectively employing biplanar views will be diagnostic. Bilateral embolization implies that the responsible disease is at or above the aortic bifurcation, whereas unilateral lesions may result from disease in the aortoiliac or femoropopliteal segment. Thus, we have based our opera-
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S P O N T A N E O US PERIPHERAL MICROEMBOLIZA TION
tive t h e r a p y in p a t i e n t s with t w o levels of d i s e a s e o n its a r t e r i o g r a p h i c s e v e r i t y . O t h e r s h a v e s u g g e s t e d a p p r o a c h i n g the m o r e p e r i p h e r a l d i s e a s e first w h e n inflow a n d o u t f l o w d i s e a s e c o e x i s t [35]. W e h a v e n o t a d o p t e d this r a t i o n a l e a n d h a v e s e e n n o recurr e n c e o f e m b o l i in o u r s u r g i c a l l y t r e a t e d p a t i e n t s . S u c c e s s f u l surgical t r e a t m e n t r e q u i r e s r e m o v a l or e x c l u s i o n of the o f f e n d i n g lesion f r o m the arterial s t r e a m a n d r e s t o r a t i o n o f arterial c o n t i n u i t y . This m a y b e a c c o m p l i s h e d b y e n d a r t e r e c t o m y for short s e g m e n t a l d i s e a s e o r b y p a s s for m o r e diffusely d i s e a s e d arteries. S y m p a t h e c t o m y m a y be helpful in h e a l i n g e x i s t i n g l e s i o n s , b u t s h o u l d be c o n s i d e r e d as a n a d j u n c t i v e p r o c e d u r e a n d o f s e c o n d a r y i m p o r t a n c e . P a t i e n t s with m y e l o p r o l i f e r a t i v e d i s o r d e r s should h a v e a p p r o p r i a t e c h e m o t h e r a p y before arterial r e c o n s t r u c t i o n to help m i n i m i z e p e r i o p e r a t i v e t h r o m b o s i s a n d h e m o r r h a g e ; we agree with the r e c o m m e n d a t i o n that p a t i e n t s with a u t o i m m u n e d i s o r d e r s be r o u t i n e l y s c r e e n e d for a n t i p h o s p h o lipid a n t i b o d i e s b e f o r e o p e r a t i v e i n t e r v e n t i o n is c o n s i d e r e d [24]. A t h e r o s c l e r o t i c arterial d i s e a s e m a y w o r k in c o n c e r t with h e m a t o l o g i c d i s o r d e r s to p r o d u c e m i c r o e m b o l i . E a r l y d i a g n o s i s c o u p l e d with a c o m p r e h e n s i v e t r e a t m e n t p l a n utilizing surgical t h e r a p y as its k e y s t o n e s h o u l d a c h i e v e limb salvage in a v e r y high p r o p o r t i o n o f p a t i e n t s with arterial microembolization.
REFERENCES 1. KARMODY AM, POWERS SR, MONACO VJ, et al. Blue toe syndrome. Arch Surg 1976;111:1263-1268. 2. KEMPCZINSKI RF. Lower extremity arterial emboli from ulcerating atherosclerotic plaques. JAMA 1979;241:807-810. 3. WAGNER RB, MARTIN AS. Peripheral atheroembolism. Surgery. 1973;73:353-359. 4. FLORY CM. Arterial occlusions produced by emboli from eroded atheromatous aortic plaque. A m J Pathol 1945;21: 549-565. 5. HOYE SJ, TEITLEBAUM S, GORE I, et al. Atheromatous embolization, a factor in peripheral gangrene. N Engl J Med 1959;261:128-130.
6. CRANE C. Atherothrombotic embolism to lower extremities in atherosclerosis. Arch Surg 1%7;94:96. 7. KWAAN JHM, CONNOLLY JE. Peripheral atheroembolism. Arch Surg 1977;112:987-990. 8. KWAAN JHM, VANDERMOLER R, STEMMER EA, et al. Peripheral embolism resulting from unsuspected atheromatous aortic plaques. Surgery 1975;78:583-588. 9. BENVEGNA S, CASSINO I, GUINTINI G, et al. Atherothrombotic microembolism of the lower extremities. J Cardiovasc Surg 1990;31:87-91. 10. McLEAN NR, IRVINE BH, CALVERT MH. Peripheral embolic phenomena from proximal arterial disease. J Roy Coll Surg Edin 1984;29:205-209.
iliU
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11. BANIS JC, RICH N, WHELAN TJ. Ischemia of the upper extremity due to noncardiac emboti. A m J Surg 1977;134: 131-139. 12. MOORE DJ, KINGSTON V, SHANIK DG. Experience with the blue toe syndrome. Irish Med J 1982;75:46--48. 13. GORE 1, COLLINS DP. Spontaneous atheromatous embolization. A m J Clin Pathol 1960;33:416-426. 14. ROSENBERG MW, SHAH DM. Bilateral blue toe syndrome. JAMA 1980;243:365-367. 15. RETAN JW, MILLER RE. Microembolic complications of atherosclerosis. Arch Int M e d 1966;118:534-545. 16. WINGO JP, NIZ LM, GREENFIELD LJ, et al. The blue toe syndrome. J Vasc Surg 1986;3:475-479. 17. RICHARDS AM, ELLIOT RS, KANJUH VI, et al. Cholesterol embolism. Am J Cardiol 1965;15:696-707. 18. MEHIGAN JT, STONEY RJ. Arterial microemboli and fibromuscular dysplasia of the external iliac arteries. Surgery 1977:81 :484-486. 19. KAUFMAN JL, STARK K, BROLIN RE. Disseminated atheroembolism from extensive degenerative atherosclerosis of the aorta. Surgeo" 1987;102:63-67. 20. MEHIGAN JT. STONEY RJ. Lower extremity atheromatous embolization. Am J Surg 1976;132:163-167. 21. NAND S, MESSMORE N. Hemostasis in malignancy. A m J Hernatol 1990;35:45-55. 22. EY FS, GOODNIGHT SH. Bleeding disorders in cancer. Semin Oncol 1990;17:187-197. 23. COLMAN RW, RUBIN RN. Disseminated intravascular coagulation due to malignancy. Semin Oncol 1990;17:172186. 24. TETTA C, MODENA V, MONTRUCCIO G, et al. Release of platetet activating factors in systemic lupus erythematosis. lnt Arch Appl lmrnunol 1990;91:244-256. 25. DAVIES GE, TRIPLETT DA. Corticosteroid associated blue toe syndrome. Ann Intern Med 1990;113:893-895. 26. WALDEN R, ADARD A, MOZES M. Gangrene of toes with normal peripheral pulses. Ann Surg 1977;185:26%271. 27. MORRIS-JONES W, PRESTON FE, GREANEY M, et al. Gangrene of the toes with palpable peripheral pulses. Ann Snrg 1981:193:462-466. 28. BRENOWITZ JB, EDWARDS WS. The management of atheromatous emboli to the lower extremities. Surg Gynecol Obstet 1976:143:941-945.
29. ROBERTS B, ROSATO FE, ROSATO EF. Heparin: a cause of arterial emboli? Surgeo' 1964;55:803-808. 30. WEISMANN RE, TOBIN RW. Arterial embolism occurring during systemic heparin therapy. Arch Surg 1958;76:219. 31. BRUNS FJ, SEGEL DP, ADLER S. Control of cholesterol embolization by discontinuation of anticoagulant therapy. Am J Med Sc 1978;275:105-107.
32. PERDUE GD, SMITH RB Ill. Atheromatous microemboli. Ann Surg 1969;169:954-959.
33. BREWER ML, KINNISON ML, PERLER BA, et al. Blue toe syndrome: treatment with anticoagulants and delayed percutaneous transluminal angioplasty. Radiology 1988;166: 31-36~ 34. DOLMATCH BL, RHOLL KS, MOSKOWITZ LB, et al. Blue toe syndrome: treatment with percutaneous atherectomy. Radiology 1989;172:795-804. 35. FISHER DF, CLAGGETT GP, BRIGHAM RA. Dilemmas in dealing with the blue toe syndrome. A m J Surg t984;148:836-839.
Over a seven year period 52 patients having a clinical diagnosis of spontaneous peripheral arterial microembolization were identified. Sixty-one percent of patients were female, 15% were diabetic, and 73% used tobacco chronically. A striking finding was the very high incidence of associated systemic disorders such as thrombocytosis (8), polycythemia vera (3), metastatic adenocarcinoma (3), or collagen disease requiring steroid therapy (4). Forty-nine patients had significant proximal arterial lesions as the origin of their emboli. Three patients had digital ischemia as a result of increased platelet aggregation without arterial obstruction. Forty-eight patients underwent surgical therapy. Operative mortality was 4% and overall limb salvage in survivors was 96%. The clinical syndrome of arterial microembolization may result from several pathophysiologic mechanisms including cholesterol embolization from ulcerated plaques, fibrino-platelet aggregation in patients with hematologic disorders, or dislodgement of mural thrombus in those with aneurysmal disease. We observed aortoiliac disease to be more frequent than femoral-popliteal disease, and both were amenable to surgical correction. We conclude that the genesis of arterial microembolization is multifactorial and that a variety of systemic diseases may work in concert with atherosclerotic arterial disease to produce this clinical syndrome. Prompt recognition and appropriate treatment of this disorder can yield high rates of limb salvage. (Ann Vasc Surg 1992;6:334-337). KEY WORDS: Peripheral vascular disease; arterial microembolization; embolism; digital ischemia; "blue toe" syndrome.
Acute digital ischemia may result from a number of causes. Absent peripheral pulses and poorly perfused extremities will account for the majority. There remains a group of patients who present with the sudden onset of painful, cyanotic digits yet well perfused limbs, unrelated to macroembolization or thrombosis. In the past, these people have often been mistakenly diagnosed as suffering from a variety of diseases including gout, vasculitis, vasoFrom the Department of Vascular Surgery, Huntington Memorial Hospital, Pasadena, California. Presented at the Tenth Annual Meeting of the Southern California Vascular Surgical Society, September 27-29, 1991, Marina Del Rey, California. Reprint requests: Steven G. Katz, MD, 10 Congress Street, Suite 504, Pasadena, California 91105.
spasm, or small vessel disease. At present, the most likely diagnosis is ischemia due to arterial microembolization [I-3]. In 1945, Florey theorized that emboli of cholesterol crystals could produce distal gangrene. Fourteen years passed until Hoye validated this hypothesis [4,5]. Crane later reported the successful treatment of this syndrome by resecting the offending proximal ulcerative artherosclerotic plaque in three patients [6]. In the early 1970s Kwaan, Connelley, and Karmody further popularized the notion that arterial microembolization accounts for the majority of cases of digital ischemia in the face of patent proximal vessels [1,7,8]. The "blue toe" syndrome has aptly described this condition. The primary investigative focus has centered on its
334
VOLUME 6 NO 4 - 1992
S P O N T A N E O U S PERIPHERAL M I C R O E M B O L I Z A T I O N
clinical presentation and its association with cholesterol microemboli. Few reports have described the associated systemic disorders that may play a role in the pathogenesis of this clinical syndrome. Over the last seven years we have encountered 52 patients who presented with digital cyanosis in otherwise well perfused extremities. This article will describe the clinical features, risk factors, associated systemic diseases, treatment, and outcomes in this group of patients. From this experience we have observed that the genesis of spontaneous arterial microembolization is multifactorial, and that cholesterol emboli from ulcerative plaques represent only one of several possible etiologies of this syndrome.
MATERIALS AND METHODS The records of all patients treated by us between January of 1984 and January of 1991 were reviewed. Fifty-two patients with the clinical diagnosis of spontaneous peripheral arterial microembolization were identified. Aortography with runoff was performed in all cases. The records of all patients were analyzed with regard to age, sex, associated risk factors, location of emboli, arterial pathology, treatment, clinical outcome, and associated disease. The diagnosis was based on the findings of digital ischemia and cyanosis in an otherwise well perfused extremity. All patients had ankle-brachial indices greater than 0.50 with arteriographically patent proximal vessels.
RESULTS The study was comprised of 32 women and 20 men. They ranged in age from 49 to 94 years, with the average being 69. Seventy-three percent of patients smoked 20 or more cigarettes per day. Sixty-one percent had hypertension, 32% had symptomatic heart disease, 17% had chronic obstructive lung disease requiring therapy, and 11% had hyperlipidemias. Only 15% were diabetic. The upper extremity was involved in six of the 52 patients. Five had unilateral, left-sided involvement, and one patient with thrombocytosis had bilateral disease. Digital cyanosis and palpable wrist pulses were present in all patients, none of whom had lower extremity involvement. Forty-six patients had emboli to the lower extremities. Fourteen patients had bilateral symptoms, and 32 patients had only one extremity affected. Palpable pulses at the ankle were present in 60% of patients with emboli to the lower extremities. Of the six patients with upper extremity involvement, five had stenotic or ulcerated atherosclerotic lesions involving the left subclavian artery. A single
335
patient with thrombocytosis had no arteriographically demonstrable large vessel pathology. All 14 patients with bilateral emboli of the lower extremity had arterial disease involving the infrarenal aorta and its abdominal branches; of these, five patients had aortic aneurysms. The remaining nine had significant atherosclerotic disease of their aorta and iliac vessels. Unilateral involvement of the lower extremities was observed in 32 patients; of these, two had aortic aneurysms. Aortoiliac occlusive disease was found in 15 patients, one of whom had mild disease (47%), and a similar number of patients (14) had disease confined to the femoral-popliteal vessels. A single patient had thrombocytosis with no demonstrable arterial pathology seen on biplanar views of the aorta, iliac, and femoral arteries. Associated systemic disease was seen in a relatively high number of patients. Twenty-one percent of patients were found to have myeloproliferative disorders (eight with essential thrombocytosis and two with polycythemia vera). Three patients had metastatic adenocarcinoma, four had collagen vascular disease requiring corticosteroid therapy, and histiocytic lymphoma and chronic lymphocytic leukemia were seen in one patient each. All but three had significant arterial pathology in addition to their associated disease.
TREATMENT Ninety-two percent of the patients in this study underwent arterial reconstruction. Four patients with emboli to the left had undergone carotidsubclavian bypass with ligation of the proximal subclavian artery. The one patient with bilateral upper extremity involvement and no large vessel disease was successfully treated with antiplatelet therapy. The remaining patient with disseminated carcinoma received supportive therapy, although a significant atherosclerotic lesion in the left subclavian artery was present; she died two months later. The seven patients with aortoiliac aneurysmal disease had aneurysm resection. Five patients with aortoiliac occlusive disease had an endarterectomy performed; 14 patients were treated with end-to-end aortobifemoral bypass; three patients had axillobifemoral bypass and femoral artery ligation; and one patient had an iliac balloon angioplasty. Of the 14 patients with femoropopliteal artery involvement, two with short segment disease were treated with endarterectomy and patch angioplasty. The 12 patients with more diffuse disease underwent femoral-popliteal bypass grafting with proximal artery ligation. Two patients received medical treatment only. The overall operative mortality was 4%. In follow-up ranging from nine months to seven years (mean 38 months), five patients required toe
336
SPONTANEOUS PERIPHERAL MICROEMBOLIZA TION
amputations and one patient required below-knee amputation. The below-knee amputation was performed despite a patent reconstruction. This patient had emboli from a large aortic aneurysm and had his amputation for gangrene before aneurysm resection. In addition to operative intervention, patients with myeloproliferative disorders or carcinoma were treated with appropriate antineoplastic chemotherapy. This included aikylating agents, radioactive phosphorus, and hydroxyurea. Patients with platelet counts of 400,000 or greater were treated with 300 mg of aspirin twice daily. The remainder received no adjunctive therapy.
DISCUSSION Arterial microembolization is now recognized as a significant cause of digital ischemia [%20]. The clinical syndrome results from embolic occlusion of vessels in the 100-600 micron range, leading to pain, lividity, cyanosis, and occasional gangrene of the affected digits [2]. Embolic material may include plaque with cholesterol crystals, laminated thrombus, or fibrin-platelet aggregates [1]. The clinical presentation is sometimes variable, and symptoms may be evanescent. Nevertheless, the appearance of a cyanotic, painful digit in an otherwise viable, well-perfused extremity should suggest the diagnosis and lead to a thorough vascular and hematologic evaluation. The clinical appearance of the extremity does help not differentiate between the various etiologic factors which may be operational in any individual patient. The demographics and risk factors in our group of patients were somewhat unusual. The ratio of female-to-male patients was unusually high, while the number of diabetic patients was low. A most striking finding was the high proportion of patients with myeloproliferative disorders, metastatic adenocarcinoma, or collagen vascular disease requiring corticosteroids. Patients with polycythemia vera or essential thrombocytosis have long been known to have increased platelet clumping. Recent studies have demonstrated that 50% of patients with carcinoma and 95% of patients with metastasis will show some laboratory evidence of increased platelet aggregability [21-23]. Thirty to 60% of cancer patients will also have some elevation of their platelet count. In addition, malignant cells have been shown to increase the response of platelets to adenosine diphosphate and thrombin [21]. Various rheumatologic disorders have been associated with an increase in platelet activity and episodes of arterial thrombosis; a recent report has also linked corticosteroid administration to occurrences of the "blue toe" syndrome in a patient with systemic lupus erythematosis [24,25]. Any disorder that increases
ANNALS OF VASCULAR SURGERY
the activity of platelets may predispose one to experience episodes of arterial microembolization with an atherosclerotic plaque often serving as the nidus for platelet aggregate formation. Ninety-four percent of our patients with arterial microembolization had significant proximal arterial disease. There were three exceptions and all had essential thrombocytosis and platelet counts in excess of 1,000,000. Karmody, who coined the term "blue toe syndrome," reported that 80% of his patients had occlusive disease predominantly involving the femoral and popliteal arteries [1]. In contrast, roughly half of our patients with unilateral symptomatology had disease primarily located in the aorta and iliac arteries, while all patients with bilateral emboli had disease located above the aortic bifurcation. The absence of pedal pulses does not eliminate the possibility of microemboli; 40% of our patients had no palpable ankle pulses and were found to have tightly stenotic but patent vessels by arteriography. Management of this disorder most often requires appropriate operative management coupled with treatment of any associated systemic disease. Medical therapy alone has met with only limited success [26,27]. Heparin and warfarin anticoagulants, which are essential to the treatment of cardiac origin emboli, have been of little value in the treatment of microemboli [28]. Some investigators have postulated that anticoagulants may in fact promote microemboli by interfering with the healing of plaque ulcerations [27,30,31]. Drugs that affect platetet aggregation may be of value in treating microemboli caused by fibrin-platelet emboli but would reasonably be expected to be of little benefit in those patients with cholesterol embolization. The modest success of medical therapy alone may be contrasted with the results of several surgical series which report 90% limb salvage rates [1-3,7,9,32]. This is only to be expected since the vast majority of patients will have significant segmental arterial disease serving as a nidus for embolization. Several recent reports have suggested that percutaneous angioplasty and atherectomy may be an alternative to surgical intervention. However, the series are anecdotal and follow-up has been too brief to allow judgment of its place in the treatment of this syndrome [33,34]. When the syndrome of arterial microembolization is suspected, a search for both a proximal embolic source as well as an underlying systemic disease should be made. Although noninvasive testing may suggest the presence of arterial pathology, only arteriography selectively employing biplanar views will be diagnostic. Bilateral embolization implies that the responsible disease is at or above the aortic bifurcation, whereas unilateral lesions may result from disease in the aortoiliac or femoropopliteal segment. Thus, we have based our opera-
VOLUME6 NO 4 - 1992
S P O N T A N E O US PERIPHERAL MICROEMBOLIZA TION
tive t h e r a p y in p a t i e n t s with t w o levels of d i s e a s e o n its a r t e r i o g r a p h i c s e v e r i t y . O t h e r s h a v e s u g g e s t e d a p p r o a c h i n g the m o r e p e r i p h e r a l d i s e a s e first w h e n inflow a n d o u t f l o w d i s e a s e c o e x i s t [35]. W e h a v e n o t a d o p t e d this r a t i o n a l e a n d h a v e s e e n n o recurr e n c e o f e m b o l i in o u r s u r g i c a l l y t r e a t e d p a t i e n t s . S u c c e s s f u l surgical t r e a t m e n t r e q u i r e s r e m o v a l or e x c l u s i o n of the o f f e n d i n g lesion f r o m the arterial s t r e a m a n d r e s t o r a t i o n o f arterial c o n t i n u i t y . This m a y b e a c c o m p l i s h e d b y e n d a r t e r e c t o m y for short s e g m e n t a l d i s e a s e o r b y p a s s for m o r e diffusely d i s e a s e d arteries. S y m p a t h e c t o m y m a y be helpful in h e a l i n g e x i s t i n g l e s i o n s , b u t s h o u l d be c o n s i d e r e d as a n a d j u n c t i v e p r o c e d u r e a n d o f s e c o n d a r y i m p o r t a n c e . P a t i e n t s with m y e l o p r o l i f e r a t i v e d i s o r d e r s should h a v e a p p r o p r i a t e c h e m o t h e r a p y before arterial r e c o n s t r u c t i o n to help m i n i m i z e p e r i o p e r a t i v e t h r o m b o s i s a n d h e m o r r h a g e ; we agree with the r e c o m m e n d a t i o n that p a t i e n t s with a u t o i m m u n e d i s o r d e r s be r o u t i n e l y s c r e e n e d for a n t i p h o s p h o lipid a n t i b o d i e s b e f o r e o p e r a t i v e i n t e r v e n t i o n is c o n s i d e r e d [24]. A t h e r o s c l e r o t i c arterial d i s e a s e m a y w o r k in c o n c e r t with h e m a t o l o g i c d i s o r d e r s to p r o d u c e m i c r o e m b o l i . E a r l y d i a g n o s i s c o u p l e d with a c o m p r e h e n s i v e t r e a t m e n t p l a n utilizing surgical t h e r a p y as its k e y s t o n e s h o u l d a c h i e v e limb salvage in a v e r y high p r o p o r t i o n o f p a t i e n t s with arterial microembolization.
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