Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Arterial thrombosis in a previously healthy woman Matthew J. Sorrentino MD To cite this article: Matthew J. Sorrentino MD (1992) Arterial thrombosis in a previously healthy woman, Postgraduate Medicine, 91:4, 247-251, DOI: 10.1080/00325481.1992.11701257 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701257
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Otago]
Date: 02 June 2016, At: 03:23
Arterial thrombosis in a previously healthy woman
Matthew J. Sorrentino, MD
Downloaded by [University of Otago] at 03:23 02 June 2016
Preview Unexpected formation of thrombi may be due to antiphospholipid antibody syndrome, a disorder in which clinical and laboratory findings seem to contradict each other. Dr Sorrentino describes a case in which appropriate testing led to the correct diagnosis.
A 43-year-old woman presented at the physician's office afi:er sudden onset of pain in the left flank and right foot. Her health had been excellent, and she had no past history of heart or autoimmune disease. At the time of admission, she was not taking any medications or contraceptives. On physical examination, the right foot was pulseless, pale, and cool. Palpation revealed exquisite tenderness over the left flank. Cardiopulmonary examination showed no abnormalities. An arteriogram revealed occlusion of a branch of the left renal artery to the middle of the kidney, and a nephrogram showed a wedge-shaped defea. The mid portion of the right anterior tibial artery was occluded, and the dorsalis pedis and plantar arteries were not visible. A large amount of dot, consistent with a thrombus on microscop1c exammanon, was surgtcally removed from the anterior tibial artery. A thorough search for a source of an embolus included transesoph•
0
•
ageal echocardiography; which showed normal cardiac chambers, valves, and function. No intracardiac masses or shunts were present. Laboratory findings included a prolonged aaivated partial throm-
• A PERPLEXING CASE
boplastin time of 38.2 seconds. A test for lupus anticoagulant was positive. Anticardiolipin IgM antibodies were weakly positive at 15 mpl; however, anticardiolipin
•
Matthew J. Sorrentino, MD Dr Sorrentino is assistant professor, department of medicine, The University of Chicago Pritzker School of Medicine, and attending physician, The University of Chicago Hospitals.
VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE • ARTERIAL THROMBOSIS
IgG antibodies were absent. Protein C, protein S, and antithrombin III values were within normal range. The diagnosis of primary anti phospholipid antibody syndrome was made, and treatment with warfarin sodium was begun. Following removal of the thrombus from the anterior tibial artery, distal pulses returned to normal and the pain in the left flank gradually resolved. After 1 year of anticoagulant therapy; thrombus formation has not recurred; follow-up tests for lupus anticoagulant and anticardiolipin antibodies were negative.
Disrussion The patient described here presented with manifestations of the primary antiphospholipid antibody syndrome. The syndrome is charaaerized by the occurrence of venous and arterial thromboses, recurrent miscarriages, or thrombocytopenia in patients with detectable levels of antiphospholipid antibodies but no underlying autoimmune disorder. 1 The lupus anticoagulant and IgM and IgG autoantibodies to cardiolipin are the most commonly measured antiphospholipid antibodies, and standardized assays are widely available. In addition, patients with antiphospholipid antibody syndrome may have falsecontinued
247
Downloaded by [University of Otago] at 03:23 02 June 2016
PERPLEXING CASE CONTINUED
positive results on tests for syphilis (eg, rapid plasma reagin, VDRL) because syphilis antibodies are also known to bind phospholipids. Patients with positive results on one test for antiphospholipid antibodies may have negative results on other assays, which suggests that different antibodies are detected by different tests. 1 The lupus anticoagulants are immunoglobulins that are directed against certain phospholipids and interfere with the activation of prothrombin to thrombin. The presence of these antibodies is often indicated by a prolonged activated partial thromboplastin time. However, hemorrhagic manifestations are unusual and thrombotic complications are common. The pathogenesis of recurrent thrombosis in patients with anti phospholipid antibodies remains unclear. One theory is that platelet aggregation increases because these antibodies diminish release by endothelial cells of prostaglandins that normally inhibit darting. Another possible mechanism is the interaction of antibodies with plasminogen activators, which impairs plasmin-mediated thrombolysis.
Finally, antiphospholipid antibodies may decrease activation of protein C or may occur with deficiency of antithrombin III, thus promoting thrombus formation. 1'2 Levels of antiphospholipid antibodies may remain elevated for many years, but thrombosis occurs sporadically. Therefore, an as-yet poorly defined cofactor may be needed to trigger binding of anti phospholipid antibodies to phospholipids and promote dot formation. Patients with high titers of antiphospholipid antibodies may be at an increased risk for thrombotic complications. 1 The prevalence of the lupus anticoagulant is about 2o/o in the general population. 3 More than one third of patients with systemic lupus erythematosus have detectable levels of antiphospholipid antibodies. Thrombotic complications develop in half of these patients. In contrast, thrombotic events occur in only 17o/o of patients without autoimmune disease who test positive for the lupus anticoagulant. 4 The frequency with which thrombosis occurs in patients with antiphospholipid antibodies is highly variable, and dots may not
Readers are invited to submit brief reports of perplexing cases related to primary medical care. Address submissions to: Manuscript Administrator, POSTGRADUATE MEDICINE, 4530 W 77th St, Minneapolis, MN 55435.
248
develop for many years. Antiphospholipid antibodies may disappear from the blood over time, although it is unknown if this reduces the risk of a thrombotic event. The deep veins are the most common site of occlusive thrombosis in patients with antiphospholipid antibodies. Peripheral arterial thrombosis, as in the patient described here, is occasionally seen. Cerebrovascular thrombosis may be an important cause of stroke in young patients with no other predisposing factors. 5 These patients should be tested for the presence of antiphospholipid antibodies. Other manifestations of the antiphospholipid antibody syndrome are myocardial infarction at an early age and skin lesions such as livedo reticularis. In addition, there may be an increased frequency of valvular hean disease, including Libman-Sacks endocarditis. Signs and symptoms of systemic lupus erythematosus should be searched for carefully because of its high association with the presence of antiphospholipid antibodies. Furthermore, careful follow-up is needed in patients who test positive for antiphospholipid antibodies, because active systemic lupus erythematosus may subsequently develop. Patients with antiphospholipid antibody syndrome should receive continued
ARTERIAL THROMBOSIS • VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE
Downloaded by [University of Otago] at 03:23 02 June 2016
PERPLEXING CASE CONTINUED
long-term anticoagulation therapy, although the efficacy of warfarin sodium (Coumadin, Panwarfin, Sofarin) therapy in preventing recurrent thrombosis is unproved. The use of corticosteroids, nonsteroidal anti-inflammatory drugs, or cytotoxic agents does not appear to affect the presence of antiphospholipid antibodies. 2 Rarely, patients with high titers of antiphospholipid antibodies may present with catastrophic formation of disseminated thrombi, which can be treated short-term with plasmapheresis.6
Summary Antiphospholipid antibodies can develop in otherwise healthy people, and their presence substantially increases the risk of thrombotic complications. Patients who have a thrombotic episode for no dear reason need to he tested for the presence of antiphospholipid antibodies. Patients with positive test results benefit from long-term anticoagulation therapy. FaVI Address for correspondence: Matthew J. Sorrentino, MD, Department of Medicine, The University of Chicago Hospitals, 5841 S Maryland Ave, Box 423, Chicago, IL 60637.
ARTERIAL THROMBOSIS
Rd"a-enccs 1. Harris EN. Antiphospholipid antibodies. Br J Haemacol1990;74(1):1-9 2. Elias M, Fldor A. Thromboembolism in patients with the 'lupus'-type circulating anticoagulant. Arch Inrem Med 1984;144(3):510-5 3. Manoussakis MN, Gbaravi AE, Drosos AA, et al. Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients. Clin Immunol lmmunopathol1987;44(3):297-307 4. ~ PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and
in non-SLE disorders: prevalence and clinical significance. Ann Intern Med 1990; 112(9):682-98 5. Asbcrson RA, Khamashta MA, Gil A. et al. Cerebrovascular disease and anti phospholipid antibodies in systemic lupus erythematosus, lupuslike disease, and the primary antiphospholipid syndrome. AmJ Med 1989;86(4):391-9 6. Grcisman SG, Thayaparan RS, Godwin TA, et al. Occlusive vaSculopathy in systemic lupus erythematosus: association with anticardiolipin antibody. Arch Inrem Med 1991;151(2): 389-92
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Arterial thrombosis in a previously healthy woman Matthew J. Sorrentino MD To cite this article: Matthew J. Sorrentino MD (1992) Arterial thrombosis in a previously healthy woman, Postgraduate Medicine, 91:4, 247-251, DOI: 10.1080/00325481.1992.11701257 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701257
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Otago]
Date: 02 June 2016, At: 03:23
Arterial thrombosis in a previously healthy woman
Matthew J. Sorrentino, MD
Downloaded by [University of Otago] at 03:23 02 June 2016
Preview Unexpected formation of thrombi may be due to antiphospholipid antibody syndrome, a disorder in which clinical and laboratory findings seem to contradict each other. Dr Sorrentino describes a case in which appropriate testing led to the correct diagnosis.
A 43-year-old woman presented at the physician's office afi:er sudden onset of pain in the left flank and right foot. Her health had been excellent, and she had no past history of heart or autoimmune disease. At the time of admission, she was not taking any medications or contraceptives. On physical examination, the right foot was pulseless, pale, and cool. Palpation revealed exquisite tenderness over the left flank. Cardiopulmonary examination showed no abnormalities. An arteriogram revealed occlusion of a branch of the left renal artery to the middle of the kidney, and a nephrogram showed a wedge-shaped defea. The mid portion of the right anterior tibial artery was occluded, and the dorsalis pedis and plantar arteries were not visible. A large amount of dot, consistent with a thrombus on microscop1c exammanon, was surgtcally removed from the anterior tibial artery. A thorough search for a source of an embolus included transesoph•
0
•
ageal echocardiography; which showed normal cardiac chambers, valves, and function. No intracardiac masses or shunts were present. Laboratory findings included a prolonged aaivated partial throm-
• A PERPLEXING CASE
boplastin time of 38.2 seconds. A test for lupus anticoagulant was positive. Anticardiolipin IgM antibodies were weakly positive at 15 mpl; however, anticardiolipin
•
Matthew J. Sorrentino, MD Dr Sorrentino is assistant professor, department of medicine, The University of Chicago Pritzker School of Medicine, and attending physician, The University of Chicago Hospitals.
VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE • ARTERIAL THROMBOSIS
IgG antibodies were absent. Protein C, protein S, and antithrombin III values were within normal range. The diagnosis of primary anti phospholipid antibody syndrome was made, and treatment with warfarin sodium was begun. Following removal of the thrombus from the anterior tibial artery, distal pulses returned to normal and the pain in the left flank gradually resolved. After 1 year of anticoagulant therapy; thrombus formation has not recurred; follow-up tests for lupus anticoagulant and anticardiolipin antibodies were negative.
Disrussion The patient described here presented with manifestations of the primary antiphospholipid antibody syndrome. The syndrome is charaaerized by the occurrence of venous and arterial thromboses, recurrent miscarriages, or thrombocytopenia in patients with detectable levels of antiphospholipid antibodies but no underlying autoimmune disorder. 1 The lupus anticoagulant and IgM and IgG autoantibodies to cardiolipin are the most commonly measured antiphospholipid antibodies, and standardized assays are widely available. In addition, patients with antiphospholipid antibody syndrome may have falsecontinued
247
Downloaded by [University of Otago] at 03:23 02 June 2016
PERPLEXING CASE CONTINUED
positive results on tests for syphilis (eg, rapid plasma reagin, VDRL) because syphilis antibodies are also known to bind phospholipids. Patients with positive results on one test for antiphospholipid antibodies may have negative results on other assays, which suggests that different antibodies are detected by different tests. 1 The lupus anticoagulants are immunoglobulins that are directed against certain phospholipids and interfere with the activation of prothrombin to thrombin. The presence of these antibodies is often indicated by a prolonged activated partial thromboplastin time. However, hemorrhagic manifestations are unusual and thrombotic complications are common. The pathogenesis of recurrent thrombosis in patients with anti phospholipid antibodies remains unclear. One theory is that platelet aggregation increases because these antibodies diminish release by endothelial cells of prostaglandins that normally inhibit darting. Another possible mechanism is the interaction of antibodies with plasminogen activators, which impairs plasmin-mediated thrombolysis.
Finally, antiphospholipid antibodies may decrease activation of protein C or may occur with deficiency of antithrombin III, thus promoting thrombus formation. 1'2 Levels of antiphospholipid antibodies may remain elevated for many years, but thrombosis occurs sporadically. Therefore, an as-yet poorly defined cofactor may be needed to trigger binding of anti phospholipid antibodies to phospholipids and promote dot formation. Patients with high titers of antiphospholipid antibodies may be at an increased risk for thrombotic complications. 1 The prevalence of the lupus anticoagulant is about 2o/o in the general population. 3 More than one third of patients with systemic lupus erythematosus have detectable levels of antiphospholipid antibodies. Thrombotic complications develop in half of these patients. In contrast, thrombotic events occur in only 17o/o of patients without autoimmune disease who test positive for the lupus anticoagulant. 4 The frequency with which thrombosis occurs in patients with antiphospholipid antibodies is highly variable, and dots may not
Readers are invited to submit brief reports of perplexing cases related to primary medical care. Address submissions to: Manuscript Administrator, POSTGRADUATE MEDICINE, 4530 W 77th St, Minneapolis, MN 55435.
248
develop for many years. Antiphospholipid antibodies may disappear from the blood over time, although it is unknown if this reduces the risk of a thrombotic event. The deep veins are the most common site of occlusive thrombosis in patients with antiphospholipid antibodies. Peripheral arterial thrombosis, as in the patient described here, is occasionally seen. Cerebrovascular thrombosis may be an important cause of stroke in young patients with no other predisposing factors. 5 These patients should be tested for the presence of antiphospholipid antibodies. Other manifestations of the antiphospholipid antibody syndrome are myocardial infarction at an early age and skin lesions such as livedo reticularis. In addition, there may be an increased frequency of valvular hean disease, including Libman-Sacks endocarditis. Signs and symptoms of systemic lupus erythematosus should be searched for carefully because of its high association with the presence of antiphospholipid antibodies. Furthermore, careful follow-up is needed in patients who test positive for antiphospholipid antibodies, because active systemic lupus erythematosus may subsequently develop. Patients with antiphospholipid antibody syndrome should receive continued
ARTERIAL THROMBOSIS • VOL 91/NO 4/MARCH 1992/POSTGRADUATE MEDICINE
Downloaded by [University of Otago] at 03:23 02 June 2016
PERPLEXING CASE CONTINUED
long-term anticoagulation therapy, although the efficacy of warfarin sodium (Coumadin, Panwarfin, Sofarin) therapy in preventing recurrent thrombosis is unproved. The use of corticosteroids, nonsteroidal anti-inflammatory drugs, or cytotoxic agents does not appear to affect the presence of antiphospholipid antibodies. 2 Rarely, patients with high titers of antiphospholipid antibodies may present with catastrophic formation of disseminated thrombi, which can be treated short-term with plasmapheresis.6
Summary Antiphospholipid antibodies can develop in otherwise healthy people, and their presence substantially increases the risk of thrombotic complications. Patients who have a thrombotic episode for no dear reason need to he tested for the presence of antiphospholipid antibodies. Patients with positive test results benefit from long-term anticoagulation therapy. FaVI Address for correspondence: Matthew J. Sorrentino, MD, Department of Medicine, The University of Chicago Hospitals, 5841 S Maryland Ave, Box 423, Chicago, IL 60637.
ARTERIAL THROMBOSIS
Rd"a-enccs 1. Harris EN. Antiphospholipid antibodies. Br J Haemacol1990;74(1):1-9 2. Elias M, Fldor A. Thromboembolism in patients with the 'lupus'-type circulating anticoagulant. Arch Inrem Med 1984;144(3):510-5 3. Manoussakis MN, Gbaravi AE, Drosos AA, et al. Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients. Clin Immunol lmmunopathol1987;44(3):297-307 4. ~ PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and
in non-SLE disorders: prevalence and clinical significance. Ann Intern Med 1990; 112(9):682-98 5. Asbcrson RA, Khamashta MA, Gil A. et al. Cerebrovascular disease and anti phospholipid antibodies in systemic lupus erythematosus, lupuslike disease, and the primary antiphospholipid syndrome. AmJ Med 1989;86(4):391-9 6. Grcisman SG, Thayaparan RS, Godwin TA, et al. Occlusive vaSculopathy in systemic lupus erythematosus: association with anticardiolipin antibody. Arch Inrem Med 1991;151(2): 389-92
