(Stroke. 1997;28:646-648.)
© 1997 American Heart Association, Inc.
Articles |
Subdural Hematoma and Lupus Anticoagulants
Presented as a poster exhibit at the 7th International Symposium on Antiphospholipid Antibodies, New Orleans, La, October 9-13, 1996. Published as an abstract in Lupus. 1996;5:522. Abstract 78.
From the Department of Medicine, Divisions of Hematology (S.M., T.L.O.), Oncology (S.M.), and Geriatrics (M.M.), and the Department of Pathology (T.L.O.), Duke University Medical Center, Durham, NC.
Correspondence to Thomas L. Ortel, MD, PhD, Box 3422, Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, NC 27710.
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Abstract |
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Background and Purpose Patients with lupus anticoagulants do not typically have a bleeding tendency. However, a few reports of hemorrhage in patients with lupus anticoagulants in the absence of known risk factors for bleeding have been published, raising the question of an etiologic connection between lupus anticoagulants and certain types of hemorrhage. The presentation of three patients with subdural hematoma and lupus anticoagulants within only 1 year at our institutions and the report of two such patients in the literature led us to conduct a retrospective study to determine whether patients with lupus anticoagulants may have an increased risk for the development of subdural hematoma.
Case Descriptions All patients with a discharge diagnosis of nontraumatic subdural hematoma and lupus anticoagulant at three medical institutions between 1985 and 1996 were identified, and their medical histories and laboratory evaluations were reviewed. Of 733 patients with a discharge diagnosis of nontraumatic subdural hematoma, 5 were diagnosed as having a lupus anticoagulant (0.7%). All had known risk factors for the development of subdural hematoma: thrombocytopenia, hypoprothrombinemia, intracerebral venous hemorrhage, warfarin therapy, and advanced age with a history of a fall.
Conclusions This study suggests that presence of a lupus anticoagulant by itself is not associated with an increased incidence of nontraumatic subdural hematoma.
Key Words: anticoagulants • antiphospholipid antibodies • hematoma • lupus anticoagulant
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Introduction |
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Lupus anticoagulants are antiphospholipid antibodies that cause prolongation of in vitro tests of coagulation. They may be associated with a hypercoagulable state with thromboembolic events. A bleeding diathesis is not typically observed unless there is associated thrombocytopenia or hypoprothrombinemia.1 2 3 There have, however, been several reports of hemorrhage in patients with lupus anticoagulants without known risk factors for bleeding,4 5 6 7 8 raising the question of whether the presence of a lupus anticoagulant by itself may lead to an increased risk for certain types of hemorrhagic events. The occurrence of subdural hematoma in patients with lupus anticoagulants has, to our knowledge, been reported twice4 5 ; in both cases, the authors suggested an etiologic association between the presence of the lupus anticoagulant and the occurrence of the subdural hematoma. Because we saw three patients with subdural hematoma and lupus anticoagulants within 1 year at our institutions, we investigated how frequently concomitant diagnoses of nontraumatic subdural hematoma and lupus anticoagulant are made.
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Methods |
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Searches in the computerized medical information systems of three medical institutions were performed to identify all patients with a discharge diagnosis of nontraumatic subdural hematoma and those with a concomitant diagnosis of a lupus anticoagulant between January 1985 and April 1996 (Duke University Medical Center, Durham, NC; Veterans Administration Medical Center, Durham, NC; University of North Carolina Hospitals, Chapel Hill). Discharge diagnoses coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) were used. Because a diagnosis of lupus anticoagulant may be miscoded or coded under a broader term, all patients were identified who were diagnosed with nontraumatic subdural hematoma (ICD-9-CM code 432.1) and the following: circulating anticoagulant (286.5), acquired coagulation factor deficiency (286.7), other and unspecified coagulation factor deficiency (286.9), systemic lupus erythematosus (710.0), connective tissue disease (710.8), and unspecified connective tissue disease (710.9). The charts of the identified patients were reviewed to determine the presence of a lupus anticoagulant and to verify the absence of any high-impact trauma. The diagnosis of lupus anticoagulant was confirmed if the patient had a prolonged activated partial thromboplastin time (aPTT) that did not correct on mixture with normal plasma but corrected after addition of excess phospholipid (eg, platelet neutralization procedure) or if the patient had abnormal dilute Russell's viper venom test results. Before 1993, these more specific confirmatory tests were not performed, and a positive tissue thromboplastin inhibition test was used for confirmation.
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Results |
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Between 1985 and 1996, 733 patients had a discharge diagnosis of nontraumatic subdural hematoma at the three institutions researched. Thirty-six of these patients (4.9%) had a discharge diagnosis of some type of coagulopathy, and 3 patients had a discharge diagnosis of systemic lupus erythematosus (0.5%). Five of the 733 patients (0.7%) with nontraumatic subdural hematoma met laboratory criteria for lupus anticoagulant (Tables 1
and 2). Four patients had a separate hemorrhagic risk factor
that may have contributed to the development of the subdural hematoma,
including 1 patient with hypoprothrombinemia (who sustained subdural
hematomas on two separate occasions), 1 patient with prolonged
thrombocytopenia, and 2 patients on anticoagulant therapy; the fifth
patient was an elderly gentleman who sustained mild trauma to the head
several weeks before presentation to the hospital (Table 1).
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Discussion |
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Subdural hemorrhage in association with a lupus anticoagulant has, to our knowledge, been reported twice in the literature. Feit and colleagues4 described a 24-year-old woman with systemic lupus erythematosus and a lupus anticoagulant who died of a massive nontraumatic subdural hematoma. All coagulation factor levels were reportedly normal, as were the platelet count and the bleeding time. It was speculated that the lupus anticoagulant might have caused a bleeding diathesis. Ohnishi and colleagues5 reported a 47-year-old man with antiphospholipid antibody syndrome who developed a subdural hematoma. The patient had a "mildly" decreased platelet count and a prolonged bleeding time. No details on factor levels were given. It was speculated that interaction of the antiphospholipid antibodies with platelet function may have led to the bleeding.
Hemorrhage of any kind in patients with a lupus anticoagulant is not a common event. When it occurs, it is almost always associated with some known risk factor for bleeding. In a literature review, Shapiro and Thiagarajan9 identified 37 patients with a lupus anticoagulant and hemorrhagic manifestations between 1948 and 1980; they found that almost all of these patients had known risk factors for bleeding, mainly thrombocytopenia or severe hypoprothrombinemia. Both are known to be associated with the antiphospholipid antibody syndrome. Thrombocytopenia appears to be immune mediated, and hypoprothrombinemia is reportedly caused by anti-prothrombin antibodies leading to rapid clearance of prothrombin.2
Of the 733 patients with a discharge diagnosis of nontraumatic subdural hematoma at three major medical centers during an 11-year period, we identified 5 (0.7%) who were found to have a lupus anticoagulant. All 5 patients had separate risk factors that by themselves have been associated with the development of subdural hematoma. The occurrence of nontraumatic subdural hematoma after bone marrow transplantation is a well-recognized complication.10 Most studies find that thrombocytopenia is an important causative factor in this setting. Intracerebral bleeding may secondarily produce subdural hematoma by rupturing through the cerebral cortex.11 Warfarin anticoagulation has been shown to lead to a significant increase in the occurrence of subdural hematoma compared with the normal population,12 13 and increasing age and intensity of anticoagulation are the main independent risk factors in these patients. Finally, elderly individuals may develop chronic subdural hematomas after trivial trauma. Brain atrophy and vascular fragility are thought to predispose these patients to bleeding as the aging brain shrinks away from the dura and places the bridging veins under stress.14 Only in patient 1 was there a highly likely relationship between the development of subdural hematoma and the presence of a lupus anticoagulant: as part of the antiphospholipid antibody syndrome, this patient had hypoprothrombinemia, predisposing him to bleeding.2
On the basis of our analysis, fewer than 1% of patients presenting with nontraumatic subdural hematoma are diagnosed with a lupus anticoagulant (0.7%). Because hemostasis testing in most patients is limited to a prothrombin time, aPTT, and platelet count, probably not every lupus anticoagulant is diagnosed; 0.7% most likely represents an underestimate of the true frequency. However, since the prevalence of lupus anticoagulant in the normal population has been reported to be as high as 3% to 8%,15 16 our data suggest that it is unlikely that there is an increased frequency of presence of a lupus anticoagulant in patients with subdural hematoma compared with the normal population.
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Acknowledgments |
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Dr Ortel is a Pew Scholar in the Biomedical Sciences.
Received November 12, 1996; revision received December 20, 1996; accepted December 20, 1996.
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