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From the Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Address correspondence and reprint requests to Juraj Sprung, MD, PhD, Department of Anesthesiology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905. Address e-mail to Sprung.juraj{at}mayo.edu.
Abstract
Primary amyloidosis is a result of proliferation of a population of plasma cells that leads to an increased secretion of monoclonal immunoglobulins (amyloid). Amyloid protein infiltrates increase capillary fragility. Such capillaries can burst, even after minor stress, resulting in periorbital hemorrhage. We describe a 64-yr-old man with primary amyloidosis who underwent general anesthesia. His eyes were gently closed with tape. Upon removal of the tape bilateral periorbital purpura was noted. All coagulation studies were normal. The periorbital hemorrhage was attributed to amyloidosis-induced capillary fragility.
Primary amyloidosis is a result of proliferation of a single population of plasma cells that leads to an increased production and secretion of monoclonal immunoglobulins, some of which can form amyloid chains. One particular protein type (M-component) is a portion of the antibody molecule called the light-chain. When this material deposits as amyloid, the resulting condition is designated light-chain or AL amyloidosis. Rarely, bleeding episodes complicate AL amyloidosis and may be related to either the increased capillary fragility or acquired coagulopathy (1–3). Here we describe a patient with AL amyloidosis who developed bilateral periorbital purpura under protective eye tape during anesthesia.
CASE REPORT
Permission (for single case) and patient consent for figure (for nonidentifiable patient’s face) were waived by the Mayo Clinic, Rochester MN, IRB. A 64-yr-old man with a history of AL amyloidosis was admitted to the hospital with large pleural effusions and acute-on-chronic renal insufficiency. His serum creatinine had recently increased from 1.8 to 3.6 mg/dL. Gross hematuria was present. An ultrasound-guided thoracentesis yielded 1.5 L of pleural exudate that was aspirated. Amyloidosis had been diagnosed in 1993 by kidney biopsy. His serum and urine were positive for a monoclonal lambda (
) protein. At that time, he received treatment with melphalan and prednisone. His last steroid treatment was 2 yr before the current admission.
His admission platelet count was 193 x 109/L, prothrombin time (PT) was 13.6 s, International Normalized Ratio (INR) was 1.4, and activated thromboplastin time (aPTT) was 33 s. Because the source of his hematuria was unclear, he was scheduled for a diagnostic cystoscopy and bilateral ureteroscopy. Cystoscopy was conducted under general anesthesia, induced with propofol and fentanyl. Tracheal intubation was facilitated with succinylcholine. Before tracheal intubation, his eyes were gently closed and taped with latex-free transparent tape (Transpore TM, 3M TM Health Care, St. Paul, MN). During anesthesia, the patient remained in mild Trendelenburg position. Anesthesia was maintained with desflurane. His 30-min anesthetic course was uneventful.
On emergence, we removed the eye tapes and large bilateral periorbital blistering purpura (raccoon eyes) were present under areas covered by tape (Fig. 1). Initially, this finding was attributed to an allergic reaction to tape; however, inspection of other sites covered with the same tape were of normal appearance. Underlying coagulopathy was also considered, but subsequent coagulation studies were within normal limits: platelet count was 203 x 109/L, PT was 12.1 s, INR was 1.2, and aPTT was 33 s. His thromboelastogram (TEG®), performed on fresh whole venous blood activated with kaolin, was normal [R 7 mm (normal, 5.7–12.8); K 2.7 mm (normal, 1.9–3.5); R + K 9.7 mm (normal, 8.2–16); maximum amplitude, 73.2 mm (normal, 57.1–72.6); angle, 74.2° (normal, 64–72.6); lysis + 30, 0% (normal, 0–4.8)]. After reviewing these results, we attributed the periorbital hemorrhage to amyloidosis-induced capillary fragility. We attributed his gross hematuria to capillary fragility as well. The purpura resolved uneventfully within 1 wk. Subsequently, a review of the archival medical records revealed a remote episode of periorbital purpura as well as archival coagulation testing obtained in April 1994: PT was 13.7 s, INR was 1.4, factor X activity moderately reduced 35%, mildly prolonged thrombin time was 29 s (normal, 16–25), reptilase time was 30 s (normal, 16–22), and mild thrombocytopenia was 70 x 109/L.
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DISCUSSION
Bilateral periorbital purpura (raccoon eyes) have been described in patients with thoracic and skull injuries (4,5). Occasionally, it may be confused with child or domestic abuse (6,7). Raccoon eyes can be a sign of a bleeding diathesis in AL amyloidosis (8). This presentation can be stressful for medical personnel unfamiliar with its pathogenesis and outcome.
After we excluded coagulopathy, periorbital hemorrhage was attributed to amyloid-associated capillary fragility in the setting of Trendelenburg position. The association between the body position and development of raccoon eyes was described in a patient with amyloidosis after proctoscopy performed in head-down position (9). This position results in venous congestion and may contribute to the development of periorbital hemorrhage.
Amyloid deposits extracellularly in various tissues, and can infiltrate capillaries leading to weakening of microvascular tensile strength. Fragile capillaries can burst after very minor stress (sneezing, coughing, or rubbing the eyes), which may result in periorbital bleeding (7,10,11) Gross painless hematuria was described in a patient with secondary amyloidosis (12) and, after failing to find a source of hemorrhage in our patient, the bleeding was attributed to amyloidosis.
Coagulation factor deficiencies may be present in patients with AL amyloidosis. Major bleeding is rare (1–3) and, when present, should prompt immediate evaluation of clotting factors, especially for inhibitors of thrombin or a factor X deficiency (2,3). Acquired deficiency of factor X may be present in 15% to 41% of patients with AL amyloidosis (2,3), presumably because of adsorption of factor X by amyloid fibrils (1). In a large series of patients with AL amyloidosis, 8.7% had factor X level below 50% of normal (1). Of those 56% had bleeding complications; two patients in this series died from gastrointestinal and genitourinary bleeding. Isolated deficiencies of other coagulation factors (II, V, VII, IX) (2) or hyperfibrinolysis (13) have been reported in these patients.
Our patient had massive genitourinary bleeding, presumably because of amyloidosis-induced capillary fragility, as his coagulation tests were normal. Although a direct measurement of the factor X level was not obtained, it could not have been significantly decreased, because the PT, aPTT, and TEG® become abnormal when factor X decreases below 20%–30% of normal. Hyperfibrinolysis was not detected by the TEG®. An association between AL amyloidosis and acquired loss of von Willebrand factor (AvWF) has been described (14). Although we did not test for AvWF (ristocetin cofactor activity), the normal aPTT in this patient argues against a clinically significant vWF factor abnormality or deficiency. Significant platelet dysfunction may be present in up to 71% of AL amyloidosis patients (2). In our patient, the platelet count was normal and an underlying platelet dysfunction was not detected with the TEG®.
Aggressive treatment of the underlying plasma cell dyscrasia in primary amyloidosis (melphalan chemotherapy, autologous stem cell transplantation) (15) and/or splenectomy can lead to the amelioration of amyloid-related factor X deficiency. Because coagulation is primarily caused by absorption of factor X by the amyloid fibrils, therapy with vitamin K is ineffective except in rare cases of vitamin K hypovitaminosis caused by amyloid-induced malabsorption. When bleeding is present, therapy should correct the underlying coagulation abnormality (for example, factor X deficiency is treated by factor replacement therapy, hyperfibrinolysis is treated with an antifibrinolytic such as tranexamic acid) (2). Use of recombinant FVIIa should be considered in patients with a factor X deficiency and uncontrollable bleeding. Recombinant FVIIa is effective in controlling bleeding because its action does not rely on missing coagulation factors, but is mediated through the generation of a thrombin burst (16).
Periorbital purpura suggests the potential for increased bleeding. To avoid periorbital purpura, head-down positions, Valsalva maneuver, and/or eye manipulation should be minimized. Second, the risk of bleeding with regional anesthesia may be increased, even if the coagulation tests are normal, as disorders such as increased capillary fragility and platelet dysfunction may be missed with routine tests. In a large prospective study of renal biopsies, amyloidosis was an independent risk factor for bleeding (17). Although spontaneous cerebral hematomas have been described in patients with amyloidosis (2,18,19), we could not find a report of spinal hematoma after neuraxial blockade in patients with amyloidosis.
In conclusion, in patients with AL amyloidosis, even a very minor stress to the eyelids may result in periorbital hemorrhage. Before surgery, these patients should be tested for coagulation factor deficiencies and/or platelet function defects, especially if neuraxial anesthesia is contemplated.
Footnotes
Accepted for publication August 10, 2007.
Support provided by the Department of Anesthesiology, Mayo Clinic, Rochester, MN.
REFERENCES
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