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From the Department of Anesthesiology, University of Occupational and Environmental Health, Fukuoka, Japan.
Address correspondence to: Dr. Masanori Ogata, Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka 807-8555, Japan. Phone: +81-93-691-7265; Fax: +81-93-601-2910; E-mail: mogata{at}med.uoeh-u.ac.jp
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Abstract |
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Clinical features: A 44-yr-old female patient with CAPS underwent resection of an ovarian cancer, which was suspected to be associated with her coagulation abnormality. She had both arterial and venous thromboembolism, including cerebral infarction, embolic gangrene, and pulmonary emboli. Serological examinations revealed increased anticardiolipin IgG antibody and decreased protein C activity. Before surgery, an inferior vena cava filter was placed to prevent perioperative pulmonary embolism. Prostaglandin E1 (PGE1; 100 ng•kg–1•min–1) was given intraoperatively to suppress platelet aggregation and thrombin generation and to maintain arterial blood flow. No apparent coagulation abnormalities were observed during surgery, neither hypercoagulation nor a tendency to bleed. No additional thrombotic symptoms developed during a six-month follow-up.
Conclusion: The use of PGE1, an inhibitor of thrombin formation and platelet function, and placement of an inferior vena cava filter were associated with the uneventful surgical resection of an ovarian cancer in a patient with CAPS.
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Introduction |
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Patients with malignant disease have an increased incidence of thromboembolic complications, commonly referred to as Trousseau’s syndrome.7 In addition to Trousseau’s syndrome, the presence of APA in cancer patients has recently been proposed as another mechanism that enhances hypercoagulability.4–6 In those patients with cancer-associated APS, APA and the thrombotic risk are believed to disappear only after surgical removal of the malignancy.4 However, the thrombotic tendency is temporarily enhanced by surgical procedures and the discontinuation of anticoagulant treatment.2,8–11 The intraoperative management for cancer resection is challenging because of the competing risks of complications: exacerbation of thrombosis triggered by surgery vs significant bleeding due to anticoagulation. In this report, we describe the intraoperative use of prostaglandin E1 (PGE1) as an antithrombotic agent in a patient with cancer-related CAPS.
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An inferior vena cava filter (Neuhaus Protect; Toray, Tokyo, Japan) was put in place two days before surgery. The oral warfarin was replaced by the infusion of unfractionized heparin (15,000 U•day–1) the day before surgery. The INR and aPTT the day before surgery were 1.88 and 35.8 sec (cont 31.6 sec) respectively. After five minutes of oxygenation, general anesthesia was induced with propofol and vecuronium and maintained with sevoflurane, nitrous oxide, fentanyl, and vecuronium. Monitoring during anesthesia included an electrocardiogram, direct arterial blood pressure, oxygen saturation, end-tidal carbon dioxide values, and the bispectral index. A PGE1 infusion (100 ng•kg–1•min–1) was started at the time the patient entered the operating room and used intraoperatively to obtain an antithrombotic effect. The heparin infusion was discontinued two hours prior to surgery. We measured the activated clotting time with Hemochron 401 (Soma Technology, Inc., CT, USA) every hour after the induction of general anesthesia. The activated clotting time remained slightly prolonged, 125 to 143 sec (normal: 90–130 sec). The operation lasted three hours and the intraoperative course was uneventful.
We did not observe any signs suggesting the development of pulmonary emboli (e.g., hypotension, deoxygenation or sudden decrease of end-tidal carbon dioxyde) or cerebral infarction (e.g., anisocoria). We did not observe uncontrollable bleeding during surgery. Thus, no apparent coagulation abnormalities were observed, neither hypercoagulation nor a tendency to bleed. Total intraoperative blood losses were 720 mL. No allogenic blood products were used perioperatively.
The trachea was extubated with the patient fully awake and there were still no signs of thromboembolic complications. The patient was transferred to the intensive care unit. After confirming that she had no postoperative bleeding, the heparin infusion was restarted and the PGE1 infusion was stopped. Heparin was changed to coumadin ten days after the operation. The pathological diagnosis confirmed clear cell carcinoma of the ovary. Her general condition continued to improve. Anticardiolipin IgG antibody disappeared after removal of the malignancy. The pulmonary emboli and mitral valve thrombus disappeared one month after resection of the cancer. No additional thrombotic symptoms developed during six months of follow-up.
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The anesthetic management of APS associated with autoimmune diseases has been reported previously.8,12 As far as we know, however, there has been no reported case of cancer-related CAPS in the anesthetic literature. In this case, the ovarian cancer was resected uneventfully with the use of PGE1 and placement of an inferior vena cava filter, in spite of the potential risks of developing thromboembolism triggered by the surgical procedure or significant bleeding during surgery.
Asherson named the severe manifestation of APS presenting with an accelerated form of thromboembolism in multiple organs "catastrophic" APS.1 The precise pathophysiology of CAPS remains unclear, although recent studies have revealed some potential mechanisms.2 One of the mechanisms involves endothelial cell activation, which leads to the development of thrombosis in the microcirculation.13 APAs recognize proteins such as ß2-glycoprotein I and pro-thrombin bound to the phospholipid surface of endothelial cells, platelets, and monocytes.14 The bonding of APAs to the protein on the cell surface triggers activation of the involved cells. Activated endothelial cells express adhesion molecules on their surface, which induce leukocyte-endothelial adhesion and promote a procoagulant state. The activation of platelets triggers platelet aggregation, which may lead to thromboembolism. Another possible mechanism is the perturbation of the protein C and S regulatory systems.15 This disturbance inhibits the downregulation of activated factors V and VIII, and leads to the increased generation of thrombin.
In the perioperative setting, the thrombotic tendency may be enhanced temporarily. Yamamoto et al. reported a catastrophic exacerbation of APS after biopsy of a lung adenocarcinoma.9 One of the authors has reported an intraoperative myocardial infarction in a patient with APS.16 Therefore, to prevent thromboembolic events, anticoagulation is necessary in the perioperative period. The anesthetic management of cancer resection for such patients includes preventing both excessive bleeding due to anticoagulation and catastrophic exacerbation of thrombosis. Preventing these opposing potential complications makes the procedure challenging.
As newer therapeutic agents for anticoagulation in APS, Triplett and Asherson have suggested the use of prostacyclin, streptokinase, tissue plasminogen activator, or urokinase, although these agents require further investigation.2 Prostacyclin, an eicosanoid, both inhibits hemostasis and is a potent vasodilator.17 PGE1, another eicosanoid, has properties similar to those of prostacyclin18 and has been used clinically to induce hypotension with the aim of reducing intraoperative bleeding.19 Yukioka et al. demonstrated a significant decrease of systolic blood pressure from 136 mmHg to 93 mmHg during PGE1 infusion.20 They also showed decreased blood losses and blood transfusion during surgery in patients with PGE1 infusion. We considered the use of PGE1 suitable both for anti-coagulation and to reduce blood losses in our patient.
PGE1 has two major properties. First, it inhibits hemostasis. PGE1 is a potent antagonist of platelet activation and functions via the platelet prostaglandin receptor by up-regulating adenylate cyclase production of intracellular cyclic adenosine monophosphate.18 PGE1 also inhibits tissue factor/factor VIIa-dependent thrombin formation,21 impairing thrombus formation. Second, PGE1 induces dilatation of smooth muscle,18 which results in mild hypotension. In spite of its hypotensive effect, cerebral, coronary, and renal blood flows are maintained with the use of PGE1. 22,23
We determined the dosage of PGE1 according to previous reports. At the dosage of 100 ng•kg–1•min–1, PGE1 reduces blood pressure by relaxing the vascular smooth muscle.19,20 Koga et al. have shown that PGE1, at clinically relevant concentrations, inhibits aggregation of platelets in platelet-rich plasma under synergic interaction with endothelial cell-derived factors.24 At this dosage, we considered that PGE1 has both smooth muscle relaxing and anti-aggregation effects.
Theoretically, PGE1 is a suitable agent for controlling the thrombotic tendency of surgical patients with APS. PGE1 has been used safely in various clinical situations, however, its use in patients with APS is not generally accepted since there have been no prospective studies of this rare disease. Further investigation is needed to establish its effectiveness and adequacy in improving thrombo-resistance in these patients.
In the patient described, the heparin infusion was discontinued prior to surgery. Although intraoperative heparin has been used successfully, the preoperative evaluation of this patient revealed a hypervascular tumour, which could have led to uncontrolled bleeding if an intraoperative heparin infusion had been used. After discussing intraoperative anticoagulation with the gynecologists, it was decided to discontinue the heparin infusion two hours before surgery, to eliminate the risk of significant bleeding. Finally, to prevent pulmonary emboli during the operation, we placed an inferior vena cava filter preoperatively. A vena cava filter is indicated for prophylaxis in high-risk patients with uncontrolled thromboembolism.25
In summary, we describe our experience with a patient suffering from multiple thromboemboli due to cancer-related CAPS. The intraoperative use of PGE1 was associated with the uneventful surgical resection of the patient’s ovarian cancer and the absence of thrombotic complications in the perioperative period.
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Footnotes |
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References |
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2 Triplett DA, Asherson RA. Pathophysiology of the catastrophic antiphospholipid syndrome (CAPS). Am J Hematol 2000; 65: 154–9.[Medline]
3 Shames DS, Broderick PA. Catastrophic antiphospholipid antibody syndrome. Conn Med 2001; 65: 3–5.[Medline]
4 Ruffatti A, Aversa S, Del Ross T, Tonetto S, Fiorentino M, Todesco S. Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome? J Rheumatol 1994; 21: 2162–3.[Medline]
5 Muir DF, Stevens A, Napier-Hemy RO, Fath-Ordoubadi F, Curzen N. Recurrent stent thrombosis associated with lupus anticoagulant due to renal cell carcinoma. Int J Cardiovasc Intervent 2003; 5: 44–6.[Medline]
6 Soltesz P, Szekanecz Z, Vegh J, et al. Catastrophic antiphospholipid syndrome in cancer. Haematologia (Budap) 2000; 30: 303–11.
7 Rickles FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 1983; 62: 14–31.
8 Menon G, Allt-Graham J. Anaesthetic implications of the anti-cardiolipin antibody syndrome. Br J Anaesth 1993; 70: 587–90.
9 Yamamoto T, Ito M, Nagata S, et al. Catastrophic exacerbation of antiphospholipid syndrome after lung adenocarcinoma biopsy. J Rheumatol 2000; 27: 2035–7.[Medline]
10 Erkan D, Yazici Y, Peterson MG, Sammaritano L, Lockshin MD. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 2002; 41: 924–9.
11 Langer F, Eifrig B, Marx G, Stork A, Hegewisch-Becker S, Hossfeld DK. Exacerbation of antiphospholipid antibody syndrome after treatment of localized cancer: a report of two cases. Ann Hematol 2002; 81: 727–31.[Medline]
12 Madan R, Khoursheed M, Kukla R, Al-Mazidi M, Behbehani A. The anaesthetist and the antiphospholipid syndrome. Anaesthesia 1997; 52: 72–6.[Medline]
13 Golden BD, Belmont HM. The role of microvasculopathy in the catastrophic antiphospholipid syndrome: comment on the article by Neuwelt et al (Letter). Arthritis Rheum 1998; 41: 751–3; author reply 753–4, 739.
14 Permpikul P, Rao LV, Rapaport SI. Functional and binding studies of the roles of prothrombin and beta 2-glycoprotein I in the expression of lupus anticoagulant activity. Blood 1994; 83: 2878–92.
15 Oosting JD, Preissner KT, Derksen RH, de Groot PG. Autoantibodies directed against the epidermal growth factor-like domains of thrombomodulin inhibit protein C activation in vitro. Br J Haematol 1993; 85: 761–8.[Medline]
16 Ozaki M, Minami K, Shigematsu A. Myocardial ischemia during emergency anesthesia in a patient with systemic lupus erythematosus resulting from undiagnosed antiphospholipid syndrome (Letter). Anesth Analg 2002; 95: 255.
17 Petrovich CT. Hemostasis and hemotherapy. In: Barash PG, Cullen BF, Stoelting R (Eds). Clinical Anesthesia, 3rd ed. Philadelphia, PA: J.B. Lippincott Company; 1996: 189–217.
18 Morrow JD, Roberts LJ II. Lipid derived autacoids. Eicosanoids and platelet-activating factor. In: Hardman JD, Limbird LE (Eds). Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, NY: McGraw-Hill Companies Inc.; 2001: 669–85.
19 Goto F, Otani E, Kato S, Fujita T. Prostaglandin E1 as a hypotensive drug during general anaesthesia. Anaesthesia 1982; 37: 530–5.[Medline]
20 Yukioka H, Asada K, Fujimori M, Shimazu A. Prostaglandin E1 as a hypotensive drug during general anesthesia for total hip replacement. J Clin Anesth 1993; 5: 310–4.[Medline]
21 Kozek-Langenecker SA, Wanzel O, Berger R, Kettner SC, Coraim F. Increased anticoagulation during cardiopulmonary bypass by prostaglandin E1. Anesth Analg 1998; 87: 985–8.
22 Abe K, Demizu A, Kamada K, Morimoto T, Sakaki T, Yoshiya I. Local cerebral blood flow with prostaglandin E1 or trimethaphan during cerebral aneurysm clip ligation. Can J Anaesth 1991; 38: 831–6.[Abstract]
23 Suzuki H, Asada M, Tateyama T, et al. Myocardial metabolism, oxygen demand and oxygen supply during prostaglandin E1 induced hypotension (Japanese). Masui 1994; 43: 680–3.[Medline]
24 Koga T, Az-ma T, Yuge O. Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cells. Acta Anaesthesiol Scand 2002; 46: 987–93.[Medline]
25 Seto A, Fukuyama H, Niijima K, Takenaka I, Kadoya T. Anesthetic management of a patient with deep venous thrombosis using temporary inferior vena cava filter (Japanese). Masui 2000; 49: 302–4.[Medline]
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