Z Rheumatol 62:80–81 (2003) DOI 10.1007/s00393-003-0420-3
CASE REPORT Redation: Prof. Dr. G. Hein, Jena
J. Gille J. Bernotat S. Böhm P. Behrens J. F. Löhr
Spontanes Hämarthros des Kniegelenkes unter einer Clopidogrel-Aspirin Kombinationstherapie n Summary We report a case of a 76-year-old-man who developed spontaneous hemarthrosis of his right knee following clopidogrelaspirin treatment. Clopidogrel is an ADP receptor antagonist and in combination with aspirin widely used in patients with atheroscle-
Eingegangen: 31.Januar 2002 Akzeptiert: 14. Mai 2002
Justus Gille, M. D. ()) · S. Böhm P. Behrens · J. F. Löhr Department of Orthopaedics University Lübeck Ratzeburger Allee 160 23538 Lübeck, Germany E-Mail:
[email protected] J. Bernotat Department of Internal Medicine II University of Lübeck, Germany
Spontaneous hemarthrosis of the knee associated with clopidogrel and aspirin treatment
rotic vascular disease to reduce the incidence of ischemic events. To date, no case of spontaneous hemarthrosis following clopidogrel-aspirin therapy has been reported. Prompt aspiration after discontinuing the ADP receptor antagonist-aspirin combination therapy can assist early diagnosis and may prevent further damage to the joint. In conclusion, spontaneous hemarthrosis is a possible complication following clopidogrelaspirin therapy and is recommended to be evaluated when appropriate clinical symptoms (e. g., intraarticular effusion) present. n Zusammenfassung Clopidogrel ist ein ADP-Rezeptorantagonist und findet in Kombination mit Aspirin weitreichenden Einsatz bei arteriosklerotischen Gefäßerkrankungen. Die Kombination aus Clopidogrel und Aspirin hat sich als Standardtherapie der koronaren Herzkrankheit nach Stentimplantation etabliert. Das Auf-
Introduction
n Key words Clopidogrel – aspirin – hemarthrosis n Schlüsselwörter Hämarthros – Clopidogrel – Aspirin
superior in improving the clinical outcome after coronary stent placement significantly more than either agent alone (2) and has emerged as the standard care after coronary stenting (3). Gastrointestinal problems (e. g., diarrhea, nausea, vomiting) are the most common side effects (4). Other adverse events include severe rash, neutropenia and thrombocytopenia (4). Both intracranial and retro-
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Clopidogrel, a thienopyridine derivative, inhibits platelet aggregation induced by ADP. It is widely used in patients with atherosclerotic vascular disease to reduce the incidence of ischemic events (1). The ADP receptor antagonist-aspirin combination is
treten eines spontanen Hämarthros unter der genannten, thrombozytenaggregationshemmenden Kombinationstherapie ist bis dato in der Literatur nicht beschrieben. Wir berichten den Fall eines 76-jährigen Patienten, der unter der Clopidogrel-AspirinTherapie ein Hämarthros des rechten Kniegelenkes entwickelte. Zwei Wochen vor Auftreten der Kniegelenkssymptomatik war bei instabiler Angina pectoris die antithrombotische Therapie eingeleitet worden. Es kann geschlussfolgert werden, dass unter einer ClopidogrelAspirin-Kombinationstherapie ein Hämarthros als Komplikation nicht ausgeschlossen werden kann und bei entsprechender klinischer Symptome differentialdiagnostisch bedacht werden sollte.
J. Gille et al. Spontaneous hemarthrosis of the knee associated with clopidogrel and aspirin treatment
peritoneal bleeding and overt hemorrhage have been described as major bleeding complications so far (3). To our knowledge, no case of hemarthrosis following ADP receptor antagonist-aspirin combination therapy has been published. We describe a case of this undesired effect associated with clopidogrel and aspirin treatment.
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limits. After discontinuing oral anticoagulant therapy, aspiration of the joint was performed. Hemorrhagic fluid (45 mL) was aspirated and processed for histopathological and microbiological analysis. After 4 days of strict bedrest, the pain disappeared as well as the intraarticular effusion, and walking was resumed without difficulties. Joint function seems to have fully returned, but long-term evaluation is needed.
Case report A 76-year-old man developed a spontaneous hemarthrosis of his right knee following clopidogrel-aspirin treatment. He had a history of myocardial infarction and unstable angina, and was diagnosed and treated for two weeks before joint symptoms occurred. Clopidogrel was administered as a loading dose of 300 mg followed by 75 mg PO daily. Aspirin was added at a daily dose of 100 mg. Furthermore he had a history of asymptomatic cholecystolithiasis, cardiac arrhythmia and arterial hypertension. Therefore, he received 90 mg Dilitazem twice daily. At the acute onset of pain in his right knee while bedresting, he was admitted to the hospital. There was no definitive precipitating event (e. g., trauma). The physical examination revealed a massive swelling, tenderness and intraarticular effusion of the right knee joint. The X ray of his knee was read as degenerative joint disease with joint space loss, subchondral sclerosis and osteophyte formation. His coagulation status was within the normal range [INR 1.09 (0.85–1.15), aPTT 26 s (24–35), Thrombin Time 15 s (12–20)]. The blood count revealed no abnormalities [WBC 10.88/nl (4–11), hemoglobin 14.1 g/dl (14.0–18.0), platelets 289/nl (150–400)]. At that same visit, his liver function tests were within the normal
Discussion To date, spontaneous hemarthrosis following anticoagulation therapy has been recognized mainly after warfarin and heparin therapy. Under warfarin treatment, hemarthrosis occurs when the prothrombin time is excessively prolonged and may remain symptomatic until anticoagulation is reduced or discontinued (5). Multiple case-reports describe hemarthrosis secondary to heparin therapy (6). Surprisingly, despite the wide use of oral anticoagulation medication, no case of spontaneous hemarthrosis following ADP receptor antagonist-aspirin therapy has been reported previously. The authors conclude that hemarthrosis seems to be a possible complication of clopidogrel-aspirin combination therapy. It can be suggested that clopidogrel in combination with nonsteroidal anti-inflammatory drugs (NSAIDS) may generally promote bleeding complications. In this case, the osteoarthritis of the knee may have predisposed the patient to the occurrence of hemarthrosis. Prompt aspiration after discontinuing of ADP receptor antagonist-aspirin combination therapy can provide early diagnosis and may prevent further damage to the joint.
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