Case Report Therapeutic challenges after successful thrombectomy in a patient with an antiphospholipid syndrome associated M1-occlusion: A case report Interventional Neuroradiology 0(00) 1–5 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1591019915590371 ine.sagepub.com Katharina Stadler1, Johannes S Mutzenbach1, Gudrun Kalss1, Johann Sellner1, Abdul R Al-Schameri2, Eugen Trinka1 and Monika Killer-Oberpfalzer3 Abstract Backround: Stroke is a frequent disorder in patients with an antiphospholipid syndrome (APS). Due to a high risk for further thromboembolic events, appropriate anticoagulation therapy in patients with an APS-associated stroke seems mandatory but drug eluting and duration is a matter of debate. Case: A 48-year-old female patient presented with Broca’s aphasia and mild hemiparesis on the right side. Diagnostic workup revealed left middle cerebral artery (MCA) occlusion yet without diffusion-weighted lesions. Due to a thrombocytopenia (67.00 g/l) systemic thrombolysis was not indicated and endovascular treatment was initiated 150 min after symptom onset. After successful clot retrieval, recurrent re-occlusions lead to the necessity of stent implantation and anticoagulation, respectively. On day 5 she developed a new severe right-sided hemiparesis. The magnetic resonance imaging (MRI) showed a subtotal restenosis of the left MCA despite the regular anticoagulation regime leading to a new left MCA ischaemic stroke. In the meantime, the unknown aetiology, the patients’ age and the thrombocytopenia let to further diagnostic workup. Elevated blood parameters such as lupus anticoagulant (LA)-1, LA-ratio, positive anti-nuclear antibody (ANA), panti-neutrophil cytoplasmic antibodies (ANCA), c-ANCA confirmed the diagnosis of APS. Conclusion: This case report showed the feasibility of mechanical clot retrieval and stent implantation in patients with APS. Due to the elevated risk of in-stent thrombosis a prolonged therapy with glycoprotein (GP)IIb/IIIa receptor antagonists in the initial postoperative period and further anticoagulation with coumarin derivate might be needed. Keywords Antiphospholipid syndrome, stroke, thrombectomy, stent Background The antiphospholipid syndrome (APS) is an acquired autoimmune condition and presents as a prothrombotic disorder in patients who have persistent antiphospholipid antibodies (aPLs). It is accompanied by recurrent pregnancy complications and miscarriages, thrombocytopenia and thrombosis.1–3 Thrombosis in patients with APS can occur in arterial, microvascular or venous locations.4 Deep vein thrombosis and stroke in patients with APS are major causes of morbidity and mortality.3 Due to a high risk for further events, anticoagulation in patients with an APS-associated stroke is of high importance in pharmacological prophylaxis.2,4 Secondary prophylaxis with warfarin is recommended in patients with APS and arterial thrombosis, an international normalized ratio (INR) level >3.0 is sometimes recommended, the INR target 2.0–3.0 is also supported.4–6 Mechanical thrombectomy in acute ischaemic stroke with a large vessel occlusion e.g. the M1-segment of the middle cerebral artery has improved over the last 1 ET Department of Neurology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria 2 Department of Neurosurgery, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria 3 Department of Neurology/Researchinstitute of Neurointervention, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria Corresponding author: Monika Killer-Oberpfalzer, Department of Neurology/Researchinstitute of Neurointervention, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria. Email: m.killer@salk.at 2 years.7,8 The currently common technique is the use of a stent retriever in combination with aspiration. Most of the newer studies report a reperfusion rate more than 80% with this technique.9,10 The need for a stent implantation after acute mechanical thrombectomy based on recurrent M1-occlusion or restenosis is not common.8,11–14 In cardiology, however, the use of stents in acute coronary artery occlusion is frequently performed. Therefore patients with APS and coronary acute syndrome have been successfully treated with stents.15–18 The complications of cardiac stent thrombosis are described in a few case reports.19,20 To our knowledge this is the first report of mechanical thrombectomy with stent implantation with further therapeutic challenges in a patient with APS and acute stroke. Case A 48-year-old woman was referred to the stroke unit due to a Broca’s aphasia and a mild paresis on the right side National Institutes of Health Stroke Scale (NIHSS) of 3. Interventional Neuroradiology 0(00) The patient’s history showed a chronic thrombocytopenia since 15 years with unknown origin and arterial hypertension. The medication prior to presentation nebivolol 5 mg and lisinopril 10 mg was taken orally once a day. Acute diagnostic work-up revealed left middle cerebral artery (MCA) occlusion yet without a significant disturbance of diffusion on magnetic resonance imaging (MRI) including diffusion weighted imaging (DWI) (Figure 1). Due to a thrombocytopenia (67,00 g/l,) systemic thrombolysis with alteplase (rtPA) was not indicated and the patient was immediately referred to interventional therapy 2.5 h after symptom onset. After successful clot retrieval, recurrent re-occlusions due to a remaining M1 stenosis lead to the necessity of implanting a stent (Figure 2). In addition, a glycoprotein (GP) IIb/IIIa receptor antagonist (aggrastat, tirofiban; Correvio, Geneva, Switzerland) was administered intra-arterially as bolus (19.69 mg/kg), followed by a continuous intravenous administration (400 mg/h) for the duration of 24 h. Figure 1. Magnetic resonance imaging (MRI) brain: (a) apparent diffusion coefficient (ADC) maps; (b) diffusion weighted imaging (DWI); (c) fluid-attenuated inversion recovery (FLAIR): without ischemic brain lesion. Note that (a) and (b) show a discrete diffusion disorder without an infarct demarcation but with hyperaemia in (c). (d) Perfusion weighted image (PWI): mismatch represent potential salvageable tissue by reperfusion therapy; (e) MR angiography (MRA) intracranial shows M1-segment occlusion. Arrow indicates area of vessel occlusion. Stadler et al. 3 Figure 2. Digital subtraction angiography (DSA): (a) occlusion of left M1-segment; (b) recanalization with restenosis of left M1-segment after mechanical thrombectomy; (c) left M1-segment re-occlusion; (d) recurrent stenosis of left M1-segment after concurrent mechanical thrombectomy; (e) reperfusion after stent implantation without stenosis. Arrow indicates area of vessel occlusion. Figure 3. Magnetic resonance imaging (MRI) brain on day 5: (a) diffusion weighted imaging (DWI) and (b) FLAIR and (c) T2. Panels (a) and (b) show the diffusion disorder with an infarct demarcation in (c). Arrow indicates area of ischemia. One day after the interventional procedure and overlapping with the end of the 24-hour intravenous administration of the GP IIb/IIIa receptor antagonist, dual antiplatelet treatment with acetylsalicyl acid 100 mg/d and clopidogrel 75 mg/d was started. The neurological deficit of the patient was unchanged with a mild hemiparesis on the right side and a mild Broca’s aphasia (NIHSS of 3). Transcranial doppler (TCD) sonography showed a recanalised M1 and M2 segment of the left MCA with a moderate stenosis in the distal part of the stent (Vmax 300 cm/s). On day 5, the patient suddenly presented a severe right hemiparesis and a global aphasia. The MRI revealed a new ischaemic stroke in the territory supplied by the left MCA (Figure 3), the MR-angiographic evaluation showed a subtotal stenosis in the left MCA. The TCD sonography showed an in-stent restenosis with a loss of vessel capture in the M1 segment and low poststenotic flow in the M1 segment. Due to the high risk of reperfusion syndrome and haemorrhagic transformation of the infarct area, an angioplasty of the stent was not performed. The dual antiplatelet treatment with acetylic salicylic acid 100 mg/d and clopidogrel 75 mg/d has been continued. Due to the stroke, the young age (<50 years) and the thrombocytopenia, further diagnostics (including abdominal ultrasonography, chest X-ray, dopplerduplex sonography of the extra- and intracranial arteries, transthoracic echocardiography, 24 h-electrocardiogram (ECG), electroencephalography) and laboratory investigations (including clinical biochemistry, haematology, coagulation, thrombophilia, urine analysis, hormones, immunology and antibodies) were performed. Laboratory evaluations showed a typical constellation with increased lupus anticoagulant (LA)1 (77.00 s), increased LA-ratio (2.3), positive anti-nuclear antibody (ANA), p-anti-neutrophil cytoplasmic antibodies (ANCA), c-ANCA, SS-A/FC, SSB/FC, Histon/FC and dsDNA/FC. The diagnosis of APS could be confirmed. Three months after discharge the patient recovered to a NIHSS of 1. As a Broca’s aphasia remained as neurological deficit, the patient was graded MRS (modified Rankin Scale) of 2. 4 Regarding stent implantation, a secondary prevention with a dual antiplatelet therapy could be deescalated to acetylsalicyl acid 100 mg/d. Due to the APS, there was additional indication for oral anticoagulation and we started a therapy with a long lasting coumarin derivate (phenprocoumon) with a target INR 2.0–3.0 was started three month after the event. Discussion We conclude that a mechanical recanalisation with stent-implantation can successfully be performed in patients with APS-associated M1-occlusion. We propose that stent implantation may be required to maintain patency and that aggressive medical treatment is required to prevent stent re-occlusion. Coster et al. reported two cases with a full recovery after a stroke based on an APS treated by intra-arterial thrombolysis. There is lack of information about platelet count in these two patients where no stent implantation was performed.21 Several case studies report patients with acute myocardial infarcts and APS as underlying disease, who were treated with percutaneous transluminal coronary angioplasty (PTCA). In these patients, the immediate start of oral anticoagulation was initiated due to the high risk of recurrent coronary stent thrombosis.15,22 As an alternative to PTCA the administration of intravenous GP IIb/IIIa receptor antagonists was needed.19,23 Su et al. recommend the additional administration of GP IIb/IIIa receptor antagonist and prolonged heparin treatment in APS patients undergoing a percutaneous coronary intervention (PCI). Warfarin (INR target 2.0–3.0) is recommended to be started as a secondary prevention. Therefore, an over-lapping (bridging) use of heparin and warfarin should be considered.19 Okuma et al. randomized 20 patients with ischaemic stroke and APS either to acetylsalicyl acid alone (n ¼ 11) or acetylsalicyl acid plus warfarin (target INR 2.0–3.0, n ¼ 9) for secondary prophylaxis. The cumulative incidence of stroke in patients with antiplatelet treatment alone was significantly higher than in patients receiving the combination of antiplatelet and anticoagulation therapy.24 Our case confirms the high risk for in-stent restenosis without anticoagulation after acute treatment with GP IIb/IIIa receptor antagonists despite following with antiplatelet therapy. This will lead us to combine in future an antiplatelet agent (acetylsalicyl acid or clopidogrel) with an anticoagulant (coumarin derivate) for patients with APS after stent implantation, considering the high risk for bleeding complications due to the thrombocytopenia. Conclusion This case report showed the feasibility of mechanical clot retrieval and stent implantation in patients with APS. Due to the elevated risk of in-stent thrombosis, Interventional Neuroradiology 0(00) a prolonged therapy with GPIIb/IIIa receptor antagonists in the initial postoperative period and further anticoagulation with coumarin derivate might be needed. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. References 1. Lim W. Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program 2009; 2009: 233–239. 2. Lim W. Antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program 2013; 2013: 675–680. 3. Cervera R, Piette J-C, Font J, et al. 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