1 Department of Medicine and 2 Division of Nephrology, Hennepin County Medical Center, Minneapolis, MN, USA
Keywords: acute renal failure; atheroembolic renal disease; ticlopidine; thrombotic thrombocytopenic purpura
Introduction
Thrombotic thrombocytopenic purpura (TTP), characterized by the pentad of thrombocytopenia, microangiopathic haemolytic anaemia (MAHA), fluctuating mental status, renal insufficiency and fever, has been associated with the use of ticlopidine following coronary artery stenting as far back as 1991 [1]. It has been described more recently in two larger reviews that suggest as much as a 50-fold increased risk for developing TTP following coronary stenting while on ticlopidine for prevention of stent thrombosis [2,3]. With a mortality rate that exceeds 20% in this most recent study, it is understandable why a heightened awareness to this relationship seems necessary. This case, however, illustrates how even well-described associations as these are sometimes misleading and can fail to identify a case of atheroembolic renal disease (AERD) following coronary artery stenting.
Case
A 78-year-old female with a past medical history remarkable for coronary artery disease, peripheral vascular disease and renovascular hypertension, for which she had autologous renal transplantation, underwent coronary artery catheterization in June 1998 as part of a pre-operative work-up for abdominal aortic aneurysm repair. She was found to have a 90% stenosis of her right coronary artery, was subsequently stented and started on ticlopidine. The patient developed acute renal insufficiency following the procedure, raising her serum creatinine from a baseline of 1.5 up to 3.6 mg/dl. This was felt secondary to radiocontrast dye nephropathy and the patient was discharged home doing well with a creatinine of 3.2 mg/dl and decreasing.
In late June 1998 the patient was re-admitted to our hospital with complaints of nausea, vomiting and intermittent diarrhoea. Serum creatinine at time of admission was found to be 3.8 mg/dl and the creatinine clearance was 8 ml/min. Haemodialysis access was deemed necessary. Early in the second admission, the patient's platelet count dropped to 20 000 from an admission count of 100 000. Ticlopidine was held and the patient was given a 6-pack platelet transfusion prior to left subclavian Quinton catheter placement in the operating room. Shortly following the procedure, the patient became acutely hypoxic with oxygen saturations in the mid 80% and was transferred to the medical intensive care unit. Chest X-ray revealed pulmonary oedema. The patient became acutely confused and was delirious for the following 3-day period.
The diagnosis of TTP was entertained at this point in the patient's hospital course given her presentation of acute renal failure, thrombocytopenia and mental status changes. A peripheral smear showed crenated red blood cells consistent with MAHA, further supporting the presumptive diagnosis of TTP. Plasmapheresis was therefore started 28 days after coronary artery stenting/initiation of ticlopidine therapy. The patient's thrombocytopenia remained refractory throughout 2 weeks of plasmapheresis and she was subsequently given vincristine and prednisone. Intravenous IgG was added given lack of response and a platelet count of 6000. Plasmapheresis was stopped shortly thereafter and the patient was re-challenged with platelet transfusions. She tolerated this well and her thrombocytopenia began to resolve with daily platelet transfusions (Figure 1).
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Comment
Given a lack of renal histological features suggestive of thrombotic microangiopathy, a lack of complications after re-challenging with platelet transfusion and no improvement in platelet count with plasmapheresis, vincristine, prednisone and IgG infusion, it seems clear that the underlying disease process involved in this patient was not TTP. Cholesterol embolization, or atheroembolic renal disease (AERD), on the other hand, as evident on renal biopsy, can account for many of the clinical features that this patient displayed, including thrombocytopenia. It is not uncommon to see thrombocytopenia with AERD. In fact it has been suggested that thrombocytopenia may favour the diagnosis of AERD when considered in the differential diagnosis of vasculitis in the setting of acute renal failure [4].
There is a possibility that this patient may have had cholesterol emboli to her autotransplant kidney from previous renovascular procedures. However, in view of her clinical features, smoldering loss of renal function over days to weeks following coronary angiography, and renal histological findings, cholesterol embolism seems to be the more likely primary disease process at work in this case.
Discussion
Renal cholesterol embolic disease or AERD, is frequently part of a larger multi-system disorder that frequently affects the skin, GI tract, eye and muscle. It was first observed in 1862 by Panum [58].
Clinical illness presentation in AERD is often unrecognized or misdiagnosed as systemic vasculitis [5,9]. Classically, AERD presents as acute renal failure, most commonly in the elderly, following angiography or vascular surgery. It is felt that cholesterol plaques are physically dislodged from atheromatous vessels during procedural manipulation, resulting in a shower of emboli downstream from the aorta, the most commonly suspected site of plaque disruption. Subsequent mottling of skin, livedo reticularis, digital gangrene, GI haemorrhage, retinal emboli and neurologic sequelae are all secondary physical findings. For unknown reasons, eosinophilia (>500 eosinophils/µl) is also present in 4080% of affected individuals [5,7].
With a mortality rate as high as 70% according to one source, usually secondary to cardiac complications, early diagnosis and supportive treatment in AERD is vital [8]. Unfortunately, an exceedingly large number of cases are discovered on autopsy. Of those discovered in living patients, renal biopsy remains the best diagnostic tool (31%), followed by muscle (21%) and skin (17%) biopsies [8]. The course of the patient's renal failure is also important in raising one's clinical suspicion following angiography. Radiocontrast nephropathy is usually within the first 2472 h after the procedure while the acute renal failure seen with AERD may come on over weeks, setting it apart temporally at least from the dye-induced nephropathy.
Almost without question, the number of cases of AERD will increase in the future. This is secondary to the increasing numbers of individuals who are living longer with their atherosclerosis, and, probably more importantly, a function of the increasing number of invasive angiographic interventions that are being carried out annually that will result in plaque rupture and showering of cholesterol emboli to the kidneys [7].
Teaching point
Even well-described associations as experienced in this case are sometimes misleading. AERD is a great masquerader.
Notes
Supported by an educational grant from
Correspondence and offprint requests to: Kulwant S. Modi, Division of Nephrology, Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA.
References