Thrombotic thrombocytopenic purpura with severe large artery branch involvement

Sir,

A 36-year-old male patient was admitted to hospital due to diffuse abdominal pain, headache and blurred vision. Physical examination showed a patient with an affected clinical condition but awake. Arterial blood pressure (BP) was 260/140 mmHg with a regular heart rhythm. Abdominal examination revealed severe mesogastrium tenderness with preserved bowel sounds, and neurological examination showed no focal abnormalities. Fundoscopy showed diffuse haemorrhagic exudates without papilloedema. Laboratory investigations at admission showed thrombocytopenia (platelets 52 x 109/l), haemolytic anaemia [haemoglobin 10 g/dl, 2–3 schistocytes, haptoglobin 23 mg/dl, lactate dehydrogenase (LDH) 37 µkat/l], direct Coombs test negative and acute renal failure (creatinine 228 µmol/l) with proteinuria (++) and haematuria (+++). Immunological studies were negative for antinuclear antibodies, anti-double-stranded DNA, anti-phospholipid antibodies and anti-Scl-70. Serologies for Epstein–Barr virus, hepatitis B and C virus as well as human immunodeficiency virus (HIV) were negative.

Despite an adequate arterial blood pressure control with antihypertensive drugs (BP 120/80 mmHg), the patient developed progressive confusion, and haemolytic anaemia and renal failure got worse at the same time. These findings led to the diagnosis of thrombotic thrombocytopenic purpura (TTP)/haemolytic uraemic syndrome (HUS), so plasma exchange (3 l per session) and haemodialysis were performed without achieving good results. The patient deteriorated; he developed an acute pancreatitis, which led to pancreaticoduodenectomy with subtotal antrectomy and cholecystectomy being performed. After surgery, there was an improvement of haemolysis (haptoglobin 168 mg/dl, LDH 13 µkat/l, 2–3 schistocytes, platelets 94 x 109/l) without recovery of renal failure (creatinine 632 µmol/l). The patient remained in a persistent coma, and a new brain computed tomography (CT) scan showed multiple ischaemic lesions in both cerebral hemispheres. Cerebral angiography showed occlusion of multiple large artery branches. On the 15th post-operative day, the patient died due to persistent ventricular arrhythmias.

The autopsy study showed thrombotic microangiopathy of small, medium and large artery branches, with extensive haemorrhagic infarction in the brain and pancreas. In the kidney, there was also intimal hyperplasia in the arterioles and middle size arteries (Figure 1). On the other hand, in the heart, there was an area of myocardial necrosis with coronary atheromatous disease involving two large arteries but without microangiopathic lesions.



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Fig. 1. Survival in patients of group 1 and group 2.

 
TTP/HUS is a multisystemic disease characterized by fever, thrombocytopenia, microangiopatic haemolytic anaemia, neurological disorders and renal failure [1]. In the majority of clinical reports of TTP/HUS, the vascular lesions are characterized by progression from endothelial swelling and microthrombi formation to intimal proliferation with hyperplasia involving capillaries and arterioles [2]. Two major types of kidney involvement have been described, a glomerular form and a vascular form with arterial lesions. In this later case, vascular involvement is usually associated with more severe hypertension, more frequent neurological disorders, higher risk of renal and neurological sequelae and higher mortality [3]. In this patient, we observed severe arterial damage affecting large artery branches, middle and small arteries of both kidneys.

Neurological symptoms are present in >90% of patients [1]. These are attributed to ischaemia of the cerebral cortex associated with transient occlusion of arterioles or microinfarcts [4]. Moreover, few reports have also shown cerebral infarcts due to an occlusion of the large artery branches [4–6]. Here we also describe a patient with TTP, who developed widespread areas of brain infarction due to occlusion by miointimal proliferation of large artery branches.

It has been established that plasma infusion or plasma exchange are the only useful therapies for the TTP/HUS, allowing induction of remission of acute episodes in 60–90% of patients [7]. In cases showing involvement of the medium and large artery branches, clinical reponse to plasma exchange was poorer than in cases limited to small arteries and arterioles. In our case, despite the fact that intensive plasma exchange therapy was started at admission, the disease steadily progressed and led to the patient's death due to multisystem failure.

In summary, we report a patient with diffuse vascular lesions leading to acute pancreatitis, acute renal failure and massive brain infarctions. Histological evaluation showed a severe involvement of large artery branches, medium-sized arteries and small vessels with arterial occlusion. Despite intensive plasma exchange therapy, the patient died due to multisystem organ failure.

Conflict of interest statement. None declared.

M. Ibernon, F. Moreso, L. Carreras, M. Carrera, T. Serrano, I. Rama, O. Bestard, J. Torras, R. Poveda and J. M. Grinyó

Departments of Nephrology and Pathology Hospital Universitari de Bellvitge Barcelona Spain Email: meribernon{at}hotmail.com

References

  1. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine 1966; 45: 139–159[ISI]
  2. Ruggenenti P, Noris P, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60: 831–746[CrossRef][ISI][Medline]
  3. Morel-Maroger L. Adult hemolytic–uremic syndrome. Kidney Int 1980; 18: 125–134.[ISI][Medline]
  4. Kelly PJ, McDonald CT, Neil GO et al. Middle cerebral artery main stem thrombosis in two siblings with familial thrombotic thrombocytopenic purpura. Neurology 1998; 50: 1157–1160[Abstract]
  5. Rinkel GJ, Wijdicks EF, Hene RJ. Stroke in relapsing thrombotic thrombocytopenic purpura. Stroke 1991; 22: 1087–1089
  6. Case records of the Massachusetts General Hospital. Case 36-1991. A 60-year-old man with multiple cerebral infarcts and cutaneous hemorrhagic lesion. N Eng J Med 1991; 325: 714–726[ISI][Medline]
  7. Rock GA, Shumak KH, Buskard NA et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 1991; 325: 393–397[Abstract]




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