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A clotting screen is essential to differentiate between causes of microangiopathic haemolytic anaemia. These can be either thrombotic microangiopathy or disseminated intravascular coagulation, possibly related to an obstetric calamity, sepsis, malignancy, or acute inflammation such as acute pancreatitis. In this case, normal clotting studies support the diagnosis of thrombotic microangiopathy.
The box lists the causes of thrombotic microangiopathy. In each situation, end organ injury will be exacerbated by hypertension. For this patient, initial management must focus on urgent treatment of her accelerated hypertension, which may even switch off the thrombotic microangiopathy. She needs immediate admission to a unit with facilities for invasive monitoring. Intravenous furosemide and nitrate infusion are appropriate if clinical signs of fluid overload are present. In acute renal failure, the response to furosemide is usually poor, and haemofiltration (or haemodialysis) should be started early. However, circulating volume can be reduced in accelerated hypertension and medical management is different, with arterial vasodilation needed rather than diuresis and venodilation.
In this case, the differential diagnosis includes haemolytic uraemic syndrome-thrombotic thrombocytopenic purpura—possibly associated with pregnancy or shigatoxin—anticardiolipin antibody syndrome, and scleroderma renal crisis. In idiopathic haemolytic uraemic syndrome-thrombotic thrombocytopenic purpura, vascular injury occurs in the context of reduced factor H activity, reduced ADAMTS13 (von Willebrand factor cleaving protease) due to an acquired antibody, or reduced concentrations of other complement regulatory proteins. Some patients may benefit from infusion of plasma (or plasma cryosupernatant), which may replace or augment the missing factors. Although plasma exchange is often used, the evidence is not strong, and benefit may be limited to patients with antibodies to ADAMTS13 or problems with volume overload.1
The pregnancy test is negative in this patient and she has no history of shigatoxin infection. Her miscarriages probably occurred during the first trimester, and the normal activated partial thromboplastin time excludes a lupus anticoagulant, although anticardiolipin antibodies could still be present. The history of Raynaud's phenomenon raises the possibility of underlying connective tissue disease. A diagnosis of acute scleroderma renal crisis is supported by the presence of strongly positive antinuclear antibodies and anti-RNA polymerase antibodies, together with the renal histology. Absence of cutaneous changes is unusual, however, and might favour a unifying diagnosis of accelerated hypertension with incidental serology. In a recent report of 115 cases of acute scleroderma renal crisis, patients were mostly female (81%), had diffuse cutaneous disease (78%) and anti-RNA polymerase antibodies (59%), and outcome was predicted by renal histology.2
The renal biopsy was consistent with accelerated hypertension or scleroderma renal crisis with widespread ischaemia. Doppler ultrasound showed poor renal perfusion with normal proximal arteries confirmed on renal angiography. By this stage, the diagnosis was much clearer and a dynamic renogram would have confirmed minimal uptake with poor prognosis due to irreversible tissue injury and avoided the need for selective angiography.