ABSTRACT
We describe the case of a 24-year-old woman who was admitted to the emergency department with dyspnea and sinus tachycardia. The suspected diagnosis of pulmonary embolism was confirmed by computed tomography (CT) scan. The patient lost consciousness soon afterwards and was found to be pulseless. Cardiopulmonary resuscitation was performed and high dosis thrombolysis was given. The patient survived without sequelae and was discharged on oral anticoagulation from the hospital 8 days after the initial admission. In our opinion unknown factor-V Leiden in combination with a local form of hormonal contraception (NuvaRing®) was responsible for the deep venous thrombosis of the left leg and the pulmonary embolism.
Subject(s)
Contraceptives, Oral, Hormonal/adverse effects , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Venous Thrombosis/diagnosis , Venous Thrombosis/etiology , Female , Humans , Pulmonary Embolism/therapy , Venous Thrombosis/therapy , Young AdultABSTRACT
Mixed cryoglobulins are complexes of immunoglobulins that reversibly precipitate in the cold and lead to a systemic disease in humans. Renal involvement usually manifests as a membranoproliferative glomerulonephritis with marked monocyte infiltration and, at times, intracapillary thrombi. Thymic stromal lymphopoietin (TSLP) is a recently cloned cytokine that supports differentiation and long-term growth of B cells. Here we report that TSLP overexpression in mice results in the development of mixed cryoglobulins, with renal involvement closely resembling cryoglobulinemic glomerulonephritis as it occurs in humans. One hundred twenty-three mice were sacrificed at monthly intervals, with at least five TSLP transgenic mice and five controls in each group. Blood, kidneys, spleen, liver, lung, and ear were collected and studied by routine microscopy, immunofluorescence, immunohistochemistry, and electron microscopy. TSLP transgenic animals developed polyclonal mixed cryoglobulinemia (type III) and a systemic inflammatory disease involving the kidney, spleen, liver, lung, and ears. Renal involvement was of a membranoproliferative type demonstrating thickened capillary walls with cellular interposition and double contours of the basement membrane, expansion of the mesangium because of increased matrix and accumulation of immune-deposits, subendothelial immune-deposits, focal occlusion of capillary loops, and monocyte/macrophage influx. In contrast to the severe glomerular lesions, the tubulointerstitium was not involved in the disease process. The renal lesions and the disease course were more severe in females when compared to males. We describe a mouse strain in which a B-cell-promoting cytokine leads to formation of large amounts of mixed cryoglobulins and a systemic inflammatory injury that resembles important aspects of human cryoglobulinemia. This is the first reproducible mouse model of renal involvement in mixed cryoglobulinemia, which enables detailed studies of a membranoproliferative pattern of glomerular injury.
