Immunosuppressive agents such as azathioprine, rituximab, and mycophenolate have been tried with mixed success and side effects. Eculizumab, an anti-C5 (complement-5) antibody has been used in catastrophic cases and inhibition of the m-TORC pathway in patients with renal disease and transplant failure is being explored. Statin drugs have a theoretical basis for use but have not been extensively tested. It is important to eliminate smoking and estrogen-containing compounds, as these greatly raise the risk of stroke in this syndrome.
The subject of systemic antiphospholipid antibody disease and its treatment has been reviewed by Garcia.
Thrombotic Thrombocytopenic Purpura (TTP, Moschcowitz Syndrome) and Hemolytic Uremic Syndrome
These are serious diseases of the small blood vessels combined with microangiopathic hemolytic anemia characterized by widespread occlusions of arterioles and capillaries involving practically all organs of the body, including the brain. It was described by Adams and colleagues (1948) and named thrombocytic acroangiothrombosis. Fibrin components have been identified by immunofluorescent techniques; some investigators have demonstrated disseminated intravascular platelet aggregation rather than fibrin thrombi. Sporadic TTP is caused by an acquired circulating IgG inhibitor of the von Willebrand factor-cleaving protease (termed “a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 [ADAMTS13]”). A rarer familial form (The Upshaw-Shulman syndrome) is caused by an inherited deficiency of ADAMTS13.
Clinically, the main features of this disease are fever, anemia, symptoms of renal and hepatic disease, and thrombocytopenia—the latter giving rise to the common hemorrhagic manifestations (petechiae and ecchymoses of the skin, retinal hemorrhages, hematuria, gastrointestinal bleeding, etc.). Neurologic symptoms are practically always present and are the initial manifestation of the disease in about half the cases. Confusion, delirium, seizures, and hemiparesis—sometimes remittent or fluctuating in nature—are the usual manifestations of the nervous system disorder and are readily explained by the widespread microscopic ischemic lesions in the brain. Garrett and colleagues have emphasized the presentation of nonconvulsive status epilepticus in TTP, and we have encountered two such cases. Gross infarction was not observed. In most patients who survive, recovery of the focal neurologic deficits can be expected unless there is an identifiable infarction on CT or MRI. The CSF is normal except for elevated protein in some cases. To our knowledge, a mononeuritis multiplex does not occur.
The diagnosis is made by finding a microangiopathic hemolytic anemia in the context of the characteristic clinical picture. An assay for ADAMTS13 activity is available using an enzyme-linked immunosorbent assay but the initiation of treatment usually cannot await confirmation of the diagnosis. There is an important overlap among TTP, HUS, toxemia of pregnancy, the hemolytic anemia with elevated liver function tests and platelet count (HELLP syndrome), hypertensive encephalopathy, and other causes of the posterior reversible leukoencephalopathy syndrome (PRES, see earlier discussion). In all of them, the central nervous system problem is mediated by endothelial dysfunction with breakdown of the blood–brain barrier. The recommended treatment for TTP is plasma exchange or plasma infusion. Further details can be found in Harrison’s Principles of Internal Medicine.
Polycythemia Vera, Thrombocytosis, and Thrombocythemia