Thrombotic Thrombocytopenic Purpura (TTP)

A genetic disorder affecting mostly adults and associated with pregnancy, HIV, cancer, bacterial infection, and vasculitis. Has also been observed after bone marrow transplantation. Clinical features include seizure, hemiplegia, fatigue, abdominal pain, arthralgias, neurological deficit, and renal insufficiency. Idiopathic presentation with a 60% female preponderance.

Moschowitz Syndrome; Thrombotic Microangiopathic Hemolytic Anemia.

First described by Eli Moschcowitz, American pathologist in 1924.

More than 75 years ago, the occurrence was 1/1,000,000 in general population. However, the incidence seems to have increased. Ten years ago, the rate was reported at 3.7 cases per 1 million patients. However, the incidence today is much higher because of greater awareness and increasing reports of TTP secondary to other illnesses and drugs. One report indicated a case rate of 1:6000 hospital admissions. The mortality rate was 100% until 1980, but a major drop has been observed with early diagnosis and improvement in therapy with plasma exchange. Untreated, mortality remains high at 95%, whereas survival is 90% if treated. Approximately 60% of patients are female. The female-to-male ratio is 3:2.

Most familial cases are recessive but dominant pedigrees have also been reported. The phenotypes might be identical but mutations in the ADAMTS13 gene are involved for Moschowitz disease; the locus is at 9q34.

Characterized by microangiopathic hemolysis and idiopathic platelet aggregation/hyaline thrombi leading to diffuse thrombosis of small blood vessels, with organ ischemia and microangiopathic hemolytic anemia. Platelet transfusion can actually cause deterioration secondary to increased activation and deposition. The thrombi partially occlude the vascular lumina with overlying proliferative endothelial cells. The endothelia of the kidneys and brain are particularly vulnerable to TTP. However, the lungs and liver are affected to a lesser extent. The megakaryocytes and endothelial cells produce and release the ultra-large von Willebrand factor multimer, which favors binding to platelets in the microcirculation. Treatment includes plasmapheresis, which either removes a platelet activator or adds an inhibitor, and immunosuppression. Splenectomy follows failure of medical therapy.

Based on clinical and laboratory findings, including the hemolytic anemia, consumptive thrombocytopenia, central nervous system (CNS) dysfunction, and petechiae.

Peak prevalence in third decade of life, hemolytic anemia, consumptive thrombocytopenia, central nervous system (CNS) dysfunction, and petechiae. Seizure activity (16%), hemiplegia (12%), and paresthesias have been reported. Also the possibility of heart failure and arrhythmias must be borne in mind. Twenty-five percent of patients present with abdominal pain due to gastrointestinal ischemia.

The heterogenicity of the patients-adults and children-renders the evaluation difficult. Obtain a full history of the concomitant illnesses (if any) and assess thoroughly the involvement of the kidneys and the CNS. The severity of the infection associated (if any) must be known. Aseptic technique, especially with immunosuppression. Supplemental steroids as needed. Check baseline renal and CNS function and obtain a complete cell blood count. Myopathy/neurotoxicity is possible with vincristine therapy.

Postpone elective surgery until patient is in remission. Avoid IM injections. Avoid central neuraxial blockade. Judicious sedation with CNS dysfunction. Careful padding. Treat coagulopathy with packed red blood cells and fresh-frozen plasma, not platelets. Consider these patients to be at high risk for bleeding therefore the necessity to place a large bore peripheral venous access. In the presence of neurological signs, standard brain protection must be instituted with moderate hyperventilation, and effort made to minimize the secondary insults. Hemodynamic control to avoid CNS bleeds.

Avoid succinylcholine with myopathy or neurologic deficit. Patients treated for seizures must receive their medications until the morning of surgery. Avoid anesthetic agents known to trigger seizure activities.

Hemolytic Uremic Syndrome (HUS): A more common disorder in children, characterized by prominent renal involvement. Associated with epidemics of diarrhea caused by verocytotoxin-producing bacteria or of familial origin (caused by mutation in the gene encoding factor H or ADAMTS13).

Upshaw-Schulman Syndrome: A very rare syndrome characterized by congenital microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura, and response to fresh plasma infusion. Neonatal onset and frequent relapses are typical.