Hayden G. Braine

Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients.

BACKGROUND AND METHODSnThrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the mortality approached 100 percent. A treatment protocol was introduced in 1979 for patients admitted to Johns Hopkins Hospital with the diagnosis of TTP-HUS. Treatment regimens included 200 mg of prednisone a day, for patients with minimal symptoms and no central nervous system symptoms, and prednisone plus plasma exchange, for patients with rapid clinical deterioration who did not improve after 48 hours of prednisone alone and for patients presenting with central nervous system symptoms and rapidly declining hematocrit values and platelet counts.nnnRESULTSnA total of 108 patients were treated, and 91 percent survived. Prednisone alone was judged to be effective in 30 patients with mild TTP-HUS (two relapses and two deaths). Plasma exchange plus prednisone was given to 78 patients with complicated TTP-HUS, resulting in 67 relapses and 8 deaths. Relapses occurred in 22 of 36 patients given maintenance plasma infusions. Neither splenectomy nor treatment with aspirin and dipyridamole was effective in those with a poor response to plasma exchange. None of the 71 patients tested had positive cultures for O157:H7 Escherichia coli. Nine percent of the patients were pregnant, and none gave birth to infants with TTP-HUS.nnnCONCLUSIONSnEffective treatment with 91 percent survival is available for patients with TTP-HUS.

White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. The Trap Study Group

BACKGROUND: Most previous studies on white cell (WBC) reduction by filtration have been small‐scale studies conducted under tightly controlled laboratory conditions. Their results would be the ideal, rather than what might be expected during routine operation. STUDY DESIGN AND METHODS: To obtain information on routine filtration of blood components, data have been collected from a large‐scale, ongoing, multicenter clinical trial designed to determine the effectiveness of WBC reduction in or ultraviolet B radiation of platelet concentrates before transfusion in preventing platelet alloimmunization and platelet transfusion refractoriness. The WBC content of blood components both before and after filtration was determined by automated cell counters and a manual propidium iodide‐staining method, respectively. Platelet and red cell losses during filtration were measured. RESULTS: The average platelet losses after filtration were 24 +/− 15 percent and 20 +/− 9 percent for apheresis platelets and pooled platelets, respectively. The frequencies at which filtered platelet concentrates contained high levels of residual WBCs (> 5 × 10(6)) were 7 percent and 5 percent for apheresis platelets and pooled platelets, respectively. Further analysis of the platelet filtration data showed that greater numbers of total initial WBCs in the pooled platelets were associated with increased percentages of filtration failure (> 5 × 10(6) residual WBCs). For packed red cells, the average losses during filtration were 23 +/− 4 percent and 15 +/− 3 percent for CPDA‐1 units and Adsol units, respectively. The frequencies at which filtered red cells contained > 5 × 10(6) residual WBCs were 2.7 percent for one type of filter and 0.3 percent for another type of filter. CONCLUSION: There were significant losses of platelets during filtration, which could add to the costs of WBC reduction and lead to possible increases in donor exposures. Filtration failures still occurred, despite careful observation of the standard filtration procedures. The number of total WBCs in pooled platelets before filtration has been identified as an important factor in determining the success of WBC reduction.

A prospective double-blind study of plasma exchange therapy for the acroparesthesia of Fabry's disease.

During a study of the effect of plasma exchange on glycosphingolipid metabolism, a patient with Fabrys disease noted a dramatic improvement in his painful acroparesthesia. A controlled study was therefore undertaken. Observations were made of nerve conduction times, graded exercise testing, and psychometric evaluations during and after two planned series of three plasma exchanges: one a true plasma exchange and the other a “sham” control in which the patient received his own plasma. All observers and the patient were blinded and unanimously attributed beneficial results to the sham procedure. This study demonstrates the need for controlled studies in diseases prone to unpredictable exacerbation or spontaneous remission and outlines one possible technique of controlling studies involving plasma exchange.

A case of severe benign intrahepatic cholestasis treated with liver transplantation.

A male patient with benign recurrent cholestasis since age 2.5 yr developed unremitting cholestasis with incapacitating pruritus and hepatic fibrosis by age 21. He was tried on numerous medical therapies for pruritus with transient or no relief. He responded only temporarily to biweekly plasmapheresis, which was carried out for 4 yr. He underwent orthotopic liver transplantation at age 25 with immediate resolution of his pruritus. At age 30 he is a happy, asymptomatic, fully employed professional.

Human histocompatibility antigens and survival in acute myelocytic leukemia

Several previous reports have suggested an association between human histocompatibility antigens (HLA) and survival in acute myelocytic leukemia (AML). The authors have retrospectively analyzed the records of 104 consecutive newly diagnosed patients with AML treated on the Leukemia Service of the Johns Hopkins Oncology Center from March 1978 through May 1982 who had HLA typing performed to further evaluate this point. The authors have been unable to demonstrate a statistically significant association of HLA phenotype with the ability to achieve a complete response (CR), length of CR, survival of the total group of treated patients, or survival of only those patients achieving a CR (P < 0.05). The available evidence does not strongly support a significant influence of HLA on survival in AML.

SERUM INHIBITOR OF GRANULOCYTE COLONY FORMATION ASSOCIATED WITH NEUTROPENIA IN TYPE I DYSGAMMAGLOBULINEMIA

A sixteen year old white male with X-linked Type I Dysgammaglobulinemia developed persistent neutropenia (total neutrophils < 500/mm3) which was unresponsive to broad spectrum antibiotics, prednisone, or a single infusion of one liter of fresh frozen plasma. His plasma agglutinated neutrophils in a microagglutination assay. His plasma (or serum) inhibited colony formation in a dose dependent fashion in a granulocyte/macrophage colony forming assay using human bone marrow cells. Complete inhibition was obtained when the patients serum reached a final concentration of 5%. This effect was similar when either the patients or normal bone marrow cells were used. Heating the patients serum to 56°C for 30 minutes did not destroy the inhibitor. Bone marrow cells cultured in a medium containing 5% of the patients serum and 5% of normal serum were also completely inhibited. Seven total plasma exchange procedures were performed over three weeks during which time the peripheral neutrophil count returned to normal and no serum inhibitor could be demonstrated. Upon completion of the plasma exchange procedures, the peripheral neutrophil count fell within three days to less than 500/mm3 and the serum inhibitor of colony formation reappeared. Three weeks after the plasma exchange procedures, the neutrophil count spontaneously returned to normal while on broad spectrum antibiotic therapy.