Inhibitor treatment using unactivated prothrombin complex concentrates: the Pennsylvania experience--1978-1982.

Data were analyzed on 48 patients with Factor VIII:C inhibitors, 31 of whom were treated with more than 6.7 million units of unactivated prothrombin complex concentrates (PCC) during the years 1978 through 1982 for more than 1,000 bleeding episodes. Twelve of the patients who were on home therapy used 3.1 million units, or 47% of the total PCC usage. Only one patient had a severe life-threatening allergic reaction to PCC, and no thrombotic complications were observed, supporting the concept that these products are safe when used in doses of 50-75 u/Kg. Fifty percent of hemarthroses and 65% of muscle hemorrhages were treated with no more than two infusions per episode, suggesting that PCC was effective at least half of the time. Comparison of the number of days hospitalized per year for inhibitor and non-inhibitor patients also indicated that PCC was effective, although not as effective as AHF therapy in non-inhibitor patients. The life styles of PCC treated patients were comparable to what might be expected for non-inhibitor patients with severe disease, and no deaths were attributed to PCC treatment failure during the four year period. Of major concern, however, was the cost of therapy. In 1981-82, the average use of PCC for inhibitor patients was 106,000 units per treated patient per year, compared to 40,000 AHF units for all Factor VIII deficient treated patients per year. Much of this usage was for recurrent hemarthroses in a small number of patients requiring eight or more infusions per episode.

Liver dysfunction in Pennsylvania's multitransfused hemophiliacs.

Transaminase values [alanine amino transferase (ALT) and aspartate amino transferase (AST)] and markers for hepatitis B were serially determined in 558 hemophiliacs exposed to blood products. Hepatitis B surface antigen (HBsAg) persistent for over 12 months was present in 6% of the patients. Antibody to hepatitis B surface antigen (anti-HBs) was noted in 90% of the 259 patients treated with factor VIII or IX concentrates but in only 49% of the 43 patients treated with fresh frozen plasma (FFP) or cryoprecipitate. Persistently abnormal transaminase values were noted in 31% of the patients treated with commercial concentrates but in only one (2%) of the patients exposed to cryoprecipitate or FFP. This difference continued even when the two groups of patients were matched for the amount of blood products, up to 50,000 units, which they had received in the study period. In the concentrate-treated patients, no correlation could be found between transaminase values and the number of units of factor VIII or IX they had received during the six years of the study (1973-1978).

Hepatitis B virus, hepatitis A virus and persistently elevated aminotransferases in hemophiliacs.

To determine the exposure to hepatitis A and hepatitis B viruses (HAV, HBV) following intravenous replacement therapy in patients with classic hemophilia and to assess the role of these viruses in persistently elevated aminotransferases, sera were studied from 136 patients from 9 months to 67 years of age were transfused with either single-donor cryoprecipitate (CRYO) or Antihemophilic Factor Concentrate (AHF) for periods ranging from a few months to 15 years. Serologic evidence of past or present infection with HBV was detected in 90% of all 136 patients and in 85% of those 34 patients 10 years of age or younger. Sixty-four percent of those with serologic markers of hepatitis B had high titers of antibody to the hepatitis B surface antigen and low titers of antibody to the hepatitis B core antigen. These findings are consistent with the known high frequency of early exposure to HBV in hemophiliacs receiving replacement therapy and with recovery from these hepatitis B infections. Sixteen percent of these patients had persistently elevated aminotransferase levels; HBV could not be implicated as the cause of the enzyme elevations in most of these cases.

Leukemic reticuloendotheliosis: report of a case with peripheral blood remission on androgen therapy.

Leukemic reticuloendotheliosis (LRE) has been generally considered to be poorly responsive to therapy other than splenectomy. The patient presented below developed a complete peripheral blood remission after prolonged therapy with an androgen (oxymetholone). There is very little published experience with androgen therapy in LRE. The experience with this patient suggests that androgens may produce a clinical remission by inducing significant improvement in the peripheral blood in some patients with this disease.

Delayed recurrence and chemotherapy of a granulosa cell tumor.

A case of proved delayed recurrence of a granulosa cell tumor 18 years after initial diagnosis is presented. L-Phenylalanine mustard was given after radiation was refused for the unresectable mass. A prolonged complete remission was produced. The present status of palliative therapy of recurrent granulosa cell tumor is discussed with a request for the reporting of experiences with more patients treated with chemotherapy.

The phase II evaluation of Bacillus Calmette-Guerin plus megestrol acetate in patients with metastatic renal adenocarcinoma.

The case is reported of a patient with pulmonary metastases from a renal adenocarcinoma who experienced subjective improvement and objective tumor regression on Bacillus Calmette-Guerin (BCG) and megestrol acetate therapy. In a subsequent Phase II trial, no objective responses were noted among 15 patients treated with megestrol acetate (160 mg/day X 56 days) and BCG (five immunizing doses intradermally, every 2 weeks X 5). It is concluded that this treatment regimen is not clinically useful in patients with metastatic renal adenocarcinoma.