Adverse reactions associated with mobile therapeutic apheresis: analysis of 17,940 procedures.

In order to evaluate the nature and frequency of adverse reactions associated with Therapeutic Apheresis (TA), database information from two large mobile apheresis services was analyzed. A total of 17,940 procedures performed on 3,583 patients were studied using an Access Database. Seventy percent (12,558) of the procedures were performed on a Fresenius AS104 blood cell separator and 30% (5,382) were performed on a COBE Spectra. The five most commonly treated diseases were Guillain-Barre Syndrome (25%), thrombotic thrombocytopenic purpura (20%), myasthenia gravis (18%), the hyperviscosity syndrome (12%), and chronic inflammatory demyelinating polyneuropathy (9%). All patients received calcium gluconate supplement during the procedures. Cardiac monitoring was used during 80% of the procedures and blood pressure monitoring was used during all procedures. All procedures were supervised by a physician. Both apheresis services fully comply with the ASFA Guidelines for Therapeutic Apheresis Providers. Adverse reactions occurred in 3.9% of all procedures. The following adverse reactions were documented: reactions related to ACD toxicity (3%), vasovagal reactions (0.5%), vascular access related complications (0.15%), reactions related to FFP (0.12%), hepatitis B from FFP (0.06%), arrhythmias (0.01%), hemolysis due to inappropriate dilution of 25% albumin (0.01%), and one death (from underlying disease) during a TA procedure (0.006%). These data demonstrate that therapeutic apheresis is associated with a low rate of side effects when performed by well-trained and certified nurses under the direction of experienced physicians, even in the diverse setting of large mobile therapeutic apheresis programs.

The use of intravenous immunoglobulin in recurrent pregnancy loss associated with combined alloimmune and autoimmune abnormalities.

PROBLEM: Several studies have evaluated the effect of intravenous gammaglobulin (IVIG) in women with unexplained recurrent spontaneous abortions (RSA). Data regarding the underlying immunologic abnormalities in these patients is scant. This study reports the pregnancy outcome and immunologic changes observed in a large group of women with RSA associated with well-defined alloimmune and autoimmune abnormalities treated with IVIG. METHODS: Thirty-five patients with three or more recurrent miscarriages were studied. None of the patients had identifiable alloimmune response to paternal lymphocytes. Twenty-four patients had anti-thyroid antibodies, ten patients had high levels of circulating immune complexes, and six patients had anti-cardiolipin antibodies. Five patients had Hashimoto's disease, one had immune thrombocytopenic purpura, and one had Crohn's disease. Twenty-three patients had more than one autoimmune abnormality. All patients received IVIG infusions (200-250 mg/kg) every 3 weeks during the first 8 months of pregnancy. RESULTS: Twenty-eight patients (80%) had a successful pregnancy. Decrease of the level of autoantibodies and circulating immune complexes was observed in all patients who had a successful pregnancy. Only three of these patients developed measurable alloimmune response to paternal antigens. CONCLUSIONS: This preliminary study suggests that IVIG may be of benefit to patients with recurrent pregnancy associated with combined alloimmune and autoimmune abnormalities. This benefit was seen in spite of lack of detectable correction of the alloimmune abnormality in the majority of patients.

Acquired factor VIII inhibitor associated with chronic interferon-alpha therapy.

Therapeutic use of interferon-alpha (IFN-alpha) has been associated with the development of a variety of autoimmune disorders. We describe a patient who received chronic treatment with IFN-alpha following autologous bone marrow transplantation for multiple myeloma. The patient developed an antibody inhibitor directed against factor VIII coagulant protein (FVIIIC) leading to a fatal hemorrhagic diathesis. The association between IFN-alpha therapy and autoimmune complications deserves wider recognition and further study.

Myasthenic crisis. Response to plasmapheresis following failure of intravenous gamma-globulin.

Myasthenic crisis is a potentially life-threatening complication of myasthenia gravis that requires aggressive therapy. We describe four patients in whom myasthenic crisis developed and who failed to respond to initial treatment with intravenous gamma-globulin. All four patients subsequently responded to intensive plasma exchange. Based on our experience, plasmapheresis appears to be superior to intravenous gamma-globulin for the treatment of myasthenic crisis in certain patients. Prognostic factors that determine the effectiveness of intravenous gamma-globulin vs plasmapheresis in these patients merit further investigation.

Pilot study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency virus infection.

Dendritic cells, the primary antigen presenting cells of the human immune system, are heavily infected with human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS). Dinitrochlorobenzene (DNCB) is a contact sensitizing agent that acts as a potent immune modulator of dendritic cells. In this pilot study, we examined the safety and efficacy of topical DNCB application in patients with early HIV disease. Topical DNCB was well tolerated by these patients, with an adverse reaction rate of 10%. CD4+ T-cell counts remained stable with repeated DNCB use. In contrast, CD8+ T-cell counts and natural killer cells increased significantly following DNCB sensitization. This increase in CD8+ T-cell and natural killer cell subsets was accompanied by a decrease in HIV replication, as measured by serum HIV RNA levels. Based on this pilot study, we conclude that topical DNCB is safe in early HIV disease and may decrease viral load via a systemic effect on dendritic cells, CD8+ T-cells and natural killer cells. These results require confirmation in larger controlled trials.

Mononeuritis multiplex associated with cryoglobulinemia in HIV infection.

We describe a patient with human immunodeficiency virus (HIV) infection who developed mononeuritis multiplex associated with polyclonal (type III) cryoglobulinemia. The patient's symptoms stabilized following treatment with plasmapheresis and removal of the cryoglobulin. Our case represents the first report of polyclonal cryoglobulinemia in HIV disease and suggests that cryoglobulinemia may play an etiologic role in some patients with HIV-associated neuropathy.

Thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus. Case report and literature review from the plasmapheresis era.

Although thrombotic thrombocytopenic purpura (TTP) has been described in patients with systemic lupus erythematosus (SLE), the relationship between these 2 diseases is controversial. We recently treated a patient with longstanding SLE who developed TTP. The patient responded to therapy with aggressive plasmapheresis. Review of the literature revealed that TTP may occur in the setting of either active or inactive SLE. Survival in SLE associated TTP correlated with the use of plasma therapy (plasma infusion or plasmapheresis) rather than with the activity of the underlying autoimmune disease. We conclude that TTP and SLE represent distinct clinical entities that may occur together in an immunologically predisposed host. The use of plasma therapy appears to have had a significant impact on survival in these patients.

Role of plasmapheresis in acute disseminated (postinfectious) encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating central nervous system disease that is associated with high morbidity and mortality. Although the recognition of ADEM may be facilitated by newer imaging techniques, the optimal treatment of this disease remains uncertain. We describe 4 patients with severe ADEM who responded to treatment that included intensive plasmapheresis. Two of the patients were in coma at the time that plasmapheresis was instituted, and all 4 patients made an excellent recovery. Immunologic studies revealed increased serum IgA levels, increased circulating immune complex levels as measured by the Raji cell assay, and decreased numbers of T and B cells prior to treatment of ADEM. These abnormalities improved following plasma exchange. Plasmapheresis appears to be effective in reversing the neuropathologic process in ADEM. The role of this treatment modality in ADEM requires further evaluation in controlled clinical trials.

Severe post-partum eclampsia: response to plasma exchange.

In their severest forms, pre-eclampsia and eclampsia may be life-threatening complications of pregnancy. We describe a patient with severe post-partum eclampsia characterized by seizures, deep coma, hypertension, renal insufficiency, coagulopathy, and microangiopathic hemolysis. The patient responded to treatment that included intensive plasma exchange, and she achieved full recovery. Our case supports the use of plasma exchange in patients with severe pre-eclampsia and eclampsia.

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Repeat thymectomy in chronic refractory myasthenia gravis.

Encouraged by recent results with "extended" thymectomy in the treatment of myasthenia gravis, we carried out repeat thymectomy in six patients with chronic, refractory disease who did not initially have extended thymectomy. All were completely disabled with longstanding myasthenia. Initial thymectomy (four transsternal, one transcervical, and one substernal) was carried out at a mean of 8.9 years previously (range, 5 to 18). There was no residual thymus observed with CT, but at repeat thymectomy, residual thymic tissue was present in five of six patients. Five patients significantly improved and four returned to full-time work. Mean prednisone dose declined from 51 mg to 18 mg/d, and mean pyridostigmine dose fell from 1,290 mg to 415 mg/d. No patient to date has had a complete remission. These results suggest that repeat thymectomy may benefit some patients with chronic disabling myasthenia gravis, especially when it is uncertain from a review of the operative report whether all thymic tissue was removed at the initial thymectomy.