Double filtration plasmapheresis can decrease factor XIII Activity

Factor XIII (FXIII) produces cross-linkages among fibrin molecules within fibrin clots. Its deficiency is related with bleeding diathesis or retardation of wound healing. We report the possibility that intense double filtration plasmapheresis (DFPP) is associated with decreased FXIII activity. Five patients with various primary diagnoses were treated with DFPP and their FXIII activity was measured. Coagulation test results remained almost normal, but FXIII activities declined to less than 20% of their initial value before starting DFPP and 10% after DFPP in most cases. The cases that received intense DFPP therapy exhibited profoundly decreased FXIII activity. The clinical course demonstrated that DFPP caused the FXIII decrease. Fortunately, with careful observation, none of the patients experienced fatal bleeding. Only one case required fresh frozen plasma and an open hemostatic procedure because of prolonged postoperative bleeding. In general, DFPP most efficiently removes substances with the following characteristics: adequate molecular weight; long half-life; and small extravascular distribution volume. The FXIII properties meet all these characteristics. Consequently, we should devote much attention to FXIII activity during DFPP because it cannot be estimated from the usual coagulation tests. Patients who receive DFPP therapy, especially intensified therapy, should have FXIII measured during the course of therapy. Results show that DFPP can decrease FXIII activity. For this reason we recommend the measurement of FXIII when patients receive intense DFPP therapy with albumin replacement.     

Treatment of Goodpasture's syndrome with plasmapheresis. A case report and review of the literature.

A case is reported of antiglomerular basement membrane antibody-induced Goodpasture's syndrome in which the patient required hemodialysis and was treated with immunosuppressive agents and plasmapheresis. A severe (80 per cent) cresentic lesion was reversed, and creatinine was stabilized at 2.5 mg/dl at one year follow-up. Earlier reports of therapy without plasmapheresis showed that 88 per cent of the patients would either die or require long-term hemodialysis. Fifteen other reported cases of Goodpasture's syndrome in which the patients were treated with plasmapheresis are reviewed. When reported, short-term follow-up showed that nine of these patients were alive without need of dialysis, five wee receiving dialysis, and only two had died. This suggests that plasmaheresis and immunosuppressive therapy may reverse the renal lesion in some patients with Goodpasture's syndrome.     

Goodpasture's syndrome

Goodpasture s syndrome (GS) is an auto-immune disease that is part of the pulmonary-renal syndrome spectrum. It is characterized by the linear deposition of anti-glomerular basement membrane antibodies (anti-GBM) in glomerular and alveolar basement membrane resulting in alveolar hemorrhage and progressive glomerulonephritis. An early diagnosis is important to decrease clinical morbidity. In the present work we illustrate a GS case initially diagnosed as Wegener s granulomatosis. The patient showed favorable clinical evolution with corticosteroid therapy associated with plasmapheresis and cyclophosphamide.     

A case of Goodpasture's syndrome associated with anti-myeloperoxidase antibodies.

A case of Goodpasture's syndrome with anti-myeloperoxidase (MPO) antibodies is reported. Histological examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular capillary walls and alveolar capillary walls by immunofluorescence microscopy. Not only anti-glomerular basement membrane (GBM) antibodies but also anti-MPO antibodies, an anti-neutrophil cytoplasmic antibody, were simultaneously detected in the serum. Although it is generally accepted that crescentic glomerulonephritis in Goodpasture's syndrome is mediated by anti-GBM antibodies, this case suggested that anti-MPO antibodies might also participate in the pathogenesis of crescentic glomerulonephritis and probably alveolar hemorrhage of Goodpasture's syndrome, especially with vasculitis.     

A case of Goodpasture's syndrome with IgA antibasement membrane antibody

This is a very rare case report of Goodpasture's syndrome with IgA antibasement membrane antibody. A 43-year old male was admitted because of severe dyspnea with slight hemoptysis. Chest X-ray demonstrated extensive bilateral infiltrates with air bronchogram, predominantly in the right lung. Laboratory data on admission showed severe anemia and moderate renal impairment. The pulmonary infiltrates resolved spontaneously within 10 days. Goodpasture's syndrome or collagen vascular disease was suspected and he underwent a percutaneous renal and transbronchial lung biopsy. The renal biopsy showed crescent formation affecting 70-80% of glomeruli. Linear IgA deposits, but not IgG, were demonstrated along the glomerular basement membrane by the direct immunofluorescence procedure. The lung biopsy contained many hemosiderin-laden macrophages in the lumen of the alveoli and showed mild thickening of alveolar walls. However, linear immunoglobulin deposits on the alveolar capillary basement membrane were not demonstrated by direct immunofluorescence. The diagnosis of Goodpasture's syndrome with IgA antibasement membrane antibody was made. His serum was negative for antibasement antibody by indirect immunofluorescence. He was treated with prednisone, 30 mg daily. His pulmonary symptoms and anemia improved markedly, but his renal function did not change. Thirteen months after his first admission, he suffered from severe bacterial pneumonia, which was complicated by disseminated intravascular coagulation. He died of respiratory failure. Autopsy was rejected.     

Chronic recurrent Goodpasture's syndrome

A distinctive case of Goodpasture's syndrome characterized by multiple recurrences occurring over 14 years was observed. Each recurrence followed cessation of prednisone and azathioprine therapy, and reinstitution of this therapy resulted in prompt remission. Initially, both glomerulonephritis and hemoptysis were prominent clinical features. In recent years, hemoptysis has been the predominant clinical problem. This and other cases suggest that Goodpasture's syndrome may comprise a wider disease spectrum than generally appreciated.     

Virus-associated haemophagocytic syndrome responsive to steroid pulse therapy and double filtration plasmapheresis

We present an adult patient with haemophagocytic syndrome (HPS) successfully treated with a combination of steroid pulse therapy and double filtration plasmapheresis (DFPP). A 58-year-old male was admitted with high fever, severe renal dysfunction, liver dysfunction and an increased level of lactate dehydrogenase. A serological test for Epstein-Barr (EB) virus showed an elevation of EBNA-IgM antibody titre. There were increased haemophagocytic histiocytes in the bone marrow in addition to thrombocytopenia and disseminated intravascular coagulation (DIC) accompanied by organ dysfunction. EB virus associated haemophagocytic syndrome was diagnosed. On admission, interferon (IFN)-gamma, interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF were elevated, and were promptly normalized after steroid pulse therapy was initiated. G-CSF and M-CSF gradually decreased after DFPPs was started. To control hypercytokinaemia until treatment for the underlying disease is initiated, steroid pulse therapy and double filtration plasmapheresis are useful.     

A case report of double filtration plasmapheresis in an acute episode of multiple sclerosis

Plasma exchange has been proposed as support therapy in both acute and chronic forms of multiple sclerosis (MS). For the first time, we aimed to assess whether double filtration plasmapheresis (DFPP) could be clinically efficacious. We describe the case of a patient affected by MS who developed a severe crisis refractory to conventional steroids, and immunosuppressive and immunomodulating therapy. The patient underwent 12 sessions of DFPP. In each session 3000 mL of plasma was treated. Before and immediately after each session the routine laboratory parameters were assessed. Before the apheresis cycle and one month after the end of treatment, encephalic magnetic resonance imaging (MRI) was performed. A neurological examination and assessment of the extended disability status scale (EDSS) were made once each week from the beginning of treatment until one month after the end of the cycle. No therapy was administered during the course of the apheresis cycle, with the exception of a scaled dose of steroids, that was completely withdrawn half-way through the cycle. The immunoglobulin (Ig) G, IgA and IgM values declined from 465 +/- 104 mg/dL, 69 +/- 18 mg/dL, 34 +/- 16 mg/dL, respectively, pre-apheresis to 331 +/- 76 mg/dL, 42 +/- 5 mg/dL, 15 +/- 6 mg/dL, respectively, post-apheresis; C3 and C4 decreased from 105 +/- 27 mg/dL and 21 +/- 5 mg/dL to 75 +/- 9 mg/dL and 15 +/- 4 mg/dL, respectively; fibrinogen went from 228 +/- 72 mg/dL to 128 +/- 28 mg/dL. The EDSS dropped from a value of 6 before the cycle to 5.5 one month after the end of the treatment. As compared with the pretreatment conditions, post-apheresis MRI showed stabilization of the lesions already present, the reduction of one lesion and a complete absence of enhancement of all lesions. DFPP, adopted for the first time in MS, seems to foster a short-term improvement in both the clinical and magnetic resonance images during an acute MS episode.     

Double filtration plasmapheresis combined with rituximab for donor-specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case–control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10–21) and 13 (10–29) days respectively. Although the cumulative incidence of II–IV aGVHD (41.4% vs. 28.1%) and 3-year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3-year non-relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo-HSCT.     

Monitoring intrapulmonary hemorrhage in Goodpasture's syndrome

Diffusing capacity of carbon monoxide (Dco) was measured frequently in a patient with recurrent intrapulmonary hemorrhage secondary to Goodpasture's syndrome. This simple test was found to be a sensitive and useful indicator of the presence or absence of recurrent intrapulmonary hemorrhage. As this is now the major cause of mortality in this disease, we recommended that frequent measurements of the Dco be an important part of its management.