Combined factor V and VIII deficiency

This review summarizes current data on the pathomechanisms and new genetic findings of combined factor V and VIII deficiency [CF5F8D]. Congenital haemorrhagic disorders characterized by deficiency of two clotting factors comprise an interesting group. Among dual coagulation disorders, CF5F8D is the most common type. For the first time combined factor V and VIII deficiency [F5F8D] was reported by Oeri et al in 1954. That is distinct from the coinheritance of both FV deficiency [parahaemophilia] and FVIII deficiency [haemophilia A] that has been reported in four families. Individuals who present with this phenotype have between 5 and 30% of normal plasma levels of FV and FVIII antigen and activity, whereas the level of other plasma proteins are not altered. Total numbers of affected individuals are less than 150 cases all over the world. At first it was assumed that deficiency of protein C inhibitor was a responsible cause, but further investigations revealed that it was due to mutations called ERGIC-53 and LMAN-1

Combination therapy with pulse cyclophosphamide plus corticosteroids improves renal outcome in patients with lupus nephritis

The prognosis of SLE is influenced by the onset of glomerulonephritis. Clinical trials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management of lupus nephritis for preserving renal function. The purpose of this study is to define the outcome of renal function with bolus pulses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. In this open-label clinical trial, to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide; twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: 1] Induction with bolus methylprednisolone and cyclophosphamide. 2] Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3] Tapering with reduction of prednisolone by 10% each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4] Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms, urine protein excretion falling below 0.3 gr/ dL or by at least 50%, RBC cast disappearance, C3, C4, Hb, and ESR return to normal limits.Twenty-three patients with lupus nephritis completed our therapeutic protocol. Renal biopsy was performed in 22 cases and indicated type IV in 20 patients [95.2%], and type V in 2 patients. After an average of 4+1.95 months 22 patients achieved remission [95.65%] and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant statistical differences were achieved between creatinine, proteinuria, hematuria, leukocyturia, urinary cast, C3, C4, ESR, and Hb before and after therapy [p<0.05]. Plasma creatinine fell from 1.44+0.95 mg/dL to 0.97+0.78 [p<0.004]. Proteinuria fell from 1879.78+1854.46 to 408.34+572.92 mg/24h [p<0.001]. Thirteen episode of relapses were treated again with repeated cycles of Cyclophosphamide and all remitted again.Intensive immunosuppression with steroid and Cyclophosphamide provides excellent results with an acceptable rate of complications in the treatment of lupus nephritis