1/17. Management of haemophilia in patients with high-titre inhibitors: focus on the evolution of activated prothrombin complex concentrate AUTOPLEX T.Numerous therapeutic strategies have been applied to the management of patients with inhibitors to factors VIII or IX. Different treatment approaches are analysed including prothrombin complex concentrates (PCCs), activated prothrombin complex concentrates (aPCCs), porcine factor VIII concentrate, inhibitor neutralization, immune tolerance therapy, immunosuppressive regimens and recombinant factor viia. Clinical data are reported in the analysis of several treatments. PCCs and aPCCs have gained widespread acceptance as the standard first-line approach for patients with inhibitors. The aPCC AUTOPLEX T has achieved a high response rate with a low level of thrombotic events. Four case studies are presented in which AUTOPLEX T has been used successfully. Administration of platelet concentrate or, in elective surgery, waiting for inhibitor levels to decline are useful adjuncts to some treatments. The optimal treatment depends on the patient's inhibitor status--low responder (minimal or no increase in inhibitor levels upon administration of replacement clotting factor) or high responder (replacement clotting factor generates inhibitor production). A suggested algorithm for treating high-responder inhibitor patients is presented.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
2/17. Deletion of the factor IX gene as a result of translocation t(X;1) in a girl affected by haemophilia B.A balanced de novo translocation t(X;1) is described in a girl with severe haemophilia B. The translocated X was shown cytologically to be preferentially active, and methylation analysis of the DXS255 locus confirmed the skewed X-inactivation with the paternal allele being the active one. Cytogenetic and molecular analysis showed that this chromosomal rearrangement led to the deletion of at least part of the factor IX gene. Therefore, the girl was heterozygous for factor IX deficiency and expression of her clinical phenotype was the result of the inactivation of the normal maternal x chromosome. The localization of one of the x chromosome translocation breakpoints in YAC clone 957F9, that was demonstrated to map distally to the factor IX gene, revealed the complexity of this chromosomal rearrangement.- - - - - - - - - - ranking = 0.16666666666667keywords = complex (Clic here for more details about this article) |
3/17. Rationale for the use of high dose rFVIIa in a high-titre inhibitor patient with haemophilia B during major orthopaedic procedures.Inhibitor development is a serious complication in patients with haemophilia A and B. Historically, a lack of optimal therapies and factor products for treating inhibitor patients resulted in many patients developing chronic haemophilic arthropathies and flexion contractures of the involved joints. The introduction of immune-tolerance protocols to eradicate high-titre inhibitors has greatly diminished the incidence of these types of complications but as in the case reported here, immune tolerance is not always successful. Various elective surgical procedures were often delayed or not even considered in patients with inhibitor because of the variability in achieving adequate haemostasis and the thrombotic risks involved with the use of activated prothrombin-complex concentrates (APCCs) over extended periods of time. The development of recombinant factor viia (rFVIIa; NovoSeven) and its demonstrated safety and efficacy in treating inhibitor patients has opened new possibilities for addressing severe arthropathy with flexion contracture. This case report demonstrates that the use of rFVIIa in such a situation must include dosing flexibility that is both patient-specific and related to the potential for bleeding; the ability to maintain clinical haemostasis with a prophylactic dose of rFVIIa given as little as once daily; and the capacity for higher doses of rFVIIa, particularly in children because their kinetic profiles differ from adults.- - - - - - - - - - ranking = 0.16666666666667keywords = complex (Clic here for more details about this article) |
4/17. Novel missense mutation in the coagulation factor IX catalytic domain associated with severe haemophilia B--Factor IXDelhi.Factor IX is a vitamin k-dependent serine protease, which exists as a zymogen in the blood. On activation to factor ixa, by factor xia or tissue factor-factor viia complex, it forms tenase complex with factor viiia, in the presence of Ca2 . This tenase complex enzymatically converts factor X to factor xa, thereby bringing about the coagulation cascade. Mutations in factor IX gene have been shown to cause haemophilia B, which is inherited as an X-linked recessive disorder. Herein we report a novel missense mutation at the nucleotide position 30829-T > A in the exon 8 of factor IX gene. This transversion leads to the substitution of histidine 236 to glutamine. This resulting abnormal protein has been named factor IXDelhi. Molecular modelling was performed to predict the molecular pathology of this mutation. We predict that this change in the catalytic domain may affect the surface loop that accommodates Ca2 , thereby leading to severe bleeding disorder.- - - - - - - - - - ranking = 0.5keywords = complex (Clic here for more details about this article) |
5/17. myocardial infarction after FEIBA therapy in a hemophilia-B patient with a factor IX inhibitor.A case of myocardial infarction (MI) in a hemophilia b patient with a factor IX (FIX) inhibitor (6 BU) is described. MI occurred after two infusions of FEIBA concentrate. Unexpectedly, these infusions resulted in a neutralization of the inhibitor and a consistent plasma FIX activity which may have increased the thrombotic risks. Four days later, a psoas hematoma was suspected. At that time the inhibitor remained undetectable, allowing a therapy with purified FIX concentrates. No recurrence of thrombotic complication was observed. This is an additional illustration of the thrombotic risks associated with the use of activated prothrombin complex concentrates, especially in patients having pre-existing risk factors for thrombosis. The management of bleeding episodes in hemophilia b patients with inhibitor represents an especially difficult challenge.- - - - - - - - - - ranking = 0.16666666666667keywords = complex (Clic here for more details about this article) |
6/17. Anasarca improved by extracorporeal ultrafiltration through an internal shunt in a case of severe haemophilia B with inhibitor and steroid-resistant nephrotic syndrome.A patient suffering from severe haemophilia B with factor IX inhibitor developed steroid-resistant nephrotic syndrome. As a result of switching to activated anti-inhibitor coagulant complex (activated prothrombin complex concentrate) agent, FEIBA, bleeding was controlled and internal shunt placement was successful, leading to control of bleeding during extracorporeal ultrafiltration (ECU) therapy. We report this case where regular ECU therapy became possible and as a result anasarca was controlled.- - - - - - - - - - ranking = 0.33333333333333keywords = complex (Clic here for more details about this article) |
7/17. Clinical experience of a new monoclonal antibody purified factor IX: half-life, recovery, and safety in patients with hemophilia b.Highly purified factor IX, produced by a monoclonal antibody immunoaffinity technique, contains a high concentration of factor IX with negligible amounts of other vitamin k-dependent coagulation factors. When infused in patients with hemophilia b, monoclonal factor IX concentrate yielded a mean half-life of 34.6 /- 13.1 ( /- SD) hours and in vivo recovery of 0.67 /- 0.14 U/dL rise per each U/kg of factor IX infused. Unlike prothrombin complex concentrate (PCC) infusion, monoclonal IX infusion was not associated with rises in factors II, VII, and X, but achieved in vivo recovery and half-life at least comparable to PCC. Long-term use of monoclonal IX as a home-care product provided excellent response in the control of bleeding episodes and was equivalent to previous patient experience with PCC. The results indicate that monoclonal IX concentrate raises factor IX levels effectively, while avoiding extraneous thrombogenic components.- - - - - - - - - - ranking = 0.16666666666667keywords = complex (Clic here for more details about this article) |
8/17. Orthotopic liver transplantation in a patient with combined hemophilia a and B.A 38-year-old man with severe factor IX and mild factor VIII deficiencies complicated by cirrhosis secondary to chronic non-A non-B hepatitis underwent orthotopic liver transplantation as treatment for both the cirrhosis and his congenital coagulopathy. Intraoperative hemostasis was obtained with factor VII-depleted prothrombin complex concentrate and fresh frozen plasma. Factor VIII and factor IX levels were assayed frequently in the perioperative period, and both returned to normal within 24 hr and remained normal postoperatively. liver transplantation can be considered as definitive therapy for hemophilia a and/or B with transfusion-related liver disease.- - - - - - - - - - ranking = 0.16666666666667keywords = complex (Clic here for more details about this article) |
9/17. disseminated intravascular coagulation and myocardial infarction in a haemophilia B patient during therapy with prothrombin complex concentrates.A case of disseminated intravascular coagulation (DIC) and fatal myocardial infarction in a haemophilia B patient is described. DIC occurred after 4 days of therapy with unactivated prothrombin complex concentrates during the post-operative period. Therapy with fresh frozen plasma, heparin and antithrombin iii concentrates was started without efficacy; after autopsy myocardial infarction was evident.- - - - - - - - - - ranking = 0.83333333333333keywords = complex (Clic here for more details about this article) |
10/17. Disappearance of inhibitor to factor IX in a patient with severe haemophilia B and immunological characterization of the inhibitor.Disappearance of an inhibitor to factor IX in an 11-year-old boy with haemophilia B is described. He had been given a total of 14,200 units of a prothrombin complex concentrate (PCC) before an inhibitor to factor IX developed. He subsequently received four separate infusions of PCC and his inhibitor titre rose in response to the treatment for the following 4 years. No inhibitor is presently detected despite repeated administration of PCC. Immunological characterization of the inhibitor by inhibitor neutralization assays, modified crossed-immunoelectrophoresis and enzyme-linked immunosorbent assay demonstrated that it contained IgG2 and IgG4 heavy chains and kappa and lambda light chains. No large deletion of the factor IX gene in the patient was observed using cDNA (cVII).- - - - - - - - - - ranking = 0.16666666666667keywords = complex (Clic here for more details about this article) |
| | Next -> |