1/203. Anaphylactoid reactions and nephrotic syndrome--a considerable risk during factor ix treatment in patients with haemophilia B and inhibitors: a report on the outcome in two brothers. anaphylaxis/anaphylactoid reactions have recently been reported after few treatments with factor ix concentrates in patients with haemophilia B at the same time as inhibitors to factor ix were demonstrated. In some of these cases nephrotic syndrome has appeared during immune tolerance induction (ITI) with high doses of factor ix concentrates. Gene deletions seem to be associated with a high risk of developing antibodies to factor ix. This report presents two brothers with deletion of 1 bp in exon f of the factor ix gene. Both showed anaphylactoid reactions and they were desensitized using slow i.v. injections of factor ix. At the time of anaphylaxis, inhibitors of factor ix in a low titre could be demonstrated. The elder brother responded well after a short time on ITI and has no spontaneous bleedings on regular prophylaxis although in a somewhat higher dose than expected. On the other hand, in spite of comparable regimens, the younger brother has so far been resistant to ITI. Moreover, during treatment with extremely high doses of factor ix concentrate he developed nephrotic syndrome which only slowly subsided after treatment with corticosteroids and withdrawal of factor ix. ( info) |
| We report the case of a 36-year-old hemophilia b who suffered from cholesteatoma and underwent tympanoplasty. Though the factor ix activity was less than 1% of normal before surgery, adequate replacement of factor ix led to the achievement of hemostasis during and after surgery. The cholesteatoma was completely extirpated with matrix, and a type I canal-up tympanoplasty was subsequently performed. Careful preoperative evaluation and close cooperation with the hematologist are required if surgery is to be successful. We also present here the use of continuous administration of monoclonal antibody-purified factor ix concentrate, Christmassin M. ( info) |
3/203. Haemophilia B Brandenberg-type promoter mutation. We report the second confirmed case of the haemophilia B 'Brandenberg' phenotype. At the time of testing, patient HB530 was a 17-year-old post-puberty male with a persistent, clinically severe bleeding disorder and markedly reduced plasma procoagulant factor ix activity (< 1%). Sequencing studies revealed a G-->A transition at bp - 26 within the promoter region of the factor ix gene. This case report confirms the observation that not all patients with promoter mutations improve after puberty and supports the hypothesis that bp - 26 is a critical binding site within the factor ix gene promoter region for both constitutive as well as androgen-inducible transcription factors. ( info) |
4/203. Failure of immunosuppression in a severe haemophilia B patient with specific antibody. Prevention of a secondary response to factor ix by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor ix had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor ix antibody was not depressed. The difficulties of modifying the anamnestic response to factor ix by chemical immunosuppression may be as real as has been reported for factor viii in classical haemophilia. ( info) |
5/203. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a patient with hiv infection. Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from lytic infection of oligodendrocytes by the papovavirus JC (JCV). PML has also been recognized as an AIDS-defining illness. The incidence of PML has increased since 1987 and it occurs in up to 4% of patients with AIDS. To date, there is no treatment available for PML and it usually results in death within 3-6 months of diagnosis. However, there are some reports of remission of PML after antiretroviral therapy. We report a 12-year-old child with hemophilia b and developing AIDS with the onset of PML. With highly active antiretroviral therapy, PML subsided with an increase of CD4 count from 10 to 300/microl in spite of about 1.0 X 10(4) human immunodeficiency virus (hiv)-1-rna copies. He has survived more than 1 year without specific therapy against JCV. Highly active antiretroviral therapy appears to have improved his prognosis in hiv-associated PML. ( info) |
6/203. Therapeutic embolization and surgical excision of haemophilic pseudotumour. Haemophilic pseudotumour is a rare complication of haemophilia. Few cases of iliac haemophilic pseudotumour have been reported in the literature. These tumours can act as a focus for infection and cause cutaneous fistulas. When they present perforations and infections of endogenous origin their course is usually fatal. Suitable treatment has been investigated on numerous occasions, most of the literature agreeing that the only curative treatment is surgical resection. We present a case of haemophilic pseudotumour of the iliac and caecum with cutaneous fistulas, with a septic process of endogenous origin. It was treated with surgical resection after performing arterial embolization to reduce the vascularization of the pseudotumour, thereby reducing its size and the risk of bleeding complications during surgery. ( info) |
7/203. 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. ( info) |
8/203. Spontaneous intracranial hemorrhage as the presenting sign of hemophilia b in a 3-month-old infant. Intracranial hemorrhage (ICH) is an uncommon complication of hemophilia in the 1st year of life and most often is reported after head trauma or birth trauma. Spontaneous ICH unrelated to birth or head trauma is rare at any age, especially in the 1st year of life. We describe a 3-month-old infant who presented to the emergency department (ED) with a spontaneous ICH as the presenting sign of hemophilia b. We review the literature and discuss the ED evaluation and management of hemophiliacs with ICH. ( info) |
9/203. Successful surgical treatment of haemophilic pseudotumour, filling the defect with hydroxyapatite. A preliminary report is made on the use of hydroxyapatite for surgical procedure of pseudotumour, a rare but serious complication of the bleeding diathesis in patients with inherited bleeding disorders. Surgical or percutaneous treatment and refilling with fibrin sealant is shown to be a successful therapy in a 19-year-old male with severe haemophilia B. The pseudotumour, in the upper pad of the left leg, was filled with hydroxyapatite after surgery. We suggest that the use of hydroxyapatite is a new and useful option in the surgical treatment of haemophilic pseudotumour. ( info) |
10/203. Hemorrhagic lymphadenopathy as a presenting feature of primary al amyloidosis. Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor x and IX deficiency. The clinical presentations were characterized by sudden spontaneous enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopathy. ( info) |