Cross‐reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand

Lloyd, John Uri; Street, Alison; Berry, Elizabeth W.; McPherson, Jean; Ekert, H.; Lammi, Ahti; McWhirter, W.; Duncan, Elizabeth M.; Maxwell, Ellen; Rowell, J.; Baker, Ross; Leahy, Michael F.; Jupe, D. M. L.

doi:10.1111/j.1445-5994.1997.tb00994.x

Cited by 14 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies and reviews have reported on the treatments and efficacy of various treatments for AH over the years. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The large prospective study by UKHCDO 2 is the largest and most recent prospective study and serves as a new benchmark for management of this rare acquired bleeding disorder. The European Acquired Hemophilia Registry has also collected >500 patients in their database, and we will have more clinical data available on this rare condition soon.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 There have been many published studies and reviews on the management of AH. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The strategy to manage AH is essentially twofold after the correct diagnosis is made: (1) to start antibody eradication or immune suppression promptly, and (2) to achieve hemostasis when there is clinically significant bleeding, particularly life-or limb-threatening bleeding.…”

Section: Abstract: Acquired Hemophilia Rituximab Recombinant Activamentioning

confidence: 99%

“…In addition, porcine FVIII was previously used 8,10 because it had less cross-reactivity against human FVIII inhibitors, especially in AH. 15 A recombinant B-domain deleted porcine FVIII is currently in clinical trial to treat bleeding in hemophilia with acquired inhibitor and will be potentially useful for AH. Minor bleeds occasionally can be managed by desmopressin (DDAVP), but bypassing agents such as activated prothrombin complex concentrates and FVIII bypassing activity (FEIBA; Baxter Healthcare Corp., Westlake Village, CA) and recombinant activated factor VII (rFVIIa) are often required to achieve hemostasis in patients with life-or limb-threatening bleeding.…”

Section: Management Of Bleedingmentioning

confidence: 99%

See 2 more Smart Citations

Twelve Years of Experience of Acquired Hemophilia A: Trials and Tribulations in South Australia

Tay

Duncan

Singhal

et al. 2009

Semin Thromb Hemost

View full text Add to dashboard Cite

Acquired hemophilia A (AH) is a rare and serious acquired bleeding disorder where prompt and correct diagnosis is crucial, and immune suppression is often required for factor VIII (FVIII) autoantibody eradication. The acquired FVIII deficiency usually manifests as bruises and bleeding, and treatment such as FVIII has limited efficacy because of the neutralizing FVIII inhibitor. Expensive bypassing agents such as recombinant activated factor VII (rFVIIa) may be required to treat clinically significant bleeding. This report summarizes the experience related to AH from a large Australian hemophilia center based in South Australia. We identified 25 patients retrospectively over 12 years (1997 to 2008) and reviewed diagnostic features, treatment for bleeds and to eradicate the autoantibody, treatment response, and survival outcomes. The incidence in South Australia was 1.20 cases per million/year with a median age of 78 years with an approximately equivalent sex ratio (12 males versus 13 females); median FVIII and inhibitor titer were 2.5 IU/dL and 11.0 BU/mL, respectively. Twenty-four patients were evaluated further. Thirteen patients (54%) required hemostatic agents, and rFVIIa was used in seven for major bleeds, of which four were limb or life threatening. Eighteen patients were treated by hematologists with immune suppression, and combination steroid and azathioprine was used most commonly to eradicate autoantibody; 15 of these 18 achieved remission (i.e., 83% response rate). Two patients had persistent low-titer inhibitor when treatments were withdrawn, and one died of a fatal bleed shortly after starting treatment. One had spontaneous remission. Five patients (33%) relapsed, three in less than 6 months after starting treatment; all were retreated successfully. Rituximab was used in six patients for high-titer inhibitor, second relapse, two life-threatening bleeds, underlying lymphoma, and steroid intolerance, respectively. Overall mortality was 25% ( N = 6), five of whom were not treated. Advanced age and lack of treatment were predictive of poor survival outcomes. The very elderly (>75 years of age) may warrant a different treatment modality such as rituximab, which is potentially more tolerable and efficacious.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Abstract: Acquired Hemophilia Rituximab Recombinant Activamentioning

confidence: 99%

Section: Management Of Bleedingmentioning

confidence: 99%

See 1 more Smart Citation

Twelve Years of Experience of Acquired Hemophilia A: Trials and Tribulations in South Australia

Tay

Duncan

Singhal

et al. 2009

Semin Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Treatment of haemorrhage is by human or porcine derived factor VIII concentrate or recombinant factor VIIa. Porcine factor VIII is effective in most cases because the level of inhibitor against it is usually low 6–8 . If the level of inhibitor to human factor VIII is low, high doses of human factor VIII may be sufficient 7 …”

Section: Patient Characteristics Associated Conditions and Coagulatimentioning

confidence: 99%

“…Porcine factor VIII is effective in most cases because the level of inhibitor against it is usually low. [6][7][8] If the level of inhibitor to human factor VIII is low, high doses of human factor VIII may be sufficient. 7 Due to the morbidity and mortality associated with this condition, treatment aimed at elimination of the autoantibody is important.…”

mentioning

confidence: 99%

Acquired haemophilia in South Australia: a case series

Burnet

Duncan

Lloyd

et al. 2001

Internal Medicine Journal

Self Cite

View full text Add to dashboard Cite

Of eight cases of acquired haemophilia presenting over an 8-year period, six received immunosuppressive treatment, five with cyclophosphamide, vincristine and prednisolone (CVP). Five patients (four on immunosuppressive treatment) entered remission, two patients died and one was lost to follow up. Initially, the remissions were only partial. The median duration until partial remission was 10 weeks (range 1-55 weeks) and until complete remission was 35 weeks (range 2-59 weeks). Partial remission may proceed to complete remission without further chemotherapy.

show abstract