Acquired haemophilia A Acquired haemophilia B Acquired von Willebrand syndrome Acquired bleeding disorder, other coagulation factors (Prothrombin, factor V, factor VII, factor X, factor XI, and factor XIII) Level of Evidence Evidence of probable benefit – more research needed (Category 2a) Evidence of probable benefit – more research needed (Category 2a) Unchanged and unlikely to change due to the rarity of the condition. Justification for Evidence Category IVIg has a role as part of a second-line immune tolerance protocol involving immunoadsorption and immunoglobulin replacement, in addition to immunosuppression and factor replacement, the Malmo protocol (Nilsson et al, 1988 and Berntorp et al, 2000 and Franchini & Lippi, 2008 and Zeitler et al, 1991). There is evidence for the beneficial effect of this protocol in patients with: • Congenital haemophilia A with acquired factor VIII inhibitors • Congenital haemophilia B with acquired factor IX inhibitors • Acquired haemophilia A. IVIg has an accepted role in the reduction of bleeding in patients with acquired von Willebrand syndrome and IgG paraproteins (Collins et al, 2013). IVIg has an uncertain role in the reduction of bleeding in patients with other acquired bleeding disorders Justification of evidence section has been drafted in line with the literature.
and Diagnostic Criteria bleeding disorders should be undertaken only by or in consultation with haemophilia treatment centres. When indicated, intravenous immunoglobulin (IVIg) only forms part of the management of these complex patients, with additional haemostatic support required. IVIg may be considered in the following circumstances: Inhibitors to factor VIII (FVIII) in haemophilia A and inhibitors to factor IX (FIX) in haemophilia B, especially in cases where there has been failure of immune tolerisation and poor response to recombinant factor VIIa or factor eight inhibitor bypassing activity (FEIBA) — only as part of the protocol for immune tolerance induction. Autoimmune acquired von Willebrand syndrome — correction of FVIII and von Willebrand factor levels for the management of bleeding and before invasive procedures, except cases associated with IgM paraprotein where response is unlikely. Use is indicated in failure to respond to chemotherapy/immunosuppressants or where there is insufficient time for chemotherapy/immunosuppressants interfere with the function of specific clotting proteins including factor VIII, factor IX and less commonly, other coagulation factors. Inhibitors can be allo-antibodies as occurs in congenital haemophilia in response to infused product, or auto-antibodies as occurs in acquired haemophilia which may be seen in the setting of other autoimmune disease, malignancy, post-partum or in response to certain drugs. The incidence of acquired cases is very low and usually respond to steroids and IVIg would only usually be considered in the setting of ongoing bleeding. Patients may present with abnormal bleeding which can be severe and life threatening, and in these circumstances treatment is best co-ordinated in association with Haemophilia Treatment Centres. The presence and level of inhibitor should be confirmed where possible by a factor specific Bethesda assay. Where laboratory confirmation is not able to be easily performed, as in acquired von Willebrand disease, significantly reduced response to infused factor concentrate or demonstration of new onset of reduced clotting factors levels can be used to make the diagnosis. section has been updated in consultation with the Australian Haemophilia Centre Directors’ Organisation to reflect the findings of more recently published evidence on disease presentation, progression and management. Malmö