Haemophagocytic syndrome

Version: 2.1
Published: 06 July 2016
Condition for which Ig has an emerging therapeutic role.

This medical condition has either been superseded or has become inactive
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Specific Conditions
  • Haemophagocytic syndrome
Indication for Ig Use
  • Management of severe haemophagocytic syndrome not responding to other treatments.
Level of Evidence Insufficient data (Category 4a)
Description and Diagnostic Criteria Haemophagocytic syndrome is characterised by fever, splenomegaly, jaundice, rash and the pathologic finding of haemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets and their precursors) in bone marrow and other tissues with peripheral blood cytopenias. Haemophagocytic syndrome has been associated with a wide range of infectious, autoimmune, malignant and other disorders (modified from Fisman 2000). Mortality is high.
Justification for Evidence Category No randomised controlled trials (RCTs) have been done, although many, mostly small, case series show evidence of benefit from intravenous immunoglobulin (IVIg) treatment.
Qualifying Criteria for Ig Therapy
  • Bone marrow diagnosis or other laboratory evidence supporting a diagnosis of haemophagocytosis.
  • AND
  • Clinical features characteristic of haemophagocytic syndrome.
  • AND
  • Non-response or ineligibility for other treatments.
Exclusion Criteria Children with haemophagocytic lymphohistiocytosis (HLH) and hypogammaglobulinaemia — see secondary hypogammaglobulinaemia unrelated to haematological malignancy. - see  Secondary hypogammaglobulinaemia (including iatrogenic immunodeficiency)
Review Criteria for Assessing the Effectiveness of Ig Use
Clincial effectiveness of Ig therapy may be demonstrated by: 
 
  • Survival and improvement in clinical and laboratory features.
Dose
  • Dose (IVIg) - 2 g/kg is the most widely published dose.

Emmenegger et al (2001) reported that better outcomes were associated with early administration of IVIg in their small case series (10 patients).

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Dosing above 1g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.
Bibliography
Arlet, JB, Le, TH, Marinho, A, et al 2006, ‘Reactive haemophagocytic syndrome in adult onset Still’s disease: report of six patients and review of the literature’, Annals of the Rheumatic Diseases, vol. 65, no. 12, pp. 1596–601.

Asci, G, Toz, H, Ozkahya, M, et al 2006, ‘High-dose immunoglobulin therapy in renal transplant recipients with hemophagocytic histiocytic syndrome’, Journal of Nephrology, vol. 19, no. 3, pp. 322–6.

Chen, RL, Lin, KH, Lin, DT, et al 1995, ‘Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis’, British Journal of Haematology, vol. 89, no. 2, pp. 282–90.

Emmenegger, U, Frey, U, Reimers, A, et al 2001, ‘Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes’, American Journal of Haematology, vol. 68, no. 1, pp. 4–10.

Fisman, D, 2000, ‘Hemophagocytic syndromes and infection’, Emerging Infectious Diseases. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640913

Freeman, B, Rathore, MH, Salman, E, et al 1993, ‘Intravenously administered immune globulin for the treatment of infection-associated hemophagocytic syndrome’, Journal of Pediatrics, vol. 123, no. 3, pp. 479–81.

Ostronoff, M, Ostronoff, F, Coutinho, M, et al 2006, ‘Haemophagocytic syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma; successful treatment with high-dose intravenous immunoglobulin’, Bone Marrow Transplantation, vol. 37, no. 8, pp. 797–8.