Article

Acquired factor VIII inhibitors.

Servizio di Immunoematologia e Trasfusione, Azienda Ospedaliera Universitaria di Parma, Parma, Italy.
Blood (Impact Factor: 9.78). 08/2008; 112(2):250-5. DOI: 10.1182/blood-2008-03-143586
Source: PubMed

ABSTRACT Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with high-titer inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors.

1 Follower
 · 
119 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acquired haemophilia is a rare but life-threatening phenomenon in patients who have undergone surgical treatment. We describe a patient with a history of pancreatic cancer and a conventional pancreaticoduodenectomy, who underwent elective resection of an enterocutaneous fistula, complicated by fulminant haemorrhagic shock, caused by acquired haemophilia A. Eventually, the bleeding was controlled by a combination of aggressive haemostatic and immunosuppressive therapy. Prompt diagnosis of acquired haemophilia is crucial to allow early and appropriate haemostatic treatment and reduce the period of increased bleeding risk by eradicating the inhibitor with immunosuppressive therapy.
    The Netherlands Journal of Medicine 05/2015; 73(4):182-6. · 2.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The incidence of acquired haemophilia A is 1.5/million/year. Elderly people are affected most frequently and the incidence is slightly higher in females. Autoimmune, infectious and malignant diseases correspond to identifiable underlying causes; postpartum occurrence is rare as the association to medication; idiopathic condition represents 50% of cases. Aims: Presentation of a case report of acquired haemophilia A with highlight to laboratory management, transfusion and haemostatic support and inhibitor eradication. Methods: Laboratory - Coagulometric techniques in ACL TOP® equipment with HemosIL® reagents, assessment of platelet function in Multiplate® and haemograms performed in Coulter LH750®. Case report - A Caucasian man, 82 years old, admitted in hospital at 19 Jan 2013 with deep muscular haematomas in right thigh and inguinal region and haematochezias in previous two months. Diagnoses: atrial fibrillation under warfarin since Jun 2011, ischemic and hypertensive cardiopathy, biological mitral prosthesis, congestive heart failure, non-recurrent rectal carcinoma submitted to anterior resection, chemotherapy and radiotherapy in 2003, two-vessel coronary disease submitted to a coronary artery bypass graft, type 2 diabetes mellitus, obesity, normocytic normochromic anaemia. Oral anticoagulation was promptly discontinued. In 4 Feb 2013 another haematoma occurred in the left thigh related to pressing in bed. In 11 Feb 2013 the haematoma in right inguinal region reappears with a new small collection in left thigh. Imaging techniques reveals massive first haematoma and smaller further haematomas without compartment syndrome. A total of 7 units (U) of red blood cells, 2 U of inactivated plasma, 1500 IU of prothrombin complex concentrate and 26 mg of recombinant activated factor (F) VII were administrated. After detection of inhibitors against FVIII the immunosuppression with prednisolone was applied at a dose 1mg/Kg/day PO since 1 Feb 2013 (temporary reduction during sepsis). Results: In 19 Jan 2013 Hb: 7.9g/dL, INR: 3.7. In 21 Jan 2013 Hb: 5.4g/dL, INR: 1.3, activated partial thromboplastin time (APTT): 58.8 sec (normal APTT in 30 Jun 2011). A reduced FVIII:C (3.6%) and inhibitors against FVIII:C (mixing tests including incubation for 2 hours at 37ºC) were detected with quantification by Bethesda (B) assay (titres: 8.6, 15.7, 11.7, 9.0 and 6.8 BU/mL at 25 Jan and 7, 14, 20 and 25 Feb 2013 respectively). Normalisation of prothrombin time (PT)/INR after suspension of warfarin; normal thrombin time; negative lupus anticoagulant (dilute Russell viper venom time and silica clotting time); D-Dimer: 357-2235ng/mL; maximum value of Hb: 11.0g/dL; normal platelet count until 13 Feb 2013 (subsequent thrombocytopenia) and function (ADP, thrombin/TRAP-6, ristocetin); increased F von Willebrand (VW): Ag and activity; negative direct antiglobulin test and tumour, viral and autoimmune markers; slightly increased gamma globulins (30 Jun 2011 and 6 Feb 2013). See table for other results. Summary/conclusions: Absence of other causes for acquired haemophilia A unless diabetes. By-passing concentrate replacement with recombinant activated FVII and corticosteroid regimen provide control of haematomas and expectable elimination of inhibitor (follow-up). We emphasize that a special caution was taken concerning the use of haemostatic agents in this older patient with prothrombotic tendency and the evidence of a high starting titre inhibitor. Background: The incidence of acquired haemophilia A is 1.5/million/year. Elderly people are affected most frequently and the incidence is slightly higher in females. Autoimmune, infectious and malignant diseases correspond to identifiable underlying causes; postpartum occurrence is rare as the association to medication; idiopathic condition represents 50% of cases. Aims: Presentation of a case report of acquired haemophilia A with highlight to laboratory management, transfusion and haemostatic support and inhibitor eradication. Methods: Laboratory - Coagulometric techniques in ACL TOP® equipment with HemosIL® reagents, assessment of platelet function in Multiplate® and haemograms performed in Coulter LH750®. Case report - A Caucasian man, 82 years old, admitted in hospital at 19 Jan 2013 with deep muscular haematomas in right thigh and inguinal region and haematochezias in previous two months. Diagnoses: atrial fibrillation under warfarin since Jun 2011, ischemic and hypertensive cardiopathy, biological mitral prosthesis, congestive heart failure, non-recurrent rectal carcinoma submitted to anterior resection, chemotherapy and radiotherapy in 2003, two-vessel coronary disease submitted to a coronary artery bypass graft, type 2 diabetes mellitus, obesity, normocytic normochromic anaemia. Oral anticoagulation was promptly discontinued. In 4 Feb 2013 another haematoma occurred in the left thigh related to pressing in bed. In 11 Feb 2013 the haematoma in right inguinal region reappears with a new small collection in left thigh. Imaging techniques reveals massive first haematoma and smaller further haematomas without compartment syndrome. A total of 7 units (U) of red blood cells, 2 U of inactivated plasma, 1500 IU of prothrombin complex concentrate and 26 mg of recombinant activated factor (F) VII were administrated. After detection of inhibitors against FVIII the immunosuppression with prednisolone was applied at a dose 1mg/Kg/day PO since 1 Feb 2013 (temporary reduction during sepsis). Results: In 19 Jan 2013 Hb: 7.9g/dL, INR: 3.7. In 21 Jan 2013 Hb: 5.4g/dL, INR: 1.3, activated partial thromboplastin time (APTT): 58.8 sec (normal APTT in 30 Jun 2011). A reduced FVIII:C (3.6%) and inhibitors against FVIII:C (mixing tests including incubation for 2 hours at 37ºC) were detected with quantification by Bethesda (B) assay (titres: 8.6, 15.7, 11.7, 9.0 and 6.8 BU/mL at 25 Jan and 7, 14, 20 and 25 Feb 2013 respectively). Normalisation of prothrombin time (PT)/INR after suspension of warfarin; normal thrombin time; negative lupus anticoagulant (dilute Russell viper venom time and silica clotting time); D-Dimer: 357-2235ng/mL; maximum value of Hb: 11.0g/dL; normal platelet count until 13 Feb 2013 (subsequent thrombocytopenia) and function (ADP, thrombin/TRAP-6, ristocetin); increased F von Willebrand (VW): Ag and activity; negative direct antiglobulin test and tumour, viral and autoimmune markers; slightly increased gamma globulins (30 Jun 2011 and 6 Feb 2013). See table for other results. Summary/conclusions: Absence of other causes for acquired haemophilia A unless diabetes. By-passing concentrate replacement with recombinant activated FVII and corticosteroid regimen provide control of haematomas and expectable elimination of inhibitor (follow-up). We emphasize that a special caution was taken concerning the use of haemostatic agents in this older patient with prothrombotic tendency and the evidence of a high starting titre inhibitor. Other Results Relevant for Diagnosis, Management and Monitoring (table)
    23rd Regional Congress of ISBT, Amsterdam, The Netherlands; 06/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The incidence of acquired haemophilia A is 1.5/million/year. Elderly people are affected most frequently and the incidence is slightly higher in females. Autoimmune, infectious and malignant diseases correspond to identifiable underlying causes; postpartum occurrence is rare as the association to medication; idiopathic condition represents 50% of cases. Aims: Presentation of a case report of acquired haemophilia A with highlight to laboratory management, transfusion and haemostatic support and inhibitor eradication. Methods: Laboratory - Coagulometric techniques in ACL TOP® equipment with HemosIL® reagents, assessment of platelet function in Multiplate® and haemograms performed in Coulter LH750®. Case report - A Caucasian man, 82 years old, admitted in hospital at 19 Jan 2013 with deep muscular haematomas in right thigh and inguinal region and haematochezias in previous two months. Diagnoses: atrial fibrillation under warfarin since Jun 2011, ischemic and hypertensive cardiopathy, biological mitral prosthesis, congestive heart failure, non-recurrent rectal carcinoma submitted to anterior resection, chemotherapy and radiotherapy in 2003, two-vessel coronary disease submitted to a coronary artery bypass graft, type 2 diabetes mellitus, obesity, normocytic normochromic anaemia. Oral anticoagulation was promptly discontinued. In 4 Feb 2013 another haematoma occurred in the left thigh related to pressing in bed. In 11 Feb 2013 the haematoma in right inguinal region reappears with a new small collection in left thigh. Imaging techniques reveals massive first haematoma and smaller further haematomas without compartment syndrome. A total of 7 units (U) of red blood cells, 2 U of inactivated plasma, 1500 IU of prothrombin complex concentrate and 26 mg of recombinant activated factor (F) VII were administrated. After detection of inhibitors against FVIII the immunosuppression with prednisolone was applied at a dose 1mg/Kg/day PO since 1 Feb 2013 (temporary reduction during sepsis). Results: In 19 Jan 2013 Hb: 7.9g/dL, INR: 3.7. In 21 Jan 2013 Hb: 5.4g/dL, INR: 1.3, activated partial thromboplastin time (APTT): 58.8 sec (normal APTT in 30 Jun 2011). A reduced FVIII:C (3.6%) and inhibitors against FVIII:C (mixing tests including incubation for 2 hours at 37ºC) were detected with quantification by Bethesda (B) assay (titres: 8.6, 15.7, 11.7, 9.0 and 6.8 BU/mL at 25 Jan and 7, 14, 20 and 25 Feb 2013 respectively). Normalisation of prothrombin time (PT)/INR after suspension of warfarin; normal thrombin time; negative lupus anticoagulant (dilute Russell viper venom time and silica clotting time); D-Dimer: 357-2235ng/mL; maximum value of Hb: 11.0g/dL; normal platelet count until 13 Feb 2013 (subsequent thrombocytopenia) and function (ADP, thrombin/TRAP-6, ristocetin); increased F von Willebrand (VW): Ag and activity; negative direct antiglobulin test and tumour, viral and autoimmune markers; slightly increased gamma globulins (30 Jun 2011 and 6 Feb 2013). See table for other results. Summary/conclusions: Absence of other causes for acquired haemophilia A unless diabetes. By-passing concentrate replacement with recombinant activated FVII and corticosteroid regimen provide control of haematomas and expectable elimination of inhibitor (follow-up). We emphasize that a special caution was taken concerning the use of haemostatic agents in this older patient with prothrombotic tendency and the evidence of a high starting titre inhibitor. Other Results Relevant for Diagnosis, Management and Monitoring (Table)
    23rd Regional Congrss of ISBT, Amsterdam, the Netherlands; 06/2013