An Acquired Factor VIII Inhibitor Responsive to High-Dose Gamma Globulin

SummaryA 55-year-old previously well woman noted easy bruising and developed a swollen, painful leg after minimal trauma. A compartment syndrome was diagnosed, and medial and lateral fasciotomies were performed with evacuation of a massive hematoma. However, blood rapidly reaccumulated in the wound. The VILI : C level was 2%, and 4 Bethesda units of factor VIII inhibitor were detected. After initial treatment with clotting factor concentrates and corticosteroids failed to control bleeding or reduce inhibitor titers, gamma globulin, 25 g daily for 5 days, was administered. The inhibitor became undetectable, VIII :C levels rose, and bleeding stopped. However, 5 days later VIII :C levels were again low and bleeding recurred. A second course of gamma globulin, 50 g daily for 2 days, was accompanied by a prompt increase in VIII :C, and uneventful recovery. In conclusion, in this patient with an autoantibody to Vili : C, a response to gamma globulin was observed on two occasions, and the second response came when steroids were being tapered and the patient was on no other medication.

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Role of Plasmapheresis In Management of Acquired Factor VIII Inhibitor

Blood ◽

10.1182/blood.v116.21.4656.4656 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4656-4656

Author(s):

Ratesh Khillan ◽

Rabia Latif ◽

Gurinder Sidhu ◽

Elizabeth Gloster ◽

Albert S. Braverman ◽

...

Keyword(s):

Factor Viii ◽

Ct Scan ◽

Case Reports ◽

High Dose ◽

Factor Viii Inhibitor ◽

Inhibitor Level ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor ◽

Dose Factor

Abstract Abstract 4656 A 91-year-old woman with past medical history of hypertension presented with hematuria. There were no ecchymosis, Petechiae or other obvious active bleeding. Her hemoglobin was 11.4 g/dl on presentation hematuria got worse and her hemoglobin drops to 7.6 g/dl over next 48 hours and she was hemodynamically unstable. She was transferred to the Medical Intensive Care Unit for resuscitation with IV fluids and PRBCs. Coagulation tests revealed a prolongation of activated partial thromboplastin time of more than 100 seconds (control 33 seconds) which could not be corrected with mixing normal plasma. Diagnosis of acquired factor VIII inhibitor was considered and recombinant activated factor VII (rFVIIa) was initiated. The factor VIII activity level was reduced to less than 1%. Bethesda assay demonstrated the presence of a factor VIII inhibitor at 103.8 Bethesda units per ml (BU/ml), other coagulation studies were with in normal range. CT scan of her abdomen showed retroperitoneal hematoma. rFVIIa was started at 50 units/kg body weight every 3 hours and subsequently increased to 200 units/kg. She was simultaneously started on steroids. Her hematuria did not improve in spite of high dose rFVIIa. On day 4 rFVIIa was tapered and switched to 50 units/kg FEIBA (Factor eight inhibitor bypass agent). She also received Rituximab 375 mg/m2. We continued FEIBA until day 7 but her hematuria did not improve, she required more than 10 units of Packed Red Blood Cells PRBCs during this period. On day 7 we decided to start plasmapheresis as there were some case reports of using plasmapheresis with or without immunoadsorption columns (which are currently not available in US). We started plasmapheresis and gave her 2 doses of IVIG (Immunoglobulin). Her pre and post plasmapheresis inhibitor levels were 104 BU/ml and 54 BU/ml respectively. Her urine turned pink and her Prbc demand decreased. A second plasmapheresis was done 2 days later showed significant decrease of inhibitor level from 80 BU/ml to 14.5 BU/ml. Her hematuria resolved by next day. We continued her on FEIBA for three more days she did not have hematuria and she did not require any PRBCs. CT scan of abdomen showed decrease in size of retroperitoneal hematoma. Cyclophosphamide 1000 mg was given for induction of immune tolerance followed by high dose factor VIII (100 IU/KG) as per Bonn protocol. Her factor VIII levels and factor VIII inhibitor levels were checked every day before and after Factor VIII infusion. Her inhibitor level is ranging between 14–16 BU/ml she is not bleeding any more and her abdominal hematoma is resolved. Her pre and post transfusion factor VIII levels ranges between 30–40% and 120–140%. respectively. Patient is still getting factor VIII everyday. Role of plasmapheresis is not very well defined in acquired Factor VIII inhibitor patients. Acquired hemophilia is a rare autoimmune disorder in which the patient develop an autoantibody directed against coagulation factor VIII leading to a clinically bleeding diathesis. There are few case reports in literature showing efficacy of Plasmapheresis in this disorder. This is a rare condition and it is very difficult to find large randomized trial to establish a standard of care. Patient mentioned above did not respond to rFVIIa or FEIBA. In our observation plasmapheresis with IVIG proved to be an effective method of rapidly reducing the inhibitor level. In case of life threatening bleeding we need to reduce the inhibitor level quickly. We also observed that once inhibitor level was low bleeding stopped. Immune induction therapy with cyclophosphamide followed by high dose factor VIII was successful in maintaining low inhibitor level. Disclosures: Kessler: Grifols S.A.: Research Funding.

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Acquired factor VIII inhibitor unresponsive to administration of high-dose immunoglobulins

Thrombosis Research ◽

10.1016/0049-3848(93)90318-i ◽

1993 ◽

Vol 70 ◽

pp. S35

Keyword(s):

Factor Viii ◽

High Dose ◽

Factor Viii Inhibitor ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor

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Acquired factor VIII inhibitor associated with chronic untreated hepatitis C

The Southwest Respiratory and Critical Care Chronicles ◽

10.12746/swrccc.v6i23.465 ◽

2018 ◽

Vol 6 (23) ◽

pp. 17-21

Author(s):

Abdussalam Shredi ◽

Benjamin W. Elberson ◽

Saif El Nawaa ◽

Amr Ismail

Keyword(s):

Hepatitis C ◽

Factor Viii ◽

Hemophilia A ◽

Autoimmune Disorders ◽

Hcv Infection ◽

Clotting Factor ◽

Prolonged Treatment ◽

Factor Viii Inhibitor ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor

Acquired inhibitors of coagulation are antibodies that either inhibit the activity or increase the clearance of a clotting factor. A hemorrhagic diathesis is a common clinical manifestation in affected patients. Acquired factor VIII inhibitor – or acquired hemophilia A – is a rare disorder and presents similarly to hemophilia A, though patients are less likely to develop hemarthroses. This inhibition is most commonly due to autoantibodies against coagulation factor VIII. These autoantibodies often occur in pregnancy, autoimmune disorders, solid tumors, and lymphoproliferative syndromes. Several drugs, including penicillins, phenytoin, and sulfa drugs, have also been associated with antibodies to factor VIII. Chronic infection with the hepatitis C virus (HCV), in addition to various degrees of liver inflammation and fibrosis, can have extrahepatic manifestations, especially autoimmune disorders. The most common hematological complications of HCV infection are thrombocytopenia, cryoglobulinemia, and anti-cardiolipin antibodies. A few cases of factor VIII inhibitors occurring in HCV patients have been reported, with a higher incidence after prolonged treatment with interferon-α. Here, we present a case of a patient with chronic untreated HCV infection developing acquired factor VIII deficiency.

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Low response to high‐dose intravenous immunoglobulin in the treatment of acquired factor VIII inhibitor

British Journal of Haematology ◽

10.1046/j.1365-2141.1996.d01-1965.x ◽

1996 ◽

Vol 95 (4) ◽

pp. 750-753 ◽

Cited By ~ 27

Author(s):

Laurent Crenier ◽

Jean Ducobu ◽

Jean‐Marin Des Grottes ◽

Jean Cerny ◽

Christian Delaunoit ◽

...

Keyword(s):

Factor Viii ◽

Intravenous Immunoglobulin ◽

High Dose ◽

Factor Viii Inhibitor ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor

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Successful long-time treatment with mycophenolate-mofetil in a child with acquired factor VIII inhibitor

Hämostaseologie ◽

10.1055/s-0037-1619780 ◽

2012 ◽

Vol 32 (S 01) ◽

pp. S75-S78 ◽

Cited By ~ 1

Author(s):

C. Niekrens ◽

K.-W. Sykora ◽

C. Wermes

Keyword(s):

Factor Viii ◽

Half Life ◽

High Titer ◽

Term Treatment ◽

High Dose ◽

Severe Bleeding ◽

Factor Viii Inhibitor ◽

Long Term Treatment ◽

Viii Inhibitor ◽

Acquired Factor Viii Inhibitor

SummaryHere, we report about a boy (age: 18 years) who developed an acquired factor VIII inhibitor at the age of 9 years. He presented with bleeding in his right ankle, multiple haematomas and a high-titer factor VIII type II inhibitor (400 BU). Therapy: He received treatment with MMF (CellCept→), dexamethasoneimmunoglobulin pulses, and rituximab together with high dose FVIII (Hannover protocol). His inhibitor titer decreased rapidly, and half-life and recovery normalized. Inhibitor titres increased after reduction of the factor VIII dose, and increased further after MMF was stopped. A second treatment course with MMF again resulted in reduction of the titre, improvement in half life and recovery, and no more bleedings. Inhibitor reappeared with MMF dose reduction, again accompanied by severe bleeding. Additional rituximab stopped the bleedings, and treatment with MMF has been continued since. Conclusion: Although the laboratory parameters showed no complete remission, severe bleedings and expensive factor replacement could be avoided by long-term treatment with MMF.

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