Potential Role of Thrombelastography in the Monitoring of Acquired Factor VIII Inhibitor Hemophilia A: Report on a 78-year-old Woman With Life-threatening Bleedings

2008 ◽  
Vol 15 (4) ◽  
pp. 470-476 ◽  
Author(s):  
Luca Spiezia ◽  
Leonardo Meneghetti ◽  
Fabio Dalla Valle ◽  
Giulio Tognin ◽  
Claudia Radu ◽  
...  
Keyword(s):  
Factor Viii ◽  
Potential Role ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Life Threatening ◽  
Viii Inhibitor ◽  
Acquired Factor Viii Inhibitor

scholarly journals Treatment of life-threatening hemorrhage due to acquired factor VIII inhibitor

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 535-541 ◽  
Author(s):  
T Pintado ◽  
HF Taswell ◽  
EJ Bowie
Keyword(s):  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Complete Disappearance ◽  
Healthy Elderly ◽  
Life Threatening ◽  
Factor Viii Concentrates ◽  
Therapeutic Measures ◽  
Viii Inhibitor ◽  
Acquired Factor Viii Inhibitor

Abstract An otherwise healthy elderly man developed massive, life-threatening, sublingual bleeding associated with an idiopathic factor VIII inhibitor. The patient was treated wtih cyclophosphamide, steroids, factor VIII concentrates, and repeated plasmapheresis (including three times with NCI-IBM blood-cell separator). Rapid clinical and laboratory improvement occurred, with complete disappearance of the inhibitor. The patient has remained well, without evidence of an inhibitor, for 8 mo. The possible role of each of the therapeutic measures in the disappearance of the inhibitor and the possible pathogenetic mechanism of this disorder are discussed. A high mortality rate and a striking incidence of sublingual hematoma have been observed in cases in the literature.

scholarly journals Treatment of life-threatening hemorrhage due to acquired factor VIII inhibitor

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 535-541 ◽  
Author(s):  
T Pintado ◽  
HF Taswell ◽  
EJ Bowie
Keyword(s):  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Complete Disappearance ◽  
Healthy Elderly ◽  
Life Threatening ◽  
Factor Viii Concentrates ◽  
Therapeutic Measures ◽  
Viii Inhibitor ◽  
Acquired Factor Viii Inhibitor

An otherwise healthy elderly man developed massive, life-threatening, sublingual bleeding associated with an idiopathic factor VIII inhibitor. The patient was treated wtih cyclophosphamide, steroids, factor VIII concentrates, and repeated plasmapheresis (including three times with NCI-IBM blood-cell separator). Rapid clinical and laboratory improvement occurred, with complete disappearance of the inhibitor. The patient has remained well, without evidence of an inhibitor, for 8 mo. The possible role of each of the therapeutic measures in the disappearance of the inhibitor and the possible pathogenetic mechanism of this disorder are discussed. A high mortality rate and a striking incidence of sublingual hematoma have been observed in cases in the literature.

Role of Plasmapheresis In Management of Acquired Factor VIII Inhibitor

Blood ◽  
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.

Acquired Factor VIII Inhibitor: A Single Institution Experience With 62 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3610-3610
Author(s):  
Ewa M. Wysokinska ◽  
Ramila Mehta ◽  
Diane Grill ◽  
Rajiv K. Pruthi
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Post Partum ◽  
Rare Condition ◽  
Factor Viii Inhibitor ◽  
Remission Rates ◽  
Autoimmune Conditions ◽  
Viii Inhibitor ◽  
Acquired Factor Viii Inhibitor

Abstract Background Acquired Factor VIII inhibitor or autoimmune hemophilia A (AHA), has an estimated incidence of up to 1.5 cases per million/year and may result in severe hemorrhagic complications and death. Approximately 50% of cases have an underlying condition such as malignancies, autoimmune disorders and post-partum state. AHA should be suspected in any patient presenting with unexplained bleeding and an inhibited aPTT. Management consists of maintaining hemostasis and elimination of the inhibitor, however management is not standardized. We present 62 cases of AHA managed at Mayo Clinic Rochester, over the course of 36 years. We also analyzed whether aPTT at presentation correlated with the strength of inhibition measured by Bethesda Titer. Methods After IRB approval, medical records of patients with AHA were reviewed and all clinical data collected. Cumulative incidence of death was estimated by Kaplan-Meier analysis. Spearman correlation was used to calculate relation of APTT to Bethesda titer. Results Between 1976 and 2012, we identified 62 patients (male: 35), with a median age at diagnosis of AHA 69 years (mean 64, range 20-86). Clinical presentation consisted of extensive ecchymoses (n=40, 64%) in majority of cases. 29/62 (47%) patients had at least 1 identifiable predisposing condition with 12/62 (19%) patients with an underlying malignancy and 16/62 (26%) with underlying autoimmune conditions. Median Bethesda titer was 29 (range 1 to 1178). Bethesda titer was not related to the number or duration of hospitalizations. Most (69%) patients had at least one hospitalization and 12 (19%) had more than one hospitalization for bleeding complication. Inpatient therapy for bleeding consisted most commonly of FEIBA in 21 pts (34%) and rFVIIa in 6 pts (10%). Prednisone was the most common immunosuppressant used in 54 (87%) patients while Rituximab was used in 11 (18%) patients. Of 32 patients with available follow up labs most (69%) achieved remission. There was no difference in remission rates between patients treated or not treated with Rituximab (p=0.1735). Conclusion Acquired Hemophilia A is a rare condition with very heterogenous presentation. It affects mostly older male patients who present with ecchymoses and elevated APTT. The degree of APTT prolongation at the time of diagnosis does not correlate with the strength of the Bethesda titer and should not guide choice of therapy in a patient presenting with an acute bleed. Rituximab use in the 11 patients treated at Mayo did not seem to influence remission rates or survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Acquired factor VIII inhibitor associated with chronic untreated hepatitis C

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.

Acquired Hemophilia A: A Single Institution’s Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4103-4103
Author(s):  
Devinderpal Randhawa ◽  
Ibrahim Sidhom ◽  
Gunwant Guron ◽  
Trevor Layne
Keyword(s):  
Factor Viii ◽  
Immunosuppressive Therapy ◽  
Hemophilia A ◽  
Treatment Modalities ◽  
Factor Viii Inhibitor ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Mortality And Morbidity ◽  
Life Threatening ◽  
Viii Inhibitor

Abstract Background: Acquired Hemophilia A (AH) due to factor VIII inhibitor is a rare life threatening disorder. If not diagnosed and treated urgently, significant mortality and morbidity results. AH can occur in setting of old age, autoimmune diseases, pregnancy, medication, malignancy, and lymphoproliferatve disorders. In majority of cases it is idiopathic. Objective: Review the treatment modalities and outcome of AH patients at our institution. Methods: A retrospective review of the data pertaining to patients who were diagnosed with AH at our institution between 1993–2004. Results: There were 5 patients diagnosed with AH, 3 female and 2 male. The median age was 67 years (range 30–84 years) the setting for development of AH in these patients was as follows: 1- postpartum, 1-HIV, 3 idiopathic. All patients presented with varying degree of spontaneous hemorrhage. The median Factor VIII inhibitor level was 16 Bethesda Unit (BU)(range 7. 2–31). Acute control of hemorrhage was achieved in all patients using either FEIBA (Factor eight inhibitor bypass activity) alone (1 patient), FEIBA and Novo seven (VIIa)(4 patients). Chronic immunosuppressive therapy was given as follows: Steroid alone (2 patients), Steroid and IVIG (1 patients), Steroid and Cyclophospamide (1 patient) and Steroid, Cyclophospamide and Rituximab (1 patient). Complete remission (CR) was obtained in 4 patients and with the final patient still receiving treatment. In one patient, the dose of Cyclophospamide was decreased due to Leucopenia. The median time to elimination of inhibitors was 5 month (range 1–10 month). There have been no mortalities. Conclusions: AH is a life threatening condition if not promptly diagnosed and treated, mortality remains significantly high. Treatment with factors replacement and immunosuppressive therapy was effective in all our patients

scholarly journals Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Nicholas B. Abt ◽  
Michael B. Streiff ◽  
Christian B. Gocke ◽  
Thomas S. Kickler ◽  
Sophie M. Lanzkron
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Term Therapy ◽  
Factor Viii Inhibitor ◽  
Factor Viii Activity ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Fviii Activity ◽  
Viii Inhibitor ◽  
Acquired Factor Viii Inhibitor

Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable.Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours.Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity.Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

scholarly journals A Clinical and Experimental Study of Acquired Inhibitors to Factor VIII

Blood ◽  
1965 ◽  
Vol 26 (6) ◽  
pp. 805-818 ◽  
Author(s):  
HAROLD R. ROBERTS ◽  
MARGARET B. SCALES ◽  
JOHN T. MADISON ◽  
WILLIAM P. WEBSTER ◽  
GEORGE D. PENICK
Keyword(s):  
Experimental Study ◽  
Factor Viii ◽  
Mode Of Action ◽  
Exchange Transfusion ◽  
Hemophilia A ◽  
Retroperitoneal Hematoma ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor ◽  
Potent Factor

Abstract Factor VIII inhibitors which developed in four patients with hemophilia A are described. These inhibitors are apparently specific for Factor VIII and are capable of inducing a transient hemophilic state when injected into dogs. The genesis, properties, and mode of action of these inhibitors can be explained on an immunologic basis and it seems most likely that they represent an antibody to Factor VIII. One hemophilia A patient, with retroperitoneal hematoma and a potent Factor VIII inhibitor, was successfully treated by an exchange transfusion followed by administration of purified porcine Factor VIII.

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