Properties of Anti-Factor VIII Inhibitor Antibodies in Hemophilia A Patients

2000 ◽  
Vol Volume 26 (Number 02) ◽  
pp. 137-142 ◽  
Author(s):  
Dorothea H. Scandella
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor

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.

scholarly journals Postpartum Acquired Hemophilia: A Rare Cause of Postpartum Hemorrhage

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
Srikanth Seethala ◽  
Sumit Gaur ◽  
Elizabeth Enderton ◽  
Javier Corral
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Vii ◽  
Normal Vaginal Delivery ◽  
Factor Viii Inhibitor ◽  
Activity Levels ◽  
Factor Viii Activity ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Viii Inhibitor

A 36-year-old female started having postpartum vaginal bleeding after normal vaginal delivery. She underwent hysterectomy for persistent bleeding and was referred to our institution. An elevation of PTT and normal PT made us suspect postpartum acquired hemophilia (PAH), and it was confirmed by low factor VIII activity levels and an elevated factor VIII inhibitor. Hemostasis was achieved with recombinant factor VII concentrates and desmopressin, and factor eradication was achieved with cytoxan, methylprednisolone, and plasmapheresis.

Hemophilic Dog Model For Evaluating Hemostatic Efetcacy Of Plasma Protein Fractions

1981 ◽  
Author(s):  
H S Kingdon ◽  
T M Hassell
Keyword(s):  
Factor Viii ◽  
Plasma Protein ◽  
Hemophilia A ◽  
Protein Fractions ◽  
Factor Viii Inhibitor ◽  
Repeat Dose ◽  
The Usa ◽  
Sharp Dissection ◽  
Viii Inhibitor ◽  
Uncontrolled Bleeding

About 15% of patients with hemophilia A develop inhibitors to Factor VIII. Because in many cases the inhibitor renders the patient refractory to treatment with Factor VIII, plasma protein fractions designed to bypass the inhibitor have been developed. In the USA these are referred to genetically as Anti Inhibitor Ccrplex Concentrates (AICCs). Development of AICCs has been hampered by lack of a suitable irodelin which to judge hemostatic efficacy. Similarly, lack pf a model has impeded research on the mechanism of action Of AICCs. Therefore, we chose to evaluate AICCs in dogs with hemophilia A, reasoning that a material capable of bypassing & Factor VIII inhibitor should be effective in Factor VIII deficient recipients with or without inhibitors. Under local anesthesia a standardized gingival biopsy was performed losing a flexible plastic template and a modified scalpel handle holding two #11 Bard-Parker blades. The parallel time is ions were 5 mm long, 2 nm apart, and 1.5 mm deep. The tissue block thus defined was removed by sharp dissection. In normal dogs, bleeding from this wound ceased in 5 ± 2min, the wound was filled with concave clot, and bleeding did not recur. In contrast, hemophilic dogs formed an abnormal (very large) clot, and rebled for several days if untreated. The hematocrit usually dropped by 2-10 percentage points in 24 hr of uncontrolled bleeding. An experimental AICC fraction under development by Cutter Laboratories was evaluated in 5 dogs, and shown to be hemostatically effective. The dose required to achieve hemostasis was 25-75 units/kg; in some dogs a second dose was required 6 hr after the first dose to maintain hemostasis. A single dog with a low titer inhibitor to Factor VIII was successfully treated with 39 u/kg, followed by a repeat dose of 39 u/kg 6 hr after the first dose. We conclude that this AICC preparation brings about nemostasis in Factor VIII deficient individuals with or without inhibitors to Factor VIII.

Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor

2016 ◽  
Vol 20 (4) ◽  
pp. E11-E13 ◽  
Author(s):  
Natarajan Gopalakrishnan ◽  
Thiruvengadam Usha ◽  
Balasubramaniyan Thopalan ◽  
Jeyachandran Dhanapriya ◽  
Thanigachalam Dineshkumar ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

A close insight to factor VIII inhibitor in the congenital hemophilia A

2016 ◽  
Vol 9 (9) ◽  
pp. 903-913 ◽  
Author(s):  
Shamsoreza Tabriznia-Tabrizi ◽  
Marzie Gholampour ◽  
Hassan Mansouritorghabeh
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor

Significance of Factor VIII Inhibitors by ELISA in Patients with Hemophilia A.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3398-3398
Author(s):  
Jamie R Brewer ◽  
Sandra Harris ◽  
David Green ◽  
Anaadriana Zakarija
Keyword(s):  
Factor Viii ◽  
Functional Status ◽  
Hemophilia A ◽  
Statistical Significance ◽  
Bleeding Event ◽  
Clinical Information ◽  
Prior History ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

Abstract Background: The Bethesda assay traditionally has been used to detect Factor VIII inhibitors in patients with Hemophilia A, but recent evidence suggests that it is not sensitive to all inhibitors, particularly non-inhibitory or low-titer antibodies. Methods: Patients with Hemophilia A without prior history of inhibitor were recruited. Study questionnaire collected demographic and clinical information, bleeding history and factor usage over the preceding 6 months. Functional status was assessed by the Hemophilia Activities List (HAL). Factor VIII inhibitor was assessed by both the Bethesda assay and Factor VIII inhibitor ELISA (GTI Diagnostics). T-test was performed to assess statistical significance. Results: Data is available for 26 patients, 19 severe, 2 moderate and 7 mild. All subjects had a negative Bethesda assay, but 10 (39%) had a detectable inhibitor by ELISA. 9/10 inhibitor patients had severe hemophilia, while one had mild hemophilia. In severe hemophiliacs, there were no differences in age, HIV status, CD4 count, Hepatitis C positivity or viral load between those with and those without inhibitors. Inhibitors were more frequent in those using plasma-derived concentrates 4/5 (80%), than in those using recombinant products 6/14 (43%), p=0.15. There was no difference in bleeding frequency or functional status in patients with or without inhibitors, although those with inhibitors had more frequent infusions.(Table). In patients on prophylaxis, those with inhibitors had a higher bleeding frequency compared to those without an inhibitor, (p =0.2). 11 patients were not on prophylaxis and had a higher bleeding frequency (p = 0.02) than patients on prophylaxis irrespective of inhibitor presence. However those with inhibitors required more factor doses per bleed compared to those without an inhibitor (4.4 vs. 1.5, p=0.16) even though the mean factor dose was the same (25.3 units/kg vs 25.2 units/kg). Conclusions: The Factor VIII ELISA assay detected inhibitors in 39 % of Hemophilia A patients who had undetectable inhibitors by standard Bethesda assay. This data suggests that these inhibitors may be clinically relevant, given that inhibitor patients who are not on prophylaxis require more doses of factor per bleeding event. Further study is necessary to determine mechanism and clinical significance of these Factor VIII inhibitors. Table. Characteristics of severe hemophilia patients with and without ELISA Factor VIII inhibitor All severe (n=19) Inhibitor (n=9) No inhibitor (n=10) Age 43.4 40.8 45.7 Plasma-derived factor 5 (26.3%) 4 (44.4%) 1 (10%) Total bleeds/6 months 8.6 8.1 9.0 Muscle bleeds/6 months 1.3 0.8 1.7 Joint bleeds/6 months 7.3 7.3 7.3 Factor infusions/6 months 50.9 57.2 45.2 On prophylaxis 8 (42%) 4 (44.4%) 4 (40%) Total bleeds/6 months 4.3 5.8 2.8 Not on prophylaxis 11 (58%) 5 (55.6%) 6 (60%) Total bleeds/6 months 11.7 10 13.2 Factor doses/bleed 2.9 4.4 1.5

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.

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