A decade-long clinical experience on the prophylactic use of activated prothrombin complex concentrate in acquired haemophilia A

Árokszállási, Anita; Rázsó, Katalin; Ilonczai, Péter; Oláh, Zsolt; Bereczky, Zsuzsanna; Boda, Zoltán; Schlammadinger, Ágota

doi:10.1097/mbc.0000000000000716

Cited by 11 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The short half-life of recombinant factor VIIa is limiting the use of this agent in prophylaxis. Activated prothrombin complex concentrate has been used for secondary prophylaxis with an apparent reduction in bleeding [ 16 , 17 ]. However, this approach may require several infusions per week, probably not feasible in many AHA patients over prolonged periods of time.…”

Section: Discussionmentioning

confidence: 99%

Reduced-intensity, risk factor–stratified immunosuppression for acquired hemophilia A: single-center observational study

2020

View full text Add to dashboard Cite

Immunosuppressive therapy (IST) is administered to patients with acquired hemophilia A (AHA) to eradicate autoantibodies against coagulation factor VIII (FVIII). Data from registries previously demonstrated that IST is often complicated by adverse events, in particular infections. This pilot study was set out to assess the feasibility of reduced-intensity, risk factor–stratified IST. We followed a single-center consecutive cohort of twenty-five patients with AHA receiving IST according to a new institutional treatment standard. Based on results from a previous study, GTH-AH 01/2020, patients were stratified into “poor risk” (FVIII < 1 IU/dl or inhibitor ≥ 20 Bethesda units (BU)/ml) or “good risk” (FVIII ≥ 1 IU/dl and inhibitor < 20 BU/ml). Outcomes were compared between the current cohort and the GTH registry as a historic control (n = 102). Baseline characteristics of the cohort were not different from the historic control. Partial remission, defined as FVIII recovered to > 50 IU/dl, was achieved by 68% of patients after a median time of 112 days, which was lower and significantly later than in the historic control (hazard ratio: 1.8, 95% confidence interval 1.2–2.8). Complete remission, overall survival, and frequency of fatal infections were not different. Grade 3 and 4 infections were more frequent. The impact of risk factors that was observed in the historic cohort was no longer apparent, as partial and complete remission and overall survival were similar in “good risk” and “poor risk” patients. In conclusion, reduced-intensity, risk factor–stratified IST is feasible in AHA but did not decrease the risk of infections and mortality in this cohort.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduced-intensity, risk factor–stratified immunosuppression for acquired hemophilia A: single-center observational study

2020

View full text Add to dashboard Cite

show abstract

“…43 APCC has also been used for secondary prophylaxis. 44,45 In a retrospective study, APCC exhibited a favorable safety profile indicating that it is well-tolerated with few adverse events. 46 Thrombotic events, including myocardial infarction and venous thrombosis, were mostly reported in patients with additional risk factors.…”

Section: Activated Prothrombin Complex Concentratementioning

confidence: 99%

International recommendations on the diagnosis and treatment of acquired hemophilia A

et al. 2020

View full text Add to dashboard Cite

A cquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors' clinical experience in treating patients with AHA.

show abstract

“…However, repeated and extended treatment was required in most cases. The administering of bypassing agent was associated low incidence of thrombotic complications [10,24] and Knoebl reported thromboembolic events occurred in about 4% of cases treated with bypassing agents [13]. Fortunately, no thrombotic events were recorded for the use of bypassing agent in patients' cohort of current study.…”

Section: Discussionmentioning

confidence: 63%

Inhibitor eradication and bleeding management of acquired hemophilia A: a single center experience in China

Liu

et al. 2019

Hematology

View full text Add to dashboard Cite

Objectives: Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies against coagulation factor VIII that leads to spontaneous bleeding. This study reports the clinical characteristics and treatment outcomes of a relatively sizable cohort of patients with AHA. Methods: We retrospectively analyzed the characteristics and outcomes of 42 patients with AHA diagnosed in our center from January 2014 through December 2018. Results: The FVIII activity (FVIII: C) was significantly suppressed (median 1.5%; interquartile range [IQR]: 0.9-3.5) by FVIII inhibitor (median 8 BU/mL; IQR: 4.0-16.0). Bypassing agents, PCC or FVIIa, were used in 14 patients for bleeding control without any adverse reaction; and most patients (90.5%, 38/42) were placed on immunosuppressive regimen, corticosteroid alone or in combination with cyclophosphamide. Patients treated with corticosteroids alone had a lower median inhibitor titer (8 BU/mL) than those treated with combination corticosteroids of cyclophosphamide (16 BU/mL) (p < 0.001). 97.4% (37/38) patients achieved complete remission (CR) after immunosuppression therapy, and the median time to CR in patients treated with corticosteroids alone was shorter than those with combination corticosteroids of cyclophosphamide (median 40 days; IQR: 31-65 vs. 51 days; IQR: 38-83, p = 0.301). 10 (26.3%) patients relapsed thereafter and were placed on combined corticosteroid and cyclophosphamide treatment, which yielded second remission in 8 patients (80%). Two patients died, one from uncontrolled post-surgical retroperitoneal hemorrhage and one from sepsis complicating corticosteroid therapy. Conclusion: The corticosteroid achieves a satisfactory outcome, particularly with low inhibitors titers; and combination of cyclophosphamide will facilitate remission in sever patients with high titers of inhibitors.

show abstract

A decade-long clinical experience on the prophylactic use of activated prothrombin complex concentrate in acquired haemophilia A

Cited by 11 publications

References 18 publications

Reduced-intensity, risk factor–stratified immunosuppression for acquired hemophilia A: single-center observational study

Reduced-intensity, risk factor–stratified immunosuppression for acquired hemophilia A: single-center observational study

International recommendations on the diagnosis and treatment of acquired hemophilia A

Inhibitor eradication and bleeding management of acquired hemophilia A: a single center experience in China

Contact Info

Product

Resources

About