Management of acquired haemophilia A

2015 ◽  
Vol 35 (04) ◽  
pp. 311-318 ◽  
Author(s):  
R. E. Scharf ◽  
C. Dobbelstein ◽  
S. Werwitzke ◽  
A. Tiede
Keyword(s):  
Factor Viia ◽  
Immunosuppressive Treatment ◽  
Coagulation Factor ◽  
Cytotoxic Agents ◽  
Haemophilia A ◽  
Recent Onset ◽  
Acquired Haemophilia ◽  
First Line Therapy ◽  
Characteristic Features ◽  
Bypassing Agents

SummaryAcquired haemophilia A (AHA) is caused by autoantibody inhibitors of coagulation factor VIII (FVIII : C). Recent onset of bleeds and isolated prolongation of the activated partial thromboplastin time (aPTT) are characteristic features of the disorder. Reduced FVIII : C activity and a detectable FVIII : C inhibitor in the Bethesda assay confirm the diagnosis. Patients should be referred to expert centres, whenever possible, and invasive procedures with a high risk of bleeding must be avoided, until haemostasis has been secured by adequate therapy.Bypassing agents capable of inducing sufficient thrombin formation in the presence of FVIII : C inhibitors are treatment of choice, including currently available recombinant factor VIIa (NovoSeven™) and activated prothrombin complex concentrate (FEIBA™). These agents represent first line therapy to control acute or severe bleeds. To eradicate inhibitors, immunosuppressive treatment (IST) is indicated in patients with AHA. Glucocorticoids, cytotoxic agents and rituximab are most widely used. However, an ideal IST regimen has not been established so far. Adverse events of IST, including infections as the foremost cause death, are frequent complications in AHA.

Inhibitor Haemophilia A - Cases with Reduced Haemostatic Response to Wildtype rFVIIa Who Achieved a Normal Clotting Profile with a Novel Potent Analogue of rFVIIa.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3215-3215
Author(s):  
Benny Sørensen ◽  
Egon Persson ◽  
Jørgen Ingerslev
Keyword(s):  
Factor Viia ◽  
Ex Vivo ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Clinical Severity ◽  
Dose Titration ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
First Case ◽  
Clinical Investigations

Abstract Development of inhibitory antibodies to coagulation factor VIII represents a serious complication in patients with congenital or acquired haemophilia A. Recombinant factor VIIa (rFVIIa, NovoSeven®, Novo Nordisk, Bagsvaerd, Denmark) has proven efficacious in management of bleeding episodes in patients with inhibitors. Recently, a novel analogue of rFVIIa (NN1731, Novo Nordisk) has been developed. NN1731 has increased potency to generate factor Xa on the surface of activated platelets. We have developed a thrombelastographic (TEG) whole blood (WB) coagulation model, employing activation with minimal amounts of tissue factor. This global clotting assay reflects the clinical severity of haemophilia A and can be used to ex vivo assess the haemostatic capacity of rFVIIa and NN1731. Adopting the TEG model, we report on two cases where ex vivo addition of rFVIIa only induced minor improvements of the WB coagulation profile. However, ex vivo addition of NN1731 revealed a normalization of the WB coagulation signature. The first case was a 74 years old female with acquired haemophilia A (APTT=51 sec, FVIII:C = 0.08 IU/mL, Inhibitor = 3.6 BU/mL. The second case was a patient with congenital haemophilia A and inhibitors (APTT=101 sec, FVIII:C<0.01 IU/mL, Inhibitor=9 BU/mL). In both cases, the WB thrombelastographic analysis demonstrated a severely compromised haemostatic capacity. Ex vivo dose titration studies with rFVIIa induced minor improvements only of the suppressed WB clot formation profile. However, ex vivo addition of NN1731 at 2 μg/mL normalized the coagulation signature. The observations that the analogue NN1731 normalized the haemostatic WB clotting profiles in cases where rFVIIa induced minor changes stimulates further pre-clinical investigations.

scholarly journals Acquired Haemophilia A. Which is the best therapeutic choice in older adults? Single center study of 4 cases

Reumatismo ◽  
2019 ◽  
Vol 71 (1) ◽  
pp. 37-41 ◽  
Author(s):  
E. Mauro ◽  
E. Garlatti Costa ◽  
A. Zanier ◽  
M. Maset ◽  
A. Ermacora ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor Vii ◽  
Haemophilia A ◽  
Recombinant Activated Factor Vii ◽  
Acquired Haemophilia ◽  
Activated Factor Vii ◽  
Activated Prothrombin Complex Concentrate ◽  
Therapeutic Choice ◽  
Single Center Study ◽  
Thrombotic Complications

Acquired haemophilia A (AHA) is a rare bleeding disorder due to autoantibodies directed against coagulation factor VIII. The treatment is based on recombinant activated factor VII and activated prothrombin complex concentrate. However, mainly in older patients, severe thrombotic complications have been reported. Here we report the different therapeutic approaches in 4 cases of elderly patients with AHA and co-morbidities.

Rituximab as first-line therapy for acquired haemophilia A: a single-centre 10-year experience

Haemophilia ◽  
2016 ◽  
Vol 22 (4) ◽  
pp. e338-e341 ◽  
Author(s):  
B. Rossi ◽  
P. Blanche ◽  
V. Roussel-Robert ◽  
A. Berezné ◽  
S. Combe ◽  
...  
Keyword(s):  
Haemophilia A ◽  
First Line ◽  
Single Centre ◽  
Acquired Haemophilia ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Acquired Haemophilia A in Association with Influenza A and Urinary Tract Infection

2020 ◽  
Author(s):  
Felipe Peña-Muñoz ◽  
Ernesto Parras ◽  
Olga Compan ◽  
Nora Gutierrez ◽  
Celestino Martin ◽  
...  
Keyword(s):  
Influenza A ◽  
Coagulation Factor ◽  
Autoimmune Disorder ◽  
Immunosuppressive Drugs ◽  
Bleeding Complications ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
Haemostatic Agents ◽  
Inhibitor Titre ◽  
Prolonged Aptt

Acquired haemophilia A (AHA) is a rare autoimmune disorder caused by an autoantibody against any circulating coagulation factor, especially factor VIII (FVIII). The lack of awareness of this condition suggests that diagnosis is a challenge and usually delayed, which leads to suboptimal treatment. Consequently, early diagnosis is mandatory to prevent potentially life-threatening bleeding complications. We present the case of an 85-year-old woman admitted to hospital with symptoms of respiratory infection who 12 hours later developed haematuria which required transfusion. Laboratory assays showed an isolated prolonged aPTT, a moderately reduced FVIII and a high inhibitor titre. Influenza A and Escherichia coli were also identified. Antivirals, antibiotics, immunosuppressive drugs and haemostatic agents were started. Two weeks later, the inhibitor was not detected, and bleeding and symptoms of infection had resolved. Immunosuppressive drugs were stopped on day 45 and there has been no recurrence since then. To date, no FVIII inhibitors have been reported in concomitant infection with influenza A and urinary E. coli. The identification of conditions potentially associated with AHA is essential to achieve complete remission.

scholarly journals SUCCESSFUL LONG TERM ERADICATION OF FACTOR VIII INHIBITOR IN PATIENTS WITH ACQUIRED HAEMOPHILIA A IN SAUDI ARABIA

2012 ◽  
Vol 4 (1) ◽  
pp. e2012021 ◽  
Author(s):  
Galila F Zaher ◽  
Soheir S Adam
Keyword(s):  
Coagulation Factor ◽  
Complex Nature ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Acquired Haemophilia ◽  
Local Experience ◽  
Fatal Bleeding ◽  
Factor Inhibitor ◽  
Initial Control ◽  
Initiation Of Therapy

Acquired haemophilia A is a serious and potentially fatal bleeding disorder. Diagnosis is difficult and maybe delayed due to its rarity. The high mortality rate and the complex nature of treatment necessitate patient management at a haemophilia centre, where the required expertise and resources are available. Prompt diagnosis is crucial and early initiation of therapy could be life saving. Management includes initial control of bleeding followed by an approach to eradicate the coagulation factor inhibitor. In this paper we describe our local experience with acquired haemophilia A, which resulted in the successful control of major bleeding at presentation and eradication of inhibitors.

scholarly journals Managing Acquired Haemophilia (A): Pan London Experience-Relating to the European Acquired Haemophilia (EACH2) Registry Data

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1512-1512
Author(s):  
Pu-Lin Luo ◽  
Steve K Austin ◽  
Daniel P Hart ◽  
Paul A Batty ◽  
Michael Laffan ◽  
...  
Keyword(s):  
Factor Viii ◽  
Treatment Response ◽  
Retrospective Analysis ◽  
Research Funding ◽  
Sustained Remission ◽  
Haemophilia A ◽  
Time To Treatment ◽  
Acquired Haemophilia ◽  
Inhibitor Titre ◽  
Bypassing Agents

Abstract Background Acquired haemophilia A (AHA) is a rare and potentially fatal bleeding disorder characterised by the development of autoantibodies directed against factor VIII. The optimal treatment for AHA remains uncertain and there is a paucity of published data to guide clinical practice. The EACH2 Registry has provided the largest observational dataset from 117 European centres on the management of AHA. The aim of this study is to provide retrospective analysis of the experience of all Haemophilia Centres across London on the management of AHA and compare it to the data presented in the EACH2 Registry. Method We performed a multicentre centre retrospective analysis of all AHA patients presenting between January 2009 and December 2012 to Haemophilia Centres across London. Data collected included demographics, aetiology, bleeding characteristics immunosuppression and haemostatic agents used to control the first bleeding episode. Results There were 65 patients identified. The median (IQR) age at diagnosis was 78 (57-85) years. At presentation, the median haemoglobin concentration, FVIII:C and inhibitor titre were 80 g/L (68-100), 2 IU/dl (0-5.5) and 13.0BU/ml(3.5-47 ). At presentation 48/65 patients demonstrated bleeding from multiple sites with 18/65 experiencing life-threatening bleeds. 4 patients had no evidence of clinical bleeding and there was no difference in haemoglobin level, baseline FVIII:C and peak inhibitor titre compared to those who bled(P>0.05). 50% of patients had idiopathic cause of AHA with malignancy being the second most common. Around 50% (33/65) of patients were treated with activated prothrombin complex concentrate (aPCC) alone and 19/65 patients alternated between aPCC and recombinant activated FVII (FVIIa). 6(9%) patients with bleeding symptoms were managed with tranexamic acid or desmopressin alone without bypassing agents. There median (IQR) time to treatment response (defined as days to factor VIII >50IU/dl or negative Bethesda) was 45(23-82) days. Single agent prednisolone was most common (32/64) immunosuppression used followed by combination therapy with prednisolone and cyclophosphamide (22/64). 87% of patients achieved treatment response. A higher proportion of patients (21/22) treated with prednisolone and cyclophosphamide achieved response compared to prednisolone alone (29/33). There was no difference in the days to response (83 vs 69 p=0.055), time to remission (days to stopping immunosuppression)(123 vs 1958 p=0.065), incidence of relapses (7/32 vs 5/22) or duration of sustained remission (264 vs 204 p= 0.42) between the 2 groups. 8 patients received rituximab in addition to prednisolone and/or cyclophosphamide and 3 was treated with rituximab alone. 16% (12/65) of patients relapsed. These patients exhibited a higher mean baseline and peak inhibitor (BU/ml) (140 vs 54 p=0.011, 143vs 64 p=0.03) There was no difference in the time to response (78vs94 p=0.50) between patients who relapsed compared to those who did not. Presenting inhibitor of >16BU was also associated with longer days to treatment response(121 vs 58 p=0.001) 70% of patients were alive at follow up with similar portions seen in the between the cyclophosphamide and prednisolone group and prednisolone only group. Figure 1 Figure 1. Figure 2 Figure 2. Summary: Our study reinforced the findings of the EACH2 Registry that FVIII level and inhibitor tire did not correspond to the presence of bleeding or the severity of bleeding. However a low presenting inhibitor titre <16BU/ml was associated with faster inhibitor eradication and normalisation of FVIII. A higher baseline and peak inhibitor titre also influenced the rate of relapse. Bypassing agents were used to treat 91% of our patients with clinical bleeding, unlike only 70% in the EACH2 registry. 70 % of patients in the registry were treated with rFVIIa alone, which was observed in only 8% of our patients. The majority of our patients receive aPCC or alternating treatment between aPCC and rFVIIa. This selection preference for aPCC may be reflected by difference in the half life between the bypassing agents. In contrast to the EACH2 Registry, we did not observe a shorter time to treatment response, a reduction in relapse rate or an increase in duration of sustained remission with the addition of cyclophosphamide to prednisolone. Despite this, our study does concur with the EACH2 Registry that the final survival outcome was not affected by the choice of first line immunosuppression. Disclosures Luo: Grifols: Research Funding. Austin:Baxter: Speakers Bureau; Novonordisk: Honoraria, Speakers Bureau. Hart:Baxter: Speakers Bureau; Octapharma: Research Funding, Speakers Bureau; Novo Nordisk: Speakers Bureau; Pfizer: Speakers Bureau. Batty:Octapharma: Research Funding.

A szerzett haemophilia A sikeres kezelése

2021 ◽  
Vol 162 (49) ◽  
pp. 1977-1981
Keyword(s):  
Partial Thromboplastin Time ◽  
Early Recognition ◽  
Coagulation Factor ◽  
Autoimmune Disorder ◽  
Severe Anaemia ◽  
Rapid Diagnosis ◽  
Activated Partial Thromboplastin Time ◽  
Haemophilia A ◽  
Adequate Treatment ◽  
Acquired Haemophilia

Összefoglaló. A szerzett haemophilia A ritka autoimmun betegség, melyben gátlótest képződik a VIII. véralvadási faktor ellen. Az inhibitor véralvadásra gyakorolt hatása súlyos, életet veszélyeztető vérzéses állapotot idéz elő. A beteg élete a gyors diagnózison múlik: a jellemző klinikai kép mellett a megnyúlt, normálplazmával nem korrigálható aktivált parciális tromboplasztinidő megléte esetén a kórkép alapos gyanúja merül fel. Egy súlyos vérszegénység miatt kórházunkba beutalt nőbeteg esetében a szerzett haemophilia A a felvételt követő napon már diagnosztizálásra került. A vérzés megszüntetésére aktivált protrombinkomplex-koncentrátumot alkalmaztunk, valamint immunszuppresszív terápiát vezettünk be. A kórkép korai felismerése és a megfelelő kezelés azonnali megkezdése a beteg gyógyulását eredményezte. Esetünkkel arra szeretnénk felhívni a figyelmet, hogy a szerzett haemophilia A gyors diagnózisa egyszerű, könnyen hozzáférhető véralvadási paraméter, az aktivált parciális tromboplasztinidő meghatározásán és nem korrigálható megnyúlásának felismerésén múlik. Orv Hetil. 2021; 162(49): 1977–1981. Summary. Acquired haemophilia A is a rare autoimmune disorder, in which antibodies are formed against coagulation factor VIII. The effect of the inhibitor on blood clotting results in severe, life-threatening bleeding diathesis. The patient’s life depends on the rapid diagnosis: besides the characteristic clinical presentation, a prolonged activated partial thromboplastin time, which is not corrigible with normal plasma, suggests the existence of the disorder. In the case of the female patient who was referred to our hospital due to severe anaemia, acquired haemophilia A was diagnosed rapidly, the day after her admission. We used activated prothrombin complex concentrate to stop the bleeding, and introduced immunosuppressive therapy. The early recognition of the disease and immediate initiation of adequate treatment resulted in the patient’s full recovery. With our case presentation, we would like to draw attention to the fact that the rapid diagnosis of acquired haemophilia A depends on the determination of a simple, easily accessible coagulation parameter, the activated partial thromboplastin time and on the immediate recognition of its incorrigible prolongation. Orv Hetil. 2021; 162(49): 1977–1981.

Critical Bleeding in Acquired Hemophilia A: Bypassing Agents or Recombinant Porcine Factor VIII?

2020 ◽  
Author(s):  
Andreas Tiede
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viia ◽  
Indirect Evidence ◽  
Coagulation Factor ◽  
Similar Efficacy ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Activated Prothrombin Complex Concentrate ◽  
Bypassing Agents

AbstractAcquired hemophilia A (AHA) is caused by autoantibodies neutralizing coagulation factor VIII (FVIII). In the presence of inhibitors against FVIII, acute bleeds can be managed with bypassing agents, including recombinant factor VIIa (eptacog alfa activated, NovoSeven) and activated prothrombin complex concentrate (FEIBA), as well as recombinant porcine FVIII (susoctocog alfa, Obizur). Studies comparing these agents directly are not available, and indirect evidence suggests an overall similar efficacy. Selecting an agent in clinical practice therefore depends on (1) availability of agent, (2) safety profile, (3) monitoring requirements, (4) cost, and (5) personal experience. This review examines available data and collects additional considerations to support decision making for bleeding emergencies in AHA.

scholarly journals Dental considerations in a patient with haemophilia

2016 ◽  
Vol 3 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Chandra Khyati ◽  
Mavinakote Gowda Triveni ◽  
Rini Gopal ◽  
Ab. Tarunkumar ◽  
Suresh Hanagavadi ◽  
...  
Keyword(s):  
Factor Viii ◽  
Dental Care ◽  
Coagulation Factor ◽  
Bleeding Risk ◽  
Factor Ix ◽  
Haemophilia A ◽  
Haemophilia B ◽  
Characteristic Features ◽  
Limited Health ◽  
Treatment Procedures

Abstract Haemophilia is a rare blood clotting disorder, characteristic features of which include extemporaneous and post-traumatic subcutaneous bleeding and mucosal haemorrhages. Genetic deficiency of coagulation factor VIII results in haemophilia A, while deficiency of factor IX leads to haemophilia B. The most common treatment for haemophilia A is administration of recombinant or plasma-derived factor VIII concentrate, to raise the levels of the deficient factor VIII. Tranexamic acid is also used as an anti-fibrinolytic agent that inhibits plasminogen activators present in oral secretion and stabilises the clot. Administration of factor IX is required in haemophilia B. Treatment leads to increased longevity and quality of life for patients. Dental conditions and treatments are more complicated and uncertain in patients with haemophilia due to bleeding risk, thus restorative dental care is of paramount importance for those with haemophilia. The fear of bleeding during treatment procedures is the primary cause of lack of proper dental care for people with haemophilia in countries with limited health care resources. This case report highlights the significance of clinical examination and investigation, and the importance of proper interaction between a haematologist and the periodontist for correct multidisciplinary and uneventful management of periodontal health of a patient with haemophilia.

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