scholarly journals Treatment of bleeding in a patient with immune coagulopathy (acquired haemophilia A)

2020 ◽  
pp. 75-76
Author(s):  
O.V. Stasyshyn ◽  
V.V. Krasivska
Keyword(s):  
Blood Loss ◽  
Immunosuppressive Therapy ◽  
Uterine Cavity ◽  
Factor Vii ◽  
Haemophilia A ◽  
Total Blood ◽  
Recombinant Activated Factor Vii ◽  
Excessive Bleeding ◽  
Transfusion Therapy ◽  
Acquired Haemophilia

Objective. We are representing the case of acquired haemophilia A and analyze the timeliness and adequacy of treatment. Materials and methods. The subject of the study was immune coagulopathy with a factor VIII (FVIII) inhibitor – acquired haemophilia A. Results and discussion. Female, 33 years old, pregnancy II, urgent delivery. There was excessive bleeding in the early postpartum period, hemostatic therapy was provided. She hospitalized three times with recurrences of uterine bleeding. Vacuum aspiration of the walls of the uterine cavity was performed twice. After the third recurrence, blood loss of 1200 ml and ineffectiveness of conservative treatment, laparotomy and extirpation of the uterus was performed. Despite intensive care, the bleeding continued, the patient was transferred to the regional clinical hospital, where she was diagnosed with DIC syndrome, stage III, severe anemia. Three relaparotomies were performed, the source of bleeding was not found, there was excessive bleeding from the operating field. The total blood loss was 24,447 ml. Intensive infusion-transfusion therapy was continued, which gave unstable hemostasis. The patient received 12,060 ml of fresh-frozen plasma (FFP), 15,130 ml of erythrocytes, 600 ml of albumin 10 %, 20 doses of cryoprecipitate (CP), 16,000 U of activated prothrombin complex (APCC), 8 mg of recombinant activated factor VII (rVIIa), 8,000 U of prothrombin complex (PC). 16.1 BU/ml of inhibitor FVIII, FVIII <1.0 %, activated partial thromboplastin time (APTT) – 146.1 s was detected on day 37. Within 30 days, blood loss was 10,608 ml; patient received 23,420 ml of FFP, 2,080 ml of erythrocytes, 17 mg of rVIIa, 19,000 U of APCC, 6000 U of PC, 61 dose of CP, 50,000 IU of FVIII. Immunosuppressive therapy (prednisolone 1-1.5 mg/kg/day) was started on day 67 and lasted for 12 months. Bleeding stopped completely 10 months after delivery, and after 14 months the inhibitor was not detected, factor levels and APTT returned to normal. Scheduled reconstructive surgery on the urinary tract was performed without the use of transfusion replacement therapy. Conclusions. Recurrent postpartum hemorrhage requires early diagnosis of coagulation factors inhibitors, which will ensure specific transfusion and immunosuppressive therapy, avoidance of serious consequences, including extirpation of the uterus and reduce the economic costs of treatment.

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.

Recombinant activated factor VII and tranexamic acid are haemostatically effective during major surgery in factor XI-deficient patients with inhibitor antibodies

2009 ◽  
Vol 102 (09) ◽  
pp. 487-492 ◽  
Author(s):  
Tami Livnat ◽  
Ilia Tamarin ◽  
Yoram Mor ◽  
Harry Winckler ◽  
Zeev Horowitz ◽  
...  
Keyword(s):  
Tranexamic Acid ◽  
Low Dose ◽  
Null Alleles ◽  
Factor Vii ◽  
Major Surgery ◽  
Haemophilia A ◽  
Factor Xi ◽  
Recombinant Activated Factor Vii ◽  
Excessive Bleeding ◽  
Activated Factor Vii

SummaryOne-third of patients with severe factor XI (FXI) deficiency caused by homozygosity for null alleles develop inhibitor antibodies following exposure to plasma. Haemostasis during surgery is achievable in such patients by recombinant activated factor VII (rFVIIa) at doses used in haemophilia A patients with an inhibitor to FVIII. However, thrombosis has occurred in three of 12 such patients. In this study we discerned whether low-dose rFVIIa would secure haemostasis and cause no thrombosis in patients with severe FXI deficiency and an inhibitor during surgery. In vitro, a very low concentration of rFVIIa (0.24 µg/ml) induced thrombin generation in FXI-deficient plasma quite similarly to 1.9 µg/ml (a concentration that is achieved in patients with haemophilia A and inhibitor after infusion of 80 µg/kg). Based on this finding, a protocol was designed for four patients with severe FXI deficiency and an inhibitor or immunoglobulin A deficiency who underwent five major surgical procedures. This included administration of tranexamic acid from two hours before surgery until seven to 14 days after, and single infusion of low-dose rFVIIa. No excessive bleeding or thrombosis were observed. In conclusion, a single low dose of rFVIIa and tranexamic acid secure normal haemostasis in patients with severe FXI deficiency who can not receive blood products.

scholarly journals Acquired haemophilia A in an elderly patient related to relapsed cervix carcinoma

2018 ◽  
Vol 5 (1) ◽  
pp. 143-146
Author(s):  
Fatos Dilan Atilla ◽  
Ahmet Alp Unat ◽  
Hale Bulbul ◽  
Murat Ulukus ◽  
Zuhal Demirci ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Total Abdominal Hysterectomy ◽  
Abdominal Hysterectomy ◽  
Factor Vii ◽  
High Dose ◽  
Haemophilia A ◽  
Cervix Carcinoma ◽  
Recombinant Activated Factor Vii ◽  
Acquired Haemophilia ◽  
Factor Assay

Abstract Acquired haemophilia A (AHA) is a rare, autoimmune disease, presenting as sudden haemorrhages without any personal or family history. Anti-factor VIII (FVIII) is the most commonly recognised autoantibody resulting in decreased factor activity. The aetiology and pathophysiology of these antibodies remains unclear. Approximately 50% of reported cases are idiopathic; the rest are associated with other conditions, mainly underlying malignancies, autoimmune diseases (eg rheumatoid arthritis (RA), systemic lupus erythematosus), drug administration and postpartum period. A 74-year-old woman presented to our institution with haematochezia and haematuria. She had a medical history of cervix carcinoma; total abdominal hysterectomy and bilateral salpingo-oophorectomy with postoperative chemoradiotherapy was performed in 2011. She had also been followed up for 20 years for deforming and severe RA, which was in low-disease activity with methotrexate and corticosteroid. Laboratory investigations for abnormal bleeding revealed prolongation of activated partial thromboplastin time (APTT). APTT prolongation was not corrected by 50:50 plasma mixing studies, and a confirmatory factor assay demonstrated FVIII deficiency (1.4 IU/dL; normal range 50-150 IU/dL). Positive FVIII antibodies on Bethesda testing confirmed a diagnosis of AHA. A rectosigmoid mass and fistula between rectum and bladder were discovered by computed tomography (CT). Bleeding was controlled with recombinant activated factor VII (rFVIIa) after two weeks. Eradication of the inhibitor was achieved with high-dose pulse methylprednisolone for two days and then 2mg/kg daily over four weeks.

scholarly journals Adaptation of recombinant activated factor VII in the treatment of acquired haemophilia A: Results from a prospective study (ACQUI-7) in France

2021 ◽  
Vol 2 ◽  
pp. 100021
Author(s):  
Benoît Guillet ◽  
Achille Aouba ◽  
Annie Borel-Derlon ◽  
Jeanne Yvonne Borg ◽  
Jean-François Schved ◽  
...  
Keyword(s):  
Prospective Study ◽  
Factor Vii ◽  
Haemophilia A ◽  
Recombinant Activated Factor Vii ◽  
Acquired Haemophilia ◽  
Activated Factor Vii ◽  
A Prospective Study

The Use of Recombinant Activated Factor VII for Controlling Bleeding in Pediatric Patients Undergoing Invasive Surgeries.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4011-4011
Author(s):  
Ampaiwan Chuansumrit ◽  
Sumate Teeraratkul ◽  
Sukasom Attanawanich ◽  
Pracha Nantnarumit ◽  
Suradej Hongeng ◽  
...  
Keyword(s):  
Blood Loss ◽  
Pediatric Patients ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Excessive Bleeding ◽  
Effective Response ◽  
Activated Factor Vii ◽  
Life Threatening ◽  
Group 2 ◽  
Group 1

Abstract Objective: Recombinant activated factor VII (rFVIIa) in controlling the pre-existing life-threatening bleeding and in preventing excessive bleeding among pediatric patients undergoing invasive surgeries, was evaluated. Methods: An open-label, prospective uncontrolled study of rFVIIa (Novo Nordisk A/S Bagvaerd, Denmark) was conducted between January 2000 to July 2004. A bolus injection of 40–100 μg/kg of rFVIIa as a single or repeated doses at 15–30 min was given until the bleeding significantly reduced, followed by 40 μg/kg at 4 h interval until the bleeding was completely ceased. The patients were divided into 2 groups. Group 1 consisted of 11 patients receiving rFVIIa for controlling pre-existing life-threatening bleeding unresponsive to conventional replacement therapy at pre-(n=1), intra-(n=1) and post-operation (n=9). The median blood loss was 2.2 ml/kg/min at the median duration of 3 h prior to rFVIIa administration. Group 2 consisted of 9 patients receiving rFVIIa for preventing excessive bleeding from invasive surgeries. The surgeries included exploratory laparotomy (n=5), surgery of cardiac (n=5), liver (n=4), brain (n=2) and lung (n=1), liver transplantation (n=1), orthopedic corrective surgery of scoliosis (n=1), and orbital translocation (n=1). Result: Two patients were the premature neonate of 1,120 and 675 g in the first 24 h of life and 17 were children with a median age of 5 years. One patient had two subsequent surgeries, 6 months apart. They had no pre-existing hemostatic disorders. Patients in group 1 were in the state of threatened shock to profound shock. Due to massive transfusion, they exhibited dilutional coagulopathy and thrombo-cytopenia. The treatment was considered effective response in 17 cases (17/20=85%), including 8 patients (8/11=72.7%) in group 1 and 9 patients (9/9=100%) in group 2. They had a complete cessation of bleeding with no recurrence. Ineffective responses were found in 3 patients (3/20=15%) in group 1. One patient exhibited massive pulmonary hemorrhage from complicated lobar pneumonia which was unresponsive to right lower lung lobectomy. The other two patients, whose bleeding temporarily slowed down, required the re-explorations revealing a tear at the right atrium and a leak at the hepatic anastomosis site respectively. Although the rFVIIa combined with adequate amounts of blood components were given, the median intra-operative blood loss among 4 patients in group 1 was 0.3 ml/kg/min which was significantly higher than that of group 2 (0.1 ml/kg/min) p=0.014. The median total dose of rFVIIa in group 2 (60 μg/kg) was significantly lower than that in group 1 (120 μg/kg) p=0.037. Ultimately, 2 patients died while all patients in group 2 survived. No clinical evidences of thrombo-embolic complication were observed. Conclusion: The rFVIIa seems to be effective in controlling life-threatening bleeding and in preventing excessive bleeding in a limited series of pediatric patients undergoing invasive surgeries. Further study is warranted.

scholarly journals Review of recombinant anti-haemophilic porcine sequence factor VIII in adults with acquired haemophilia A

2017 ◽  
Vol 8 (9) ◽  
pp. 263-272 ◽  
Author(s):  
Emma Fosbury ◽  
Anja Drebes ◽  
Anne Riddell ◽  
Pratima Chowdary
Keyword(s):  
Treatment Algorithm ◽  
Individual Variability ◽  
Response To Treatment ◽  
Factor Vii ◽  
Fixed Dose ◽  
Haemophilia A ◽  
Recombinant Activated Factor Vii ◽  
Acquired Haemophilia ◽  
Activated Factor Vii ◽  
Activated Prothrombin Complex Concentrates

Acquired haemophilia A (AHA) is a rare, serious bleeding disorder most often encountered in elderly patients. The mainstay of haemostatic management is with bypassing agents (BPAs) including recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCCs). Their major limitation is incomplete efficacy, potential risk for thrombosis and the lack of routine laboratory assays for monitoring treatment response. Plasma-derived porcine FVIII (pd-pFVIII, Hyate C®), first used in the 1950s for the management of congenital haemophilia, has sufficient sequence homology to be haemostatic in humans, but the lack of complete homology facilitates efficacy even in the presence of human allo- and autoantibodies against human FVIII (hFVIII). In a small phase II/III study, recombinant porcine FVIII (rpFVIII, Obizur®, OBI-1, susoctocog alfa) was shown to be safe and effective for the management of bleeding episodes in patients with AHA with anti-porcine FVIII (anti-pFVIII) antibody levels of 20 BU/ml or less. Treatment outcome was judged on clinical response and FVIII levels after an initial fixed dose of 200 IU/kg. The rise in FVIII levels showed considerable inter-individual variability and was significantly influenced by the presence of anti-pFVIII antibodies. Based on the baseline levels of anti-pFVIII antibodies and response to treatment, three potential patient groups were identifiable. In the first group, the absence of cross-reacting antibodies was associated with supra-therapeutic FVIII levels, fewer infusions and lower rpFVIII utilization per treatment episode. The second group had patients with low levels of cross-reacting anti-pFVIII antibodies (0.8–5 BU/ml) with near-normal response to rpFVIII. The last group had higher titres of anti-pFVIII antibody (10–30 BU/ml) associated with lower FVIII levels, more infusions and higher consumption of rpFVIII. We propose a new treatment algorithm for the haemostatic management of AHA that includes the potential first-line clinical use of rpFVIII that takes into account availability of anti-pFVIII antibody results, titre of anti-pFVIII antibodies and severity of bleeding episode.

The use of recombinant activated factor VII in patients with acquired haemophilia

Blood Reviews ◽  
2015 ◽  
Vol 29 ◽  
pp. S19-S25 ◽  
Author(s):  
Andreas Tiede ◽  
Kagehiro Amano ◽  
Alice Ma ◽  
Per Arkhammar ◽  
Soraya Benchikh el Fegoun ◽  
...  
Keyword(s):  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Acquired Haemophilia ◽  
Activated Factor Vii

Effect of Recombinant Activated Factor VII (rFVIIa) on Platelet and Clotting Systems in Healthy Volunteers.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4053-4053
Author(s):  
Don A. Gabriel ◽  
Brett E. Skolnick ◽  
Stephanie Seremetis ◽  
Philip Leese ◽  
David Mathews
Keyword(s):  
Healthy Volunteers ◽  
Ex Vivo ◽  
Clot Formation ◽  
Factor Vii ◽  
Maximal Effect ◽  
Ex Vivo Model ◽  
Recombinant Activated Factor Vii ◽  
Excessive Bleeding ◽  
Pre Treatment

Abstract The generation of thrombin is a critical step in clot formation and securing hemostasis. Inadequate thrombin generation may result in excessive bleeding, while uncontrolled thrombin production has the potential to induce thromboses. Recombinant FVIIa has been shown to control bleeding in hemophilia patients with inhibitors to coagulation factors VIII and IX, and several other clinical conditions in which life- and limb-threatening bleeding may occur. However, for non-hemophilia patients the dose and dosing regimen still require refinement. The use of ex-vivo assessment systems (Thromboelastograph assay, Hemodyne Hemostasis Analyzer) to generate an in vitro model of hemostasis may be useful to determine the effect of rFVIIa on the dynamics of clot formation, particularly in a patient population where clinical trials are difficult. A series of pilot studies were performed to establish an optimal punch biopsy location and biopsy size to create an effective bleeding site for further study. The current study (48 subjects consented for an IRB approved protocol) examined, in an ascending dose-escalation manner, the effect of an individual dose of rFVIIa on bleeding time, blood loss volume, coagulation parameters and coagulation status in healthy volunteers. All patients underwent three punch biopsies: the first (baseline biopsy) with no treatment, the second and third biopsy with either a low or high rFVIIa dose administered prior to biopsy. The treatment pair sequences were placebo/10, 10/20, 20/40, 40/80, 80/120, and 120/160 μg/kg. Blood samples were drawn 15 minutes pre-, 15 minutes post-, 1 hour and 5 hours post-biopsy to conduct ex-vivo assessments of hemostasis. The results indicate that overall there was a trend towards an increase in platelet contractile force and clot elastic modulus with an apparent maximal effect at 1 hour post-biopsy. At the higher doses this effect, although reduced, does not return to pre-treatment values by 5 hours post-biopsy. For the lower doses these values decreased to levels comparable to those at pre-treatment. These observations are consistent with the reports of a dose-related half-life of rFVIIa. These data imply that the administration of rFVIIa may have an effect in non-coagulopathic individuals. Although the heterogenity observed in this sample of patients may limit interpretations, it is proposed that this ex-vivo model with further refinements may be useful for evaluating the effects of future pro-hemostatic agents. Figure Figure

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