Consecutive complex percutaneous coronary interventions using emicizumab and recombinant activated factor VII in a patient with severe haemophilia A and high‐titre inhibitor

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.

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Home treatment of haemarthrosis with recombinant activated factor VII in patients with haemophilia A or B and inhibitors

Blood Coagulation & Fibrinolysis ◽

10.1097/mbc.0000000000000564 ◽

2016 ◽

pp. 1

Author(s):

Meriem Bensadok ◽

Abdulkareem Almomen ◽

Azzam Alzoebie ◽

Soraya Benchikh el Fegoun ◽

Yasser Wali ◽

...

Keyword(s):

Home Treatment ◽

Factor Vii ◽

Haemophilia A ◽

Recombinant Activated Factor Vii ◽

Activated Factor Vii

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Successful management of Mallory-Weiss syndrome in a haemophilia A patient with inhibitor by recombinant activated factor VII

Haemophilia ◽

10.1111/j.1365-2516.2008.01752.x ◽

2008 ◽

Vol 14 (4) ◽

pp. 841-843 ◽

Cited By ~ 1

Author(s):

Y. UCHIDA ◽

Y. SAKURAI ◽

K. OGIWARA ◽

T. CHIYONOBU ◽

B. HIGUCHI ◽

...

Keyword(s):

Factor Vii ◽

Haemophilia A ◽

Successful Management ◽

Recombinant Activated Factor Vii ◽

Activated Factor Vii

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

Thrombosis and Haemostasis ◽

10.1160/th09-03-0172 ◽

2009 ◽

Vol 102 (09) ◽

pp. 487-492 ◽

Cited By ~ 45

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.

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Intra-patient variability of thromboelastographic parameters following in vivo and ex vivo administration of recombinant activated factor VII in haemophilia patients. A multi-centre, randomised trial

Thrombosis and Haemostasis ◽

10.1160/th09-04-0212 ◽

2010 ◽

Vol 103 (02) ◽

pp. 351-359 ◽

Cited By ~ 27

Author(s):

Gili Kenet ◽

Camilla Stenmo ◽

Allan Blemings ◽

Wolfgang Wegert ◽

Jenny Goudemand ◽

...

Keyword(s):

Ex Vivo ◽

Randomised Trial ◽

Factor Vii ◽

Haemophilia A ◽

Strong Positive Correlation ◽

Post Dose ◽

Recombinant Activated Factor Vii ◽

Activated Factor Vii ◽

Rfviia Administration

SummaryThromboelastography methods have been used to predict or monitor treatment of haemophilia patients with recombinant activated factor VII (rFVIIa). However, neither of the two thromboelastographic methods (ROTEM and TEG) has as yet been validated. This multi-centre, randomised trial compared both methods in terms of intra- and inter-patient variability following in vivo and ex vivo rFVIIa administration to haemophilia A and B patients with and without inhibitors. Patients (≥16 years old) received the same intravenous rFVIIa dose (45, 90 or 180 μg/kg) twice, 1–12 weeks apart. Blood samples were collected pre-dose and 15, 60, 120 and 240 minutes post-dose for ROTEM and TEG analysis. Pre-dose samples were also spiked ex vivo with rFVIIa (0.6, 1.2 or 2.4 μg/ml), to correspond to the three in vivo doses. Twenty-six haemophilia A and four haemophilia B patients were enrolled. A significant treatment effect was observed with in vivo rFVIIa (p<0.05) with more pronounced effects in inhibitor (n=14) versus non-inhibitor (n=16) patients. There was a strong positive correlation between ROTEM and TEG parameters. Intra- and inter-patient variation was large for all thromboelastography parameters at all time points and rFVIIa doses. Intra-patient variation was generally lower for non-inhibitor than inhibitor patients, and lower following ex vivo spiking versus in vivo rFVIIa administration. In conclusion, there was a clear effect of rFVIIa on all thromboelastography parameters, but the large intra- and inter-patient variability following in vivo rFVIIa administration renders the use of our method unsuitable for dose-response prediction for haemophilia patients in the clinical setting.

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The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

Thrombosis and Haemostasis ◽

10.1160/th07-04-0301 ◽

2007 ◽

Vol 98 (12) ◽

pp. 1323-1328 ◽

Cited By ~ 6

Author(s):

Douwe Pons ◽

Pascalle Monraats ◽

Moniek de Maat ◽

Nuno Pires ◽

Paul Quax ◽

...

Keyword(s):

Thrombus Formation ◽

Factor V Leiden ◽

Factor Vii ◽

Factor V ◽

Percutaneous Coronary Interventions ◽

Coronary Interventions ◽

Increased Risk ◽

Percutaneous Coronary ◽

Prospective Study Design ◽

Pai 1

SummarySince activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to play a role in the haemostatic system and the risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER) study,a multicenter prospective study design that enrolled 3,104 consecutive patients after successful PCI. Target vessel revascularization (TVR) was the primary endpoint. All patients were genotyped for six polymorphisms in the Factor II, Factor V, Factor VII and PAI-1 genes. The PAI-1 4G variant was associated with an increased risk ofTVR. When compared to 5G/5G homozygotes, heterozygous patients were at higher risk for TVR (HR: 1.46, 95%CI: 1.05–2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95%CI: 1.19–2.41). In contrast, the factor V 506Gln (factor V Leiden) amino acid substitution was associated with a decreased risk of TVR (HR: 0.41, 95%CI: 0.19–0.86). Our findings indicate that polymorphisms in the factorV and PAI-1 genes may play a role in the process of restenosis.

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