scholarly journals Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e022719 ◽  
Author(s):  
Lisette M Schütte ◽  
Marjon H Cnossen ◽  
Reinier M van Hest ◽  
Mariette H E Driessens ◽  
Karin Fijnvandraat ◽  
...  
Keyword(s):  
Factor Viii ◽  
Combination Treatment ◽  
Bleeding Risk ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Registration Number ◽  
Concentrate Treatment ◽  
Factor Viii Concentrates ◽  
Von Willebrand

IntroductionHaemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysisIn the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and disseminationThe DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences.Trial registration numberNTR5383; Pre-results.

scholarly journals Influence of blood group, von Willebrand factor levels, and age on factor VIII levels in non‐severe haemophilia A

2020 ◽  
Vol 18 (5) ◽  
pp. 1081-1086
Author(s):  
Judit Rejtő ◽  
Oliver Königsbrügge ◽  
Ella Grilz ◽  
Stefanie Hofer ◽  
Lisa‐Marie Mauracher ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Dental management of patients with haemophilia in the era of recombinant treatments: increased efficacy and decreased clinical risk

2019 ◽  
Vol 12 (4) ◽  
pp. e227974
Author(s):  
Antonio Liras ◽  
Luis Romeu
Keyword(s):  
Factor Viii ◽  
Conventional Treatment ◽  
Coagulation Factors ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Optimal Result ◽  
Dental Management ◽  
Efficient Access

Haemophilia is a hereditary X-linked recessive disorder caused by a deficiency of either clotting factor VIII (haemophilia A) or IX (haemophilia B). Conventional treatment is currently based on the use of either plasma derived or recombinant coagulation factors. This paper reports on the case of a patient with severe haemophilia who presented with mesial decay and interproximal tartar build-up, for which extraction and scaling to remove tartar deposits were indicated. Following extraction, the usual haemostasis techniques were applied, and postoperative prophylactic antihaemophilic treatment was indicated for 2 or 3 days. The patient presented with moderate bleeding for a few minutes immediately after the procedure. Administration of factor VIII before surgery as well as the patient’s favourable pharmacokinetic response allowed for an optimal result. This treatment has afforded patients with haemophilia a better quality of life, and safe and efficient access to invasive surgical procedures.

Carrier Detection In Haemophilia A By Measurement Of Factor VIII Clotting Antigen (VIIICAg) And Factor VIII Related Antigen (VIIIRAg

1981 ◽  
Author(s):  
I R Peake ◽  
R G Newcombe ◽  
B L Davies ◽  
R A Furlong ◽  
C A Ludlam ◽  
...  
Keyword(s):  
Factor Viii ◽  
Laboratory Data ◽  
Carrier Detection ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Immunoradiometric Assay ◽  
Plasma Samples ◽  
Severe Haemophilia ◽  
Likelihood Ratios ◽  
Unequal Variance

In order to assess the value of measurement of VIIICAg in the detection of carriers of haemophilia A, plasma samples were obtained on three separate occasions from each of 23 obligate carriers of mild and severe haemophilia, and 26 normal females. At each visit each sample was divided into three and each aliquot was then assayed for VIIICAg (immunoradiometric assay), clotting factor VIII (VIIIC) (two stage assay) and VIIIRAg (Laurell immu noelectrophoresis). After calculating median values at each visit, and for the three visits, a comparison of the ratios VIIIC/VIIIRAg and VIIICAg/VIIIRAg was made. Likelihood ratios (of being a carrier) were calculated using an unequal variance predictive method for both ratios. These showed that laboratory data calculated on the median of the three-visit medians had greater discriminatory power than a single-visit median value. Using the median of three visits both VII IC/VIIIRAg and VIIICAg/VIIIRAg gave the same proportional misclassification of carriers as normals (4 of 23- 17%). However the ratios VII ICAg/VIIIRAg were more discriminatory due to the greater reproducibility between visits of VIIICAg results than those of VIIIC. There was no statistically significait difference between VII ICAg/VIIIRAg (or VII IC/VIIIRAg) ratios obtained from carriers of mild or severe haemophilia. The ratio VII ICAg/VIIIRAg was therefore shown to be the method of choice for carrier detection except theoretically in the rare CRM+ families.

Absence of Inhibitors in Previously Untreated Patients with Severe Haemophilia A after Exposure to a Single Intermediate Purity Factor VIII Product

1997 ◽  
Vol 78 (03) ◽  
pp. 1027-1029 ◽  
Author(s):  
T T Yee ◽  
M D Williams ◽  
F G H Hill ◽  
C A Lee ◽  
K J Pasi
Keyword(s):  
Factor Viii ◽  
High Purity ◽  
Specific Activity ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
True Incidence ◽  
Conventional Fractionation ◽  
Heat Treated ◽  
Recombinant Fviii ◽  
Von Willebrand

SummaryUse of high purity and recombinant factor VIII (FVIII) concentrates has been thought to be associated with an increased incidence of FVIII inhibitors in patients with severe haemophilia A. Comparison with comparable historical control groups has suggested that the true incidence of inhibitors in patients with severe haemophilia A was ~20-25%, similar to the incidence seen with new high purity and recombinant FVIII products.We have conducted a study of inhibitor development in a cohort of 37 boys with severe haemophilia A (VIII: C <2 u/dl) exposed only to a single FVIII concentrate (BPL 8Y) with no previous blood or blood product exposure. This factor VIII concentrate is an intermediate purity product with a specific activity of ~2 IU/mg protein and contains well preserved von Willebrand factor multimers. It is manufactured by conventional fractionation technologies and terminally dry heat treated at 80° C for 72 h.

scholarly journals The Effect of DDAVP Infusion on Thrombin Generation in Platelet-rich Plasma of von Willebrand Type 1 and in Mild Haemophilia A Patients

2000 ◽  
Vol 84 (10) ◽  
pp. 638-642 ◽  
Author(s):  
Irene Keularts ◽  
K. Hamulyak ◽  
H.C. Hemker ◽  
Suzette Béguin
Keyword(s):  
Factor Viii ◽  
Thrombin Generation ◽  
Platelet Rich Plasma ◽  
Von Willebrand Disease ◽  
Clotting Factor ◽  
Haemophilia A ◽  
The Individual ◽  
Von Willebrand ◽  
Mild Haemophilia

SummaryIn von Willebrand disease (vWD) type 1 and mild haemophilia A patients we studied the effect of an infusion of DDAVP (0.3 µg/kg body weight) on thrombin generation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Baseline thrombin generation in PRP was diminished both in the haemophilia A and vWD patients. It was normal in vWD plasma when sufficient procoagulant phospholipids were present, either via adding phospholipid vesicles to PPP or via scrambling of the platelet membrane with ionomycin in PRP. In haemophilia A plasma, thrombin generation did not normalize by providing procoagulant phospholipids. Treatment with DDAVP temporarily restored thrombin generation in PRP to normal in both diseases.To investigate the individual roles of von Willebrand factor (vWF) and factor VIII, we also studied the effect of factor VIII infusion on thrombin generation in a severe haemophilia patient. It appears that at a fixed normal vWF concentration, <25% factor VIII is sufficient for normal thrombin generation in PRP. At a sufficient factor VIII concentration, however, thrombin generation is still lower than normal in vWD patients; ∼40% of vWF is required for half-normal thrombin generation in PRP.It thus appears that vWF is also a clotting factor, in the sense that it is required for normal thrombin generation. This underlines the importance of the interaction between coagulation and the platelets in normal haemostasis. Thrombin generation in PRP appears to be a suitable test to reflect the combined function.

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