HUMAN AND PORCINE FVIII INHIBITOR RESPONSE FOLLOWING INFUSION OF HUMAN FVIII CONCENTRATE - MEASUREMENT USING AN AGAROSE GEL SYSTEM

1987 ◽  
Author(s):  
D J Perry ◽  
F G H Hill

Conventional methods for determining inhibitor levels in haemophiliacs are time consuming and labour intensive. The agarose gel technique of Jorquera et al. (1) has been modified and standardized to measure human and porcine inhibitors to VIII:C.26 samples from 12 haemophiliacs with inhibitors were analysed and in all cases antibody to human and porcine VIII:C was detected.Six haemophiliac patients with 'high responder-type' inhibitors were studied using stored plasma and the rise in antibody titres to both human and porcine VIII:C was determined sequentially during treatment with human FVIII concentrate.One patient (J. C.) had received a single treatment with porcine concentrate (Hyate:C) with no rise in porcine VIII:C.In 5 of 6 patients both porcine and human inhibitor titres rose but the porcine levels were less than the human. However, in the remaining high responder patient (I. I.) with previously mild haemophilia and no exposure to porcine FVIII, the rise in porcine antibody titre greatly exceeded that of human. This patient has continued to be treated with human FVIII concentrate during which time the human inhibitor titres have fallen more than the porcine.This method is simple to perform and has the advantage that both human and porcine inhibitor titres can be easily and quickly assessed so that the most appropriate therapy can be given.1. Jorquera JI, Carmona E, Aznar JA, Peiro A and Sanchez-Cuenca JM. (1985) A Standardized Method for Measuring Anti-FVIII:C Inhibitors in Haemophilia A by Coagulation Inhibition in Agarose Gel. Thromb. Haemostas. 54(2): 377-380.

2012 ◽  
Vol 32 (S 01) ◽  
pp. S48-S51 ◽  
Author(s):  
G. Marx ◽  
B. Lentz ◽  
C. Bokemeyer ◽  
F. Langer ◽  
K. Holstein

Summary Background Development of FVIII inhibitors represents a major challenge in patients with mild haemophilia A (HA), because they tend to occur at an older age and classical immune tolerance induction appears to be less effective. Case report A man (age: 60 years) with mild HA due to the missense mutation, Leu1929Arg, received a single dose of rFVIII at 35 IU/kg prior to routine colonoscopy, totalling 25 lifetime exposure days. Two months later, rFVIII was infused for a traumatic hip haematoma. However, FVIII recovery was inappropriate, and a FVIII inhibitor of 19 BU with type-2 kinetics was detected, resulting in FVIII:C of < 1%. Two weeks later, the patient experienced spontaneous iliopsoas bleeding. Parallel to bypassing therapy, we started single-agent immunosuppression with prednisolone at 1.5 mg/kg. FVIII : C “normalized” at 10.2% after four weeks. After five months, the inhibitor titre fell to < 0.4 BU with sustained remission after one year of follow-up. Conclusion In mild HA, FVIII inhibitors may share characteristic features with FVIII autoantibodies commonly observed in acquired HA. Therefore, immunosuppressive therapy alone could be successful at least in a subset of patients.


1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.


1994 ◽  
Vol 235 (5) ◽  
pp. 443-450 ◽  
Author(s):  
Ó. JENSSON ◽  
S. STENBJERG BERNVIL ◽  
S. JÖNSÖDTTIR ◽  
J. INGERSLEV

Haemophilia ◽  
2014 ◽  
Vol 20 (4) ◽  
pp. 550-558 ◽  
Author(s):  
M. Trossaert ◽  
A. Lienhart ◽  
C. Nougier ◽  
M. Fretigny ◽  
M. Sigaud ◽  
...  

Haemophilia ◽  
2017 ◽  
Vol 23 (5) ◽  
pp. e473-e474 ◽  
Author(s):  
M. S. Evans ◽  
M. E. Eyster

2004 ◽  
Vol 92 (08) ◽  
pp. 425-426 ◽  
Author(s):  
Jean-Louis Kerkhoffs ◽  
Douwe Atsma ◽  
Pranobe Oemrawsingh ◽  
Jeroen Eikenboom ◽  
Felix Van der Meer

Haemophilia ◽  
2019 ◽  
Vol 25 (6) ◽  
pp. 960-968 ◽  
Author(s):  
Lisette M. Schütte ◽  
Nils Rooij ◽  
Hendrika C. A. M. Hazendonk ◽  
Ron A. A. Mathôt ◽  
Reinier M. Hest ◽  
...  

2010 ◽  
Vol 30 (S 01) ◽  
pp. S172-S175 ◽  
Author(s):  
W. Miesbach ◽  
S. Krekeler ◽  
O. Dück ◽  
B. Llugaliu ◽  
G. Asmelash ◽  
...  

SummaryThe efficacy of DDAVP (1-deamino-8-D-argi-nine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29 ± 0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP.: Results, conclusion: Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.


Haemophilia ◽  
2020 ◽  
Author(s):  
Hongfei Kang ◽  
Jingjing Li ◽  
Shengmei Chen ◽  
Bai Li ◽  
Yin Feng ◽  
...  

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