Plasma-derived biological medicines used to promote haemostasis

2008 ◽  
Vol 99 (11) ◽  
pp. 851-862 ◽  
Author(s):  
John Freedman ◽  
John W. Semple ◽  
Frederick A. Ofosu
Keyword(s):  
Factor Viii ◽  
Safety Concern ◽  
Von Willebrand Disease ◽  
Factor Ix ◽  
Clotting Factor ◽  
Perioperative Bleeding ◽  
Haemostatic Agents ◽  
Reduction Strategies ◽  
Clinical Consequences ◽  
Von Willebrand

SummarySeveral biological medicines derived from human and animal plasmas can effectively improve haemostasis in individuals with inherited or acquired defects in haemostasis. Factor VIII and factor VIII/vWF and factor IX concentrates are used to treat haemophilia A, von Willebrand disease and hemophilia B respectively. Cryoprecipitates are used to treat hypofibrinogenemia and von Willebrand disease where desmopressin (DDAVP) is ineffective or when plasma-derived factor VIII/vWF concentrates are unavailable. Thrombin-containing topical haemostatic agents and fibrin sealants are used to control perioperative bleeding. Intravenous immunoglobulin has several uses, including management of patients with autoimmune thrombocytopenias and patients with acquired factor VIII deficiency. Similar to most protein- based biological medicines, all the above products can elicit some level of antibody response, with clinical consequences that vary from mild anaphylaxis to loss of product efficacy. An ongoing potential safety concern with any biological medicine derived from blood/plasma is transmission of blood-borne pathogens. This safety concern has lessened significantly in the past decade as a result of the institution of more effective pre- and post-donation screening that tests for potential pathogens, and institution of pathogen reduction strategies to which many plasma-derived biological medicines are now routinely subjected. This article considers the manufacture, standardization, clinical efficacy and adverse event profiles of the plasma-derived biological medicines currently used to promote haemostasis in patients with inherited or acquired functional defects in haemostasis. It also considers approaches employed to minimize infectivity of biological medicines derived from human and animal plasmas and to manage patients who develop antibodies (inhibitors) to clotting factor concentrate infusions.

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.

The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard
Keyword(s):  
Body Weight ◽  
Factor Viii ◽  
Factor Ix ◽  
Clotting Factor ◽  
Blood Ph ◽  
Order Of Magnitude ◽  
Dose Dependent ◽  
Generation Test ◽  
Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

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.

The D′ domain of von Willebrand factor requires the presence of the D3 domain for optimal factor VIII binding

2018 ◽  
Vol 475 (17) ◽  
pp. 2819-2830 ◽  
Author(s):  
Małgorzata A. Przeradzka ◽  
Henriet Meems ◽  
Carmen van der Zwaan ◽  
Eduard H.T.M. Ebberink ◽  
Maartje van den Biggelaar ◽  
...  
Keyword(s):  
Factor Viii ◽  
Binding Affinity ◽  
Von Willebrand Factor ◽  
Conformational Changes ◽  
Effective Interaction ◽  
Von Willebrand Disease ◽  
Binding Assays ◽  
Surface Plasmon Resonance Analysis ◽  
Von Willebrand ◽  
Willebrand Factor

The D′–D3 fragment of von Willebrand factor (VWF) can be divided into TIL′-E′-VWD3-C8_3-TIL3-E3 subdomains of which TIL′-E′-VWD3 comprises the main factor VIII (FVIII)-binding region. Yet, von Willebrand disease (VWD) Type 2 Normandy (2N) mutations, associated with impaired FVIII interaction, have been identified in C8_3-TIL3-E3. We now assessed the role of the VWF (sub)domains for FVIII binding using isolated D′, D3 and monomeric C-terminal subdomain truncation variants of D′–D3. Competitive binding assays and surface plasmon resonance analysis revealed that D′ requires the presence of D3 for effective interaction with FVIII. The isolated D3 domain, however, did not show any FVIII binding. Results indicated that the E3 subdomain is dispensable for FVIII binding. Subsequent deletion of the other subdomains from D3 resulted in a progressive decrease in FVIII-binding affinity. Chemical footprinting mass spectrometry suggested increased conformational changes at the N-terminal side of D3 upon subsequent subdomain deletions at the C-terminal side of the D3. A D′–D3 variant with a VWD type 2N mutation in VWD3 (D879N) or C8_3 (C1060R) also revealed conformational changes in D3, which were proportional to a decrease in FVIII-binding affinity. A D′–D3 variant with a putative VWD type 2N mutation in the E3 subdomain (C1225G) showed, however, normal binding. This implies that the designation VWD type 2N is incorrect for this variant. Results together imply that a structurally intact D3 in D′–D3 is indispensable for effective interaction between D′ and FVIII explaining why specific mutations in D3 can impair FVIII binding.

Clinical cases of using coagulation factor VIII with von Willebrand factor in parturient women with type III von Willebrand disease

2020 ◽  
Author(s):  
И.В. Куртов ◽  
Е.С. Фатенкова ◽  
Н.А. Юдина ◽  
А.М. Осадчук ◽  
И.Л. Давыдкин
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Coagulation Factor Viii ◽  
Vitro Fertilization ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Болезнь Виллебранда (БВ) может представлять определенные трудности у рожениц с данной патологией. Приведены 2 клинических примера использования у женщин с БВ фактора VIII свертывания крови с фактором Виллебранда, показана эффективность и безопасность их применения. У одной пациентки было также показано использование фактора свертывания крови VIII с фактором Виллебранда во время экстракорпорального оплодотворения. Von Willebrand disease presents a certain hemostatic problem among parturients. This article shows the effectiveness and safety of using coagulation factor VIII with von Willebrand factor for the prevention of bleeding in childbirth in 2 patients with type 3 von Willebrand disease. In one patient, the use of coagulation factor VIII with von Willebrand factor during in vitro fertilization was also shown.

The Most Prominent Hemophilia Clotting Factors in the Province of Nineveh

2021 ◽  
pp. 85-91
Author(s):  
Salih khudhair Abdullah ◽  
Asmaa Mohammed Khaleel ◽  
Khalid Satam Sultan
Keyword(s):  
Von Willebrand Disease ◽  
Clotting Factor ◽  
Recessive Mutation ◽  
Clotting Factors ◽  
Ibn Sina ◽  
Genetic History ◽  
Study Results ◽  
Different Types ◽  
Von Willebrand

Background: Hemophilia is a recessive mutation in X-linked chromosome. Hemophilia A is characterized by a deficiency of clotting factor F-VIII. Hemophilia B is characterized by a deficiency of clotting factor F-IX. Fibrin Stabilizer is a deficiency of F-XIII. Alexander's disease is a deficiency of clotting factor F-VII. Von Willebrand disease is a deficiency of clotting factor VWF. Afibrinogenemia is a deficiency of clotting factor F-I. Aim: This study amid to find out prevalence of deficiency clotting factors in Nineveh province. Methods: This research was conducted at Ibn-Sina Teaching Hospital. Staco special kits were used to determine factors under the study. Results: 365 out of 829 total patients have been detected deficiency in one or more of different types of factors. The most prevalence of deficiency factors in Nineveh are F-VIII, FIX and VWF. Infected males are more than females. The ages between 1-20 years and blood groups (A⁺, B⁺, and O⁺) are most prevalent. Conclusions: It is necessary to monitor patients during the initial disease, follow it up, and use effective treatment methods to limit the increased number of cases. Moreover, it is necessary to follow up on the family's genetic history to avoid new infections.

scholarly journals Selective absence of large forms of factor VIII/von Willebrand factor in acquired von Willebrand's syndrome. Response to transfusion

Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 600-606 ◽  
Author(s):  
D Meyer ◽  
D Frommel ◽  
MJ Larrieu ◽  
TS Zimmerman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Procoagulant Activity ◽  
Factor Viii Related Antigen ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

Abstract A previously healthy elderly man with mucocutaneous bleeding was found to have a benign monoclonal IgG gammapathy associated with criteria for severe von Willebrand disease (Factor VIII procoagulant activity, Factor-VIII-related antigen, and ristocetin cofactor activity, less than 10% of normal). Associated qualitative abnormalities of factor VIII/von Willebrand factor were demonstrated by radiocrossed immunoelectrophoresis and immunoradiometric assay. The late clinical onset and negative family history are in favor of an acquired form of vWD. The monoclonal gammapathy and abnormalities of factor VIII/von Willebrand factor have been stable over a 10-yr period. No inhibitor to Factor VIII procoagulant activity, ristocetin cofactor activity, or Factor-VIII-related antigen could be demonstrated. Following transfusion of cryoprecipitate (with a normal cross immunoelectrophoretic pattern), there was a rapid removal of the large forms of Factor.-VIII-related antigen, paralleled by a decay of ristocetin cofactor activity. The transfusion study of this patient with acquired von Willebrand disease type II (variant of von Willebrand disease) serves to emphasize the relationship between polydispersity of Factor VIII/von Willebrand Factor and functional heterogeneity.

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