scholarly journals Bleeding in Patients with Antiphospholipid Antibodies

2021 ◽  
Author(s):  
Peter Kubisz ◽  
Pavol Holly ◽  
Jan Stasko
Keyword(s):  
Antiphospholipid Antibodies ◽  
Antithrombotic Therapy ◽  
Neutralizing Antibodies ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Anticardiolipin Antibodies ◽  
Clinical Severity ◽  
Common Finding ◽  
Bleeding Complications ◽  
Membrane Glycoproteins

The antiphospholipid antibodies (aPL) are commonly associated with thrombotic events and obstetric complications. However, apart from the bleeding complications of antithrombotic therapy, the acquired coagulopathy caused by the aPL, particularly by lupus anticoagulant and anticardiolipin antibodies, might be occasionally manifested as a hemorrhagic syndrome with various clinical severity. Bleeding symptoms vary from mild (mucocutaneous) up to life-threatening (gastrointestinal, intracranial). The bleeding may be the first manifestation of aPL or appear concomitantly with thrombosis. The underlying hemostatic changes include thrombocytopenia, platelet function disorders, and coagulation factor inhibitors or deficiencies, namely prothrombin, FVII, FVIII, FX, and FXI. Thrombocytopenia is the most common finding, seen in up to 53% of patients with aPL, although it is usually mild to moderate and associated with significant bleeding only in a minority of cases. Of interest, patients with severe thrombocytopenia appear to be less likely to suffer from thrombotic events. The involved pathophysiological mechanisms are heterogeneous. Non-neutralizing antibodies against coagulation factors resulting in increased clearance, specific antibodies against platelet membrane glycoproteins, increasing platelet activation and aggregation with subsequent consumption, and immune-mediated platelet clearance are among those identified. Immunosuppression, preferably with corticosteroids, represents the first-choice therapeutic approach. Plasmapheresis is efficient in the case of catastrophic antiphospholipid syndrome. Antithrombotic therapy can be challenging, but its administration should continue as much as possible.

Antiphosplipid Antibodies and Thrombosis in Cancer Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5071-5071
Author(s):  
Ahmad Jajeh
Keyword(s):  
Antiphospholipid Antibodies ◽  
Conflicts Of Interest ◽  
Anticoagulation Therapy ◽  
Coagulation Factors ◽  
Elisa Test ◽  
Anticardiolipin Antibodies ◽  
Human Virus ◽  
Factors Affecting ◽  
Vein Thrombosis ◽  
The Impact

Abstract 5071 Antiphospholipid antibodies,Abs are common in hospitalized patients,particularly with cancer and acquired human virus immunodeficieny HIV/AIDS. The role of antiphospholipid antibodies in deep vein thrombosis DVT, pulmonary embolism PE and thrombocytopenia is underestimated in clinical practice. The matter is also complicated by many other confounding factors affecting the interpretation of the result for lupus anticoagulant LAC; a coagulation/qualitative test and ELISA test for anticardiolipin antibodies(quantitative). Anticoagulation therapy, presence of antithrombin antibodies, coagulation factors deficiency, the lag time between collection of blood and testing, reagent used and the dilution are all contributing to the accuracy of results. In this study all patients with cancer and thrombosis, thrombocytopenia with coagulopathy not related to coumadin or disseminated intravascular coagulopathy or coagulation factors deficiency were tested for antiphospholipid antibodies. A total of three hundred patients over a year period were randomly selected. All patients were consulted for hematological evaluation. Fifty patients had thrombotic events. this include DVT with or without PE. Eighty percent had cancer. Twenty percent had other problems including HIV infection or AIDS. Female:male ratio is 1:1. Fifty percent were LAC positive with moderately to high titers for phospholipid antibodies. Thirty percent were LAC borderline with discordant results for ELISA anticardiolipin antibodies IgG and IgM. All patients had negative workup for other hypercoagulability panel. This study was done at a single institution with limited internal bias regarding ordering physician. In conclusion: This study indicates the impact of antiphospholipid antibodies in the pathophysiology of thrombosis. Larger prospective multicenter trials needed to confirm this fact. Disclosures No relevant conflicts of interest to declare.

scholarly journals Validation of the Relationship Between Coagulopathy and Localization of Hydroxyethyl Starch on the Vascular Endothelium in a Rat Hemodilution Model

2021 ◽  
Author(s):  
Ryu Azumaguchi ◽  
Yasuyuki Tokinaga ◽  
Satoshi Kazuma ◽  
Motonobu Kimizuka ◽  
Kosuke Hamada ◽  
...  
Keyword(s):  
Hydroxyethyl Starch ◽  
Von Willebrand Factor ◽  
Shear Viscosity ◽  
Formation Rate ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
High Shear ◽  
Membrane Glycoproteins ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract BackgroundVarious anticoagulant properties have been associated with hydroxyethyl starch (HES), including coagulation disorders measured by point-of-care devices, decreases in von Willebrand factor and coagulation factor VIII, and inhibition of the interactions between platelet-membrane glycoproteins and of coagulation factors by coating of platelets. However, the mechanism for these properties remains unclear. The aim of this study was to test the hypothesis that coagulopathy induced by HES is caused by endothelial or glycocalyx damage as a result of localization of HES on the endothelium, due to the high shear viscosity of blood, using a rat model.MethodsWe compared blood coagulability measured by Sonoclot®, levels of endothelial and glycocalyx damage markers and coagulation factors, and blood shear viscosity when hemodilution was performed with physiological saline (PS), 6% HES 130/0.4 in PS (HES130) and 10% HES 200/0.5 in PS (HES200). To precisely evaluate the basic mechanism of coagulopathy induced by HES, we performed hemodilution with an emphasis on dilutional equality by taking into consideration the intravascular residual rates of the infusion preparations. We also evaluated the localization rates of fluorescently labeled HES on endothelium in the isolated aorta. Statistical analyses were performed by one-way ANOVA followed by Tukey’s test or Kruskal–Wallis test, and then Dunn’s test for multiple comparisons.ResultsSonoclot® measurements revealed that HES130 and HES200 decreased the fibrin gel formation rate to a greater extent than PS, and HES200 decreased the rate more than HES130. Similarly, HES130 and HES200 decreased von Willebrand factor levels to a greater extent than PS. HES130 and HES200 had a more protective effect than PS, with no evidence of damage to the endothelium or glycocalyx. Shear viscosity was variable between all pairs, and was lowest for PS and highest for HES200. HES130 and HES200 demonstrated comparable degrees of localization on the endothelium.ConclusionsHES was shown to cover the endothelium, possibly due to its high shear viscosity, and this mechanism potentially acted to protect the endothelium and glycocalyx. However, this covering effect may be the cause of coagulopathy due to inhibition of von Willebrand factor secretion from the endothelium.

scholarly journals Thromboelastography in the Characterization of Coagulation Status in Antiphospholipid Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4983-4983 ◽  
Author(s):  
Natalie H Wallace ◽  
Anne Dumont ◽  
Adrienne Burns ◽  
Tormey A Christopher ◽  
Henry M Rinder ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Conflicts Of Interest ◽  
Trauma Surgery ◽  
Anticardiolipin Antibodies ◽  
Bleeding Complications ◽  
Blood Collection ◽  
Transfusion Therapy ◽  
Beta 2

Abstract INTRODUCTION/ BACKGROUND Antiphospholipid syndrome (APS) is an immunologic disorder characterized by thrombotic or obstetrical complications and persistent positivity of anticardiolipin antibodies, lupus anticoagulant, or beta-2 glycoprotein-1 antibodies. Bleeding complications in APS may sometimes occur, in the form of adrenal hemorrhage, immune thrombocytopenia (ITP), or, rarely, the lupus anticoagulant-hypoprothrombinemia syndrome (LAHS). Traditional laboratory markers of coagulation are not reliable in evaluating thrombotic or hemorrhagic risk in APS due to baseline prolongation of the prothrombin time (PT) and/or partial thromboplastin time (PTT). Thromboelastography (TEG) is a global assay of hemostasis that has been utilized in trauma surgery, emergency medicine, and chronic liver disease to identify specific coagulation defects and guide transfusion therapy. We sought to explore the role of TEG in evaluation of APS. METHODS TEG was performed on whole blood obtained from 10 patients with APS (n = 6), catastrophic APS (CAPS; n = 3), or antiphospholipid antibodies without thrombosis (n = 1). Chronic aspirin (ASA) was used as monotherapy in 2 patients; 8 were on either warfarin or enoxaparin (some in combination with ASA). Immunomodulatory treatments included hydroxychloroquine, mycophenolate, azathioprine, monthly IVIG, rituximab, or eculizumab. Prior to blood collection, patients were instructed to hold ASA for 7 days, warfarin for 5 days, or enoxaparin for 2 days, as appropriate. For patients on enoxaparin in whom cessation of anticoagulation was not feasible, heparinase was added to samples for TEG measurements. The following data was compiled for each patient: baseline PTT; lupus anticoagulant, anticardiolipin IgG and IgM, and beta-2 glycoprotein-1 IgG and IgM titers; and thrombotic, hemorrhagic, and obstetrical events. RESULTS Baseline PTT was prolonged in most patients. TEG values were within or near the normal range in almost all cases, with no consistent differences among patients with thrombotic or obstetrical APS, CAPS, or antiphospholipid antibodies without thrombosis. R time (a measure of clot initiation) was mildly prolonged in 3 cases and minimally reduced in 1. One patient with lupus, ITP, arterial and venous thrombosis, and multiple miscarriages showed minor prolongation of K time (a measure of time to maximum clot amplification) and a slight decrease in ▢ angle (a measure of thrombin burst). LY30 (a measure of fibrinolysis) was normal in all cases. One patient with LAHS and severe hemorrhagic complications had marked prolongation of R and K times and marked reduction of ▢ angle and MA (a measure of clot tensile strength), consistent with a strong bleeding phenotype. CONCLUSIONS Despite abnormal baseline coagulation studies, APS patients generally do not demonstrate a major bleeding propensity in global hemostasis assays. TEG may have potential utility in identifying APS patients with bleeding due to LAHS. Disclosures No relevant conflicts of interest to declare.

PAICA: A Method for Characterizing Platelet-Associated Antibodies - Its Application to the Study of Idiopathic Thrombocytopenic Purpura and to the Detection of Platelet-bound c7E3

1996 ◽  
Vol 76 (06) ◽  
pp. 1020-1029 ◽  
Author(s):  
Laurent Macchi ◽  
Gisèle Clofent-Sanchez ◽  
Gérald Marit ◽  
Claude Bihour ◽  
Catherine Durrieu-Jais ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Antithrombotic Therapy ◽  
Membrane Glycoproteins ◽  
Serum Antibodies ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Capture Assay ◽  
Specific Membrane

SummaryIn idiopathic thrombocytopenic purpura (ITP), autoantibodies reacting with antigens on the platelet membrane bring about accelerated platelet destruction. We now report PAICA (“Platelet-Associated IgG Characterization Assay”), a method for detecting autoantibodies bound to specific membrane glycoproteins in total platelet lysates. This monoclonal antibody (MAb) capture assay takes into account the fact that antibodies on circulating platelets may be translocated to internal pools as well as being on the surface. A total of twenty ITP patients were examined by PAICA, and the results compared with those obtained by measuring (i) serum antibodies bound to paraformaldehyde-fixed control platelets by ELISA, (ii) IgG bound to the surface of the patient’s own platelets by flow cytometry (PSIgG), (iii) total platelet-associated IgG (PAIgG) by ELISA and (iv) serum antibodies reacting with control platelets by MAIPA (“Monoclonal Antibody-specific Immobilization of Platelet Antigens”). Of twelve patients with elevated PAIgG, nine had increased PSIgG yet eleven reacted positively in PAICA. Of these, eight possessed antibodies directed against GP Ilb-IIIa, two against GP Ib-IX and one patient possessed antibodies directed against GP Ilb-IIIa and GP Ia-IIa respectively. Only seven of the patients possessed serum antibodies detectable by MAIPA. PAICA was also able to detect platelet-associated c7E3 (the chimeric form of Fab fragments of the MAb 7E3) following its infusion during antithrombotic therapy, when it proved more sensitive over a seven-day period than a MAIPA assay adapted for assessing surface-bound antibody. We propose that PAICA provides added sensitivity to the detection of platelet-associated antibodies in immune thrombocytopenias or following therapy with humanized MAbs.

scholarly journals FRI0154 SHOULD BE OLDER PATIENTS TESTED FOR ANTIPHOSPHOLIPID ANTIBODIES? 695 CASES FROM THE RETROSPECTIVE SERIES HIBISCUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 661.2-661
Author(s):  
C. Belizna ◽  
O. Latino ◽  
L. Stojanovich ◽  
P. Saulnier ◽  
K. Devreese ◽  
...  
Keyword(s):  
Relapse Rate ◽  
Antiphospholipid Antibodies ◽  
Older Patients ◽  
Clinical Laboratory ◽  
Late Onset ◽  
Recurrent Stroke ◽  
Therapeutic Option ◽  
International Study ◽  
Anticardiolipin Antibodies ◽  
Male Predominance

Background:Although guidelines do not recommend antiphospholipid antibodies testing after 60 yo, recent data reported late onset antiphospholipid syndrome (APS).Objectives:To comparatively analyse the clinical, laboratory features and outcomes in 695 cases with primary APS between patients older and younger than 70 yo.Methods:we have performed an international study within the framework of the International Registry of primary APS patients treated with Hydroxychloroquine, HIBISCUS (an ongoing retrospective and prospective register launched in 2016). 28 centres from 17 countries participate. Data about late onset APS were analysed in 695 patients and were obtained from a standardized form registered in the database containing 66 items with respect to demographics, clinical and biological features.Results:Arterial events and especially stroke represented the main initial and recurrent clinical manifestation in 40 primary APS patients older than 70 yo. There were not statistically significant differences with respect to cardiovascular risk factors between the two groups of patients. A significant male predominance, a familial APS history, a higher prevalence of triple positivity, lower complement levels, and anticardiolipin antibodies (aCL) IgA isotype were found in older patients. Low anticoagulation regimens were safe and efficient, with a low relapse rate in older patients.Conclusion:we suggest that the detection of aPL antibodies should be included into the initial screening panel tests in elderly with thrombotic events, especially arterial, in particular those with recurrent stroke and familial APS.Our study further suggests that lower intensity anticoagulation regimens could be a therapeutic option in older APS patients, as no differences in outcomes and relapse rate were found between patients with high and low intensity anticoagulation regimens.References:[1]Grimaud F et al. Rheumatology. 2019;58:1006-10.[2]Goldman-Mazur S et al. Thromb Res. 2019;176:67-73.[3]Hirmerova J et al. 2017;36:167-73.Disclosure of Interests:Cristina Belizna: None declared, Omar Latino: None declared, Ljudmila Stojanovich: None declared, Patrick Saulnier: None declared, Katrien Devreese: None declared, Sebastien Udry: None declared, Natasa Stanisavljevic: None declared, Aleksandra Djokovic Speakers bureau: KRKA, Astra Zeneca, Actavis, Jaume Alijotas-Reig: None declared, Enrique Esteve-Valverde: None declared, Raquel Ferrer-Oliveras: None declared, Angela Tincani: None declared, Laura Andreoli: None declared, Francesca Regola: None declared, Maarten Limper: None declared, Alexander Makatsariya: None declared, Jamilya Khizroeva: None declared, Viktoria Bitsadze: None declared, Cecilia Chighizola: None declared, Francesca Pregnolato: None declared, Maria Orietta Borghi: None declared, Pier Luigi Meroni: None declared

scholarly journals Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Fluorescent Protein ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Coagulation Factor Viii ◽  
Liver Sinusoidal Endothelial Cells ◽  
Genetically Engineered Mice

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.

EXPRESSION IN ONTOGENESIS OF HUMAN BLOOD COAGULATION FACTORS

1987 ◽  
Author(s):  
H J Hassan ◽  
A Leonardi ◽  
C Chelucci ◽  
R Guerriero ◽  
P M Mannucci ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Protein C ◽  
Antithrombin Iii ◽  
Liver Homogenate ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Adult Liver ◽  
Blood Coagulation Factors ◽  
Guanidine Isothiocyanate

We have analyzed the expression of several blood coagulation factors (IX, VIII, X, fibrinogen chains) and inhibitors (antithrombin III, protein C) in human embryonic and fetal livers, obtained from legal abortions at 6-11 week post-conception. The age was established by morphologic staging and particularly crown-rump lenght measurement.Total cellular RNA was isolated from partially purified hepatocytes or total liver homogenate using the guanidine isothiocyanate method. Poly(A)+ RNA was selected by oligodT cellulose chromatography. The size and the number of the embryonic and fetal transcripts are equivalent to those observed in adult liver, as evaluated by Northern blot analysis of total or poly(A)+ RNA hybridized to human cDNA probes.The level of coagulation factor transcripts in embryonic and fetal liver was evaluated by dot hybridization of total RNA (0.5-10 ug), as compared to RNA extracted from normal adult liver biopsies. The expression of blood coagulation factors in embryos is generally reduced for all factors, but at a different degree. In 5-11 wk liver, the level of factor IX is 5-10% of that observed in adults, while fibrinogen, protein C, antithrombin III RNA level rises from 25 to 50% and factor X is expressed at a level comparable to that observed in adult liver.We conclude that during these stages of development blood coagulation factors are expressed according to three different time, curves, possibly due to the effect of different types of regulatory mechanisms.

scholarly journals Antiphospholipid Antibodies in Sickle Cell Disease: A Systematic Review and Exploratory Meta-Analysis

2021 ◽  
Vol 27 ◽  
pp. 107602962110029
Author(s):  
Mira Merashli ◽  
Alessia Arcaro ◽  
Maria Graf ◽  
Matilde Caruso ◽  
Paul R. J. Ames ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Antiphospholipid Antibodies ◽  
Meta Analysis ◽  
Age Groups ◽  
Anticardiolipin Antibodies ◽  
Cell Disease ◽  
Pooled Prevalence ◽  
The Relationship

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.

scholarly journals Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 516
Author(s):  
Shuyi Yang ◽  
Keith R. Jerome ◽  
Alexander L. Greninger ◽  
Joshua T. Schiffer ◽  
Ashish Goyal
Keyword(s):  
Production Rate ◽  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Natural Infection ◽  
Viral Clearance ◽  
Clinical Severity ◽  
Igg Antibodies ◽  
Igm Antibodies ◽  
Specific Igg ◽  
Specific Igg Antibodies

While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.

Development of neutralizing antibodies in application of various concentrates of blood coagulation factor VIII in the treatment of hemophilia A

2021 ◽  
Author(s):  
Н.И. Зозуля
Keyword(s):  
Factor Viii ◽  
Cell Line ◽  
Neutralizing Antibodies ◽  
Hemophilia A ◽  
Chinese Hamster ◽  
Coagulation Factor ◽  
Human Cell Line ◽  
Chinese Hamster Cell ◽  
Coagulation Factor Viii ◽  
Recombinant Fviii

Серьезным осложнением, связанным с лечением гемофилии А, является развитие ингибиторов. В последние годы был проведён ряд исследований, посвящённых данной проблеме: RODIN, INSIGHT, FranceCoag, SIPPET и NuProtect. В данном обзоре суммируются основные результаты этих исследований. Согласно результатам рандомизированного исследования SIPPET, препараты плазматического фактора свертывания крови VIII (FVIII) обладают меньшей иммуногенностью, чем препараты рекомбинантного FVIII, синтезированного из клеточной линии китайских хомячков, что следует учитывать при выборе стратегии лечения. Согласно результатам исследования NuProtect, опубликованным в 2019 г., концентрат рекомбинантного FVIII, полученный из клеточной линии человека, демонстрирует профиль иммуногенности, сходный с таковым у препаратов плазматического FVIII. У ранее нелеченых пациентов с ненулевыми мутациями при применении симоктоког альфа не наблюдалось образования ингибиторов, также как и в случае применения препаратов плазматического FVIII в исследовании SIPPET. Inhibitor development is a serious complication associated with hemophilia A therapy. A number of studies have been carried out of this issue — RODIN, INSIGHT, FranceCoag, SIPPET, and NuProtect. This review summarizes the main results of these studies. According to the results of the SIPPET randomized trial, plasma-derived coagulation factor VIII (FVIII) products are less immunogenic than recombinant FVIII products synthesized from a Chinese hamster cell line; this fact should be taken into account in choosing a treatment strategy. According to the results of NuProtect study published in 2019, the concentrate of human cell line-derived recombinant FVIII demonstrates immunogenicity profi le similar to the one in plasma-derived FVIII products. Previously untreated patients with non-zero mutations receiving simoctocog alfa did not show development of inhibitors as well as in case of administration of plasma-derived FVIII products in SIPPET study.

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