Lack of Antibodies to Clotting Factors in the Blood of Hemophiliacs Refractory to Transfusions)

1957 ◽  
Vol 01 (03/04) ◽  
pp. 353-358
Author(s):  
Jorge A Penalver ◽  
R. R Holburn ◽  
R. T Carroll ◽  
L. M Tocantins
Keyword(s):  
Hemophilia A ◽  
Blood Transfusions ◽  
Clotting Time ◽  
Clotting Factors ◽  
Normal Individuals ◽  
Refractory State ◽  
Human Sera ◽  
Fraction I ◽  
Source Of Error ◽  
Positive Results

Summary1. The blood of 11 Hemophilia “A” patients refractory to transfusions has been studied for the presence of precipitins against certain clot-accelerating fractions. The tests were invariably negative. Identical results were observed in 10 Hemophilia “A” patients non-refractory to transfusions, in 2 cases of Hemophilia B, in 5 patients with miscellaneous conditions and in 11 normal individuals.2. When unheated Fraction I of Cohn is used as antigen, false positive results due to formation of fibrin clots were observed with all human sera tested. This may be a source of error in the interpretation of the tests, especially in the blood of refractory Hemophilia “A” patients with an unusually long clotting time and slow prothrombin conversion.3. These observations do not support the hypothesis that the refractory state to blood transfusions observed in some Hemophilia “A” patients is due to the presence of antibodies against certain clot-accelerating fractions of normal plasma.

Hemophilia therapeutics

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Bispecific Antibody ◽  
Hemophilia A ◽  
Blood Transfusions ◽  
Clotting Factors ◽  
Promising Alternative ◽  
Viii And Ix ◽  
The 1950S ◽  
The Cost

Hemophilia is a genetic hemorrhagic condition marked by uncontrollable and persistent bleeding following surgery or trauma. Hemophilia A is the more common of the two, affecting 1:5000 newborn males in the population. Injecting factor replacement treatments are the most common therapy for hemophilia. The drugs that replaced the clotting factors VIII and IX were developed in the 1950s and 60s. They have been used to treat blood transfusions since the mid-1970s. The development of a humanized bispecific antibody (emicizumab; ACE910) that binds to FIX and FX and replicates the action of FVIII was a key breakthrough in hemophilia therapy. The cost of maintaining this antibody is high, and the feasibility of developing antibodies against the reactant has yet to be determined. Gene therapy is a promising alternative.

scholarly journals Antibody responses in patients with farmer's lung disease to antigens fromThermoactinomyces vulgaris

1975 ◽  
Vol 74 (1) ◽  
pp. 35-41 ◽  
Author(s):  
M. R. Hollingdale
Keyword(s):  
Lung Disease ◽  
Sodium Periodate ◽  
Latex Agglutination ◽  
Antibody Responses ◽  
Muramic Acid ◽  
Farmer’S Lung ◽  
Farmer's Lung ◽  
Human Sera ◽  
Thermoactinomyces Vulgaris ◽  
Positive Results

SUMMARYA serological analysis of mycelial antigens ofThermoactinomyces vulgarisin immunodiffusion with human sera revealed five individual antigens. Three antigens were proteins, sensitive to pronase and soluble in phenol. Two were cationic polysaccharides, sensitive to sodium periodate, and containing glucosamine and muramic acid.Latex coated with mycelial antigens was compared with precipitin tests in detecting antibodies toT. vulgaris;the number of positive results detected by each test differed slightly, and a combination of the two tests detected the highest number. Counterimmunoelectrophoresis (CIE) was shown to be a very sensitive method for detecting precipitins, but not for their measurement. A prospective evaluation of immunodiffusion, latex agglutination and CIE as potential serodiagnostic techniques for farmer's lung disease is suggested.

scholarly journals Transoperative refusion: a simple and safe method in emergency surgery

2014 ◽  
Vol 41 (4) ◽  
pp. 292-296
Author(s):  
Luiz Carlos Buarque Gusmão ◽  
Sérgio Henrique Chagas Valoes ◽  
José da Silva Leitão Neto
Keyword(s):  
Cost Benefit ◽  
Blood Transfusions ◽  
Factor V ◽  
West Nile Fever ◽  
Clotting Factors ◽  
Blood Contamination ◽  
Simple Method ◽  
Cost Benefit Ratio ◽  
The Cost ◽  
Selection Of

The objective is to reinforce the importance of blood reinfusion as a cheap, safe and simple method, which can be used in small hospitals, especially those in which there is no blood bank. Moreover, even with the use of devices that perform the collection and filtration of blood, more recent studies show that the cost-benefit ratio is much better when autologous transfusion is compared with blood transfusions, even when there is injury to hollow viscera and blood contamination. It is known that the allogeneic blood transfusion carries a number of risks to patients, among them are the coagulation disorders mediated by excess enzymes in the conserved blood, and deficiency in clotting factors, mainly the Factor V, the proacelerin. Another factor would be the risk of contamination with still unknown pathogens or that are not investigated during screening for selection of donors, such as the West Nile Fever and Creutzfeldt-Jacob, better known as "Mad Cow" disease. Comparing both methods, we conclude that blood autotransfusion has numerous advantages over heterologous transfusion, even in large hospitals. We are not against blood transfusions, just do not agree that the patient's own blood is discarded without making sure there will be enough blood in stock to get him out of the hemorrhagic shock.

scholarly journals The Relationship between Hemophilia A Severity and Hemophilia Activities List

2021 ◽  
Author(s):  
Faizal Muhammad
Keyword(s):  
High Risk ◽  
Hemophilia A ◽  
Bleeding Event ◽  
Clinical Manifestations ◽  
Self Care ◽  
Daily Activities ◽  
Clotting Factors ◽  
Household Tasks ◽  
The Relationship ◽  
Lying Down

Hemophilia is a hereditary bleeding disorder due to clotting factors deficiency. Its clinical manifestations including spontaneous and recurrent joints and muscle bleeding. Thus, hemophilia can limit the patients’ daily activities. This study aims to assess the relationship of hemophilia A severity on daily activities and the Hemophilia Activities List (HAL). The research subjects were thirty men with hemophilia A aged 18 years old or older who went to the Hematology-Oncology Clinic of Dr. Moewardi General Hospital during February - September 2020. Standardized seven aspects of routine activities with high-risk for bleeding event were assessed using the HAL questionnaire including lying down/ sitting/ kneeling/ standing, functions of the legs, functions of the arms, use of transportation, self-care, household tasks, leisure activities and sports. Based on the frequency of activity difficulty due to hemophilia A, each average score of HAL aspect was categorized into never (100% - 76%); rarely (75% - 51%), sometimes (50% - 26%), and impossible (25% - 0%). Based on Factor VIII level, hemophilia A severity was categorized into mild, moderate, and severe. Spearman’s correlation test was used for statistical analysis. The result showed significant correlation (p < 0.05) on five aspects, including lying down/ sitting/ kneeling/ standing, functions of the legs, use of transportation, self-care, and household tasks. The aspects of arms functions and leisure sports activities were not significantly correlated (p > 0.05). Nevertheless, these two aspects showed positive sufficient (r = 0.330) and weak (r = 0.177) correlation respectively. Joint and muscle bleeding are an undeniable pathological event in hemophilia patients. Hemophilia A severity positively correlates with the bleeding event frequency in the essential routine musculoskeletal activities. According to the HAL questionnaire, it needs to be a concern for clinicians and patient education to prevent bleeding in any high-risk musculoskeletal activities.

scholarly journals Antibodies to human T-cell leukemia virus type III in hemophiliacs from Spain

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1473-1475 ◽  
Author(s):  
L Kitchen ◽  
M Leal ◽  
I Wichmann ◽  
E Lissen ◽  
M Ollero ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Leukemia Virus ◽  
Polyacrylamide Gel Electrophoresis ◽  
The United States ◽  
Hemophilia B ◽  
Clotting Factors ◽  
Serum Samples ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Abstract We tested serum samples from 50 hemophiliacs from Sevilla, Spain, for antibody to HTLV-III by indirect membrane immunofluorescence (IMI) and radioimmunoprecipitation with SDS polyacrylamide gel electrophoresis (RIP-SDS/PAGE). All had received commercial clotting factors from the United States with the exception of one hemophiliac who had never been transfused. Thirty-four (68%) reacted with HTLV-III-infected cells (H9/HTLV-III) by both methods, but not with the uninfected line (H9). Of 41 hemophilia-A patients tested, 28 (68%) were positive, and of nine hemophilia-B patients, six (66%) were positive. The nontransfused hemophilia-B patient was negative for antibody to HTLV-III by both methods. One patient with clinical AIDS tested positive as did six of seven with chronic unexplained lymphadenopathy. The eight individuals with AIDS or lymphadenopathy all had hemophilia A. We conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain.

Solving the problem of antibody interference in commercial "sandwich"-type immunoassays of carcinoembryonic antigen.

1989 ◽  
Vol 35 (1) ◽  
pp. 146-151 ◽  
Author(s):  
H J Hansen ◽  
G LaFontaine ◽  
E S Newman ◽  
M K Schwartz ◽  
A Malkin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Carcinoembryonic Antigen ◽  
False Positive ◽  
Room Temperature ◽  
Murine Monoclonal Antibody ◽  
Heat Extraction ◽  
Normal Individuals ◽  
Sandwich Type ◽  
Commercial Enzyme Immunoassay ◽  
Positive Results

Abstract We evaluated the effect of human anti-murine antibodies (HAMA) on apparent concentrations of carcinoembryonic antigen (CEA) as measured in serum with commercial enzyme immunoassay (EIA) kits manufactured by Abbot ("two-step" double monoclonal antibody assay), Roche, and Hybritech (room-temperature protocol). In sera from patients given parenteral murine monoclonal antibody for experimental diagnostic and immunotherapy studies, HAMA titers were determined with Immunomedics' "ImmuSTRIP HAMA-EIA" kit reagents. "True" CEA titers were established by using the ImmuCEA/MA-EIA and heat-extraction to destroy HAMA before assay for CEA. The concordance of the ImmuCEA/MA assay with the Abbott and Roche CEA EIAs was established with sera from normal individuals and from patients who had not received parenteral injections of murine monoclonal antibody. At high (100 mg/L) concentrations of HAMA, false-positive results were observed with all three kits. The Hybritech and Roche assays were more sensitive to interference by HAMA than was the Abbott CEA-EIA, false-positive results being observed at HAMA concentrations between 1 and 10 mg/L. Similar sensitivity of the three kits to interference by primate anti-MAb sera was demonstrated. Use of primate anti-MAb sera to create controls with HAMA activity and of analyte is recommended to evaluate MAb assays for potential HAMA interference and for use to devise methods to eliminate HAMA interference.

The Value of Urinary β-Thromboglobulin Measurements in Clinical Situations

1979 ◽  
Author(s):  
J. Dawes ◽  
R.C. Smith ◽  
D. Borsey ◽  
D. Aronstam
Keyword(s):  
Renal Function ◽  
Hip Replacement ◽  
Normal Individual ◽  
Plasma Concentrations ◽  
Diabetic Patients ◽  
Plasma Samples ◽  
Normal Individuals ◽  
Before And After ◽  
Serial Samples ◽  
Positive Results

Plasma β-thromboglobulin (ß -TG) measurements are subject to occasional false high values arising during sampling and processing. In the normal individual urinary β-TG is maintained at a constant low level (0.14 ± 0.09 ng. ml-1), and elevations in this value reflect raised plasma concentrations. Plasma and urinary β-TG concentrations were measured in normal individuals, in 18 patients presenting with suspected deep venous thrombosis, and in 75 diabetic patients. Serial samples were also taken before and after 9 hip replacement operations. The results indicate that measurement of urinary β-TG concentration in patients may be a simpler and more reliable means of detecting platelet activation than assay of plasma samples. False positive results do not occur when urinary concentrations are measured, unless renal function is abnormal;grossly elevated values may even detect occult renal disease.

Inhibition of Thrombotic Side Effects of II, VII, IX and X Concentrates

1975 ◽  
Author(s):  
A. J. Johnson ◽  
V. E. Macdonald ◽  
D. Brandt ◽  
S. Middleton ◽  
J. K. Smith
Keyword(s):  
Side Effects ◽  
Antithrombin Iii ◽  
Coagulation Factors ◽  
Thrombin Time ◽  
Average Yield ◽  
Clotting Time ◽  
Clotting Factors ◽  
Partial Activation ◽  
Peg Treatment ◽  
Fractionation Method

Well documented thrombotic side effects of II, VII, IX and X concentrates are thought to be due to spontaneous partial activation of one or more coagulation factors. Using the unactivated PTT method of Kingdon and the thrombin time as global assays of activation, we have confirmed this concept. It has been suggested that heparin should be added to the concentrate, but preparations vary in antithrombin content and activated factor. The amount of heparin for each preparation would have to be titrated in order to neutralize the activated factors without anticoagulating the patient. We sought to extend the range of added heparin without producing an anticoagulant effect, by adding heparin to the concentrates prior to use of the PEG fractionation method to remove the hepatitis antigen. Thus, heparin-activated antithrombin III can inhibit activated clotting factors while residual free heparin is removed by PEG fractionation. When 1 unit of heparin per mg of protein in the concentrate was added prior to PEG treatment, the final products from more than 80 runs on 15 batches (3 major manufacturers) were almost invariably neutral; neither anticoagulated nor activated. The thrombin clotting time, when measured, was 6-24 hours. The average yield with use of the PEG fractionation method was 85%; depending on the initial purity of the concentrate, the final product had an additional purification of 1.0-2.5 X that of the starting material.(Supported in part by USPHS Grant HL 15596 and HRC (N.Y.) 1-681.)

Consumption Of Viiirrag During Delayed Coagulation Process

1981 ◽  
Author(s):  
M Hada ◽  
S Ikematsu ◽  
M Fujimaki ◽  
K Fukutake
Keyword(s):  
Whole Blood ◽  
Hemophilia A ◽  
Negative Relationship ◽  
Rabbit Serum ◽  
Clotting Time ◽  
Crossed Immunoelectrophoresis ◽  
Qualitative Assay ◽  
Similar Quantity

Coagulational functions of VIIIR:AG are still unknown, while its serological significance in laboratory medicine has been established. In this study it will be analyzed the mechanism of the consumption of VIIIR:AG during the process of prolonged blood coagulation.Quantitative assay of VIIIR:AG in plasma and serum is measured by Laurell’s method using 1% agarose with anti-F.VIII rabbit serum and qualitative assay of VIIIR:AG is performed by crossed-immunoelectrophoresis with anti F.VIII rabbit serum.In 28 patients with Hemophilia A a negative relationship between serum VIIIR:AG / plasma VIIIR:AG ratio and prolongation of PTT is estimated and also a positive relationship between serum VIIIR:AG / plasma VIIIR:AG ratio and serum VIII:vW / plasma VIII:vW ratio is obtained. However, serum VIIIR:AG shows the similar quantity to plasma VIIIR:AG in the cases within normal clotting time, which have been treated by the in vitro addition of thrombin or by transfusion of AHG in vivo. When heparin or synthetic antithrombin ( MCI-9038 ) is added into normal whole blood or F.XIII deficient whole blood, the case of normal whole blood shows delayed clotting time and decrease of serum VIIIR:AG, but the case of F.XIII deficient whole blood indicates no decrease of serum VIIIR:AG. Furthermore, in those conditions change of the concentration of CIg in serum, which has been pointed out with fibrin crosslinking, indicate the similar behavior as serum VIIIR:AG.The results obtained above might suggest that serum VIIIR:AG tend to decrease in the cases with prolonged clotting time, and the F.XIII activity might be involved in the consumption mechanism of serum VIIIR:AG in such an abnormal condition, as fibrin crosslinkage could not carry out properly.

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