scholarly journals The Management of two Cases of “Spontaneous” Factor VIII Inhibitors with high Dose Cyclophosphamide

1977 ◽  
Author(s):  
E.D. Gomperts
Keyword(s):  
Factor Viii ◽  
White Male ◽  
Rational Approach ◽  
White Female ◽  
High Dose ◽  
Excessive Bleeding ◽  
Antigenic Stimulus ◽  
Inhibitor Level ◽  
Fresh Plasma ◽  
Antigenic Load

Two patients with excessive bleeding associated with “spontaneous” Factor VIII inhibitors were studied. The first, a White male aged 52 years, was treated with high dosage cyclophosphamide and steroids together with plasmapheresis. An antigenic stimulus via concentrate and fresh plasma was given together with the stat dose of cyclophosphamide (1.6gm) together with prednisolone 60mg/day. Repeat plasmopheresis was carried out on two subsequent occasions shortly thereafter. The inhibitor level dropped progressively from 6.6 u/ml to almost unrecordable levels. However, escape from control was associated with the onset of hepatitis. Further therapy with an identical form of treatment failed to subsequently modify the inhibitor level which rose progressively to very high levels. In the second case, a White female aged 79 years, plasmapheresis was not carried out (inhibitor level 2.0 u/ml). Cyclophosphamide and prednisone were given in doses of 20 mg/Kg and 60 mg/day respectively. A Factor VIII antigenic load was given 24 hours before the cyclosphosphamide. Two subsequent cyclophosphamide pulses of similar dosage were given at approximately 10 day intervals without an antigenic stimulus. The patient was then maintained on a small daily dose of cyclophosphamide (50 mg/day). The inhibitor level responded to this therapy resulting in disappearance of the inhibitor and a progressive rise in the Factor VIII to levels greater than normal (170%). Our experience with these two cases suggests that a more rational approach to immunotherapy in the second case resulted in a sustained satisfactory immunosuppressive response.

Role of Plasmapheresis In Management of Acquired Factor VIII Inhibitor

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4656-4656
Author(s):  
Ratesh Khillan ◽  
Rabia Latif ◽  
Gurinder Sidhu ◽  
Elizabeth Gloster ◽  
Albert S. Braverman ◽  
...  
Keyword(s):  
Factor Viii ◽  
Ct Scan ◽  
Case Reports ◽  
High Dose ◽  
Factor Viii Inhibitor ◽  
Inhibitor Level ◽  
Viii Inhibitor ◽  
Acquired Factor Viii Inhibitor ◽  
Dose Factor

Abstract Abstract 4656 A 91-year-old woman with past medical history of hypertension presented with hematuria. There were no ecchymosis, Petechiae or other obvious active bleeding. Her hemoglobin was 11.4 g/dl on presentation hematuria got worse and her hemoglobin drops to 7.6 g/dl over next 48 hours and she was hemodynamically unstable. She was transferred to the Medical Intensive Care Unit for resuscitation with IV fluids and PRBCs. Coagulation tests revealed a prolongation of activated partial thromboplastin time of more than 100 seconds (control 33 seconds) which could not be corrected with mixing normal plasma. Diagnosis of acquired factor VIII inhibitor was considered and recombinant activated factor VII (rFVIIa) was initiated. The factor VIII activity level was reduced to less than 1%. Bethesda assay demonstrated the presence of a factor VIII inhibitor at 103.8 Bethesda units per ml (BU/ml), other coagulation studies were with in normal range. CT scan of her abdomen showed retroperitoneal hematoma. rFVIIa was started at 50 units/kg body weight every 3 hours and subsequently increased to 200 units/kg. She was simultaneously started on steroids. Her hematuria did not improve in spite of high dose rFVIIa. On day 4 rFVIIa was tapered and switched to 50 units/kg FEIBA (Factor eight inhibitor bypass agent). She also received Rituximab 375 mg/m2. We continued FEIBA until day 7 but her hematuria did not improve, she required more than 10 units of Packed Red Blood Cells PRBCs during this period. On day 7 we decided to start plasmapheresis as there were some case reports of using plasmapheresis with or without immunoadsorption columns (which are currently not available in US). We started plasmapheresis and gave her 2 doses of IVIG (Immunoglobulin). Her pre and post plasmapheresis inhibitor levels were 104 BU/ml and 54 BU/ml respectively. Her urine turned pink and her Prbc demand decreased. A second plasmapheresis was done 2 days later showed significant decrease of inhibitor level from 80 BU/ml to 14.5 BU/ml. Her hematuria resolved by next day. We continued her on FEIBA for three more days she did not have hematuria and she did not require any PRBCs. CT scan of abdomen showed decrease in size of retroperitoneal hematoma. Cyclophosphamide 1000 mg was given for induction of immune tolerance followed by high dose factor VIII (100 IU/KG) as per Bonn protocol. Her factor VIII levels and factor VIII inhibitor levels were checked every day before and after Factor VIII infusion. Her inhibitor level is ranging between 14–16 BU/ml she is not bleeding any more and her abdominal hematoma is resolved. Her pre and post transfusion factor VIII levels ranges between 30–40% and 120–140%. respectively. Patient is still getting factor VIII everyday. Role of plasmapheresis is not very well defined in acquired Factor VIII inhibitor patients. Acquired hemophilia is a rare autoimmune disorder in which the patient develop an autoantibody directed against coagulation factor VIII leading to a clinically bleeding diathesis. There are few case reports in literature showing efficacy of Plasmapheresis in this disorder. This is a rare condition and it is very difficult to find large randomized trial to establish a standard of care. Patient mentioned above did not respond to rFVIIa or FEIBA. In our observation plasmapheresis with IVIG proved to be an effective method of rapidly reducing the inhibitor level. In case of life threatening bleeding we need to reduce the inhibitor level quickly. We also observed that once inhibitor level was low bleeding stopped. Immune induction therapy with cyclophosphamide followed by high dose factor VIII was successful in maintaining low inhibitor level. Disclosures: Kessler: Grifols S.A.: Research Funding.

Acquired Hemophilia After a Spider Bite

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4637-4637
Author(s):  
Namita Vinayek ◽  
Goetz H Kloecker ◽  
Beth C. Riley
Keyword(s):  
Factor Viii ◽  
Conflicts Of Interest ◽  
Bleeding Complications ◽  
White Female ◽  
High Dose ◽  
Functional Assay ◽  
Factor Viii Inhibitor ◽  
Vascular Abnormality ◽  
Viii Inhibitor ◽  
Spider Bite

Abstract Abstract 4637 A 59 year old white female with no history of bleeding diathesis presented with swelling of her left forearm two days after a brown recluse spider bite. Hematology was consulted for uncontrolled bleeding from the fasciotomy site after compartment syndrome. The hand surgeons did not see any vascular abnormality at the site of surgery. Due to ongoing bleeding for days from the surgical site, she required 8 PRBCs, 6 FFPs and 6 apheresis platelets units. PT, PTT, and platelet count were normal, ristocetin cofactor was 339% and vWF antigen 306% and vW Factor VIII binding capacity was normal. Her platelet functional assay was normal. Factor levels of II, V, VII, XI, X, XI and lupus anticoagulant were all with in normal range. A Bethesda assay however showed a low titer of antibody against factor VIII (1.25 BU). Factor VIII was low at 6% and remained low at 16% with no significant response to recombinant factor VIII.The bleeding however responded well to recombinant factor VIIa. She was maintained on high dose steroids for few months and tapered. She eventually had a skin graft to the site of injury and is now followed in our hemophilia clinic with no further bleeding complications. To our knowledge only one case of spider bite resulting in factor VIII inhibitor has been documented in the literature. We hypothesize that direct antigenic stimulation by spider venom can transiently develop factor VIII inhibitor in individuals. Disclosures: No relevant conflicts of interest to declare.

A Higher than Expected Incidence of Factor VIII Inhibitors in Multitransfused Haemophilia A Patients Treated with an Intermediate Purity Pasteurized Factor VIII Concentrate

1993 ◽  
Vol 69 (02) ◽  
pp. 115-118 ◽  
Author(s):  
Kathelijne Peerlinck ◽  
Jef Arnout ◽  
Jean Guy Gilles ◽  
Jean-Marie Saint-Remy ◽  
Jos Vermylen
Keyword(s):  
Factor Viii ◽  
Randomized Trials ◽  
Specific Factor ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Viral Inactivation ◽  
Gradual Decline ◽  
Inhibitor Level ◽  
Factor Viii Concentrates ◽  
Viii Inhibitor

SummaryIn May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation.Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII.This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials.

scholarly journals Newly detected rapid eye movement associated sleep apnea after coronavirus disease 2019 as a possible cause for chronic fatigue: two case reports

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Andreas Rembert Koczulla ◽  
Antje Stegemann ◽  
Rainer Gloeckl ◽  
Sandra Winterkamp ◽  
Bernd Sczepanski ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Eye Movement ◽  
Case Reports ◽  
White Male ◽  
Chronic Fatigue ◽  
White Female ◽  
Rapid Eye Movement ◽  
Pressure Therapy ◽  
Fatigue Syndrome ◽  
Case Presentations

Abstract Background Coronavirus disease 2019 has become a health problem spreading worldwide with pandemic characteristics since March 2020. Post coronavirus disease 2019 symptoms are more frequent than initially expected, with fatigue as an often-mentioned issue. Case presentations We describe a 32-year-old white male and a 55-year-old white female who suffered from post coronavirus disease 2019 fatigue syndrome. On polysomnography, rapid eye movement associated sleep apnea with an increased hypopnea index during rapid eye movement phases of 36.8 and 19.5 events per hour was found. Based on the patients’ burdensome fatigue symptoms, we initiated automatic positive airway pressure therapy, which diminished sleep apnea (rapid eye movement index: 0.0 in both patients) and, consequently, also the fatigue symptoms. Conclusions Since sleep apnea and coronavirus disease 2019 are both associated with fatigue, a screening for sleep apnea might be considered in coronavirus disease 2019 patients with fatigue syndrome.

Improved Factor VIII Yield in Cryoprecipitate Using a Quick Thaw Technique

1975 ◽  
Author(s):  
J. F. Davidson ◽  
J. H. McAdam ◽  
M. J. Mackenzie ◽  
M. L. Kavanagh
Keyword(s):  
Factor Viii ◽  
Standard Method ◽  
Liquid Bath ◽  
Activity Factor ◽  
Factor Viii Antigen ◽  
Fresh Plasma

Standard Cryoprecipitate was prepared from fresh citrate phosphatedextrose plasma by snap freezing at —70° C and then thawing at +4° C in air for 18 hours. In 143 experiments the yield of Factor VIII from the starting plasma was 42%.In 64 paired experiments the Factor VIII yield in Cryoprecipitate from fresh plasma was increased, from 43% in the standard method to 56% when a quick thaw of 50 minutes at +4° C in a liquid bath was introduced. In 10 other paired experiments the yield in the standard method was raised from 51% to 61% when 90 minutes of super-cooling at —6° C in a liquid bath was introduced prior to snap freezing. When, however, the quick thaw and super-cooling modifications were combined in 42 paired experiments, the yield was only 49% compared with 42% by the standard method.It is concluded that this simple quick thaw modification will produce a greater yield of Factor VIII in Cryoprecipitate and that the addition of the technically more demanding super-cooling modification does not give a significantly greater yield.It seems likely that the longer period at +4° C in the standard method leads to denaturation of a proportion of the Factor VIII and loss of activity. Factor VIII antigen, however, was not lost. In a smaller number of experiments approximately all the Factor VIII was recovered in the Cryoprecipitate and its supernatant. Furthermore, the relative proportions of Factor VIII antigen and procoagulant in the Cryoprecipitate were found to vary in concert suggesting that the Factor VIII molecule is not dissociated in the process of cryoprecipitation.

Impoliteness in hip-hop music

2021 ◽  
Author(s):  
Panagiotis Delis
Keyword(s):  
African American ◽  
Black Male ◽  
Hip Hop ◽  
Selection Process ◽  
White Male ◽  
White Female ◽  
Race And Gender ◽  
The Social ◽  
Determining Factors ◽  
And Gender

Abstract The aim of this paper is to examine the functionality of impoliteness strategies as rhetorical devices employed by acclaimed African American and White hip-hop artists. It focuses on the social and artistic function of the key discursive element of hip-hop, namely aggressive language. The data for this paper comprise songs of US African American and White performers retrieved from the November 2017 ‘TOP100 Chart’ for international releases on Spotify.com. A cursory look at the sub-corpora (Black male/ Black female/ White male/ White female artists’ sub-corpus) revealed the prominence of the ‘use taboo words’ impoliteness strategy. The analysis of impoliteness instantiations by considering race and gender as determining factors in the lyrics selection process unveiled that both male groups use impoliteness strategies more frequently than female groups. It is also suggested that Black male and White female singers employ impoliteness to resist oppression, offer a counter-narrative about their own experience and self (re)presentation and reinforce in group solidarity.

Histological and Biochemical Evaluation of Urethral Scar following Three Different Hypospadias Repairs: An Experimental Study in Rabbits

2017 ◽  
Vol 28 (05) ◽  
pp. 420-425 ◽  
Author(s):  
Xiao-Hui Tan ◽  
Chun-Lan Long ◽  
De-Ying Zhang ◽  
Tao Lin ◽  
Da-Wei He ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
White Male ◽  
Transforming Growth Factor Β1 ◽  
Rational Approach ◽  
Hypospadias Repair ◽  
Tubularized Incised Plate ◽  
Biochemical Evaluation ◽  
Tubularized Incised Plate Urethroplasty ◽  
Tgf Β1

Introduction Several urethroplasties have been employed in the surgical treatment of hypospadias. Neourethral strictures are among the most common postoperative complications that often require reoperation. Materials and Methods We created a hypospadias model in New Zealand white male rabbits through a hypospadias-like defect and acute repair. A total of 24 animals were randomly allocated into three groups: tubularized incised-plate urethroplasty (TIPU) group (8), perimeatal-based flap urethroplasty (Mathieu) group (8), onlay island flap urethroplasty (onlay) group (8), and corresponding surgical procedures were immediately performed to reconstruct neourethra. The rabbits were killed postoperatively at 5 days, 2 weeks, 6 weeks, and 3 months, respectively. The penile tissue was harvested for histological and biochemical investigations to evaluate the expressions of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMactin) in all groups. Results All rabbits were operated on uneventfully. The amount of collagen content was increased in the Mathieu and onlay groups than in the TIPU group (p < 0.05). Biochemical analysis showed that the expression of TGF-β1 in the TIPU group was decreased compared with the two other groups at 2 or 6 weeks postoperatively (p < 0.01). The expression pattern regarding α-SMactin was similar at 6 weeks or 3 months postoperatively (p < 0.01). Conclusion The neourethra repaired by TIPU was practically resumed to normal anatomy and scarring was less apparent than the two other groups. Therefore, TIPU is considered as a relatively rational approach for hypospadias repair. The activity of fibroblasts has been increased in the long term, which may be the pathogenesis of neourethral stricture following hypospadias repair.

scholarly journals Determination of the cumulative and skin-resorptive action of the Zoodizin disinfectant

2020 ◽  
Vol 22 (97) ◽  
pp. 26-30
Author(s):  
O. L. Nechyporenko ◽  
A. V. Berezovskyy ◽  
T. І. Fotina ◽  
R. V. Petrov
Keyword(s):  
Skin Irritation ◽  
White Male ◽  
Cumulative Effect ◽  
Female Rats ◽  
Male Rats ◽  
White Female ◽  
Test Substance ◽  
High Concentration ◽  
White Rats ◽  
Single Effect

The rational organization and implementation of effective disinfection activities plays an important role in the complex of measures for the prevention of infections. The development and introduction of new disinfectants into production is an urgent issue of modern poultry farming. When developing a disinfectant, it is important to determine the cumulative effect of the drug. The purpose of the study was to determine the cumulative and skin-resorptive action of the disinfectant “Zoоdizin”. For the toxicological study of the drug used healthy white male rats and white female rats weighing 200 ± 10 g 1.5 years of age. To study the toxicity of the drug “Zoоdizin” when applied to the skin used the method of immersion of the tails of rats in a test tube with the test substance. The tail was injected 2/3 into a regular tube with a 5 % solution of the drug “Zoоdizin”. The tube was closed with a cork ring whose diameter was slightly larger than the tail diameter. For 15 days, the tubes were placed daily in a water bath at 28–30 °C for 2 hours. Control animals tails were immersed in distilled water. To establish the local action of the drug “Zoodizin” on the mucous membranes of the study drug was introduced into the conjunctival sac of the right eye of the rabbit at a dose of 50 mg, and in the left eye was buried saline in a volume of 0,05 cm3. When studying the cumulative effect of Zoоdizin, no significant changes in the biochemical parameters in the serum of rats were observed. In the study of possible irritant or damaging effect on the skin and the development of contact non-allergic dermatitis found that a single application of disinfectant “Zoоdizin” on the unaffected skin of the back of white rats in the maximum significant recommended concentration of working solutions (2 %) did not cause signs. The single effect of the drug on the intact areas of the skin did not cause skin irritation, but it can be stated that prolonged daily epicutaneous exposure of high concentration (5 %) of the solution of the drug “Zoоdizin”, which is 2.5 times higher than the maximum recommended concentration, caused a general resorption. When assessing the cumulative properties, it was taken into account that the total dose administered to rats was Zodizin 42000 mg/kg body weight and did not result in animal death. It did not allow to calculate the cumulative coefficients for the “lethal effect”. A single effect of the product on the intact areas of the skin did not cause skin irritation, but it can be stated that prolonged daily epicutaneous exposure of a high concentration (5 %) of the Zodizin solution, which is 2.5 times the maximum recommended concentration, caused a general resorption. In the future, it is planned to study the virulidal properties of the biocide “Zoоdizin”.

Investigating the Role of Inflammasome Caspases 1 and 11 in the Acute Radiation Syndrome

2021 ◽  
Author(s):  
Andrea R. Daniel ◽  
Lixia Luo ◽  
Chang-Lung Lee ◽  
David G. Kirsch
Keyword(s):  
Cell Death ◽  
Drug Targets ◽  
Acute Radiation ◽  
Rational Approach ◽  
High Dose ◽  
Acute Radiation Syndrome ◽  
Alternative Pathways ◽  
Caspase 1 ◽  
Organ Systems ◽  
Sensitive Organ

Exposure to high dose radiation causes life-threatening acute and delayed effects. Defining the mechanisms of lethal radiation-induced acute toxicity of gastrointestinal and hematopoietic tissues are critical steps to identify drug targets to mitigate and protect against the acute radiation syndrome (ARS). For example, one rational approach would be to design pharmaceuticals that block cell death pathways to preserve tissue integrity in radiation-sensitive organ systems including the gastrointestinal tract and hematopoietic compartment. A previous study reported that the inflammasome pathway, which mediates inflammatory cell death through pyroptosis, promotes ARS. However, we show that mice lacking the inflammatory executioner caspases, caspase-1 and caspase-11, are not protected from ARS when compared directly to littermates expressing caspase-1 and caspase-11. These results suggest that alternative pathways will need to be targeted by drugs that successfully mitigate and protect against the ARS.

“He Is Psychotic and Always Will Be”

2019 ◽  
pp. 153-189
Author(s):  
Martin Summers
Keyword(s):  
Black Male ◽  
White Male ◽  
Clinical Encounter ◽  
The Other ◽  
White Female ◽  
Medical Surveillance ◽  
Institutional Management ◽  
Black Patients ◽  
Male Patients ◽  
Somatic Therapies

This chapter continues an examination of the superintendency of William Alanson White but offers a more granular discussion of how ideas about racial difference shaped the clinical encounter in the era of dynamic psychiatry. Specifically, it looks at how Saint Elizabeths’ staff applied particular somatic “therapies”—including seclusion, restraint, and hydrotherapy—to black female, white female, black male, and white male patients. It also argues that the clinical staff’s limited psychotherapeutic engagement with African American patients was further undermined by two things. One was the psychiatrists’ assumptions about the inaccessibility of the black psyche—either because of the absolute cultural foreignness or natural duplicity of African Americans. The other was their tendency to prioritize black patients’ rehabilitation as laborers. Finally, the chapter looks at the quotidian ways that patients exerted their agency in the clinical encounter by resisting medical surveillance and institutional management.

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