Factor VIII Level Comparison in Patients with Severe Hemophilia a on Emicizumab with Inhibitors with One Stage, Bovine and Human Chromogenic Assays and the Factor VIII Equivalency of Emicizumab Using In Vivo Global Hemostasis Assays

Introduction Emicizumab is a recombinant, humanized bispecific monoclonal antibody that mimics the function of factor VIII (FVIII) which results in a significant reduction in the annualized bleeding rate in patients with hemophilia A (HA), however, the degree with which emicizumab corrects the coagulation defect remains unclear. The objective of this study was to compare the current available laboratory methods in clinical practice; one-stage clotting factor assays (OSCA), bovine and human chromogenic FVIII activity (bovCHR and humCHR, respectively) and FVIII Equivalency of Emicizumab by Thrombin Generation (F8EmT). Aims The aim of this study is to address the differences of FVIII activity with different techniques in patients with severe HA with inhibitors on emicizumab. Materials and Methods Factor VIII levels are determined with an activated partial thromboplastin time (aPTT), OSCA using SynthASil on the ACL TOP 500 (Instrumentation Laboratory, Bedford, MA). Factor VIII activity is also determined photometrically via the Chromogenix Coatest® SP4 FVIII chromogenic assay kit (bovCHR, Diapharma Group, West Chester, OH) and the Biophen FVIII:C chromogenic assay kit (humCHR, Aniara Diagnostica, West Chester, OH). For F8EmT, linear regression was utilized to model the FVIII levels as a function of the endogenous thrombin potential (ETP) and peak thrombin values for patients with mild/moderate hemophilia. Then, we used the ETP and peak thrombin results of the severe HA patients on emicizumab with the calibration curve to calculate their F8EmT. Association between patient weight and their F8EmT were also examined and evaluated by linear regression. Results Data is presented for eight patients with severe HA with inhibitors on emicizumab in the non-bleeding state (Table-1). All patients' FVIII levels measured with OSCA are in or above the normal range (94.0-289.1). Bovine chromogenic FVIII activity is in the severe hemophilia range for five out of eight patients, for the rest it is in the moderate hemophilia range. Human chromogenic FVIII activity ranged between 12.5-49.8%. Factor VIII Equivalency of Emicizumab by Thrombin Generation is either in the mild hemophilia or normal range in all participants of the study. Conclusion One-stage clotting factor assays demonstrated falsely high results as expected since it is activated partial thromboplastin time based. Bovine chromogenic FVIII activity results were consistent with the severe HA range of the patients though a few had results slightly above that level. Previous literature has stated that the humCHR in patients on emicizumab results in FVIII levels of ∼30% when emicizumab is at its therapeutic concentration (∼50 mcg/ml). This study also demonstrated similar results with 5/8 patients having levels 30-50%. F8EMT levels were mostly consistent with the humCHR. In conclusion, understanding the degree to which emicizumab corrects the coagulation defect of is an important goal as it has clinical implications.Certainly, additional studies with higher participant numbers are needed to confirm these findings. Figure 1 Figure 1. Disclosures Young: Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding.

Management of Neuraxial Analgesia in a Parturient with Factor XIII Deficiency: A Case Report and Proposed Management Algorithm

Factor XIII (FXIII) deficiency is a rare coagulation defect that can be associated with significant bleeding. A 28-year-old pregnant woman, with a history of hemorrhagic stroke secondary to severe congenital FXIII deficiency, presented in active labor requesting an epidural. Factor XIII levels had been monitored throughout her pregnancy and treated with intermittent factor XIII infusions to maintain factor levels above 30% of normal. After careful multidisciplinary peripartum evaluation and FXIII replacement, neuraxial analgesia was performed without complication. Neuraxial analgesia can be performed without complication in patients with FXIII deficiency if FXIII levels are carefully managed and no other coagulopathy exists.

A ENDODONTIC CONSIDERATION IN HAEMOPHILLIAC PATIENTS: A REVIEW

One who manage dental patient who has a bleeding disorder should have knowledge about the coagulation system and the patient's specific coagulation defect. Such patient can receive quality comprehensive dental care, provided appropriate preoperative planning and evaluation with the patient's physician or hematologist is accomplished. Patient should be provided appropriate replacement therapy before the dental procedure, selection of conservative treatment approaches, and use of local hemostatic measures to facilitate hemostasis.

Pattern of Common Inherited Coagulation Disorders: Evaluation of 100 Cases

Introduction: The bleeding disorders having inherited abnormality of haemostasis may present with significant difficulties in diagnosis and management. The overall frequency of these disorders in the general population is low. Objectives: To study the frequency of inherited coagulation disorders and their prevalent clinical manifestations. Materials and Methods: A prospective cross sectional study of one hundred patients of all age group and both sexes was organized as both in-patient and out-patient based in the Department of haematology, Armed Forces Institute of Pathology (AFIP) from July 2012 to June 2013. Results: In this study, out of 100 patients, haemophilia A, diagnosed in 75% patients, was the most common disorder. Age group ranging from 5-15 years constituted 48% of total patients. Male to female ratio of patients having hereditary coagulation defect was 73:2 in haemophilia A whereas 2:3 in vWD. Consanguinity was documented in 60% of vWD and 24% of haemophilia A. The most common clinical symptom in hereditary coagulation defect (HCD) was echymosis (60%). The most common presenting feature of haemophilia was haematoma (57.95%) whereas menorrhagia was the most common presentation of female patients with vWD. Among 97 patients of haemophilia and vWD, 59(60.82%) cases were in mild form and 04(4.12%) cases were found to have severe coagulation defect. Fresh frozen plasma (FFP) is the most common modality of treatment in HCD. Conclusion: It has become the need of the time to find out such a cost effective diagnostic parameter to make an early diagnosis of inherited coagulation disorders. Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 64-66

Tissue coagulation in laser hemorrhoidoplasty – an experimental study

BackgroundLaser hemorrhoidoplasty (LHP) is a new technique for treatment of hemorrhoids. The exact extent of coagulation is not visible at the time of the procedure. There currently is no experimental or clinical data on the subject.ObjectiveTo evaluate the length of coagulation defect according to power and activation time of 1470nm diode laser on the perianal tissue model.MethodsFresh anorectal tissue of twenty-four pigs was used to produce 54 experimental samples. Each sample was randomly assigned to the laser power of 6, 8 and 10 W and 1, 2 or 3-second pulses. The procedure was performed using Biolitec Ceralas © diode laser with 1.85 mm optical fiber. The fiber was inserted in a manner, similar to intrahemorrhoidal laser application. Samples were evaluated using low-power and high-power light microscopy by a single pathologist. The length of tissue injury was measured on high-magnification microscopy.ResultsThe longest tissue injury (mean 3.93 mm) was caused by the longest laser exposure time (3 sec) with no significant difference between laser power used.Conclusions8 W 3-second application of the 1470nm diode laser results in coagulation area approximately 4 mm, and further coagulation should be initiated approximately 5 mm from the first one.

Understanding of Thromboembolism by Ayurveda

Thromboembolism term is used to define a type of blood pathology which involves two terms basically i.e. Thrombo + Embolism. Thromboembolism is defined as the blocking or obstruction of a blood vessel by a clot (or a part of clot, debris) that has broken off from the place where it is formed and travelled to another organ. (Debris includes blood clots, cholesterol containing plaques, masses of bacteria, cancer cells, amniotic fluid, fat from the marrow of broken bones and injected substances). Thromboembolism is coagulation defect of blood which is responsible for certain life threatening conditions of human being. Ayurveda Samhita also has references regarding good as well as bad properties of the Rakta and Margavarana Janya pathological states that lead to defect of the Kapha, Rakta that produces features similar to Thromboembolism. Present article will help to understand Thromboembolism as per the Ayurveda perspective.

Combined Factor V and Factor VIII Deficiency: A Case Report

Background: Combined factor V and factor VIII deficiency (F5F8D, OMIM 227300) is a rare autosomal recessive bleeding disorder. It seems more common among Jews and Iranians, particularly in regions with frequent consanguineous marriages. Case Report: We describe a 5-yearold girl born out of consanguineous marriage with a complaint of prolonged bleeding after dental extraction. There were no history of spontaneous bleeding and other coagulation defect symptoms. Conclusion: In frequent consanguineous marriage regions, inherited deficiency of factor V and VIII should be considered in patients with coagulation defect symptoms.[GMJ. 2016;5(1):42-44]