Elevated APTT? How Best to Follow Up
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Section 8: Hematology CHAPTER 47: ANEMIA
Section 8: Hematology CHAPTER 47: ANEMIA Q.1. A 56-year-old man presents with symptoms of severe dyspnea on exertion and fatigue. His laboratory values are as follows: Hemoglobin 6.0 g/dL (normal: 12–15 g/dL) Hematocrit 18% (normal: 36%–46%) RBC count 2 million/L (normal: 4–5.2 million/L) Reticulocyte count 3% (normal: 0.5%–1.5%) Which of the following caused this man’s anemia? A. Decreased red cell production B. Increased red cell destruction C. Acute blood loss (hemorrhage) D. There is insufficient information to make a determination Answer: A. This man presents with anemia and an elevated reticulocyte count which seems to suggest a hemolytic process. His reticulocyte count, however, has not been corrected for the degree of anemia he displays. This can be done by calculating his corrected reticulocyte count ([3% × (18%/45%)] = 1.2%), which is less than 2 and thus suggestive of a hypoproliferative process (decreased red cell production). Q.2. A 25-year-old man with pancytopenia undergoes bone marrow aspiration and biopsy, which reveals profound hypocellularity and virtual absence of hematopoietic cells. Cytogenetic analysis of the bone marrow does not reveal any abnormalities. Despite red blood cell and platelet transfusions, his pancytopenia worsens. Histocompatibility testing of his only sister fails to reveal a match. What would be the most appropriate course of therapy? A. Antithymocyte globulin, cyclosporine, and prednisone B. Prednisone alone C. Supportive therapy with chronic blood and platelet transfusions only D. Methotrexate and prednisone E. Bone marrow transplant Answer: A. Although supportive care with transfusions is necessary for treating this patient with aplastic anemia, most cases are not self-limited. -
Method Development and Validation of Vitamin D2 and Vitamin D3 Using Mass Spectrometry
Method Development and Validation of Vitamin D2 and Vitamin D3 Using Mass Spectrometry Devon Victoria Riley A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science University of Washington 2016 Committee: Andrew Hoofnagle Geoffrey Baird Dina Greene Program Authorized to Offer Degree: Laboratory Medicine ©Copyright 2016 Devon V. Riley ii University of Washington Abstract Method Development and Validation of Vitamin D2 and Vitamin D3 Using Mass Spectrometry Devon V. Riley Chair of the Supervisory Committee: Associate Professor Andrew Hoofnagle, MD, PhD Vitamin D has long been known to maintain bone health by regulating calcium and phosphorous homeostasis. In recent years, scientists have discovered additional physiological roles for vitamin D. The complex interaction between the active vitamin D hormone and its metabolic precursors continues to be a rich area of research. Fundamental to this research is the availability of accurate and precise assays. Few published assays for vitamins D2 and D3 have contained sufficient details on method validation or performance characteristics. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay developed for this thesis has undergone a rigorous validation and proven to yield a sensitive and specific method that exceeds the capabilities of all previously published methods. Developing and validating a novel assay is often complicated by the lack of established acceptability standards. This thesis explores this challenge, specifically for establishing meaningful interpretations and qualification standards of the lower limit of the measuring interval. Altogether, future research focused on vitamins D2, D3 and the Vitamin D pathway can benefit from this robust LC-MS/MS assay and the associated quality parameters outlined in this thesis. -
Molecular Basis of Fibrinogen Naples Associated with Defective Thrombin Binding and Thrombophilia
Molecular basis of fibrinogen Naples associated with defective thrombin binding and thrombophilia. Homozygous substitution of B beta 68 Ala----Thr. J Koopman, … , J Grimbergen, P M Mannucci J Clin Invest. 1992;90(1):238-244. https://doi.org/10.1172/JCI115841. Research Article In an abnormal fibrinogen (fibrinogen Naples) associated with congenital thrombophilia we have identified a single base substitution (G----A) in the B beta chain gene that results in an amino acid substitution of alanine by threonine at position 68 in the B beta chain of fibrinogen. The propositus and two siblings were found to be homozygous for the mutation, whereas the parents and another sibling were found to be heterozygous. Individuals homozygous for the defect had a severe history of both arterial and venous thrombosis; heterozygous individuals had no clinical symptoms. The three homozygotes had a prolonged thrombin clotting time in plasma, whereas the heterozygotes had a normal thrombin clotting time. Fibrinopeptide A and B (FpA and FpB) release from purified fibrinogen by human alpha-thrombin was delayed in both the homozygous propositus and a heterozygous family member. Release of FpA from the normal and abnormal amino-terminal disulfide knot (NDSK) corresponded to that found with the intact fibrinogens, indicating a decreased interaction of thrombin with the NDSK part of fibrinogen Naples. Binding studies showed that fibrin from homozygous abnormal fibrinogen bound less than 10% of active site inhibited alpha-thrombin as compared with normal fibrin, while fibrin formed from heterozygous abnormal fibrinogen bound approximately 50% of alpha-thrombin. These results suggest that the mutation of B beta Ala 68----Thr affects the binding of alpha-thrombin […] Find the latest version: https://jci.me/115841/pdf Molecular Basis of Fibrinogen Naples Associated with Defective Thrombin Binding and Thrombophilia Homozygous Substitution of BB 68 Ala -- Thr Jaap Koopman,** Frits Haverkate,t Susan T. -
Evaluation of Prolonged Surface Activated Coagulation Time
Biomedical Science Faculty of Health and Society Malm¨oUniversity SE-205 06 Malm¨o Sweden Master programme in Biomedical Surface Science http://edu.mah.se/en/Program/VABSE Evaluation of prolonged surface activated coagulation time Master degree thesis, 30 ECTS Author: Amalie Jesting Supervisors: Sebastian Bj¨orklund,PhD, Lecturer, Malm¨oUniversity Jens Peter Gøtze, MD, DMSc Professor, Chief-Physician, Rigshospitalet Søren Frank Jørgensen, MSc, Senior Lecturer, Metropolitan University College August 2018 MALMO¨ UNIVERSITY Abstract Faculty of Health and Society Master programme in Biomedical Surface Science Evaluation of prolonged surface activated coagulation time by Amalie Jesting Background: Blood coagulation is an essential defense mechanism to prevent bleeding. Disorders in the coagulation system can be severe and blood tests measuring the blood's ability to coagulate are important. Activated partial thromboplastin time (APTT) is a blood test that measures blood coagulation time. An abnormal prolonged APTT can both be associated with a bleeding tendency or a risk of thrombosis. Additional blood tests are needed to discover the cause of a prolonged APTT. One potential test is the APTT mixing study, which can separate samples with and without inhibitors. The aim of this project is to investigate how the cause of a prolonged APTT is evaluated today and to examine if it is possible to indicate the cause of a prolonged APTT using the APTT mixing study performed on routine samples. The goal is to be able to indicate the cause of a prolonged APTT immediately when is it first discovered. This will save time and help guide the physicians in their work with the patient. -
MGH Clinical Laboratories
MGH Laboratory Handbook Online Lab Handbook: http://mghlabtest.partners.org Reference Intervals - MGH Clinical Laboratories MGH Department of Pathology 55 Fruit Street, GRJ 220 Boston, MA 02114-2696 Report generated: August 19, 2009 Test name Reference Interval Laboratory 1-25-OH Vitamin D Core lab (Sendouts) 1-3-Beta D glucan assay Core lab (Sendouts) 17-OH Progesterone Core lab (Sendouts) 25-OH Vitamin D Desired: > 32 ng/mL Core 3-Methylhistidine, urine Age matched reference range and interpretation Neurochemistry provided 5-Nucleotidase Core lab (Sendouts) A1AT deficiency profile Core lab (Sendouts) ABO/Rh Type Blood Transfusion Service Acetaminophen Negative Core Acetone Negative Core Acetylaspartate, urine Interpretation provided Neurochemistry ACTH 6-76 pg/ml Core Acylcarnitines (plasma) Core lab (Sendouts) ADAMTS13 activity/inhibitor Core lab (Sendouts) Adenosine deaminase (fluid--NOT CSF) Core lab (Sendouts) Adenovirus antibody Reported with results Microbiology Adenovirus antigen Negative Microbiology Adenylosuccinase deficiency, screen Interpretation provided Neurochemistry AFP (non-maternal specimens) Core Alanine, CSF Interpretation and age-matched reference ranges Neurochemistry provided. Wednesday, August 19, 2009 Page 1 of 26 Test name Reference Interval Laboratory Alanine, plasma Interpretation and age-matched reference ranges Neurochemistry provided. Albumin 3.1-4.3 g/dl Chelsea Healthcenter Albumin 3.3-5.0 g/dl Core Albumin (fluid--NOT CSF) Core Alcohols (ethanol, MeOH, isoprop) Negative Core Aldolase Core lab (Sendouts) -
A Life-Threatening Case of Pregnancy-Related Atypical
Puri et al. BMC Nephrology (2020) 21:488 https://doi.org/10.1186/s12882-020-02100-4 CASE REPORT Open Access A life-threatening case of pregnancy- related atypical Haemolytic uremic syndrome and successful treatment with Eculizumab Prianka Puri1,2* , Anida Hanxhiu1, Daniel V. O’Hara1,3, Danny Hsu4 and Mirna Vucak-Dzumhur1,5 Abstract Background: Pregnancy-related Atypical Haemolytic Uremic Syndrome (P-aHUS) is a rare condition affecting genetically predisposed women during pregnancy. It is often difficult to diagnose and has a significant impact on maternal and foetal outcomes. It is characterised by microangiopathic haemolytic anaemia and kidney injury from thrombotic microangiopathy. Case presentation: A 27-year-old female of Lebanese descent presented at 36 weeks’ gestation with foetal death in-utero (FDIU) with placental abruption on a background of previously normal antenatal visits. She was coagulopathic and anaemic with anuric acute kidney injury, requiring emergency Caesarean section, intubation and dialysis. Her coagulopathy rapidly resolved, however, her anaemia and renal dysfunction persisted. A diagnosis of P-aHUS was made, and she was empirically treated with Eculizumab. Her ADAMTS13 level was normal, effectively excluding thrombotic thrombocytopenic purpura. Within 2 weeks of treatment her haematological parameters improved, and her renal function began to recover and within 2 months she became dialysis independent. Conclusion: This case highlights the challenges of a timely diagnosis of P-aHUS from other pregnancy-related diseases. Although our patient is dialysis-independent, her risk of relapse remains high with subsequent pregnancies. Currently we are awaiting her genetic sequencing to complete her assessment for underlying mutations and are determining the safest approach to a future planned pregnancy. -
Mixing Studies
Welcome Jim DeMase, Senior National Technical Sales Manager Sunday March 19, 2017/CAMLT/Kaiser Regional Reference Lab Welcome Your Presenter Today Jim DeMase, Senior National Technical Sales Manager, Precision BioLogic Account Manger for Western and Central USA and British Columbia, Alberta, Saskatchewan and Manitoba CANADA. H A L L A Hemostasis Is Unique-The Cascade, the Diseases and the Tests-All Mixed Up Part 1- What is Hemostasis Part 2- Intro to Hemophilia Part 3- Mixing Studies Objectives 1. Describe the stages of hemostasis as well as common bleeding and thrombotic disorders. 2. Explain the types of hemophilia, symptoms, diagnosis and common treatments. 3. Relate the methods and clinical application for a mixing study and the steps to perform one. What is Hemostasis? Pathology Study of diseases Especially the structural and functional changes (to the body) caused by the diseases Many disciplines Biochemistry Blood Transfusion Services Histology Microbiology Hematology Hematology Science of blood and its diseases Sub-disciplines: Immunology Microscopy Molecular Biology Hemostasis (Coagulation) Hemostasis The process of stopping bleeding Greek roots heme, blood + stasis, halt = halt of the blood Blood Red viscous liquid in arteries, veins and capillaries Pumped by the heart Irrigates every tissue Transport of gases, nutritive materials and elements for immunity Blood Leading the way in experimental and clinical research in hematology Blood composition Cellular Red cells: hemoglobin White cells: neutrophils, monocytes, lymphocytes Platelets: small cells, essential role in prevention of blood loss Liquid Plasma: yellow liquid, composed mainly of lightly salted water containing nutritional materials, waste products and numerous different proteins Proteins in the Plasma Albumin Globulins Coagulation proteins Procoagulant (e.g. -
Outpatient Laboratory Requisition
Yale-New Haven Hospital Department of Laboratory Medicine Outpatient Laboratory Requisition 20 York Street, New Haven, Connecticut 06510-3202 · 203-688-3670 · 1-800-305-3278 DATE: _____/____/_____ Unit #___________________________ Visit #_______________________________ Patient Name _______________________________________________________________________________ (Last, First, Middle Initial) Date of Birth______/_____/______ ❑ Female ❑ Male Patient Telephone: (______) ________-_____________ Address ___________________________________________________________________________________ (Street, City, State, Zip) ❑ Mr. Insured’s Name ❑ M r s . _______________________________________________________________________ Ms. Insured’s I.D. # __❑____________________________________________________________________________ Payor Number ______________________________________________________________________________ Primary Insurance: Name & State _______________________________________________________________ Relationship to patient: ❑ Self ❑ Spouse ❑ Child ❑ Other __________________________________________ Group # _________________________________ Insured’s Employer ________________________________ Diagnosis / ICD 9 Code _________________________ TIME DRAWN: ________ ❑ YNHH Blood Draw ❑ Fasting Specimen Type: ❑ Blood ❑ Urine ❑ Other_______________________ ❑ CSF ❑ Fluid____________ ❑ Bone Marrow ❑ Call / ❑ Fax Results ❑ Timed Urine Date Collected _______ Time Collected ________ To:________________________________ CC: X TEST NAME SCC CODE X TEST NAME SCC CODE -
The Role of the Laboratory in Treatment with New Oral Anticoagulants
Journal of Thrombosis and Haemostasis, 11 (Suppl. 1): 122–128 DOI: 10.1111/jth.12227 INVITED REVIEW The role of the laboratory in treatment with new oral anticoagulants T. BAGLIN Department of Haematology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK To cite this article: Baglin T. The role of the laboratory in treatment with new oral anticoagulants. J Thromb Haemost 2013; 11 (Suppl. 1): 122–8. tion of thromboembolism in patients with atrial fibrilla- Summary. Orally active small molecules that selectively tion. For some patients, these drugs offer substantial and specifically inhibit coagulation serine proteases have benefits over oral vitamin K antagonists (VKAs). For the been developed for clinical use. Dabigatran etexilate, majority of patients, these drugs are prescribed at fixed rivaroxaban and apixaban are given at fixed doses and doses without the need for monitoring or dose adjustment. do not require monitoring. In most circumstances, these There are no food interactions and very limited drug inter- drugs have predictable bioavailability, pharmacokinetic actions. The rapid onset of anticoagulation and short half- effects, and pharmacodynamic effects. However, there life make the initiation and interruption of anticoagulant will be clinical circumstances when assessment of the therapy considerably easier than with VKAs. As with all anticoagulant effect of these drugs will be required. The anticoagulants produced so far, there is a correlation effect of these drugs on laboratory tests has been deter- between intensity of anticoagulation and bleeding. Conse- mined in vitro by spiking normal samples with a known quently, the need to consider the balance of benefit and risk concentration of active compound, or ex vivo by using in each individual patient is no less important than with plasma samples from volunteers and patients. -
Approach to Coagulopathy in the Icu Dic and Thrombotic Emergencies
APPROACH TO COAGULOPATHY IN THE ICU DIC AND THROMBOTIC EMERGENCIES NEIL KUMAR, MD UNIVERSITY OF ROCHESTER MEDICAL CENTER Disclosures u I have no financial disclosures u I am NOT A HEMATOLOGIST Outline u Review of hemostasis and coagulopathy u Discuss laboratory markers for coagulopathy u Discuss an approach to a few specific coagulopathies and thrombotic emergencies Outline u Review of hemostasis and coagulopathy u Discuss laboratory markers for coagulopathy u Discuss an approach to a few specific coagulopathies and thrombotic emergencies Coagulation u Coagulation is the process in which blood clots u Fibrinolysis is the process in which clot dissolves u Hemostasis is the stopping of bleeding or hemorrhage. u Ideally, hemostasis is a balance between coagulation and fibrinolysis Coagulation (classic pathways) Michael G. Crooks Simon P. Hart Eur Respir Rev 2015;24:392-399 Coagulation (another view) Gando, S. et al. (2016) Disseminated intravascular coagulation Nat. Rev. Dis. Primers doi:10.1038/nrdp.2016.37 Coagulation (yet another view) u Inflammation and coagulation intersect with platelets in the middle u An example of this is Disseminated Intravascular Coagulation. Gando, S. et al. (2016) Disseminated intravascular coagulation Nat. Rev. Dis. Primers doi:10.1038/nrdp.2016.37 Outline u Review of hemostasis and coagulopathy u Discuss laboratory markers for coagulopathy u Discuss an approach to a few specific coagulopathies and thrombotic emergencies PT / INR u Prothrombin Time u Test of Extrinsic Pathway u Take plasma (blood without cells) and re-add calcium u Calcium was removed with citrate in tube u Add tissue factor u See how long it takes to clot and normalize PT to get INR Coagulation (classic pathways) Michael G. -
Diagnosis of Hemophilia and Other Bleeding Disorders
Diagnosis of Hemophilia and Other Bleeding Disorders A LABORATORY MANUAL Second Edition Steve Kitchen Angus McCraw Marión Echenagucia Published by the World Federation of Hemophilia (WFH) © World Federation of Hemophilia, 2010 The WFH encourages redistribution of its publications for educational purposes by not-for-profit hemophilia organizations. For permission to reproduce or translate this document, please contact the Communications Department at the address below. This publication is accessible from the World Federation of Hemophilia’s website at www.wfh.org. Additional copies are also available from the WFH at: World Federation of Hemophilia 1425 René Lévesque Boulevard West, Suite 1010 Montréal, Québec H3G 1T7 CANADA Tel.: (514) 875-7944 Fax: (514) 875-8916 E-mail: [email protected] Internet: www.wfh.org Diagnosis of Hemophilia and Other Bleeding Disorders A LABORATORY MANUAL Second Edition (2010) Steve Kitchen Angus McCraw Marión Echenagucia WFH Laboratory WFH Laboratory (co-author, Automation) Training Specialist Training Specialist Banco Municipal Sheffield Haemophilia Katharine Dormandy de Sangre del D.C. and Thrombosis Centre Haemophilia Centre Universidad Central Royal Hallamshire and Thrombosis Unit de Venezuela Hospital The Royal Free Hospital Caracas, Venezuela Sheffield, U.K. London, U.K. on behalf of The WFH Laboratory Sciences Committee Chair (2010): Steve Kitchen, Sheffield, U.K. Deputy Chair: Sukesh Nair, Vellore, India This edition was reviewed by the following, who at the time of writing were members of the World Federation of Hemophilia Laboratory Sciences Committee: Mansoor Ahmed Clarence Lam Norma de Bosch Sukesh Nair Ampaiwan Chuansumrit Alison Street Marión Echenagucia Alok Srivastava Andreas Hillarp Some sections were also reviewed by members of the World Federation of Hemophilia von Willebrand Disease and Rare Bleeding Disorders Committee. -
Tracking Oxidation-Induced Alterations in Fibrin Clot Formation by NMR
www.nature.com/scientificreports OPEN Tracking oxidation‑induced alterations in fbrin clot formation by NMR‑based methods Wai‑Hoe Lau1, Nathan J. White2, Tsin‑Wen Yeo1,4, Russell L. Gruen3* & Konstantin Pervushin5* Plasma fbrinogen is an important coagulation factor and susceptible to post‑translational modifcation by oxidants. We have reported impairment of fbrin polymerization after exposure to hypochlorous acid (HOCl) and increased methionine oxidation of fbrinogen in severely injured trauma patients. Molecular dynamics suggests that methionine oxidation poses a mechanistic link between oxidative stress and coagulation through protofbril lateral aggregation by disruption of AαC domain structures. However, experimental evidence explaining how HOCl oxidation impairs fbrinogen structure and function has not been demonstrated. We utilized polymerization studies and two dimensional‑nuclear magnetic resonance spectrometry (2D‑NMR) to investigate the hypothesis that HOCl oxidation alters fbrinogen conformation and T2 relaxation time of water protons in the fbrin gels. We have demonstrated that both HOCl oxidation of purifed fbrinogen and addition of HOCl‑ oxidized fbrinogen to plasma fbrinogen solution disrupted lateral aggregation of protofbrils similarly to competitive inhibition of fbrin polymerization using a recombinant AαC fragment (AαC 419–502). DOSY NMR measurement of fbrinogen protons demonstrated that the difusion coefcient of fbrinogen increased by 17.4%, suggesting the oxidized fbrinogen was more compact and fast motion in the prefbrillar state. 2D‑NMR analysis refected that water protons existed as bulk water (T2) and intermediate water (T2i) in the control plasma fbrin. Bulk water T2 relaxation time was increased twofold and correlated positively with the level of HOCl oxidation. However, T2 relaxation of the oxidized plasma fbrin gels was dominated by intermediate water.