DOCSLIB.ORG

Population Differences in the Frequency of the Factor V Leiden Variant Among People with Clinically Symptomatic Protein C Defici

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Population Differences in the Frequency of the Factor V Leiden Variant Among People with Clinically Symptomatic Protein C Defici 7 Med Genet 1995;32:543-545 543 Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency J Med Genet: first published as 10.1136/jmg.32.7.543 on 1 July 1995. Downloaded from Paula J Hallam, David S Millar, Michael Krawczak, Vijay V Kakkar, David N Cooper Abstract geographical origin, all of whom shared a per- The factor V Leiden variant, responsible sonal history of venous thrombosis. for the phenomenon of activated protein C resistance, was found to be less frequent among British (0.06) and Swedish/Danish Materials and methods (0'15) protein C deficiency patients than PROTEIN C DEFICIENCY PATIENTS previously reported in a Dutch study Blood samples from 120 unrelated patients (0.19). In the Swedish population, a sig- with (1) a personal history of venous throm- nificantly increased frequency ofthe factor bosis, (2) a reduced level of protein C antigen V Leiden allele was apparent in protein C or activity, and (3) a family history of protein deficiency patients as compared to healthy C deficiency or venous thrombosis or both, controls. However, this was not found in were collected for analysis. The majority of the British population. Coinheritance of these patients came from either Great Britain the factor V Leiden variant is therefore (white origin, n = 47) or Scandinavia (Swedish/ unlikely to be the sole determinant of Danish, n = 34) while the remainder was of whether a person with protein C deficiency variable geographical ethnic origin, including will come to clinical attention. Never- whites of other nationalities, AfroCaribbeans, theless, when patient data were analysed and Asians. A sample of 173 healthy people by type of protein C deficiency, it was (108 German, 65 British; all white) was se- noted that the frequency of the factor V lected as controls. Leiden variant was 2-8-fold higher in type II patients compared to type I patients. A possible explanation of this disparity is SCREENING FOR THE FACTOR V LEIDEN LESION Charter discussed. Molecular Genetics A 222 bp fragment of the factor V gene Laboratory, containing exon 10 (the location of the Thrombosis (J Med Genet 1995;32:543-545) CGA-.CAA transition responsible for the http://jmg.bmj.com/ Research Institute, Manresa Road, Arg506--Gln substitution in FV Leiden) was London A high prevalence of the newly discovered fac- PCR amplified from DNA derived from the 120 SW3 6LR, UK tor V (FV) Leiden variant (Arg506-+Gln),' protein C deficient patients and 173 controls as P J Hallam D S Millar responsible for the phenomenon of activated described.' The amplified fragments were slot V V Kakkar protein C (APC) resistance,2-6 has been re- blotted onto duplicate Genescreen filters which D N Cooper cently reported in subjects with clinically symp- were then hybridised to end labelled sequence Institut fir tomatic protein C deficiency.7 Coinheritance specific oligonucleotide probes to discriminate on September 25, 2021 by guest. Protected copyright. Humangenetik, of this frequent variant with a protein C gene between the wild type allele and the FV Leiden Medizinische lesion could therefore explain the difference in variant.' Filters were subsequently washed at Hochschule, the discriminant temperature for 20 D-30623, thrombotic risk noted between families with (58°C) Hannover, Germany clinically symptomatic (overt) protein C de- minutes in 3 mol/l tetramethylammonium M Krawcz#k ficiency and those with the much more com- chloride before autoradiography."' Correspondence to: mon clinically asymptomatic (covert) Dr Cooper. deficiency state.89 In order to examine this Received 9 December 1994 postulate, we have determined the prevalence Results and discussion Revised version accepted for publication 17 February of the FV Leiden variant among unrelated FV LEIDEN ALLELE FREQUENCY IN PATIENTS 1995 protein C deficient patients of different ethnic/ AND CONTROLS In our sample (table 1), the frequency of the FV Leiden variant was found to be significantly Table I Frequency ofFV Leiden variant in subjects with inherited protein C deficiency lower among British patients (0 064) than and controls by geographical origin noted previously in a Dutch study7 (0- 190, n = Group No FV Leiden FV Leiden FV Leiden allele 48). Comparison by means of a small sample heterozygotes homozygotes frequency Fisher permutation test assigned an error prob- Controls ability of p = 0009 to this finding. Among British 65 4 0 0-031 German 108 7 0 0-032 Swedish/Danish protein C deficient patients, Patients however, the frequency of FV Leiden (0-147) British 47 4 1 (4-2) 0-064 was intermediate and failed to differ sig- Swedish/Danish 34 6 2 0-147 Others 39 0 0 0-000 nificantly from both the British and Dutch data, most probably because of the com- Figure in brackets denotes the relative risk of protein C deficiency conferred by homozygosity for the FV Leiden variant. Others: patients of diverse ethnic origin other than British or Swedish/ paratively small sample size. In the control Danish. group, by contrast, the prevalence ofFV Leiden 544 Hallam, Millar, Krawczak, Kakkar, Cooper Table 2 Frequency of FV Leiden variant by protein C deficiency type table 1), were analysed by type of protein C Protein C deficiency type No FV Leiden FV Leiden FV Leiden allele deficiency, it was noted that the frequency of heterozygotes homozygotes frequency the FV Leiden variant was 2-8-fold higher in I 80 5 2 0-056 type II patients than in type I patients (table II 13 2 1 0-154 Unknown 27 3 0 0-056 2). Although the significance ofthis observation J Med Genet: first published as 10.1136/jmg.32.7.543 on 1 July 1995. Downloaded from was borderline (Fisher's p=0 089), and thus Type I: plasma activity and antigen values concomitantly reduced. Type II: greater reduction in activity than in antigen reflecting the synthesis of a dysfunctional protein. awaits confirmation by further studies, we offer the following possible explanation. Together with protein S and factor V, APC forms a 1:1:1 stoichiometric complex on the variant (0.031) was similar to that noted in the phospholipid surface that is capable of in- normal Dutch (0 023),7 German (0032, table activating factor VIIIa. 5 The FV Leiden defect 1), and Swedish populations (0 035).4 is likely to reduce the level of this inactivating The extent of association between the FV complex. This is because thrombin generation Leiden allele and protein C deficiency thus is increased in APC resistant plasma owing to appears contentious. On one hand, the fre- the excess of factor Va."' Factor V activated by quency of the variant in British protein C de- thrombin is, however, inefficient as a cofactor ficient patients is only slightly higher than in in the inactivation of factor VIIIa.'5 Although controls from the same population (Fisher's the reduced synthesis of protein C, char- p = 020) and the relative risk" for protein C acteristic of type I protein C deficiency state, deficiency conferred by heterozygous or ho- would presumably reduce the level of factor mozygous carriership of the FV Leiden allele VIIIa inactivating complex still further, a nor- is 1 8. In Swedish protein C deficient patients, mal level offactor V is still available to wild type however, the frequency of the FV Leiden allele protein C molecules for complex formation. By is significantly higher than noted in healthy contrast, a dysfunctional (type II) protein C controls from the same population4 (p = molecule might still be able to interact with 0-0001, by reference to the underlying Ber- protein S and factor V to generate a non- nouilli distribution), and a relative risk of 4d1, functional complex. Once formed, this inactive conferred by heterozygous or homozygous car- complex could sequester factor V and protein riership of the FV Leiden allele, results when S thereby reducing the amount of factor V a Hardy-Weinberg equilibrium frequency of accessible to wild type protein C (it might also healthy non-carriers is assumed. compete with its functional counterpart for In summary, we conclude that the prevalence access to factor VIIIa). This reduction might of the FV Leiden variant among patients with explain why carriership of the FV Leiden vari- symptomatic protein C deficiency may not be ant increases the likelihood of clinical detection consistently as high as previously suggested7 more dramatically for type II protein C de- and that geographical differences in the pattern ficiency than for type I deficiency patients. of coinheritance of the two traits may exist. We are most the relative risk for grateful to the following colleagues who have http://jmg.bmj.com/ Nevertheless, higher protein contributed blood samples: NN Abdelshaheed, J Allgrove, C deficiency conferred by homozygosity for the E Bemtorp, D Bevan, P Bolton-Maggs, N de Bosch, J E Braith- FV Leiden variant 1, British waite, J F Burman, M Chisholm, B T Colvin, A Copplestone, (table patients), R Egbring, J T Epplen, I M Franklin, A Girolami, I R Grant, although subject to considerable sampling vari- P J Green, F G H Hill, S Holding, B J Hunt, N Lanir, B that C deficient Laursen, C Legnani, M Layton, P M Mannucci, E Melissari, ance, suggests protein subjects U Martinowitz, A Minford, E H Moffat, J Reiss, J C Reverter, who are homozygous for the FV Leiden variant J Reynaud, M Ryynanen, B Schneider-Ratzke, M Stuhrmann, are more likely to come to clinical attention S Schulamn, G L Scott, R Simioni, L Tengborn, E G D are Tuddenham, J Voke, R Wensley, M Winter, P Woods, B Zoll. than those who heterozygous. The generous financial support ofCharter plc, British-American on September 25, 2021 by guest.
Load more

Recommended publications
  • Protein C Deficiency
    Protein C deficiency Description Protein C deficiency is a disorder that increases the risk of developing abnormal blood clots; the condition can be mild or severe. Individuals with mild protein C deficiency are at risk of a type of blood clot known as a deep vein thrombosis (DVT). These clots occur in the deep veins of the arms or legs, away from the surface of the skin. A DVT can travel through the bloodstream and lodge in the lungs, causing a life-threatening blockage of blood flow known as a pulmonary embolism (PE). While most people with mild protein C deficiency never develop abnormal blood clots, certain factors can add to the risk of their development. These factors include increased age, surgery, inactivity, or pregnancy. Having another inherited disorder of blood clotting in addition to protein C deficiency can also influence the risk of abnormal blood clotting. In severe cases of protein C deficiency, infants develop a life-threatening blood clotting disorder called purpura fulminans soon after birth. Purpura fulminans is characterized by the formation of blood clots in the small blood vessels throughout the body. These blood clots block normal blood flow and can lead to localized death of body tissue ( necrosis). Widespread blood clotting uses up all available blood clotting proteins. As a result, abnormal bleeding occurs in various parts of the body, which can cause large, purple patches on the skin. Individuals who survive the newborn period may experience recurrent episodes of purpura fulminans. Frequency Mild protein C deficiency affects approximately 1 in 500 individuals. Severe protein C deficiency is rare and occurs in an estimated 1 in 4 million newborns.
    [Show full text]
  • Cutaneous Findings in Patients on Anticoagulants Caleb Creswell, MD Dermatology Specialists Disclosure Information
    Cutaneous findings in patients on Anticoagulants Caleb Creswell, MD Dermatology Specialists Disclosure Information • I have no financial relationships to disclose Objectives 1) Identify underlying causes of actinic or senile purpura 2) Recognize coumadin skin necrosis and understand proper treatment 3) Recognize heparin skin necrosis and understand that underlying HIT is often present Actinic (Senile) Purpura • Common on forearms of elderly individuals • Most important factor is chronic sun exposure – Thins dermal collagen and blood vessel walls • Anticoagulants may exacerbate but are rarely the main culprit Actinic Purpura Actinic Purpura Leukocytoclastic Vasculitis • Don’t mistake LCV for actinic purpura Ecchymoses • No topical agents have been shown to speed resorption of RBCs and hemosiderin • Pulsed-dye Laser can help Coumadin Induced Skin Necrosis • Coumadin: Occurs between 3-5 days after initiating therapy – Due to transient protein C deficiency – Increased risk with intrinsic protein C deficiency – Occurs in areas with significant adipose tissue – Treatment: Heparinize and continue coumadin Coumadin Induced Skin Necrosis Other Coumadin Skin Reactions • Extremely rare cause of morbilliform drug rash • Can cause leukocytoclastic vasculitis – Can occur weeks to months after starting medication Photo of Morbilliform CADR Leukocytoclastic Vasculitis Heparin Induced Skin Necrosis • Heparin: Occurs 1-14 days after starting – Often starts at injection site and spreads – Due to HIT Type II (Thrombocytopenia will be present) Heparin Induced
    [Show full text]
  • Protein C Product Monograph 1995 COAMATIC® Protein C Protein C
    Protein C Product Monograph 1995 COAMATIC® Protein C Protein C Protein C, Product Monograph 1995 Frank Axelsson, Product Information Manager Copyright © 1995 Chromogenix AB. Version 1.1 Taljegårdsgatan 3, S-431 53 Mölndal, Sweden. Tel: +46 31 706 20 00, Fax: +46 31 86 46 26, E-mail: [email protected], Internet: www.chromogenix.se COAMATIC® Protein C Protein C Contents Page Preface 2 Introduction 4 Determination of protein C activity with 4 snake venom and S-2366 Biochemistry 6 Protein C biochemistry 6 Clinical Aspects 10 Protein C deficiency 10 Assay Methods 13 Protein C assays 13 Laboratory aspects 16 Products 17 Diagnostic kits from Chromogenix 17 General assay procedure 18 COAMATIC® Protein C 19 References 20 Glossary 23 3 Protein C, version 1.1 Preface The blood coagulation system is carefully controlled in vivo by several anticoagulant mechanisms, which ensure that clot propagation does not lead to occlusion of the vasculature. The protein C pathway is one of these anticoagulant systems. During the last few years it has been found that inherited defects of the protein C system are underlying risk factors in a majority of cases with familial thrombophilia. The factor V gene mutation recently identified in conjunction with APC resistance is such a defect which, in combination with protein C deficiency, increases the thrombosis risk considerably. The Chromogenix Monographs [Protein C and APC-resistance] give a didactic and illustrated picture of the protein C environment by presenting a general view of medical as well as technical matters. They serve as an excellent introduction and survey to everyone who wishes to learn quickly about this field of medicine.
    [Show full text]
  • PROTEIN C DEFICIENCY 1215 Adulthood and a Large Number of Children and Adults with Protein C Mutations [6,13]
    Haemophilia (2008), 14, 1214–1221 DOI: 10.1111/j.1365-2516.2008.01838.x ORIGINAL ARTICLE Protein C deficiency N. A. GOLDENBERG* and M. J. MANCO-JOHNSON* *Hemophilia & Thrombosis Center, Section of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Colorado Denver and The ChildrenÕs Hospital, Aurora, CO; and Division of Hematology/ Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA Summary. Severe protein C deficiency (i.e. protein C ment of acute thrombotic events in severe protein C ) activity <1 IU dL 1) is a rare autosomal recessive deficiency typically requires replacement with pro- disorder that usually presents in the neonatal period tein C concentrate while maintaining therapeutic with purpura fulminans (PF) and severe disseminated anticoagulation; protein C replacement is also used intravascular coagulation (DIC), often with concom- for prevention of these complications around sur- itant venous thromboembolism (VTE). Recurrent gery. Long-term management in severe protein C thrombotic episodes (PF, DIC, or VTE) are common. deficiency involves anticoagulation with or without a Homozygotes and compound heterozygotes often protein C replacement regimen. Although many possess a similar phenotype of severe protein C patients with severe protein C deficiency are born deficiency. Mild (i.e. simple heterozygous) protein C with evidence of in utero thrombosis and experience deficiency, by contrast, is often asymptomatic but multiple further events, intensive treatment and may involve recurrent VTE episodes, most often monitoring can enable these individuals to thrive. triggered by clinical risk factors. The coagulopathy in Further research is needed to better delineate optimal protein C deficiency is caused by impaired inactiva- preventive and therapeutic strategies.
    [Show full text]
  • Congenital Protein C Deficiency: Family Report from Argentina
    Frontiers in Medical Case Reports | October 2020 | Volume 01| Issue 05 | PAGE 1-05 Veron D et al., Congenital Protein C Deficiency: Family Report from Argentina Case Report Congenital Protein C Deficiency: Family Report from Argentina David Veron1*, Mariana Varela1, Claudio Rosa2, Diego Colimodio2, Mercedes Rojas2, Sofía Juárez Peñalva3, Gabriel Musante4 and Manuel Rocca Rivarola5 *Corresponding author: David Veron Address: 1Division of Hematology and Oncology, Department of Pediatrics, Hospital Universitario Austral, Pilar, Argentina; 2Central Laboratory, Hospital Universitario Austral, Pilar, Argentina; 3Division of Genetics, Department of Pediatrics, Hospital Universitario Austral, Pilar, Argentina; 4Division of Neonatology, Department of Pediatrics, Hospital Universitario Austral, Pilar, Argentina; 5Department of Pediatrics, Hospital Universitario Austral, Pilar, Argentina e-mail [email protected] Received: 26 September 2020; Accepted: 02 October 2020 ABSTRACT Severe Congenital Protein C Deficiency occurs with an incidence of 1 per 4 million births. Due to the exceptional nature of this entity and the little experience in the literature, we propose to make known some main points of interest of this family. Keywords: Neonatal thrombosis, Purpura fulminans, Protein C 1 Introduction The incidence of asymptomatic Protein C (PC) deficiency has been reported to be between 1 in 200 and 1 in 500 healthy individuals. Based on a carrier rate of 0.2%, a homozygous or compound heterozygous PC deficiency incidence of 1 per 4 million births could be predicted. Due to the exceptional nature of this entity and the little experience in the literature, we propose to make known some main points of interest of this family. Family Report A 2-year-old girl with prenatal diagnosis of a Central Nervous System hemorrhage (Fig.
    [Show full text]
  • Congenital Thrombophilia
    Congenital thrombophilia The term congenital thrombophilia covers a range of Factor V Leiden and pregnancy conditions that are inherited by someone at birth. This means It is important that women with Factor V Leiden who are that their blood is sticker than normal, which increases the pregnant discuss this with their obstetrician as they have an risk of blood clots and thrombosis. increased risk of venous thrombosis during pregnancy. Some Factor V Leiden and Prothrombin 20210 are the most evidence suggests that they may also have a slightly higher common thrombophilias among people of European origin. risk of miscarriage and placental problems. Other congenital thrombophilias include Protein C Deficiency, Protein S Deficiency, and Antithrombin Deficiency. Prothrombin 20210 Prothrombin is one of the blood clotting factors. It circulates Factor V Leiden in the blood and when activated, is converted to thrombin. Factor V Leiden is by far the most common congenital Thrombin causes fibrinogen, another clotting factor, to thrombophilia. In the UK it is present in 1 in 20 individuals of convert to fibrin strands, which make up part of a clot. European origin. It is rare in people of Black or Asian origin. The condition known as Prothrombin 20210 is due to a Factor V Leiden is caused by a change in the gene for Factor mutation of the prothrombin gene. Individuals with the V, which helps the blood to clot. To stop a clot spreading a condition tend to have slightly stickier blood, due to higher natural blood thinner, known as Protein C, breaks down prothrombin levels. Factor V.
    [Show full text]
  • Protein C and S Deficiency, Thrombophilia, and Hypofibrinolysis: Pathophysiologic Causes of Legg-Perthes Disease
    0031-3998/94/3504.Q383$03.00/0 PEDIATRIC RESEARCH Vol. 35. No.4. 1994 Copyright © 1994 International Pediatric Research Foundation. Inc. Printed in U.S.A. Protein C and S Deficiency, Thrombophilia, and Hypofibrinolysis: Pathophysiologic Causes of Legg-Perthes Disease CHARLES J. GLUECK, HELEN I. GLUECK, DAVID GREENFIELD, RICHARD FREIBERG . ALFRED KAHN. TRACEY HAMER. DAVIS STROOP. AND TRENT TRACY Cholesterol Center. Jewish Hospital[CJ.G.. T.H.. T.T.}: Departments of Orthopedics, Jewish [D.G.. R.F.j and Christ /A.K.}Hospitals: and Departments 0/Pathology and Laboratory Medicine. University 0/Cincinnati College0/ Medicine[H./.G.. D.S.}. Cincinnati. Ohio45229 ABSTRACf. In eight patients with Legg-Perthes disease, be caused by intravascular thrombosis as a result of reduced we assessed the etiologic roles of thrombophilia caused by fibrinolysis (9). protein C and protein S deficiency and hypofibrinolysis We have recently shown that hypofibrinolysis mediated by mediated by low levels of tissue plasminogen activator high levels of the major inhibitor of fibrinolysis, PAl, is a activity. We speculated that thrombosis or hypofibrinolysis common major cause of idiopathic osteonecrosis (10, 11). Nine were common causes of Legg-Perthes disease. Three of of 12 adults with idiopathic osteonecrosis had high levels of PAl the eight patients had protein C deficiency; they came from with hypofibrinolysis (10, 11). The thrombogenic, atherogenic kindreds with previously undiagnosed protein C deficiency. apolipoprotein, Lp(a), was elevated in 14 of 18 patients with In one of these three kindreds there were six protein C­ secondary osteonecrosis, and protein C deficiency was present in deficient family members (beyond the proband child), four I of the 18 patients, suggesting that thrombophilia and hypofi­ of whom had thrombotic events as adults.
    [Show full text]
  • Two Cases of Recurrent Vascular Events Due to Protein C Deficiency
    linica f C l To o x l ic a o n r l o u g o y J Li et al., J Clin Toxicol 2015, 5:2 Journal of Clinical Toxicology DOI: 10.4172/2161-0495.1000243 ISSN: 2161-0495 Case Report Open Access Two Cases of Recurrent Vascular Events Due to Protein C Deficiency Honghong Li * Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China *Corresponding author: Honghong Li, M.D., Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 West Yanjiang Road, Guangzhou 510120, China, Tel: +86 20 8133 2620; Fax: +86 20 8133 2833; Email: [email protected] Received date: Mar 04, 2015; Accepted date: Apr 25, 2015; Published date: Apr 30, 2015 Copyright: © 2015 Li H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Protein C deficiency is a rare autosomal dominant disorder with a characteristic of hypercoagulation state and recurrent venous thrombosis in clinics. It is one important cause for youth vascular ishcaemic events including cerebral stroke. However, less attention was focused on the disorder of protein C deficiency so that misdiagnosis is very common. Here, we reported two cases of recurrent vascular ischaemic events due to protein C deficiency. They accepted warfarin and fresh frozen plasma respectively and fully recovered. Our report suggest the importance of early recognition of protein C deficiency in youth with recurrent vascular thrombosis and personalized management should be emphasized.
    [Show full text]
  • Hypercoagulable State Practice Guidelines
    Hypercoagulable State Practice Guidelines FOR EDUCATIONAL PURPOSES ONLY Washington State Clinical Laboratory Advisory Council The individual clinician is in the best position to determine which Originally Published November 2005 Reviewed/Revised: Sept. 2007/ May 2008/July 2010 tests are most appropriate for a particular patient Definition: Hypercoagulable state: balance of the coagulation system is tipped toward thrombosis, due to either acquired or inherited increase in pro-coagulant elements (e.g. cancer pro coagulant) or decrease in anti-coagulant elements (e.g. Protein C deficiency). Hypercoaguable states are suspected in patients who have: 1)" Spontaneous" thrombosis without obvious associated risk factors 4) Family history of recurrent venous thrombosis at an early age. 2) Thrombosis, even with a concomitant risk factor, at an early age (e.g. less than 40) 5) Thrombosis in unusual locations (for example: visceral thrombosis or upper extremity 3) Recurrent thrombosis, especially in different sites thrombosis) Acquired Disorders and applicable laboratory test Inherited Disorders and applicable laboratory test Initial testing for all patients: PT, aPTT, TT, Platelet, Fibrinogen Initial testing for all patients: PT, aPTT, TT, Platelet, Fibrinogen (Refer to Coagulation Guideline for Unexplained Bleeding Disorders on the reverse side) (Refer to Coagulation Guideline for Unexplained Bleeding Disorders on the reverse side) 1) Antiphospholipid antibody (aPL) Syndrome (Lupus anticoagulant) 1) Factor V Leiden/aPC resistance (most common) Tests: 1:1 mix showing inhibitor Test: aPC (activated Protein C) resistance assay OR DNA analysis for factor V Leiden - Hexagonal phase lupus inhibitor assay or dilute Russell viper venom time (dRVVT) both can determine if patient is heterozygote or homozygote Anticardiolipin or anti-beta-2-GPI antibodies by ELISA (with titers) 2) Factor II (Prothrombin G20210) polymorphism 2) Heparin induced thrombocytopenia (HIT) in appropriate clinical setting.
    [Show full text]
  • Coagulopathies Evangelina Berrios- Colon, Pharmd, MPH, BCPS, CACP • Julie Anne Billedo, Pharmd, BCACP
    CHAPTER33 Coagulopathies Evangelina Berrios- Colon, PharmD, MPH, BCPS, CACP • Julie Anne Billedo, PharmD, BCACP Coagulopathies include hemorrhage, thrombosis, and Activated protein C ( APC) inhibition is catalyzed by protein embolism, and represent common clinical manifestations of S, another vitamin K–dependent plasma protein, and also hematological disease. Normally, bleeding is controlled by requires the presence of platelet phospholipid and calcium. a fi brin clot formation, which results from the interaction Antithrombin III (AT III) primarily inhibits the activity of of platelets, plasma proteins, and the vessel wall. The fi brin thrombin and Factor X by binding to the factors and block- clot is ultimately dissolved through fi brinolysis. A derange- ing their activity. This inhibition is greatly enhanced by hep- ment of any of these components may result in a bleeding arin. Loss of function and/or decreased concentrations of or thrombotic disorder. In this chapter, individual disease these proteins result in uninhibited coagulation and hence a states are examined under the broad headings of coagulation predisposition to spontaneous thrombosis otherwise known factor defi ciencies, disorders of platelets, mixed disorders, as a hypercoagulable state. acquired thrombophilias, and inherited thrombophilias. Fibrinolysis is a mechanism for dissolving fi brin clots. Plasmin, the activated form of plasminogen, cleaves fi brin to produce soluble fragments. Fibrinolytics, such as tissue n ANATOMY, PHYSIOLOGY, AND PATHOLOGY plasminogen activator, streptokinase, and urokinase, acti- vate plasminogen, resulting in dissolution of a fi brin clot. Coagulation is initiated after blood vessels are damaged, enabling the interaction of blood with tissue factor, a pro- n CLASSES OF BLEEDING DISORDERS tein present beneath the endothelium ( Figure 33.1).
    [Show full text]
  • Relevance of Proteins C and S, Antithrombin III, Von Willebrand
    Bone Marrow Transplantation, (1998) 22, 883–888 1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http://www.stockton-press.co.uk/bmt Relevance of proteins C and S, antithrombin III, von Willebrand factor, and factor VIII for the development of hepatic veno-occlusive disease in patients undergoing allogeneic bone marrow transplantation: a prospective study J-H Lee1, K-H Lee1, S Kim1, J-S Lee1, W-K Kim1, C-J Park2, H-S Chi2 and S-H Kim1 Division of Oncology-Hematology, Departments of 1Medicine and 2Clinical Pathology, Asan Medical Center, University of Ulsan, Seoul, Korea Summary: ted venules. Factors that enhance hypercoagulability fol- lowing BMT may have a pathogenetic role in the Factors that enhance hypercoagulability following BMT development of VOD.4 In fact, a decrease in the natural may have a pathogenetic role in VOD. To investigate anticoagulants such as protein C,5,6 protein S5 and the relevance of hemostatic parameters for the develop- antithrombin III (AT III)6 as well as an increase in plasma ment of VOD, we prospectively measured protein C, fibrinogen4 and von Willebrand factor (vWF)7 have been protein S, antithrombin III (AT III), von Willebrand observed after BMT. Several investigators have reported factor, and factor VIII in 50 consecutive patients that these hemostatic derangements may have pathogenetic undergoing allogeneic BMT. Each parameter was relevance for the occurrence of VOD.8–10 determined before conditioning, on day 0 of BMT and In this study, we prospectively measured the levels of weekly for 3 weeks, and patients were monitored pro- protein C, protein S (total and free), AT III, vWF and factor spectively for the occurrence of VOD.
    [Show full text]
  • Von Willebrand's Disease
    Coagulopathy Case – 5 Andy Nguyen, M.D. 2009 CLINICAL HISTORY PATIENT: 45 year-old woman CLINICAL HISTORY This patient was admitted with massive hemoptysis. At the time of admission, she was receiving Coumadin (sodium warfarin) for superficial thrombophlebitis. The patient’s prothrombin time was 21 seconds, although she had not taken Coumadin since the day preceding admission MEDICAL HISTORY: The patient had an episode of deep vein thrombosis after the birth of her second daughter when she was 30 years old. The patient was placed on heparin, which was then followed by oral anticoagulants for 6 months. After a spontaneous abortion at the age of 32, the patient was placed on oral contraceptives. She subsequently experienced superficial left calf vein thrombophlebitis, and the oral contraceptives were discontinued. Two months prior to this admission, patient developed superficial thrombophlebitis of the legs that were not associated with trauma. Patient was started on Coumadin at that time. FAMILY HISTORY: The paternal grandfather, who died at 32 years of age, had a history of “swollen legs”. The patient’s father had a pulmonary embolism at 27 years of age after appendectomy, and he died suddenly at 42 years of age after an episode of DVT of the left leg. Also, a cousin died at 39 years of age after several episodes of thrombophlebitis. Another cousin, 63 years of age, had a number of problems with thrombotic disease, including a history of arterial embolism that necessitated amputation of the left leg at the knee. DRUG HISTORY: At the time of the initial evaluation, the patient was on no medication.
    [Show full text]