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Article ; Online: Hepcidin and the Anemia of Critical Illness.

Houston, Donald S

2018 Volume 46, Issue 6, Page(s) 1030–1031

MeSH term(s)	Anemia ; Critical Care ; Critical Illness ; Hepcidins ; Humans ; Prospective Studies
Chemical Substances	Hepcidins
Language	English
Publishing date	2018-05-15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000003100
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Zs.A 1261: Show issues

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Article ; Online: The riddle of thrombocytopenia following transcatheter aortic valve implantation.

Houston, Donald S

Thrombosis research

2017 Volume 156, Page(s) 193–194

MeSH term(s)	Aortic Valve Stenosis/surgery ; Cardiac Catheterization ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Thrombocytopenia ; Transcatheter Aortic Valve Replacement ; Treatment Outcome
Language	English
Publishing date	2017
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2017.06.019
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Zs.A 863: Show issues

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Article: Bleeding by the numbers: The utility and the limitations of bleeding scores, bleeding prediction tools, and bleeding case definitions.

Rimmer, Emily K / Houston, Donald S

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2018 Volume 57, Issue 4, Page(s) 458–462

Abstract: A patient's history of bleeding, whether spontaneous or in response to challenges, provides important information about both the likelihood of that patient having a biochemically-defined hemostatic defect, and that patient's risk of future bleeding. ... ...

Abstract	A patient's history of bleeding, whether spontaneous or in response to challenges, provides important information about both the likelihood of that patient having a biochemically-defined hemostatic defect, and that patient's risk of future bleeding. Other variables including age, comorbidities and medications influence these probabilities. Scoring systems have been devised in an effort to make the estimates quantitative in specific populations. An example of a bleeding score is the MCMDM1-VWD questionnaire, which was developed to predict the likelihood of a patient having von Willebrand disease. It sums standardized details of the bleeding history, weighted by severity. The HAS-BLED score typifies bleeding prediction tools, developed to predict bleeding during anticoagulant therapy. Although prior bleeding is one item in this score, other comorbidities like hypertension or a history of stroke count for more. A third and related concept is that of bleeding case definitions, which are critical to standardize the reporting of outcomes in trials of antithrombotic agents, and which have entrenched the recognition of different severities of bleeding. We advocate that future efforts should blend some of these features. Information about comorbidities and medication use could refine the interpretation of bleeding events in a bleeding score. So could the introduction of a denominator reflecting the number and duration of challenges to which the patient has been exposed when bleeding might have been expected. More detailed information about the type, frequency and severity of prior bleeding could improve the prognostic power of bleeding prediction tools. More detailed history-based scores might ultimately supersede biochemical testing in many cases.
MeSH term(s)	Female ; Hemorrhage ; Hemostatics/metabolism ; Humans ; Male
Chemical Substances	Hemostatics
Language	English
Publishing date	2018-07-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2018.07.004
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Zs.A 1739: Show issues

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Article ; Online: Acquired haemophilia A: A 15-year population-based review of incidence rate, patient demographics and treatment outcomes.

Tian, Chantal / Perija, Brittany / Kotb, Rami / Houston, Brett L / Israels, Sara J / Houston, Donald S / Rimmer, Emily / Zarychanski, Ryan

Haemophilia : the official journal of the World Federation of Hemophilia

2023 Volume 29, Issue 5, Page(s) 1269–1275

Abstract: Introduction: Acquired haemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies against coagulation factor VIII (FVIII). Estimates of AHA incidence are largely based on registry data, which may be prone to referral bias. ... ...

Abstract	Introduction: Acquired haemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies against coagulation factor VIII (FVIII). Estimates of AHA incidence are largely based on registry data, which may be prone to referral bias. Population-based studies can enhance our understanding of the epidemiology, presentation and outcomes of AHA. Methods: We conducted a retrospective, population-based cohort study of all AHA diagnosed and treated in Manitoba, Canada over a 15-year period. Using records from the sole provincial reference laboratory, we identified all patients with FVIII inhibitors who did not have congenital haemophilia. Using a piloted case report form, patient data was ascertained from hospital and bleeding disorder clinic records. Results: From 2006 to 2021, we identified 34 patients with AHA, corresponding to a population-based incidence rate of AHA of 1.78 cases per million per year. The median age at presentation was 76 years and most cases were idiopathic (79%). Almost all patients (97%) presented with bleeding, of which 58% were considered major bleeds and required haemostatic agents in 67%. Longstanding unexplained bleeding symptoms were commonly reported, suggesting delayed diagnosis. Immunosuppressive therapy (IST) was administered in 88% of patients. Remission was achieved in 79% of patients; median time to remission was 2.1 months. There were two deaths due to bleeding. No deaths due to IST were reported. Conclusion: The population-based incidence of AHA in Manitoba is 1.78 cases/million/year. Bleeding is common and can be life-threatening. AHA outcomes are encouraging with the use of haemostatic agents and IST. Serious treatment-associated morbidity and mortality is uncommon.
MeSH term(s)	Humans ; Hemophilia A/drug therapy ; Hemophilia A/epidemiology ; Incidence ; Cohort Studies ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14845
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Zs.A 4249: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 450: Show issues

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Article ; Online: Assessing thrombocytopenia in the intensive care unit: the past, present, and future.

Zarychanski, Ryan / Houston, Donald S

Hematology. American Society of Hematology. Education Program

2017 Volume 2017, Issue 1, Page(s) 660–666

Abstract: Thrombocytopenia is common among patients admitted to the intensive care unit (ICU). Multiple pathophysiological mechanisms may contribute, including thrombin-mediated platelet activation, dilution, hemophagocytosis, extracellular histones, ADAMTS13 ... ...

Abstract	Thrombocytopenia is common among patients admitted to the intensive care unit (ICU). Multiple pathophysiological mechanisms may contribute, including thrombin-mediated platelet activation, dilution, hemophagocytosis, extracellular histones, ADAMTS13 deficiency, and complement activation. From the clinical perspective, the development of thrombocytopenia in the ICU usually indicates serious organ system derangement and physiologic decompensation rather than a primary hematologic disorder. Thrombocytopenia is associated with bleeding, transfusion, and adverse clinical outcomes including death, though few deaths are directly attributable to bleeding. The assessment of thrombocytopenia begins by looking back to the patient's medical history and presenting illness. This past information, combined with careful observation of the platelet trajectory in the context of the patient's clinical course, offers clues to the diagnosis and prognosis. Management is primarily directed at the underlying disorder and transfusion of platelets to prevent or treat clinical bleeding. Optimal platelet transfusion strategies are not defined, and a conservative approach is recommended.
MeSH term(s)	Critical Care/methods ; Humans ; Intensive Care Units ; Platelet Transfusion ; Thrombocytopenia/blood ; Thrombocytopenia/etiology ; Thrombocytopenia/therapy
Language	English
Publishing date	2017-12-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2084287-9
ISSN	1520-4383 ; 1520-4391
ISSN (online)	1520-4383
ISSN	1520-4391
DOI	10.1182/asheducation-2017.1.660
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Article ; Online: Transfusion thresholds in high-risk patients after hip surgery.

Houston, Donald S / Zarychanski, Ryan

The New England journal of medicine

2012 Volume 366, Issue 13, Page(s) 1253; author reply 1254–5

MeSH term(s)	Erythrocyte Transfusion ; Female ; Hip Fractures/surgery ; Humans ; Male
Language	English
Publishing date	2012-03-29
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1201459#SA1
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Ua VI Zs.34: Show issues

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Article ; Online: White blood cell count trajectory and mortality in septic shock: a historical cohort study.

Rimmer, Emily / Garland, Allan / Kumar, Anand / Doucette, Steve / Houston, Brett L / Menard, Chantalle E / Leeies, Murdoch / Turgeon, Alexis F / Mahmud, Salah / Houston, Donald S / Zarychanski, Ryan

Canadian journal of anaesthesia = Journal canadien d'anesthesie

2022 Volume 69, Issue 10, Page(s) 1230–1239

Abstract: Purpose: Septic shock is associated with a mortality of 20-40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information ...

Title translation	Évolution de la numération leucocytaire et mortalité en cas de choc septique : une étude de cohorte historique.
Abstract	Purpose: Septic shock is associated with a mortality of 20-40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information about outcomes. We aimed to identify groups of patients with different WBC trajectories and the association of WBC trajectory with mortality. Methods: We included adult patients with septic shock in two academic intensive care units (ICU) in Winnipeg, MB, Canada between 2006 and 2012. We used group-based trajectory analysis to group patients according to their WBC patterns over the first seven days in the ICU. Our primary analysis was the association of WBC trajectory group on 30-day mortality using multivariable Cox proportional hazards regression. Results: We included 917 patients with septic shock. The final model identified seven distinct WBC trajectories. The rising WBC trajectory was independently associated with increased mortality (hazard ratio, 3.41; 95% confidence interval, 1.86 to 6.26; P < 0.001) compared with the stable WBC trajectory. Conclusion: In patients with septic shock, distinct and clinically relevant groups can be identified by analyzing WBC trajectories. A rising WBC trajectory was associated with higher mortality.
MeSH term(s)	Adult ; Cohort Studies ; Humans ; Intensive Care Units ; Leukocyte Count ; Prognosis ; Retrospective Studies ; Shock, Septic
Language	English
Publishing date	2022-07-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	91002-8
ISSN	1496-8975 ; 0832-610X
ISSN (online)	1496-8975
ISSN	0832-610X
DOI	10.1007/s12630-022-02282-5
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Zs.A 109: Show issues

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Article ; Online: Clinical characterization and hematopoietic stem cell transplant outcomes for congenital sideroblastic anemia caused by a novel pathogenic variant in SLC25A38.

Uminski, Kelsey / Houston, Donald S / Hartley, Jessica N / Liu, Jing / Cuvelier, Geoffrey D E / Israels, Sara J

Pediatric blood & cancer

2020 Volume 67, Issue 10, Page(s) e28623

Abstract: Background: Congenital sideroblastic anemia (CSA) constitutes an uncommon category of inherited anemia often associated with pathologic iron accumulation. Pathogenic variants in several genes have been identified as causative for CSA. Autosomal ... ...

Abstract	Background: Congenital sideroblastic anemia (CSA) constitutes an uncommon category of inherited anemia often associated with pathologic iron accumulation. Pathogenic variants in several genes have been identified as causative for CSA. Autosomal recessive pathogenic variants in the mitochondrial glycine transporter SLC25A38 have been implicated in a subset of patients with CSA. Procedure: We describe seven individuals of Canadian Cree descent with a known or inferred homozygous novel founder missense variant in SLC25A38 (c.560G>A, p.Arg187Gln). Results: All individuals presented as young children (median age 6 months) with severe microcytic, hypochromic anemia associated with pretransfusion iron overload, requiring red cell transfusion support and iron chelation. Six individuals received pyridoxine supplementation; two demonstrating transient partial responses. Three individuals underwent allogeneic hematopoietic stem cell transplantation (HSCT). One individual with significant iron loading died in the posttransplant period due to complications of sepsis. The other two individuals remain transfusion-free following HSCT. Conclusions: Despite a common genetic etiology, phenotypic variability was noted in this cohort. A transient response to pyridoxine was noted in two individuals but should not be considered a long-term therapeutic strategy. HSCT was curative when performed before significant iron loading occurred. Early identification of CSA and timely HSCT can result in excellent long-term outcomes.
MeSH term(s)	Anemia, Sideroblastic/genetics ; Anemia, Sideroblastic/pathology ; Anemia, Sideroblastic/therapy ; Child, Preschool ; Female ; Follow-Up Studies ; Genetic Diseases, X-Linked/genetics ; Genetic Diseases, X-Linked/pathology ; Genetic Diseases, X-Linked/therapy ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Infant ; Male ; Mitochondrial Membrane Transport Proteins/genetics ; Mutation ; Prognosis ; Retrospective Studies
Chemical Substances	Mitochondrial Membrane Transport Proteins ; Slc25a38 protein, human
Language	English
Publishing date	2020-08-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.28623
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Zs.A 1131: Show issues

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Article ; Online: Tissue factor - a therapeutic target for thrombotic disorders.

Houston, Donald S

Expert opinion on therapeutic targets

2002 Volume 6, Issue 2, Page(s) 159–174

Abstract: Exposure of blood to tissue factor (TF) sets off the coagulation cascade. TF is a transmembrane protein that serves as an essential cofactor for activated coagulation factor VII (FVIIa). TF may be exposed locally by vascular injury (such as balloon ... ...

Abstract	Exposure of blood to tissue factor (TF) sets off the coagulation cascade. TF is a transmembrane protein that serves as an essential cofactor for activated coagulation factor VII (FVIIa). TF may be exposed locally by vascular injury (such as balloon angioplasty) or by spontaneous rupture of an atherosclerotic plaque. Expression of TF may also be induced on monocytes and endothelial cells in conditions like sepsis and cancer, causing a more generalised activation of clotting. TF may thus play a central role in thrombosis in a number of settings, and attention has turned to blocking TF as a means to prevent thrombosis. Inhibiting the inducible expression of TF by monocytes can be achieved by 'deactivating' cytokines, such as interleukin (IL)-4, -10 and -13, or by certain prostanoids; by drugs that modify signal transduction, such as pentoxifylline, retinoic acid or vitamin D(3), or by antisense oligonucleotides. Such approaches are for the most part at a preclinical stage. The function of TF can be blocked by antibodies that prevent the binding of FVIIa to TF; by active site-inhibited FVIIa, which competes with native FVIIa for binding; by antibodies or small molecules that block the function of the TF/FVIIa complex; and by molecules, such as TF pathway inhibitor or nematode anticoagulant peptide C2, which inhibit the active site of FVIIa in the TF/FVIIa complex after first binding to activated factor X. The latter two agents have entered Phase II clinical trials. Perhaps most intriguing is the use of anti-TF agents locally, which holds the promise of stopping thrombosis at a specific site of injury without the bleeding risk associated with systemic anticoagulation.
MeSH term(s)	Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Arteriosclerosis/blood ; Arteriosclerosis/complications ; Blood Coagulation/drug effects ; Blood Coagulation/physiology ; Clinical Trials as Topic ; Cytokines/antagonists & inhibitors ; Cytokines/physiology ; Drug Design ; Endothelium, Vascular/metabolism ; Enzyme Activation/drug effects ; Factor VIIa/antagonists & inhibitors ; Factor VIIa/physiology ; Fibrinolytic Agents/adverse effects ; Fibrinolytic Agents/pharmacology ; Fibrinolytic Agents/therapeutic use ; Glycoproteins/physiology ; Helminth Proteins/pharmacology ; Helminth Proteins/therapeutic use ; Hemorrhage/chemically induced ; Hemorrhage/prevention & control ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Lipoproteins/physiology ; Mice ; Monocytes/drug effects ; Monocytes/metabolism ; Multiprotein Complexes ; Neoplasms/blood ; Neoplasms/complications ; Oligonucleotides, Antisense/pharmacology ; Oligonucleotides, Antisense/therapeutic use ; Prostaglandins/physiology ; Signal Transduction/drug effects ; Swine ; Swine, Miniature ; Thrombophilia/drug therapy ; Thrombophilia/physiopathology ; Thromboplastin/antagonists & inhibitors ; Thromboplastin/immunology ; Thromboplastin/physiology ; Thrombosis/drug therapy ; Thrombosis/physiopathology
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Antibodies, Monoclonal ; Cytokines ; Fibrinolytic Agents ; Glycoproteins ; Helminth Proteins ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins ; Multiprotein Complexes ; Oligonucleotides, Antisense ; Prostaglandins ; lipoprotein-associated coagulation inhibitor ; tissue-factor-pathway inhibitor 2 ; Thromboplastin (9035-58-9) ; Factor VIIa (EC 3.4.21.21)
Language	English
Publishing date	2002-09-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1517/14728222.6.2.159
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Zs.A 5244: Show issues

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Article ; Online: Transfusion in orthopaedic surgery : a retrospective multicentre cohort study.

Blankstein, Anna R / Houston, Brett L / Fergusson, Dean A / Houston, Donald S / Rimmer, Emily / Bohm, Eric / Aziz, Mina / Garland, Allan / Doucette, Steve / Balshaw, Robert / Turgeon, Alexis / Zarychanski, Ryan

Bone & joint open

2021 Volume 2, Issue 10, Page(s) 850–857

Abstract: Aims: Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe ... ...

Abstract	Aims: Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. Methods: We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. Results: Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. Conclusion: Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies. Cite this article:
Language	English
Publishing date	2021-10-19
Publishing country	England
Document type	Journal Article
ISSN	2633-1462
ISSN (online)	2633-1462
DOI	10.1302/2633-1462.210.BJO-2021-0077.R1
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