The historical origins of modern international normalized ratio targets.

Prothrombin time (PT) and its derivative international normalized ratio (INR) are frequently ordered to assess the coagulation system. Plasma transfusion to treat incidentally abnormal PT/INR is a common practice with low biological plausibility and without credible evidence, yet INR targets appear in major clinical guidelines and account for the majority of plasma use at many institutions. In this article, we review the historical origins of INR targets. We recount historical milestones in the development of the PT, discovery of vitamin K antagonists (VKAs), motivation for INR standardization, and justification for INR targets in patients receiving VKA therapy. Next, we summarize evidence for INR testing to assess bleeding risk in patients not on VKA therapy and plasma transfusion for treating mildly abnormal INR to prevent bleeding in these patients. We conclude with a discussion of the parallels in misunderstanding of historic PT and present-day INR testing with lessons from the past that might help rationalize plasma transfusion in the future.

El servicio de transfusión del ejército republicano durante la Guerra Civil Española y su influencia en Gran Bretaña en la Segunda Guerra Mundial / The blood transfusion service of the republican army during the Spanish Civil War and its influence in Great Britain in World War II

Al final de la Primera Guerra Mundial, el valor de la transfusión sanguínea era ampliamente reconocido, pero no fue hasta la Guerra Civil Española (1936-1939) cuando se crearon grandes organizaciones civiles de donantes de sangre para proporcionar sangre conservada (citratada) para la transfusión en pacientes civiles y militares en ambos bandos. Se desarrollaron técnicas de transfusión indirecta para administrar esta sangre, con instrumental de fácil manejo, capaz de ser llevado a cabo en cualquier lugar y por cualquiera con experiencia en la administración de inyecciones endovenosas. También se establecieron sistemas eficaces de transporte y distribución, a fin de abastecer adecuadamente las instalaciones sanitarias que prestaban servicio en los frentes de batalla en movimiento. Este trabajo pionero permitió la creación, por primera vez en la historia, de servicios militares de transfusión de sangre. Si bien este fue el caso tanto de las fuerzas insurgentes (nacionalistas) como del Gobierno republicano español, es este último el que constituye el foco de estudio aquí. Esto es posible gracias a las publicaciones del hematólogo catalán Frederic Duran Jordà, creador y director del Servicio Republicano de Transfusión de Sangre, que detallan las técnicas y procedimientos desarrollados durante la guerra para la recogida, análisis, distribución y transfusión de sangre. Esta información se amplía, especialmente con respecto a la aplicación práctica de la transfusión en primera línea, gracias a diferentes publicaciones del Dr. Reginald Saxton, voluntario británico integrado en la Sanidad Militar de la Republica. Es nuestra intención demostrar que las autoridades británicas se beneficiaron de la experiencia española en vísperas del estallido de la Segunda Guerra Mundial en 1939. Les ayudó a desarrollar planes para los servicios de transfusión que resultarían cruciales en el tratamiento de bajas civiles y militares durante la contienda. Frederic Duran Jordà y Reginald Saxton fueron asesores clave, junto con otros que regresaban de España, incluyendo a la reconocida hematóloga británica, Janet Vaughan. Además, los principios desarrollados en España (1936-39) para la práctica militar de transfusiones de sangre siguen respaldando las medidas actuales de reanimación de heridos en el campo de batalla.

By the end of the First World War, the value of blood transfusion was widely recognized, but it was not until the Spanish Civil War (1936-1939) that large civilian blood donor organizations were created to provide preserved (citrated) blood for transfusion, for both civilian and military patients. Indirect transfusion techniques were developed to administer this blood, with easy-to-use instruments, capable of being carried out anywhere and by any medical personnel with experience in the administration of intravenous injections. Efficient transportation and distribution systems were also established in order to adequately supply the sanitary facilities that served the moving battle fronts. This pioneering work enabled the creation, for the first time in history, of military blood transfusion services. While this was the case for both the insurgent (Nationalist) forces and those of the Spanish Republican Government, it is the latter that forms the focus of this particular study. This is made possible by the publications of Catalan hematologist Frederic Duran Jordà, creator and director of the Republican Blood Transfusion Service, who details the techniques and procedures developed during the war for the collection, testing, distribution and transfusion of blood. Further insight - especially with regard to the practical application of front-line transfusion - can be gleaned from the various writings of Dr Reginald Saxton, British volunteer with the Republican Sanidad Militar. It is the intention, here, to demonstrate that the British authorities benefitted greatly from the Spanish experience in the development of plans for transfusion services that would prove crucial in treating civilian and military casualties during World War II (1939-1945). Frederic Duran Jordà, and Reginald Saxton were key advisers, together with others returning from Spain, including renowned British hematologist, Janet Vaughan. Moreover, the principles developed in Spain (1936-39) for delivery of military blood transfusion practice still support current measures in battlefield casualty resuscitation.

Evaluating the appropriateness of platelet transfusions compared with evidence-based platelet guidelines: An audit of platelet transfusions at 57 hospitals.

BACKGROUND: Platelet transfusions are used to prevent or control bleeding in patients with thrombocytopenia or platelet dysfunction. The pretransfusion platelet count threshold has been studied extensively in multiple patient settings yielding high-quality evidence that has been summarized in several comprehensive evidence-based platelet guidelines. STUDY DESIGN AND METHODS: A prospective 12-week audit of consecutive platelet transfusions using validated and evidence-based adjudication criteria was conducted. Patient demographic, laboratory, and transfusion details were collected with an electronic audit tool. Each order was adjudicated either electronically or independently by two transfusion medicine physicians. The aim was to determine platelet transfusion appropriateness and common scenarios with deviations from guidelines. RESULTS: Fifty-seven (38%) of 150 hospitals provided data on 1903 platelet orders, representing 90% of platelet usage in the region during the time period. Overall, 702 of 1693 adult (41.5%) and 133 of 210 pediatric orders (63.3%) were deemed inappropriate. The most common inappropriate platelet order was for prophylaxis in the absence of bleeding or planned procedure in patients with hypoproliferative thrombocytopenia and a platelet count over 10 x 109 /L (53% of inappropriate orders in adults and 45% in pediatrics). Platelet transfusions ordered with either a preprinted transfusion order set (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.44-2.73) or technologist prospective screening (OR, 1.40; 95% CI, 1.10-1.78) were more likely to be appropriate. CONCLUSION: There is a discrepancy between clinical practice and evidence-based platelet guidelines. Broad educational and system changes will be needed to align platelet transfusion practice with guideline recommendations.

Transfusion in the Spanish Civil War: Supply and demand, the role of the "blood transfusion officer" and British planning for the outbreak of the Second World War.

During the First World War blood transfusion progressed from being a rarely used treatment to a major component of the resuscitation of exsanguinated casualties, relying on local donation and availability of medical expertise. In the 1920s and early 1930s, clinical use of transfusion gradually increased supported by growing civilian, often volunteer, blood donor systems. The Spanish Civil War (1936-1939) introduced the first systematic use of aerial bombardment to intimidate the civilian population and to destroy infrastructure; it also saw more mobile battlefronts, replacing the relatively static trench warfare of 1914-1918. New measures for the delivery of transfusion services emerged rapidly from primitive beginnings. These included large civilian blood donor organizations providing anti-coagulated "stored" blood for civilian and military medical use and land delivery services to civilian and military hospitals. Surgical units for the emergency management of casualties were required to be agile in moving as battlefronts evolved and carefully concealed to avoid air attack. Ideally the blood supply would follow. Under threat of a wider European conflict in 1938-1939, British authorities started developing plans for transfusion support in the management of civilian casualties of air attack and military casualties of armed conflict. The involvement, directly and indirectly, of British and other volunteer physicians returned from Spain, together with their Spanish colleagues, ensured that awareness of the Spanish experience was available to the British authorities. The system that was eventually put in place involved a civilian blood donor capability with one centre dedicated particularly to military supplies. Separate distribution systems were organized for civilian and military purposes, with the latter including distribution overseas by air. The military system delivered blood and components through a supply chain to mobile field transfusion units under command of a medical officer specially trained in transfusion and resuscitation, supporting mobile surgical units in the immediate rear of battlefronts. The broad principles developed in Spain (1936-39) for delivery of military blood transfusion practice still support current measures in battlefield casualty resuscitation.

Variations in RBC and frozen plasma utilization rates across 62 Ontario community hospitals.

BACKGROUND: Recent province-wide audits of frozen plasma (FP) and RBC use in Ontario showed a high rate of inappropriate transfusions. STUDY DESIGN AND METHODS: This was a retrospective, ecological study to determine variations in RBC and FP utilization rates across Ontario community hospitals between 2012 and 2017. Annual utilization rates were reported using descriptive statistics. Rates of blood component use were correlated with size of hospital, presence of specialized programs, and quality improvement (QI) initiatives, using Poisson regression. RESULTS: RBC and FP utilization rates decreased from 2012 to 2017 (p = 0.03 for FP; p < 0.01 for RBC). There was a 10-fold difference in RBC and FP transfusion rates between the highest and lowest users. Smaller hospitals (p < 0.05) and sites with any QI initiative (p = 0.006) were associated with lower FP utilization rates. Hospitals without cancer programs (p = 0.02) and sites with RBC guidelines (p = 0.05) or with technologists who prospectively screened transfusion orders (p = 0.01) had lower RBC transfusion rates. RBC utilization rates decreased further after the implementation of RBC guidelines (p = 0.02) and order sets (p = 0.005). There was a positive correlation between FP and RBC transfusion rates for each fiscal year (p < 0.005 for all years). CONCLUSION: RBC and FP utilization showed wide variation across community hospitals in Ontario. Overall, transfusion rates decreased over time. A further decrease was observed at sites with QI initiatives, supporting their implementation in reducing utilization. These data will serve as a baseline to highlight sites and practices where QI initiatives may be most beneficial and replicated in other jurisdictions.

Utilization of frozen plasma in Ontario: a provincewide audit reveals a high rate of inappropriate transfusions.

BACKGROUND: Frozen plasma (FP) is frequently transfused inappropriately, an intervention that results in risk without benefit for the patient. To better understand current utilization practices in our region, we undertook a provincewide prospective audit to evaluate the clinical indications and appropriateness of FP transfusion. STUDY DESIGN AND METHODS: All hospitals in the Canadian province of Ontario with transfusion medicine services were invited to participate in a 5-day audit of FP utilization. FP dose, indication, and clinical patient data were collected for each transfusion request. Indications for FP transfusions were independently adjudicated as appropriate, inappropriate, or indeterminate based on predefined criteria. RESULTS: Seventy-six (49%) of 155 invited hospitals participated in the audit, which included 573 requests for 2012 units of FP. A total of 559 transfusions (1909 units) were administered. Of 573 requests, 164 (28.6%) were deemed inappropriate most often because: 1) they were administered to patients with an international normalized ratio below 1.5 or 2) they were administered in absence of bleeding or emergency surgery. The most frequent indications for FP transfusions were before surgery and warfarin reversal. Overall, patients admitted to the clinical areas of surgery, internal medicine, and the emergency department represented the largest users of FP, but this varied by hospital type (community vs. academic). The most frequently requested doses of FP were 2 and 4 units. CONCLUSION: This point-prevalence hospital audit revealed that transfusion of FP is frequently inappropriate. Focusing on reducing the two most common reasons for inappropriate FP transfusions could lead to a significant improvement in FP utilization.

Canadian surgeons and the introduction of blood transfusion in war surgery.

Canadian surgeons serving in the Canadian Army Medical Corps in the First World War were responsible for introducing transfusion in the management of war casualties to the British Army. They were uniquely placed to do so by a coincidence of circumstances. They were aware of developments occurring in the field of blood transfusion in the United States, which was at the time leading the research and development of transfusion as a therapeutic measure. The ties between Britain and Canada in 1914 were such that Canada entered the war immediately, and Canadians served closely with the British, volunteering promptly and in large numbers. Britain, by contrast with the United States, had little interest in or expertise with blood transfusion. Thus, Canadian surgeons went to war aware of the value of blood transfusion and with some who had actually learned how to use transfusion. They arrived to find no interest or expertise on the part of their British colleagues and had to work hard to convince them of the merits of blood transfusion in the management of hemorrhage. Their efforts were reinforced by the arrival in 1917 of American surgeons bringing their experience with transfusion. By war's end, blood transfusion was generally accepted as the treatment of choice for severe blood loss.

Norman Bethune, eccentric, man of principle, man of action, surgeon, and his contribution to blood transfusion in war.

Norman Bethune was a Canadian surgeon born of a family with wide interests and varied and influential careers. He himself had wide interests in medicine, politics, and the arts. One phase of his career, lasting about 6 months, involved the rapid development and exploitation of a (then) unique mobile blood transfusion service delivering citrated stored blood to hospitals and casualty clearing stations in support of the Republican ("anti-fascist") forces in the Spanish Civil War in 1936 to 1937. He was among the first to recognize the importance of prompt transfusion in the severely injured. His contributions to transfusion medicine were not immediately acknowledged by his contemporaries interested in transfusion, perhaps a consequence of his failure to publish his experience in the relevant medical literature, although other factors probably also played a part. In the past 30 years or so, as part of a wider appreciation of his career (particularly his work in China in 1938-1939), details of his endeavors in transfusion in Spain have come to light.