Journal of Thrombosis and Haemostasis, 15: 1–2
DOI: 10.1111/jth.13733
OBITUARY
Emil Alfred Loeliger €rich 28 June 1924–Leiden 29 May 2017) (Zu Legend has it that in February 1952 Fredi Loeliger travelled 850 km by Vespa scooter from Z€ urich to Leiden for a rotation in the Department of Pathology, headed by George Lignac. In Z€ urich, he had just completed his thesis on coagulation factor VII in the laboratory of Fritz Koller. He met his future wife, Paultje Salomonson, in Leiden and there, against the wish of his boss Lignac, he worked on his second love, blood coagulation. He had to return to Z€ urich to start his internal medicine training with Wilhelm L€ offler, but when a vacancy occurred in Leiden he finished his training with Andries Querido. From then on he would remain in Leiden until his death on 29 May 2017. The chief of medicine, Jacob Mulder, provided him with the opportunity to start a research program in the new field of hemostasis and thrombosis. Highly focussed, he worked for 30 years on oral anticoagulation, first and foremost on the prothrombin time and its standardization and secondly on the application of vitamin K antagonists for the secondary prevention of myocardial infarction. In his personal historical review of 1985 ‘In de greep van de protrombinetijd’ (In the grasp of the prothrombin time), he describes Armand Quick’s opinion that ‘his’ (rabbit brain) thromboplastin time should normally be 12 s and that doubling of that time provided an optimal anticoagulant effect with the smallest risk of bleeding. It led to lots of scientific work, to fierce debates and some animosity between American and European experts, to numerous conferences and finally after many years to the insight that different thromboplastins have varying sensitivities to the effect of vitamin K antagonists. If the International Normalized Ratio is now well known to any medical student, we may thank Fredi Loeliger for that as one of its principal champions. These insights were essential for making oral anticoagulation as safe as it is today. As early as 1956 he founded the regional anticoagulation clinic in Leiden for the centralized monitoring of oral anticoagulation, with a rigorous quality control system and he was instrumental in the foundation of the federation of Dutch anticoagulation clinics in 1971. His legacy in this area was carried on by Ton van den Besselaar, Felix van der Meer and others. On the clinical side, he held the controversial conviction that recurrent myocardial infarction could be prevented by long term oral anticoagulation. He organized a double blind placebo controlled study in 200 patients on long term anticoagulation after a myocardial infarction. Half of them continued anticoagulation and the other © 2017 International Society on Thrombosis and Haemostasis
half stopped. The continuing patients fared better than the stoppers, but a priori scepticism, methodological shortcomings and publication in a second-tier journal failed to convince the medical community in 1967. The subsequent ‘Sixty-Plus Reinfarction Study’ (Lancet 1980), the later ASPECT study (Lancet 1994) and ASPECT-2 study with a comparison between oral anticoagulation and acetylsalicylic acid (Lancet 2002) all convincingly demonstrated favourable outcomes, but the time for oral anticoagulation in arterial disease seemed to have passed. For many years, Fredi Loeliger was professor and head of the Department of Hematology. In this capacity, he laid the foundation not only for an outstanding thrombosis and hemostasis center, but also for an important clinical hematology and bone marrow transplantation program. He attracted Coen Hemker to add biochemical expertise for the unravelling of the mechanism of action of oral anticoagulants; he discovered PIVKA’s, later identified as non-carboxylated clotting factors. Jan Veltkamp started a strong research program on the inherited
2 Obituary
abnormalities of blood coagulation, which resulted in pivotal publications on carriers of hemophilia, Hemophilia B Leyden and later on, inherited thrombophilia, thanks to the contribution of newcomers such as Rogier Bertina, Ernest Bri€et, Frits Rosendaal and Pieter Reitsma. For the clinical hematology program he invited his compatriot Bruno Speck who supervised the hematooncology section for a number of years before Roel Willemze took over and gave the department its leading position, with high end patient care and ditto research program. Writing manuscripts with Loeliger was an exercise in science as well as in language and required some degree of patience and perseverance. Jan Veltkamp wrote that he spent hours of discussion about the difference between a deficiency and a defect (of a clotting factor). Similarly, he conscientiously read all patient discharge letters by his residents and took the trouble to fill the margins with detailed comments in small handwriting, an effort that was not invariably highly appreciated. His weekly professorial round on the ward with the head nurse, clinical supervisor, residents and interns remains the source of many anecdotes due to his questions and suggestions that were not always understood. This was certainly not due
to language problems, for his Dutch was flawless. Interns and younger residents sometimes needed some consolation and, rarely, a handkerchief for the occasional tear. He felt the responsibility of his position as a heavy burden and he was relieved when in 1977 Jan Veltkamp took over his position as department head and as member of the internal medicine management team. After his retirement in 1985, he kept visiting the offices of the department and showed a sincere interest in our work as well as in our wellbeing. From a department head who was strict, rigorous, tenacious, stubborn and at times fearsome, he turned into a friendly grandfather, proud with the successes of his descendants. He ended his historical booklet with a plea for delegation and delegate he did. For somebody with such a strong sense of responsibility it is remarkable how he placed complete confidence in his successors as soon as he had handed over a task. When he stopped working professionally, he turned his attention to his gardens, to culturing orchids, to the study of butterflies (on which he kept publishing scientifically [Nota Lepidopterologica 2000]) and of course to the care for his wife. His pupils will remember this mildly eccentric man with great appreciation and love, a true ‘Bon Patron’.
© 2017 International Society on Thrombosis and Haemostasis
DOI: 10.1111/jth.13733
OBITUARY
Emil Alfred Loeliger €rich 28 June 1924–Leiden 29 May 2017) (Zu Legend has it that in February 1952 Fredi Loeliger travelled 850 km by Vespa scooter from Z€ urich to Leiden for a rotation in the Department of Pathology, headed by George Lignac. In Z€ urich, he had just completed his thesis on coagulation factor VII in the laboratory of Fritz Koller. He met his future wife, Paultje Salomonson, in Leiden and there, against the wish of his boss Lignac, he worked on his second love, blood coagulation. He had to return to Z€ urich to start his internal medicine training with Wilhelm L€ offler, but when a vacancy occurred in Leiden he finished his training with Andries Querido. From then on he would remain in Leiden until his death on 29 May 2017. The chief of medicine, Jacob Mulder, provided him with the opportunity to start a research program in the new field of hemostasis and thrombosis. Highly focussed, he worked for 30 years on oral anticoagulation, first and foremost on the prothrombin time and its standardization and secondly on the application of vitamin K antagonists for the secondary prevention of myocardial infarction. In his personal historical review of 1985 ‘In de greep van de protrombinetijd’ (In the grasp of the prothrombin time), he describes Armand Quick’s opinion that ‘his’ (rabbit brain) thromboplastin time should normally be 12 s and that doubling of that time provided an optimal anticoagulant effect with the smallest risk of bleeding. It led to lots of scientific work, to fierce debates and some animosity between American and European experts, to numerous conferences and finally after many years to the insight that different thromboplastins have varying sensitivities to the effect of vitamin K antagonists. If the International Normalized Ratio is now well known to any medical student, we may thank Fredi Loeliger for that as one of its principal champions. These insights were essential for making oral anticoagulation as safe as it is today. As early as 1956 he founded the regional anticoagulation clinic in Leiden for the centralized monitoring of oral anticoagulation, with a rigorous quality control system and he was instrumental in the foundation of the federation of Dutch anticoagulation clinics in 1971. His legacy in this area was carried on by Ton van den Besselaar, Felix van der Meer and others. On the clinical side, he held the controversial conviction that recurrent myocardial infarction could be prevented by long term oral anticoagulation. He organized a double blind placebo controlled study in 200 patients on long term anticoagulation after a myocardial infarction. Half of them continued anticoagulation and the other © 2017 International Society on Thrombosis and Haemostasis
half stopped. The continuing patients fared better than the stoppers, but a priori scepticism, methodological shortcomings and publication in a second-tier journal failed to convince the medical community in 1967. The subsequent ‘Sixty-Plus Reinfarction Study’ (Lancet 1980), the later ASPECT study (Lancet 1994) and ASPECT-2 study with a comparison between oral anticoagulation and acetylsalicylic acid (Lancet 2002) all convincingly demonstrated favourable outcomes, but the time for oral anticoagulation in arterial disease seemed to have passed. For many years, Fredi Loeliger was professor and head of the Department of Hematology. In this capacity, he laid the foundation not only for an outstanding thrombosis and hemostasis center, but also for an important clinical hematology and bone marrow transplantation program. He attracted Coen Hemker to add biochemical expertise for the unravelling of the mechanism of action of oral anticoagulants; he discovered PIVKA’s, later identified as non-carboxylated clotting factors. Jan Veltkamp started a strong research program on the inherited
2 Obituary
abnormalities of blood coagulation, which resulted in pivotal publications on carriers of hemophilia, Hemophilia B Leyden and later on, inherited thrombophilia, thanks to the contribution of newcomers such as Rogier Bertina, Ernest Bri€et, Frits Rosendaal and Pieter Reitsma. For the clinical hematology program he invited his compatriot Bruno Speck who supervised the hematooncology section for a number of years before Roel Willemze took over and gave the department its leading position, with high end patient care and ditto research program. Writing manuscripts with Loeliger was an exercise in science as well as in language and required some degree of patience and perseverance. Jan Veltkamp wrote that he spent hours of discussion about the difference between a deficiency and a defect (of a clotting factor). Similarly, he conscientiously read all patient discharge letters by his residents and took the trouble to fill the margins with detailed comments in small handwriting, an effort that was not invariably highly appreciated. His weekly professorial round on the ward with the head nurse, clinical supervisor, residents and interns remains the source of many anecdotes due to his questions and suggestions that were not always understood. This was certainly not due
to language problems, for his Dutch was flawless. Interns and younger residents sometimes needed some consolation and, rarely, a handkerchief for the occasional tear. He felt the responsibility of his position as a heavy burden and he was relieved when in 1977 Jan Veltkamp took over his position as department head and as member of the internal medicine management team. After his retirement in 1985, he kept visiting the offices of the department and showed a sincere interest in our work as well as in our wellbeing. From a department head who was strict, rigorous, tenacious, stubborn and at times fearsome, he turned into a friendly grandfather, proud with the successes of his descendants. He ended his historical booklet with a plea for delegation and delegate he did. For somebody with such a strong sense of responsibility it is remarkable how he placed complete confidence in his successors as soon as he had handed over a task. When he stopped working professionally, he turned his attention to his gardens, to culturing orchids, to the study of butterflies (on which he kept publishing scientifically [Nota Lepidopterologica 2000]) and of course to the care for his wife. His pupils will remember this mildly eccentric man with great appreciation and love, a true ‘Bon Patron’.
© 2017 International Society on Thrombosis and Haemostasis
