It was with profound sadness we learned that the world had lost a pioneer in the field
of blood coagulation with the passing of Eberhard F. Mammen (Fig. [1
Figure 1 Eberhard F. Mammen (1930–2008).
Eberhard studied medicine at the University of Munich and obtained his M.D. at the
University of Giessen in 1956. He started his research in blood coagulation and coauthored
his first article with Fritz Beller on thromboplastin formation while still an undergraduate.[1 2
One of us (A.P.) had the great fortune of collaborating with Eberhard in the discovery
of Fibrinogen Detroit. During 1966, I (A.P.) was taking care of a 17-year-old girl
who used to bleed severely every month during her menses. All the clotting factors
were normal, including the fibrinogen level as determined by turbidometric and immunologic
techniques. Although Eberhard was in the Department of Physiology, he had a great
interest in clinical hematology, and very often I used to send him blood samples from
patients who had clotting problems. I sent the blood from my patient to Eberhard,
and he reported that he could not demonstrate clottability of plasma fibrinogen by
addition of thrombin during the 30-minute test period. Other coagulation factors were
present in normal amounts, and prothrombin activation was normal. Family studies showed
that the defect in this fibrinogen had an autosomal dominant pattern of heredity,
and immunologic studies revealed some differences from patients with two other known
dysfibrinogenemia cases, Fibrinogen Baltimore and Fibrinogen Cleveland.
During those days, my (A.P.) laboratory was involved with studies related to gamma
globulins, and I decided to undertake detailed physicochemical studies of Fibrinogen
Detroit. Native and cleaved Fibrinogen Detroit had the same sedimentation constants
and molecular weights as those of normal fibrinogen. In fresh samples, the free SH
groups/mole of fibrinogen were similar in both normal fibrinogen and Fibrinogen Detroit.
The amino acid composition revealed a decreased content of lysine, glucosamine, and
galactosamine in the abnormal fibrinogen. Total carbohydrates, protein-bound hexose,
sialic acid, and hexosamine were also decreased in the abnormal fibrinogen.
At the end of these extensive studies, both Eberhard and I (A.P.) were totally frustrated.
What caused Fibrinogen Detroit not to clot when treated with thrombin remained a puzzle.
One day, during a Walter Seegers symposium, Eberhard and I were having lunch with
Birger and Margarita Blomback (Karolinska Institute, Sweden; see Fig. [2 Nature in London by Birger and published promptly within 3 months. This was the first demonstration
of a molecular defect in an abnormal fibrinogen.[3
Figure 2 Left to right: unknown scientist, Birger Blomback, Margarita Blomback, Ananda Prasad,
and Eberhard F. Mammen. Photo taken in 1968 in Detroit, Michigan, at the time of the
discovery of Fibrinogen Detroit (see Ref. 3).
Eberhard participated regularly in the teaching of our hematology fellows, who truly
admired his clarity and simplicity of presentation of topics dealing with the area
of “complicated clotting.” Eberhard worked with me (A.P.) as an associate editor of
the American Journal of Hematology for 30 years. He was very fair and prompt in his reviews and was truly a great supporter
of the journal, and I enjoyed his association immensely. He contributed to the American Journal of Hematology enormously both as a teacher and as a scientist. Over a span of five decades, he
published more than 300 articles on various topics in thrombosis and hemostasis.
Perhaps as a result of the influence of his country-doctor father, who had intended
his son to follow his footsteps, Eberhard had always tried to excel in a broad area
of medicine rather than confine himself in any single discipline. Thus, it was not
surprising to see him working with the distinguished German obstetrician Fritz Beller
in his earlier career, laying the groundwork for his later joining the Department
of Obstetrics and Gynecology. Only a few people would ever possess the talent and
experience of Eberhard's, being also on the faculty of the Department of Physiology
and Pharmacology, the Department of Pathology, and of the Department of Surgery, Wayne
State University School of Medicine, Detroit, Michigan. But his first and true research
love was blood coagulation. Mentored by the pioneer of mechanisms of coagulation,
Walter Seegers, he engaged in extensive studies in a wide variety of disorders of
hemostasis. His published work covers both basic investigations of clotting proteins
and the scientific basis of clinical complications ranging from disseminated intravascular
coagulation to thrombosis in preeclampsia.
Eberhard could not be happier when he founded the journal Seminars in Thrombosis and Hemostasis , becoming the editor in chief and remaining so until the time of his death. Under
his guidance, this journal has blossomed into a publication that embraces education
and research of the highest caliber, treasured by both basic scientists and clinicians.
One of us (H.C.K.) was most privileged to be the guest editor of this journal for
eight issues on subjects ranging from thrombosis to fibrinolysis to hyperviscosity.
On each occasion, Eberhard was most attentive to my needs and generously gave me valuable
advice.
We shall all be missing Eberhard's enthusiasm, his cheerful smile, and, most of all,
his unique sense of humor.
