# Robert W. Colman
Robert W. Colman (also cited as R. W. Colman) is an American hematologist and physician-scientist based at the Thrombosis Research Center and the Hematology-Oncology Section of the Department of Medicine, Temple University School of Medicine in Philadelphia[1](https://doi.org/10.1172/jci111326). According to "Fifty years of research on the plasma kallikrein-kinin system" (*Thrombosis and Haemostasis*, 2007), his research established the composition and behavior of the plasma contact activation system, also called the plasma kallikrein-kinin system, or the intrinsic activation system of coagulation, the pathway by which contact with negatively charged surfaces activates high-molecular-weight kininogen (HK), prekallikrein, and factor XII, culminating in the release of bradykinin[2](https://doi.org/10.1160/th07-04-0250). Before Temple he worked at the [Hospital of the University of Pennsylvania](https://www.edgepedia.org/hospital-of-the-university-of-pennsylvania), where he published a 1974 review of kinin formation in the New England Journal of Medicine[3](https://doi.org/10.1056/nejm197409052911008).
| Fact | Detail |
|---|---|
| Training | Harvard College (1956), Harvard Medical School (MD 1960), Boston City Hospital internship (1961), Washington University residency (1962), and fellowship (1967)[4](https://www.doctorhelps.com/doctor/robert-colman-hdfhacaecdedcfhecdedcfhe) |
| Prior post | Hospital of the University of Pennsylvania (1974 kinin review)[3](https://doi.org/10.1056/nejm197409052911008) |
| Temple role | Thrombosis Research Center and Hematology-Oncology Section; NIH NHLBI T32 training grant in thrombosis and hemostasis, July 1993 to June 2003[1](https://doi.org/10.1172/jci111326) • [5](https://grantome.com/grant/NIH/T32-HL007777-06) |
| Signature work | 1983 NEJM study of prekallikrein activation in hereditary angioedema; ["Prekallikrein Activation and High-Molecular-Weight Kininogen Consumption in Hereditary Angioedema"](https://doi.org/10.1056/nejm198305053081802), *New England Journal of Medicine*, 1983 |
| Honors | AIMBE College of Fellows, class of 1996 |
| Textbook | Co-editor of *Hemostasis and Thrombosis: Basic Principles and Clinical Practice* (J. B. Lippincott)[6](https://doi.org/10.1097/00001721-199504000-00015) |
## Training and early career
His research career then developed at the Hospital of the University of Pennsylvania, where his 1974 review in the *New England Journal of Medicine* framed bradykinin release as one of four interlocking proteolytic networks mediating vascular responses in hemostasis, inflammation, and repair; it described bradykinin as the most potent mammalian vasodilator[3](https://doi.org/10.1056/nejm197409052911008).
## Temple University and the Thrombosis Research Center
According to *Surface-mediated defense reactions. The plasma contact activation system*, by 1984 Colman was publishing from the Thrombosis Research Center and Hematology-Oncology Section of Temple University School of Medicine[1](https://doi.org/10.1172/jci111326). An Institutional National Research Service Award (T32) from the [National Heart, Lung, and Blood Institute](https://www.edgepedia.org/national-heart-lung-and-blood-institute) supported training in thrombosis and hemostasis in Temple's Department of Internal Medicine from July 1, 1993 to June 30, 2003[5](https://grantome.com/grant/NIH/T32-HL007777-06). In October 1994 the *American Journal of Hematology* published a collection of clinical studies in hemostasis and thrombosis at Temple University School of Medicine that he edited[7](https://doi.org/10.1002/ajh.2830470229).
## Representative work
His 1983 *New England Journal of Medicine* study showed that in hereditary angioedema, prekallikrein activation and high-molecular-weight kininogen consumption occur in vivo, providing biochemical evidence of contact-phase activation during attacks[8](https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0038-1656330).
Other landmark results followed from the same program. In 1976 his group identified prekallikrein and high-molecular-weight kininogen as a bimolecular complex in human plasma, published in *PNAS*[8](https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0038-1656330). In 1991 a *Blood* study showed that alpha 2-macroglobulin-kallikrein complexes can detect contact system activation in hereditary angioedema and human sepsis[9](https://doi.org/10.1111/j.1749-6632.1994.tb44323.x).
## The contact activation system explained
The contact system is initiated when factor XII binds a negatively charged surface and autoactivates to factor XIIa; Colman's own review noted that the origin of the trace amount of XIIa that starts the cascade remains controversial[1](https://doi.org/10.1172/jci111326). The zymogens factor XII (Mr 80,000), prekallikrein (Mr 88,000), and factor XI (Mr 160,000) are converted by limited proteolysis into the active serine proteases XIIa, kallikrein, and XIa, with high-molecular-weight kininogen acting as a nonenzymatic cofactor[1](https://doi.org/10.1172/jci111326). Kallikrein cleaves high-molecular-weight kininogen to release bradykinin[3](https://doi.org/10.1056/nejm197409052911008). HK is a 120 kDa beta-globulin with a plasma concentration of about 80 µg/ml (670 nM)[2](https://doi.org/10.1160/th07-04-0250).
**The clinical paradox** of the pathway is that its protein deficiencies look severe in the laboratory but mild in patients. Congenital deficiencies of factor XII (Hageman trait), prekallikrein (Fletcher trait), and high-molecular-weight kininogen (Williams, Fitzgerald, and Flaujeac traits) produce profound in vitro abnormalities in surface-activated coagulation, yet affected individuals otherwise appear asymptomatic; in contrast, deficiency of C1 esterase inhibitor causes hereditary angioedema, with significant morbidity and mortality[1](https://doi.org/10.1172/jci111326) • [10](https://doi.org/10.1055/s-0038-1651896).
## From the contact system to sepsis, thrombosis, and inflammation
Colman's work mapped the pathway onto disease states. [In vivo](https://www.edgepedia.org/in-vivo) activation of factor XII-initiated pathways occurs in septic shock, disseminated or [localized intravascular coagulation](https://www.edgepedia.org/localized-intravascular-coagulation), typhoid fever, polycythemia vera, coronary artery disease, nephrotic syndrome, transfusion reactions, hemodialysis, and extracorporeal bypass[10](https://doi.org/10.1055/s-0038-1651896). A 1988 study from his record found contact-system activation in the adult respiratory distress syndrome[8](https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0038-1656330), and the 1991 alpha 2-macroglobulin-kallikrein marker study extended detection of activation to human sepsis[9](https://doi.org/10.1111/j.1749-6632.1994.tb44323.x).
## Patents and applied work
Colman's laboratory findings carried into patented applications. His US patents include treatment of disease with antibodies against high-molecular-weight kininogen domain 5 (7,332,161, 2008) and inhibition of angiogenesis by such antibodies (6,994,852, 2006), listing his Temple affiliation[11](https://idiyas.com/inventor/robert-w-colman). The American Institute for Medical and Biological Engineering elected him to its College of Fellows in 1996, citing his "imaginative studies of the biochemistry of surface-mediated proteolysis in blood-surface interactions"[12](https://aimbe.org/college-of-fellows/COF-1322/). He also co-edited the standard reference work *Hemostasis and Thrombosis: Basic Principles and Clinical Practice* (J. B. Lippincott)[6](https://doi.org/10.1097/00001721-199504000-00015).
## The contact system in drug development since 2024
Drugs now target the pathway Colman mapped. Garadacimab, a fully human recombinant IgG4λ monoclonal antibody against the catalytic domain of activated factor XII, was approved by the [European Medicines Agency](https://www.edgepedia.org/european-medicines-agency) in February 2025 and by the US Food and Drug Administration in June 2025 for prophylaxis of hereditary angioedema; it is given subcutaneously once a month and blocks FXIIa, preventing plasma kallikrein activation and bradykinin release[13](https://www.mdpi.com/1422-0067/27/7/3336). In the anticoagulation direction, the FXII-pathway inhibitor is available under the trade name BIOX-101 and has been granted orphan drug designation for intracerebral hemorrhage in both the United States and the European Union[13](https://www.mdpi.com/1422-0067/27/7/3336), and the oral FXIIa inhibitor KV998086 (IC50 7.2 nM) suppresses dextran sulfate-stimulated generation of kallikrein and FXIIa and cleavage of HK in human plasma[14](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1287487/full).
## References
1. Surface-mediated defense reactions. The plasma contact activation system. Journal of Clinical Investigation (1984). https://doi.org/10.1172/jci111326
2. Fifty years of research on the plasma kallikrein-kinin system. Thrombosis and Haemostasis (2007). https://doi.org/10.1160/th07-04-0250
3. Formation of Human Plasma Kinin. New England Journal of Medicine (1974). https://doi.org/10.1056/nejm197409052911008
4. Dr. Robert W Colman, MD, Hematology, Philadelphia, PA. DoctorHelps directory. https://www.doctorhelps.com/doctor/robert-colman-hdfhacaecdedcfhecdedcfhe
5. Training in Thrombosis and Hemostasis (T32-HL007777-06). NIH/NHLBI grant record. https://grantome.com/grant/NIH/T32-HL007777-06
6. Hemostasis and Thrombosis. Blood Coagulation & Fibrinolysis (1995). https://doi.org/10.1097/00001721-199504000-00015
7. Clinical studies in hemostasis and thrombosis at Temple University School of Medicine. American Journal of Hematology (1994). https://doi.org/10.1002/ajh.2830470229
8. Contributions of Mayme Williams to the Elucidation of the Multiple Functions of Plasma Kininogens. Thrombosis and Haemostasis (2018). https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0038-1656330
9. Significance of the Regulation of Plasma Kallikrein by α2-Macroglobulin. Annals of the New York Academy of Sciences (1994). https://doi.org/10.1111/j.1749-6632.1994.tb44323.x
10. Participation of Hageman Factor Dependent Pathways in Human Disease States. Thieme. https://doi.org/10.1055/s-0038-1651896
11. Robert W Colman: Inventions and Patents. Idiyas patent database. https://idiyas.com/inventor/robert-w-colman
12. Robert Colman, M.D. COF-1322. AIMBE College of Fellows. https://aimbe.org/college-of-fellows/COF-1322/
13. Factor XII in Thrombosis and Thromboinflammation: From Molecular Biology to Clinical Translation. International Journal of Molecular Sciences (2025). https://www.mdpi.com/1422-0067/27/7/3336
14. Oral FXIIa inhibitor KV998086 suppresses FXIIa and single chain FXII mediated kallikrein kinin system activation. Frontiers in Pharmacology (2023). https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1287487/full
15. Factor XII, A New Therapeutic Target? A Systematic Review. International Journal of Molecular Sciences (2025). https://www.mdpi.com/1422-0067/27/3/1331
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*Topic: Encyclopedia › Life and health › Life and health scientists › Medical and health researchers › Hematology and blood disorder researchers › Coagulation and fibrinolysis researchers › Surnames A to Ki*
*Initially written Sep 20, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026 · Last review: Sep 25, 2026*
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