Book Review

Molecular Genetics of Haemostasis and Its Inherited Disorders

N Engl J Med 1995; 332:402-403February 9, 1995

Article

Molecular Genetics of Haemostasis and Its Inherited Disorders
(Oxford Monograph on Medical Genetics. No. 25.) By Edward G.D. Tuddenham and David N. Cooper. 585 pp. New York, Oxford University Press, 1994. $145. ISBN: 0-19-261661-7

As a clinician-scientist with a long-standing interest in coagulation disorders and thrombosis, I find it exciting that the molecular genetics of hemostasis now merits its own monograph. When i entered the field two decades ago, purification of even the most abundant coagulation proteins was an arduous task, and information on the primary sequence or gene structure of these proteins did not exist. Thanks to the molecular-biology revolution and the work of many academic and industrial laboratories, we now know a great deal about the structure and function of the coagulation proteins and the molecular basis of bleeding disorders.

Tuddenham and Cooper have attempted to summarize a large body of information in Molecular Genetics of Haemostasis and Its Inherited Disorders. They are to be commended for completing this difficult project. The obvious questions for a reviewer are these: How well did they accomplish the task? Who will benefit from purchasing and reading this book? And what, if anything, might have been done to improve the monograph?

An obvious strength of the book is that it is comprehensive and well organized. Each chapter follows precisely the same format and is organized under logically numbered subheadings. Many illustrations and large and detailed tables of primary sequences, evolutionary relations, gene structure, and mutations enhance the text. The authors have compressed a great deal of useful information into 585 pages, and the reader should be able quickly to find detailed information about any of the plasma coagulation or platelet proteins and their disorders.

The book introduces the reader to the intricacies of primary and secondary hemostasis and fibrinolysis and the techniques of mutational analysis, all compressed into 19 pages. The reader with a good background in hemostasis or genetics would do well to skip this chapter, whereas the novice may find it dense and hard to digest. The remainder of the book systematically analyzes each of the proteins and the related diseases. In keeping with the expertise and interests of the authors, the sections on factors VIII and IX and the hemophilias are exhaustive. Experts in this area will find much useful reference material; those who are less well versed in the subject can review the massive amount of information that is now available on mutations causing hemophilia A and B. Virtually everything that was known about the genetics of coagulation proteins through the middle of 1992 has been included.

There are, however, some problems. The writing style is terse and journalistic. All the facts are presented, but no attempt has been made to synthesize the data or to provide guideposts for the reader. The authors have relied heavily on figures reprinted from original articles or other reviews. Some are good, but others are too cluttered and could have been improved by a medical illustrator.

Finally, there is the important issue of timing. Is it really possible to capture the essence of this field in a monograph and make it timely and relevant? In a rapidly changing field, one might argue that there will never be a perfect time to write the definitive monograph. Paradoxically, interest is most keen in the areas that are evolving rapidly and are most difficult to capture in such a book. Despite the best efforts of authors and publishers, such a monograph may rapidly become dated. For example, since the completion of the monograph, an inversion in the X chromosome has been described that accounts for up to 50 percent of the cases of hemophilia A. A mutation in the factor V gene that abolishes an activated protein C cleavage site has also been discovered; it may be the cause of 25 percent of the cases of venous thromboembolism.

Genetic analysis has also advanced so rapidly that some of the approaches outlined in the book have been superseded. For example, linkage analysis can now be efficiently carried out by the polymerase chain reaction with the variable-number tandem repeats that are scattered throughout the genome. They are often more informative than the biallelic restriction-fragment–length polymorphisms described in the book. Single-stranded conformational polymorphism analysis has now become established as a rapid way to screen genes for potential mutations. It is mentioned only briefly in the appendix as a new and promising technique.

Molecular Genetics of Haemostasis and Its Inherited Disorders is clearly an archival reference work. It belongs on the bookshelves of laboratory investigators who study hemostasis or the genetics of coagulation, and in departmental or university libraries. The general reader seeking an introduction to this field may be better served by perusing the sections of a major hematology textbook that cover coagulation or one of several new books devoted entirely to coagulation.

Robert Handin, M.D.
Boston, MA 02115 Brigham and Women's Hospital