R. MEHTA* and A. D. SHAPIRO?
*Department of Clinical Medicine, Section of Hematology/Oncology, Indiana University School of Medicine, Indianapolis,
IN; and ?Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, and Department of Pediatrics, Michigan State
University, East Lansing, MI, USA
Summary. Plasminogen deficiency has emerged as a
well-recognized disorder in which reduced levels of
plasminogen lead to the development of pseudo
membranes on mucosal surfaces, with subsequent
end-organ damage of the affected tissue. Ligneous
conjunctivitis is the most recognizable, well-docu-
mented, and common presentation of the clinical
syndromes associated with plasminogen deficiency,
although numerous other organs have been reported
to be affected. Interestingly, while plasminogen
deficiency was initially believed to be related to
development of venous thromboembolic disease,
more recent data suggest that decreased plasminogen
levels may not, in and of themselves, increase the
risk of thrombosis. Two types of plasminogen
deficiency have been described in the literature. Type
I represents a quantitative deficiency and type II a
qualitative deficiency. It appears that hypoplasmino-
genaemia (type I deficiency) is the type most associ-
ated with pseudomembrane disease. A variety of
genetic mutations has been identified recently and is
reported to lead to these disorders. These defects have
been identified in diverse populations, with no
specific ethnic predilection. However, this disorder
may have increased prevalence in areas and commu-
nities where consanguinity is more common. Despite
the fact that the characteristic lesions are now better
recognized and plasminogen levels are accurately and
easily measured, adequate treatment of the clinical
manifestations of this disorder is lacking. For ligne-
ous conjunctivitis, a plasminogen concentrate formu-
lated into an ophthalmologic preparation has been
found to be an effective local therapy. Unfortunately,
no plasminogen concentrate is currently available
commercially for either systemic or local therapy.
ligneous, plasminogen, pseudomembranes
described in 1847 by Bouisson . During the next
several decades, further cases of this chronic con-
junctivitis were reported with an improved descrip-
granulation tissue. In 1933, the term ligneous con-
junctivitis was proposed because of the wood-like
appearanceof these lesions
pseudomembranes were described that affected the
gingiva, ear, respiratory tract, female genitourinary
coveringtheeye were first
tract, skin and renal collecting system . In addi-
tion, several children with ligneous conjunctivitis
were also reported to have developed hydrocephalus.
Concurrently, the pathophysiology of dissolution
of blood clots was undergoing investigation. It had
long been recognized that a component of blood was
capable of dissolving blood clots . In the 19th
century, several investigators documented that blood
clots could spontaneously dissolve. Jules A. F. Dastre
recognized that once a clot in blood dissolved, it
could not reform into a clot. He deduced that the
fibrin had been broken down and coined the term
fibrinolysis . The factor that could dissolve clots
was determined to be an enzyme and was isolated in
the 1940s. Christensen and MacLeod labelled the
zymogen plasminogen and the enzyme plasmin .
In 1978, the first patient with plasminogen defi-
ciency was described . This case related an
increased risk of venous thrombosis with low levels
of plasminogen. Interestingly, this initial case was
Correspondence: Rakesh Mehta, MD, Department of Clinical
Medicine, Section of Hematology/Oncology, Indiana University
School of Medicine, 535 Barnhill Drive, RT-473, Indianapolis, IN
Tel.: 317 278 6871; fax: 317 274 3684;
Accepted after revision 5 July 2008
Haemophilia (2008), 14, 1261–1268 DOI: 10.1111/j.1365-2516.2008.01825.x
? 2008 The Authors
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R. MEHTA and A. D. SHAPIRO
? 2008 The Authors
Haemophilia (2008), 14, 1261–1268Journal compilation ? 2008 Blackwell Publishing Ltd