At a Glance

Plasminogen deficiency is an inherited disorder that, in its severe homozygous form, is associated with compromised extracellular fibrin clearance, abnormal mucous membrane wound healing, and pseudomembranous (ligneous) lesions on affected mucous membranes, particularly the eyes (ligneous conjunctivitis) and mouth (ligneous gingivitis).

Ligneous conjunctivitis is characterized by early chronic tearing and redness of the conjunctiva followed by progressive development of pseudomembranes on the palpebral surfaces and white/yellow-white/red masses with a wood-like consistency (ligneous). This typically first occurs in childhood but can occur for the first time in adulthood. It may be triggered by local injuries, infections, or surgical interventions.

The conjunctiva are affected most often (81%), followed by ligneous lesions of the gingiva (30%) that may lead to loss of teeth, upper and lower respiratory tracts (20%), middle ear (15%), female genital tract (9%), and other mucosal surfaces.

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Plasminogen deficiency, in its mild heterozygous or severe homozygous forms, is not associated with an increased risk of venous thrombosis.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

In patients with a history of ligneous lesions of the mucosal membranes and suspected plasminogen deficiency, plasminogen activity and plasminogen antigen levels should be ordered. There are two types of plasminogen deficiency. In type 1 plasminogen deficiency, patients have parallel reductions in plasminogen activity and antigen because of reduced production of plasminogen. In type 2 plasminogen deficiency, patients have a reduction in plasminogen activity but normal or only slightly reduced plasminogen antigen due to a dysfunctional or abnormal plasminogen molecular. Only type 1 plasminogen deficiency results in ligneous lesions. Type 2 plasminogen deficiency, even when plasminogen activity is quite low, is not associated with ligneous lesions or venous thrombosis.

Typically, patients that are symptomatic have severe homozygous or compound heterozygous plasminogen deficiency with low levels of both plasminogen antigen and activity, but levels can be quite variable. Plasminogen antigen levels in symptomatic patients range from less than 1 mg/dL to 9 mg/dL, whereas plasminogen activity levels range from less than 1% to 51%.

The mild heterozygous form of type 1 plasminogen deficiency occurs in about 3 out of 1,000 individuals of Asian or European ancestry. The severe homozygous or compound heterozygous forms are very rare, occurring in less than 1 out of 1 million individuals. The heterozygous asymptomatic type 2 deficiency occurs in about 3 out of 100 individuals from Asia and about 3 out of 10,000 individuals from Europe.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Antifibrinolytic medications, including epsilon amino caproic acid, tranexamic acid, and aprotinin, if present in the sample, can lead to falsely low plasminogen activity measurements and should be avoided. Tranexamic acid has been reported to trigger episodes of ligneous lesions in some patients.

What Lab Results Are Absolutely Confirmatory?

Genetic testing for plasminogen mutations is not routinely done, as there are many different mutations that can cause plasminogen deficiency, the cost of testing is high, clinical availability is low, and definitive diagnosis is poor unless the mutation is previously well described and known to be associated with deficiency and increased risk of ligneous lesions.

Additional Issues of Clinical Importance

Severe plasminogen deficiency is associated with impaired wound healing after surgery and infertility in women. Additional problems include fibrin-rich thrombotic occlusions of implanted cerebral catheters, such as cerebrospinal fluid shunts.

The risk of venous thrombosis is not significantly different in patients with mild heterozygous deficiency compared to family members without deficiency, and no patients with severe plasminogen deficiency have ever developed deep venous thrombosis.

Errors in Test Selection

If you suspect plasminogen deficiency, it is important to obtain both plasminogen activity and antigen levels.