Hemophilia is a congenital bleeding disorder that results in the blood failing to clot normally. It is caused by a deficiency of a protein in the blood called a clotting factor. People with hemophilia bleed easily and often excessively. Untreated, hemophilia can be life-threatening. There are two types of hemophilia: “hemophilia A” is the most common type and is caused by the deficiency of what is known as Clotting Factor VIII; “hemophilia B” is caused by deficiency of Clotting Factor IX.
Hemophilia occurs in about 1 in 10,000 births and it is much more common in males than females because it is an “X-linked” disorder. The number of affected persons worldwide is estimated to be about 400,000. Hemophilia A accounts for some 80-85% of all hemophilia cases.
You should speak to your physician if you have a history of:
- Easy bruising in early childhood.
- Spontaneous bleeding (bleeding for no apparent/known reason), especially into the joints, muscles, and soft tissues.
- Excessive bleeding following trauma or surgery.
A definitive diagnosis depends on a blood analysis to determine deficiency of Clotting Factor VIII or IX.
Because each type of hemophilia requires a different therapy, accurate diagnosis is essential.
Hemophilia can be very successfully managed by simply replacing the deficient clotting factor. Therapy can be either “on demand” – the treatment of active bleeding, or “prophylactic” – regular treatments to maintain adequate levels of clotting factor to prevent bleeding.1 Before the development of effective treatment, the life expectancy of boys with hemophilia was drastically reduced. Now, in developed countries where these factor treatments are readily available, the life expectancy of males suffering from hemophilia is essentially the same as for males in the general population.
Plasminogen Deficiency Type 1
Plasminogen deficiency type 1 is an ultra-rare genetic condition associated with inflamed growths on the mucous membranes.2 It is characterized by a deficiency of a protein in the blood called plasminogen, which causes the formation of fibrin-rich, ligneous pseudomembranous lesions on mucous membranes that can impair normal tissue and organ function.3 The most common clinical finding is ligneous conjunctivitis, a condition of the eyes marked by redness and subsequent formation of pseudomembranes that progress to white, yellow-white or red thick masses with a wood-like consistency that replace the normal mucosa.2 Untreated, plasminogen deficiency can lead to blindness, to life-threatening airway obstruction, or can impair the function of almost every organ. There are two types of plasminogen deficiency: “plasminogen deficiency type 1” can become symptomatic. Patients present with no or very little plasminogen. This leads to reduced fibrin clearance in lesions on mucous membranes.4,5 So far, it seems that patients with plasminogen deficiency type 2 are not symptomatic.
Plasminogen deficiency type 1 occurs in about 1.6 in 1 million people5 and it is slightly more common in females than in males (1.27-1.88:1).6
The patient journey to a confirmed diagnosis can take years and usually involves several different physicians and specialists because disease awareness is limited.
- A common initial presentation is an infant under age 1 with red, teary eyes that a pediatrician or pediatric ophthalmologist diagnoses and treats as pink eye, which does not resolve. The physician will talk to you about your family history, will examine the eyes, will check for possible involvement of additional mucosal sites, and will check for the recurrence of lesions on the eyelid and clinical appearance.
- If the physician suspects a plasminogen deficiency, a blood test will be done to determine plasminogen activity and antigen level.
- The next step to confirm the diagnosis is genetic testing to see if there are mutations on both chromosomes.6
- The last step is a biopsy of the removed lesion to look for a buildup of fibrin-rich deposits when viewed under a microscope.
With a confirmed diagnosis of plasminogen deficiency type 1, the physician may consider treatment with plasminogen.
So far, therapeutic options to treat plasminogen deficiency type 1 have been limited because an FDA-approved treatment was not available,7 and other treatment, with fresh frozen plasma (FFP), for example, was successful in some cases but failed in others. In 2021, the first plasminogen concentrate was approved by FDA,7 and the first commercial product is expected to be available by early 2022. In clinical trials, the product has shown in clinical trials that it can successfully manage plasminogen deficiency type 1 by temporarily increasing plasminogen levels in blood.3 Mean absolute plasminogen activity in adult and pediatric patients reached physiological levels (70% to 130%) immediately after the first infusion, were sustained for approximately 24 hours, and remained an absolute 10% above baseline 72 hours after dosing. After 12 weeks, mean absolute plasminogen activity in adult and pediatric patients reached physiological levels (70% to 130%) immediately after dosing, were sustained for approximately 24 hours, and continued to maintain an absolute 10% above baseline 96 hours after dosing.3 After 12 weeks of treatment during clinical trials, all patients with any lesion at baseline had at least 50% improvement in the number/size of their lesions, that is, 100% of study participants reached the primary study goal.3 In addition, 78% of external lesions and 75% of internal lesions, respectively, were resolved at the end of week 48. No recurrent or new lesions were found in any patient through week 48.3 The therapy requires regular treatment with IV plasminogen to maintain a protective plasminogen level.
The development of this treatment helps address an unmet medical need for those/ patients affected by this rare genetic disease7 and may enable most patients to resume normal daily activities. Kedrion is making every effort to ramp up the supply of this treatment quickly to support as many patients as possible.
- Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47. doi:10.1111/j.1365-2516.2012.02909.x
- GARD Rare Disease Information Center. Type 1 plasminogen deficiency. https://rarediseases.info.nih.gov/diseases/4380/type-1-plasminogen-deficiency. Updated June 13, 2016. Accessed November 14, 2021.
- RYPLAZIM [prescribing information]. Fort Lee, NJ. Kedrion Biopharma Inc. 2021.
- Schuster V, Hügle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007;5(12):2315-2322. doi:10.1111/j.1538-7836.2007.02776.
- Tefs K, Gueorguieva M, Klammt J, et al. Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients. Blood. 2006;108(9):3021-3026. doi:10.1182/blood-2006-04-0173
- Shapiro AD, Menegatti M, Palla R, et al. An international registry of patients with plasminogen deficiency (HISTORY). Haematologica. 2020;105(3):554-561. doi:10.3324/haematol.2019.241158
- FDA News release: FDA approves First Treatment for Patients with Plasminogen Deficiency, a Rare Genetic Disorder, June 4, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-plasminogen-deficiency-rare-genetic-disorder. Accessed November 14, 20