Alpha2-Plasmin Inhibitor Deficiency Follow-up
- Author: Olga Kozyreva, MD; Chief Editor: Perumal Thiagarajan, MD more...
Further Outpatient Care
Continuation of oral antifibrinolytic therapy on an outpatient basis is warranted, particularly if the drug was effective in controlling bleeding, as in persons with hemophilia following oral surgical procedures. Only a brief period of therapy is recommended for acquired disorders of alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency). Monitor patients closely, and determine the appropriate duration of therapy by clinical observation of the patient.
For prophylactic care, long-term oral therapy with antifibrinolytics has successfully reduced the incidence of bleeding in patients with inherited alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency).
Further Inpatient Care
Prolonged therapy with FFP or PLAS+SD and antifibrinolytics may be needed in those who have alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency), depending on the clinical circumstance.
Inpatient & Outpatient Medications
Long-term maintenance therapy with oral antifibrinolytic agents has reduced the incidence of bleeding complications in alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency). For dosing, please see the Medication section.
Avoidance of antiplatelet drugs is essential because these agents increase bleeding risk.
A patient with persistent bleeding in the postoperative period resulting from alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) may require transfer to a tertiary medical center if specialists with expertise are not available at the local community hospital.
Avoidance of trauma and the use of NSAIDs can minimize the frequency of bleeding complications.
Prevention is not feasible for the genetic defect that causes alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency). Prenatal testing of a known defect may be attempted in a family in which members experience severe bleeding.
Immunization against HAV and HBV is useful in patients who require administration of plasma products. Although reports of blood-borne HAV infection resulting from tainted donations are sporadic only, the superimposition of acute HAV infection on chronic hepatitis (which may exist in patients with repeated exposure to blood products) clearly puts patients at higher risk of hepatic failure. Therefore, immunizing patients against any form of hepatitis for which a vaccine is available is wise.[12, 16] HAV vaccination conforms with recommendations of the National Hemophilia Foundation for patients receiving any kind of blood products on a recurrent basis.
Complications of alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) relate to the site at which excessive bleeding develops. Bleeding is aggravated by concomitant use of drugs that induce additional hemostatic dysfunction, such as acetylsalicylic acid (ASA) or other NSAIDs. Other complications include the following[12, 13, 16] :
Infection by HIV (including type 2 and HIV group O), HHV-8, acquired immunodeficiency syndrome (AIDS), hepatitis (hepatitis A-E viruses, hepatitis GB virus C, hepatitis G virus), parvovirus infection, and SEN viruses
CJD and nvCJD resulting from prions: One review raised concerns about the transmission of CJD or its variant form (vCJD) from blood products.  The FDA's Transmissible Spongiform Encephalopathies Advisory Committee has proposed excluding donors who have resided or traveled in Europe for more than 5 years starting in 1980 or donors who have resided in the United Kingdom for more than 3 months. The availability of a new test for vCJD is anticipated.
Other complications may result from viral illnesses transmitted by human plasma.
People who are homozygous for alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) have a severe bleeding disorder, but if appropriate treatment is received, long-term survival is possible. The frequent need for plasma transfusions exposes the patient to the risks of virally transmitted illnesses, including HIV, hepatitis, parvovirus, TTV, nvCJD due to prions, and other pathogens.
People who are heterozygous for alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) have variable bleeding, generally mild or none. Cautious treatment is warranted to protect the patient from unneeded surgery with subsequent bleeding.
Educate patients with alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) on a continuing basis, and encourage them to seek appropriate information, which will strengthen their ability to deal with this inherited disorder.
Discuss the potential thrombotic risk of antifibrinolytic agents. This author's practice is to request the pharmacist to provide the patient and family with package inserts for special drugs.
If plasma is used, discuss the potential risks of blood product use. No source of plasma is 100% safe. Moreover, the risks of transmission of viral illnesses vary according to the country of source of the plasma (see the Medscape Reference topic Factor VIII for a discussion of these issues, as well as Transfusion-Transmitted Diseases).
The National Hemophilia Foundation provides information and support for patients with bleeding disorders and their families.
Koie K, Kamiya T, Ogata K, Takamatsu J. Alpha2-plasmin-inhibitor deficiency (Miyasato disease). Lancet. 1978 Dec 23-30. 2(8104-5):1334-6. [Medline].
Kluft C, Vellenga E, Brommer EJ, Wijngaards G. A familial hemorrhagic diathesis in a Dutch family: an inherited deficiency of alpha 2-antiplasmin. Blood. 1982 Jun. 59(6):1169-80. [Medline]. [Full Text].
Bachmann F. Plasminogen-plasmin enzyme system. Colman RW, Hirsh J, George JN, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 275-320.
Bachmann F. The fibrinolytic system and thrombolytic agents. Bachmann F, ed. Fibrinolytics and Antifibrinolytics. Berlin, Germany: Springer-Verlag; 2001. 3-15.
Francis CW, Marder VJ. Physiologic regulation and pathologic disorders of fibrinolysis. Colman RW, Hirsh J, George JN, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 975-1002.
Castellino FJ, Ploplis VA. Plasminogen and streptokinase. Bachmann F, ed. Fibrinolytics and Antifibrinolytics. Berlin: Springer-Verlag; 2001. 26-56.
Hedner U, Hirsh J, Marder VJ. Therapy with antifibrinolytic agents. Colman RW, Hirsh J, George JN, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 796-813.
Bachmann F. Disorders of fibrinolysis and use of antifibrinolytic agents. Beutler E, Lichtman MA, Coller BS, et al, eds. Williams Hematology. 6th ed. New York, NY: McGraw-Hill; 2001. 1829-40.
Davis R, Whittington R. Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery. Drugs. 1995 Jun. 49(6):954-83. [Medline].
American Red Cross. PLAS+SD (pooled plasma, solvent-detergent treated) (monograph). 1999.
PLAS+SD (Pooled Plasma, (Human) Solvent Detergent Treated) [package insert]. Washington DC: American Red Cross, VI Technologies, Inc. October 2000.
MediView Express. Recombinant therapy enhances safety and quality of life for hemophilia patients. Paper presented at: 53rd Annual Meeting of the National Hemophilia Foundation. November 16, 2001; Nashville, Tenn.
Rigas B, Hasan I, Rehman R, et al. Effect on treatment outcome of coinfection with SEN viruses in patients with hepatitis C. Lancet. 2001 Dec 8. 358(9297):1961-2. [Medline].
Di Bisceglie AM. SEN and sensibility: interactions between newly discovered and other hepatitis viruses?. Lancet. 2001 Dec 8. 358(9297):1925-6. [Medline].
Senior K. New variant CJD fears threaten blood supplies. Lancet. 2001 Jul 28. 358(9278):304. [Medline].
Dale GL, Friese P, Batar P, et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature. 2002 Jan 10. 415(6868):175-9. [Medline].
Favier R, Aoki N, de Moerloose P. Congenital alpha(2)-plasmin inhibitor deficiencies: a review. Br J Haematol. 2001 Jul. 114(1):4-10. [Medline].
Hanss MM, Farcis M, Ffrench PO, de Mazancourt P, Dechavanne M. A splicing donor site point mutation in intron 6 of the plasmin inhibitor (alpha2 antiplasmin) gene with heterozygous deficiency and a bleeding tendency. Blood Coagul Fibrinolysis. 2003 Jan. 14(1):107-11. [Medline].
Lijnen HR, Okada K, Matsuo O, Collen D, Dewerchin M. Alpha2-antiplasmin gene deficiency in mice is associated with enhanced fibrinolytic potential without overt bleeding. Blood. 1999 Apr 1. 93(7):2274-81. [Medline]. [Full Text].
Maino A, Garagiola I, Artoni A, Al-Humood S, Peyvandi F. A novel mutation of alpha2-plasmin inhibitor gene causes an inherited deficiency and a bleeding tendency. Haemophilia. 2008 Jan. 14(1):166. [Medline].
Mangel WF, Lin BH, Ramakrishnan V. Characterization of an extremely large, ligand-induced conformational change in plasminogen. Science. 1990 Apr 6. 248(4951):69-73. [Medline].