Alpha2-Plasmin Inhibitor Deficiency Treatment & Management

The extent of medical care depends on the severity of the bleeding. Minor bleeding can be handled with oral antifibrinolytic drugs, but more extensive bleeding may require temporary plasma supplementation. Bleeding into critical sites may also require surgical intervention.

Patients with inherited or acquired alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) that is a cause or the cause of acute excessive bleeding should receive a transfusion of fresh frozen plasma (FFP) as a source of alpha 2-plasmin inhibitor (alpha 2-PI , a2-PI) .

Pooled plasma treated with solvent-detergent (PLAS+SD) is available to treat any condition in which FFP typically is used and for which no factor concentrate is available.^{[10, 11]} Viral inactivation using the solvent-detergent (SD) process has been used in preparation of coagulation factor concentrates in the past. In vitro treatment of donor plasma with 1% of the solvent tri(n- butyl) phosphate (TNBP) and 1% of the detergent Triton X-100 leads to significant inactivation of a broad spectrum of lipid-enveloped viruses. Note the following:

• Studies of viral inactivation using the solvent-detergent process show significant inactivation of the human pathogenic viruses hepatitis B (HBV) and C (HCV) and human immunodeficiency virus (HIV). Other lipid-enveloped viruses (eg, Sindbis virus, bovine viral diarrhea virus) have also been used to monitor inactivation.
• Information made available by the American Red Cross shows that although antiplasmin levels were somewhat reduced following solvent-detergent treatment, a higher-than-expected recovery of alpha 2-plasmin inhibitor (alpha 2-PI, a2-PI) levels occurred in vivo after infusion of solvent detergent-treated plasma (untreated plasma = 0.70-1.30 U/mL, 5 lots tested; SD-treated plasma = 0.48 +/– 0.04 U/mL, 5 lots tested; in vivo recovery, 237 +/– 146%; n = 7).
• PLAS+SD is ABO blood type specific, and solvent detergent-treated plasma should be ABO compatible with the recipient's red cells.
• The frozen product is supplied in 200-mL bags. Each 200-mL bag has been demonstrated to raise factor levels by approximately 2-3%, with 4-6 bags raising the factor level of a 70-kg person by approximately 8-18%.
• Monitoring of specific factor levels before and after product infusion is important to ensure that hemostatically adequate levels are achieved and maintained to provide adequate hemostasis.

Oral or IV therapy with antifibrinolytic drugs, such as EACA or tranexamic acid (AMCA; trans -p -aminomethyl-cyclohexane carboxylic acid, Cyklokapron), helps prevent the generation of plasmin and blocks its action.

• EACA and AMCA are synthetic lysine analogues that bind to the lysine-binding sites of plasminogen and induce a conformational change, probably prevent plasminogen activation, and in large doses, also bind to plasmin, preventing it from binding to fibrin.
• Prolonged oral therapy with antifibrinolytic drugs reduces the frequency of bleeding in patients with severe alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency).
• Other patients who have benefited from antifibrinolytic therapy, when appropriate, include individuals with acute promyelocytic leukemia, amyloidosis, some patients with liver disease (during the anhepatic phase of liver transplantation), some types of cancers, and acquired alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency).
• Excluding a significant element of DIC is essential before using drugs inhibiting fibrinolysis, because thrombosis secondary to DIC is accelerated by adequately inhibiting fibrinolysis.
• The increase in serious thrombotic complications, such as acute myocardial infarction and stroke, which was anticipated with wider use of antifibrinolytic drugs, has not materialized.

Some authors have suggested prophylactic platelet transfusion, given the possible secretion of alpha 2-plasmin inhibitor (alpha 2-PI, a2-PI) contained in the alpha granules of activated transfused platelets.

Serious bleeding complications in those with alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency), such as epidural or CNS hematomas, demand immediate surgical intervention. Such interventions must be coupled with plasma infusions to correct alpha 2-plasma inhibitor deficiency and with inhibitors of fibrinolysis to prevent rebleeding. In addition, pay careful attention to avoiding perioperative use of drugs such as NSAIDs that potentiate bleeding. Serial laboratory assessments of the level of alpha 2-plasmin inhibitor (alpha 2-PI, a2-PI) must be performed in the postoperative period to ensure maintenance of adequate levels of over 70%.

In patients undergoing open heart surgery, local and systemic use of antifibrinolytic drugs have reduced blood loss and the requirement for transfusions. Despite these beneficial results, routine use of these agents in patients undergoing open heart surgery is uncommon. After open heart surgery, local irrigation of the chest wall with EACA can arrest excessive bleeding, but it also can lead to formation of firm fibrin thrombi that do not lyse.

Antifibrinolytic therapy has been successful in reducing blood loss and transfusion requirements in patients undergoing orthotopic liver transplantation, without causing hepatic artery thrombosis.

Patients undergoing supraceliac clamping of the aorta develop a predictable hyperfibrinolytic state that should be treated with antifibrinolytic drugs if bleeding is excessive.

Close consultation with a hematologist is necessary. A geneticist should also be consulted as needed. Collaboration with a specialized hemostasis laboratory is indicated.

A patient with alpha 2-plasmin inhibitor deficiency (alpha 2-PI deficiency, a2-PI deficiency) should follow a normal healthy diet.

If active bleeding occurs, either spontaneously or postoperatively, rest is appropriate, depending on the site and extent of the bleeding. Physical therapy for patients receiving FFP replacement therapy is necessary following joint bleeding.