Medical Care
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 alpha2–plasmin inhibitor (alpha2-PI) deficiency that is a cause or the cause of acute significant bleeding should receive a transfusion of fresh frozen plasma (FFP) as a source of alpha2-PI.
Pooled plasma treated with solvent-detergent (SDP) is available to treat any condition in which FFP typically is used and for which no factor concentrate is available. [20, 21] 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. Although it also reduces levels of alpha2-PI, [16] an in vivo study found a statistically significant increase in plasma levels of alpha2-PI after infusion of SDP. [20] Note also the following:
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SDP is ABO blood type specific, so it should be ABO compatible with the recipient's blood type.
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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%.
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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 intravenous therapy with antifibrinolytic drugs, such as epsilon-aminocaproic acid (EACA) or tranexamic acid (Cyklokapron), helps prevent the generation of plasmin and blocks its action. EACA and tranexamic acid 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. Excluding a significant element of disseminated intravascular coagulation (DIC) is essential before using drugs inhibiting fibrinolysis, because inhibition of fibrinolysis will accelerate thrombosis secondary to DIC.
Prolonged oral therapy with antifibrinolytic drugs reduces the frequency of bleeding in patients with severe congenital alpha2-PI deficiency. Patients with acquired alpha2-PI deficiency who have benefited from antifibrinolytic therapy, when appropriate, include those with acute promyelocytic leukemia, amyloidosis, and some patients with liver disease (during the anhepatic phase of liver transplantation).
Some authors have suggested prophylactic platelet transfusion, given the possible secretion of alpha2-PI contained in the alpha granules of activated transfused platelets.
Essential surgical procedures in patients with alpha2-PI deficiency should be performed only after re-evaluating the level of alpha2-PI and after deciding on the need for plasma or an antifibrinolytic agent.
Surgical Care
Serious bleeding complications in those with alpha2-plasmin inhibitor (alpha2-PI) deficiency, such as epidural or CNS hematomas, demand immediate surgical intervention. Such interventions must be coupled with plasma infusions to correct alpha2-PI 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 alpha2-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.
Consultations
Close consultation with a hematologist is necessary. A geneticist should also be consulted as needed. Collaboration with a specialized hemostasis laboratory is indicated.
Activity
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.
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The role of alpha2-plasmin inhibitor (alpha2-antiplasmin) in fibrinolysis.
