The Case of a Late Bleeder Plasminogen Activator Inhibitor 1 Deficiency

Case Report

Ann Hematol Oncol. 2015; 2(10): 1068.

The Case of a Late Bleeder Plasminogen Activator Inhibitor 1 Deficiency

Del Rosario M¹* and Tsai H1,2

¹Eisenhower Medical Center, USA

²Luci Curci Cancer Center, USA

*Corresponding author: Michael Del Rosario, Eisenhower Medical Center, 39000 Bob Hope Dr, Rancho Mirage, CA 92270, USA

Received: September 23, 2015; Accepted: November 30, 2015; Published: December 02, 2015


A 79-year-old post-menopausal Caucasian woman was investigated for lifelong history of bleeding including heavy menses, epistaxis, and minor postoperative bleeding such as post tonsillectomy and wisdom teeth extraction. Her history included significant hemorrhagic effusion post MRI scans of the right knee with no apparent cause for bleeding. Abnormalities and deficiencies of the coagulation system, platelet quantity/quality, alpha-2 plasmin inhibitor, and von Willebrand factor were negative. Patient was finally found to have heterozygous PAI-1 locus 4G, 5G deletion and insertion allele, demonstrating intermediate PAI-1 activity. This is striking, as normally severe PAI-1 deficiency is associated with recurrent bleeding episodes. These findings highlight the fact that even intermediate deficiency of the plasma PAI-1 can result in morbid clinical outcomes, therefore requiring the astute clinician to at least think about PAI-1 deficiency in a patient with recurrent bleeding episodes.

Keywords: Plasminogen Activator Inhibitor 1 Deficiency; Delayed Postoperative Bleeding; Bleeding Disorders; Coagulation Disorders; Alpha-2 Plasmin Inhibitor; Von Willebrand Factor Type 2N (Normandy); Hypofibrinogenemia; Dysfibrinogenemia


Plasminogen Activator Inhibitor type 1 (PAI-1) is a little known but vital component of the body’s coagulation system. PAI- 1 is responsible for down regulating degradation of thrombi to help regulate fibrinolysis [1]. Normally, plasminogen activators circulate in plasma as a complex with PAI-1 as a reversible complex. When the fibrin clot is formed, plasminogen and t-PA bind to the surface of the clot. After protein interaction, plasmin is formed, which leads to fibrinolysis of the cross-linked fibrin resulting in fibrindegradation products. PAI-1 also binds to fibrin, and when bound, it can irreversibly bind to inhibitor t-PA (Figure 1) [2]. As one can expect, PAI-1 deficiency may end up as increased bleeding with up regulation of fibrinolysis. However, case reports of PAI-1 deficiency are rare. The first case report has been initially identified in the 1980s [3]. The affected patients express mild to moderate bleeding symptoms ranging from epistaxis to delayed bleeding after surgical procedures. Complete deficiency, however, is linked to life threatening hemorrhage and prolonged wound healing [4]. Aminocaproic acid or tranexamic acid are excellent fibrinolysis inhibiting drugs used as prophylaxis or treatment of bleeding episodes in patients with PAI-1 deficiency [5].