Patients with α2-AP much like those with hemophilia have increased bleeding tendencies during surgical procedures. Generally, adequate hemostasis can be managed with administration of anti-fibrinolytic agents. As in our case, there remains the potential for thrombotic events related to antifibrinolyitic therapy and the benefits versus risks of treatment will need to be considered in every surgical case in patients with diagnosis of homozygous α2-AP deficiency. Since it is a rare entity, there is limited medical literature to utilize as guidelines in managing such patients. It can be even more difficult when the diagnosis of α2-AP deficiency is not known. One report describes the case of a 6-year-old boy with a history of severe bleeding after an elective adenoidectomy. Standard perioperative tests for coagulation parameters remained within normal limits, but patient had profound bleeding after his procedure which required two repeat attempts of surgical hemostasis in the operating room. He was discovered to have homozygous α2-AP deficiency with a serum α2-AP concentration of 24 percent (normal > 60 percent) .
Shahian and Levine reported a case of open aortic valve replacement and coronary bypass in an individual with known heterozygous α2-AP deficiency with serum α2-AP concentration of 52 percent. Patient underwent infusion of 3000 mL of FFP, which increased perioperative α2-AP levels to 78 percent . Morimoto et al describes management of intraoral bleeding in those with α2-AP deficiency with 7.5-10 mg/kg of tranexamic acid orally every 6 hours starting 3 hours before procedure to be continued for 7 days . There are no published recommendations for aminocaproic acid dosing in this setting. As recommended by our Hemophilia Treatment Center, our patient received two units of FFP and 1g of IV tranexamic acid bolus pre-operatively with a continuous infusion of 1g tranexamic acid over eight hours intraoperatively and transition to oral tranexamic acid 1300 mg q 8 hours. The incidence of thrombosis and pulmonary embolism is not known for aminocaproic acid administration, but for tranexamic acid, the incidence for either entity is < 1% .
The guidelines for DVT prophylaxisin patients with α2-AP deficiency are also not established given the rarity of this condition. In xenograft models of Pulmonary Emboli (PE), α2-AP was shown to play a critical role in resistance to thrombolysis  and its inhibitionled to thrombolysis in a comparable manner to tPA administration , perhaps even with synergistic effects with tPA in decreasing mortality from PE . These findings open the possibility of utilizing α2-AP in a therapeutic capacity for thrombotic events. Despite the antithrombotic tendencies inherent in those with α2-AP deficiency, orthopedic procedures on weight bearing bones and joints in particular result in higher postoperative risk of DVT given the likelihood of post-operative immobility. Similarly, in patients with hemophilia, pharmacologic thromboprophylaxis is also considered controversial. At least one source does not recommended thromboprophylaxis for those hemophilia patients with aninhibitor given the high risk of bleeding but does recommended thromboprophylaxis after orthopedic procedures in those without inhibitor .
In our patient, prophylactic LMWH at 30g bid in conjunction with tranexamic acid was sufficient in preventing post-operative hemorrhage, but was unsuccessful in preventing DVT. It is unknown whether full dose therapeutic LMWH would have been more successful in preventing the DVT without compromising post-operative bleeding risk. Heparin products work by binding antithrombin and accelerating its activity by 1000 fold. The result is decrease in Factor Xa and IIa (activated Thrombin) influence in the coagulation system. This seemingly predates the formation of Fibrin and hence the fibrinolytic pathway as well. In reality, these opposing forces that balance hemostasis are occurring simultaneously. In α2-AP deficiency, Plasmin is left activated and able to degrade Fibrin leading to clot dissolution. Inhibition of the fibrinolytic pathway with tranexamic acid can lead to unopposed fibrin longevity with possible propagation to pathologic thrombosis. The approach to post-operative DVT prophylaxisin individuals with defects in the fibrinolysis pathway should be considered on a case-by-case basis taking into consideration additional risk factors for bleeding and thrombosis such as thrombocytopenia, extend of surgical trauma, immobility, malignancy, obesity, and concurrent medications. Recognizing that both entities are increased in this patient population is paramount. Although this situation is rare, it is our practice to utilize anti-fibrinolytic agents to correct the known hereditary defect while administering standards of care anticoagulation to minimize the thrombotic risk. As this case demonstrates, even with careful consideration, morbidity can occur.