【Anesthesia Hotspot】Use of recombinant factor VIIa in cardiac surgery

Click the blue word to follow our notes on the use of recombinant factor VIIa in the Laba Festival Happy Heart Surgery: Guan Yong Typesetting: Dingdang Maruko Ma Case Form: Retrospective Case Analysis The patient, female, 73 years old, is scheduled to undergo aortic valve and mitral valve replacement
.

For the past 6 months, the patient complained of worsening dyspnea and occasional chest pain with activity
.

Preoperative echocardiography revealed severe aortic stenosis and moderate to severe mitral regurgitation
.

The patient underwent coronary artery bypass grafting 10 years ago, and the procedure went well
.

Recent coronary angiography showed that the bypassed vessels were patency and no new coronary stenosis was seen
.

The patient was successfully weaned from cardiopulmonary bypass (CPB) postoperatively.
Although the patient's ACT had reached the basal level after protamine administration, there was still significant bleeding
.

No obvious surgical bleeding factors were found
.

Despite the patient's hemodynamic stability, chest tube drainage continued after infusion of 4 units of fresh frozen plasma
.

Anesthesiologists considered infusion of recombinant factor VIIa (rFVIIa)
.

Discussion The management of multifactorial coagulopathy in patients undergoing cardiopulmonary bypass surgery is challenging for medical professionals, especially after reoperation or prolonged CPB
.

Predisposing factors include preoperative antiplatelet therapy, residual heparin effects, hypothermia, decreased relative or absolute platelet count and function, fibrinolytic activation, and decreased number and function of coagulation factors
.

What is the first step in bleeding after CPB? Treatment of excessive bleeding after CPB: First, analyze the reasons, including surgical factors, and immediately take heat preservation measures for the patient, and decide whether to add protamine according to the body temperature and ACT value
.

And perform platelet count and related coagulation function tests
.

Thromboelastography provides a relatively quick and reliable, but nonspecific, assessment of a patient's coagulation status (including coagulation factor deficiencies, platelet dysfunction, and fibrinolytic activation)
.

rFVIIa Mechanism of Action In 1988, rFVIIa was used in a patient with hemophilia A who was undergoing synovectomy
.

Patients with hemophilia often receive allogeneic blood components and thus have inhibitory antibodies to factors VII and IX, limiting their effectiveness in the treatment of acute bleeding
.

Binding of FVIIa to tissue factor released after injury activates factors IX and X, promoting the formation of fibrin
.

When the infusion dose of rFVIIa exceeds the physiological concentration, rFVIIa directly increases thrombus formation, and the secondary product prevents its degradation by plasmin
.

What are the indications for the use of rFVIa? Current indications for transfusion include the treatment of bleeding in hemophilia A, congenital factor VII deficiency, and thrombocytopenia
.

rFVIIa has been used unconventionally in non-surgical hemorrhage after trauma, hepatic lobectomy and liver transplantation, prostatectomy, intra-abdominal hemorrhage, intracranial hemorrhage and cardiac surgery
.

Can rFVIIa be used in cardiac surgery patients? Widespread infusion of rFVIIa in cardiac surgery patients is based on early case reports that the use of rFVIIa after complex coronary artery bypass grafting, placement of ventricular assist devices, and re-thoracotomy significantly reduces post-CPB bleeding
.

Case report: The anticoagulant effect of lepirudin (an antithrombotic drug) was antagonized with rFVIIa after CPB in a patient with a prior history of heparin-induced thrombocytopenia
.

Another case report: replacement of protamine by rFVIIa (in this patient with protamine allergy) neutralized after CPB
.

Several retrospective studies have shown that rFVIIa is effective in the treatment of refractory bleeding after CPB, reducing blood loss, normalizing coagulation factors, and reducing blood product requirements
.

The medical records show that rFVIIa can rapidly reduce postoperative bleeding, but has no effect on blood transfusion volume 24 hours after surgery
.

Current prospective, randomized, controlled trials on the use of rFVIIa after cardiac surgery are limited by small sample sizes
.

One study showed that the need for allogeneic blood products was significantly reduced with rFVIIa in 10 patients undergoing complex cardiac surgery under cardiopulmonary bypass, and there was a trend toward a reduction in blood loss
.

Another study showed that in children undergoing cardiac surgery, infusion of rFVIIa did not reduce blood loss and the need for blood products
.

Therefore, large, randomized, placebo-controlled trials evaluating the efficacy of rFVIIa in reducing postoperative bleeding or blood transfusion in cardiac surgery patients are necessary
.

The ideal dose of rFVIIa to reduce bleeding in patients without increasing adverse effects has not yet been established
.

The recommended dose range in the literature is 25~195ug/kg (usually 90ug/kg)
.

The use of 40ug/kg of rFVIIa can significantly stabilize uncontrolled bleeding after cardiac surgery
.

Research trials of doses of rFVIIa in cardiac surgery are required
.

Risk of thrombotic events The main concern with the use of rFVIIa is thrombosis
.

At low concentrations, rFVIIa can activate thrombosis at the site of tissue factor exposure
.

At higher concentrations, the generated thrombus can spread from the site of vascular injury and initiate intravascular thrombus formation
.

Typically, anticoagulant proteins such as antithrombin III inactivate excessive thrombus formation
.

However, after surgery under CPB or after acute illness, the concentration of antithrombin III decreases, predisposing the body to intravascular thrombosis
.

Multiple retrospective studies and prospective, randomized, blinded, placebo-controlled studies have shown that rFVIIa has a significant effect in the treatment of excessive bleeding after cardiac surgery without an increase in thrombotic events
.

Two patients with hemophilia had thrombotic events possibly due to the use of rFVIIa after lung transplantation
.

Therefore, the safety of using rFVIIa in the perioperative period needs to be further studied
.

Key messages 1.
Nonsurgical bleeding after cardiac surgery is multifactorial
.

2.
Directly increased thrombus formation after infusion of rFVIIa at supraphysiological concentrations
.

3.
The currently established indications for rFVIIa include: the treatment of hemophilia (with FVIII inhibition), congenital FVII deficiency and bleeding with thrombocytopenia
.

4.
The safety of rFVIIa in the treatment of perioperative bleeding remains to be further studied
.

Question 1.
What is the physiological role of FVII in coagulation? Answer: FVIIa (the activated form of FVII) binds to tissue factor released by injured cells, activates factors IX and X, and initiates the formation of fibrin
.

2.
What are the current indications for the use of rFVIIa? Answer: rFVIIa can be used to treat bleeding in hemophilia (with FVIII inhibition), congenital FVII deficiency, and thrombocytopenia
.

3.
What is the dose of rFVIIa used to treat bleeding after cardiac surgery? Answer: The recommended dose range in the literature is 25~195ug/kg, and the commonly used one is 90ug/kg
.