Fræðigrein

Introduction: We evaluated the efficacy of activated recombinant factor VIIa (rFVIIa) administration for critical bleeding during cardiothoracic surgery in Iceland.

Materials and Methods: Over a 33 month period, 10 consecutive patients with major life-threatening bleeding during or right after open cardiac surgery that received rFVIIa in 11 operations. Clinical information was retrospectively collected from hospital charts.

Results: The 10 patients were on average 66 year old, ranging 36-82 yrs. All patients were NYHA-class III or IV, there of three undervent emergency surgery. Complicated AVR±CABG was the most common type of operation (n=5), with average operation time 673 min. (range 475-932) and perfusion time 287 min. (range 198-615). After the administration of rFVIIa, haemostasis was acquired in 8 of 11 operations, with a significant improvement in coagulation parameters. Three patiens needed reoperation for bleeding. Transfusion of packed red cell (p=0.002) and plasma (p<0.02) decreased significantly after administration of rFVIIa and prothrombin time was shortened (p<0.004). Five patients succumbed, one of them with a cerebral infarction and pulmonary embolus, the latter confirmed at autopsy. Other causes of death were intractable bleeding, myocardial infarction, multiorgan failure and disseminated intravascular coagulopathy.

Conclusions: rFVIIa can be used effectively to stop intractable bleedings in open heart surgery, with 8 out of 11 patients in this small series achieving hemostasis after its administration. Mortality in this group of patients was high (50%), however, in all cases rFVIIa was used as an end-of-the-line treatment where other therapy had failed. One patient died from pulmonary embolism and cerebral infarct, raising the question of hypercoagulation. Further studies on the side effects and indications of rFVIIa treatment are necessary.

 

Table 1:  Guidlines for the use of Novoseven^® at Landspitali University Hospital.

 

Physician perscribing NovoSeven^® shall answer all of the following questions:

1.      Is there a reasonable hope of recovery? Is the nature of underlying disease (e.g. heart disease, malignancy) such that recovery can be expected if the patient survives the current haemorrhage?

2.      If the haemorrhage life threatening?

3.      Have coauglopathies been correct to the maximum extent? (FFP, platelets, fibrinolysis inhibitors)

4.      Has hypotheria been corrected?

5.      In case of post operative haemorrhage, have surgical methods been fully tried?

6.      Has DIC-panel been measured?

7.      Has a consultation of heamotoligst on call been aquired?

If the answer is no to any of the above questions than the use of NovoSeven^® is discouraged.

If the answer is yes to any of the above questions than the use of the drug can be cosidered.

 

 

Table 2.           Patients that received treatment with rFVIIa during or after open heart surgery in Iceland 2003-2006.

 

No.	Age / Gender	Type of operation	Dose of  rFVIIa	Bleeding stopped after administration of rFVIIa	Lenght of stay in ICU and hospital (days)	Operative mortality	Alive (Sept.  1st 2007)	Comments
1	75 / M	AVR + CABG +  MVR + Maze-procedure	100 μg/kg	Yes	34/34	No	No	Bleeding stopped and the operation was finished. Died of multi-organ failure after 3 operations and 34 days in hospital.
2	73 / M	CABG +MVP + Maze prodedure - rFVIIa  administrated during redo for bleeding	40 μg/kg	No	7/24	No	Yes	First a reduction in bleeding was seen that later increased. Later he received tranexamic acid, aprotinin, plasma and thromboytes that helped to stop the bleeding
3	51/ F	Acute aortic dissection	40 μg/kg	Yes	8/41	No	Yes	Diffuse bleeding stopped and the operation could be finished.
4	63 / M	Emergency CABG + resection of left ventricular aneurysm, secondary to AMI.	80 μg/kg + 40 μg/kg + 40 μg/kg	No	0/1	Yes	No	Only temporary effect of treatment after first dose. Died in the operating room due to profuse bleeding. Rupture ventricle at start of operation
5	35 / M	AVR	40 μg/kg	Yes	9/45	No	No	Bleeding stopped. Died 1 month postoperatively of acute cardiac failure. No signs of coronary artery disease at autopsy.
6	82 / F	AVR + CABG	80 μg/kg	Yes	18/18	Yes	No	Bleeding stopped in several minutes. Died of sepsis and diffuse intravascular coagulopathy 18 days later.
7	70 / F	Redo for bleeding after AVR.	40 μg/kg	Yes	3/3	Yes	No	Bleeding stopped. Died of pulmonary embolism. At autopsy a braininfarctation was found, but thrombosis in intracranial arteries could not be identified.
8	81 / F	AVR + CABG	60 μg/kg í	Óljóst	2/2	See pat. no. 9	See pat. no. 9	Bleeding stopped after 90 min. But started again 12 hours later, see pat. no. 9.
9	81 / F	Redo for bleeding on pat. no. 8	60 μg/kg	Yes	See pat no. 8	Yes	No	Bleeding stopped. Died of AMI 2 days later.
10	74 / K	AVR + CABG	40 μg/kg	Yes	27/42	No	Yes	Bleeding stopped immediately.
11	59 / K	CABG	80 μg/kg	Yes	4/12	No	Yes	Diffuse bleeding stopped

CABG = coronary artery bypass graft, AVR = aortic valve replacement, MVR = mitral valve replacement, MVP = mitral valve plasty, AMI = acute myocardial infarct.

 

Table 3.           Comparison of transfusions, plasma, thrombocytes and coagulation parameters, before and after the administration of rFVIIa.

 

	Before administration of rFVIIa			After administration of  rFVIIa			p-value#
	Mean	Median	Range	Mean	Median	Range
Blood components (units)
Packed red cells	16.7	12	(5 - 61)	1.6	0	(0 - 6)	0.002
Thrombocytes	3.2	3.5	(2 - 4)	1.6	0.5	(0 - 8)	0.1484
Plasma	13.9	11.5	(0 - 28)	1.4	0.5	(0 - 7)	0.0156
Coagulation tests (sec)
PT	23.	18	(10 - 86)	14.1	12.1	(9.3-38)§	0.0039
APTT	89.	68	(38 - 180)*	56.1	62	(36.0 – 68.0)§	0.0547
ACT	255	131	(129-1000)°	115	87	(75-209)§	0.1563

PT = prothrombin time, APTT = activated protrombin time, ACT = activated clotting time, * 180 as a max. value on instrument, ° 1000 as a max. value on instrument, § some differencenes in the timing of measurement from the administration of rFVIIa, # Wilcoxon signed rank test.