PREVENTING, MINIMIZING, AND MANAGING POSTOPERATIVE COMPLICATIONS

Preventing, Minimizing, and Managing

Postoperative Bleeding
Alain Pavie, MD, Jacques Szefner, MD, Philippe Leger, MD, and
Iradj Gandjbakhch, MD
Department of Thoracic and Cardiovascular Surgery, La Pitie Hospital, Paris, France

Background. Most bleeding in cardiovascular surgery is

biological, not surgical, the result of disseminated intravascular coagulation in its latter phases. Disseminated intravascular coagulation bleeding affects all levels of the coagulation systems, requiring stabilization of the platelet
system, balancing the procoagulant system and its regulation, and stopping the fibrinolytic systems activation.
Methods. The article discusses the multisystem protocol put into place at the Cardiovascular Surgery Department of La Pitie Hospital in Paris to diagnose and treat
DIC bleeding so as to slow down causes of its occurrence
and prevent further deterioration of the hemostatic
systems.

Results. All biological bleeding was controlled, permitting detection of other causes of bleeding and allowing rational use of blood products. No thromboembolic
accident occurred. There was an absence of iatrogenic
bleeding. The protocol also detects disseminated intravascular coagulation in patients who did not bleed to
take early and frequently lifesaving measures.
Conclusions. This demonstrates the need to treat bleeding through a multisystem approach, monitoring its
evolution by means of biological tests to be able to
provide appropriate treatment.
(Ann Thorac Surg 1999;68:70510)
1999 by The Society of Thoracic Surgeons

for bridge to transplant [3], the odds ratio predicting

survival in case of bleeding was 2.07.
Furthermore, bleeding contributes to the development of renal and respiratory failure and increases the
risk of infection. Infections arise in 3.9% of patients
receiving up to 2 U of red cells, in 6.9% receiving 3 to
5 U, and in 22% of those receiving 6 U [4]. In
addition, the need of large amounts of blood derivatives for transfusion can stimulate antibody production
and increase duration under support. The major factors affecting bleeding during implantation include,
among others, one or more of the following: the previous clinical status of the patient, particularly in case
of severe hepatic failure or severe coagulopathy; the
previous treatments that the patient has undergone,
most notably fibrinolytic treatment, as well as anticoagulation and antiaggregation therapy; technical surgical ability; the device itself, which introduces foreign
material into the body triggering hyperactivity of the
various coagulation systems; and a long cardiopulmonary bypass (CPB) time (eg, reoperations), hypothermia, hemodilution, surgically damaged tissues, platelet
dysfunction, shear rate conditions, depletion of one or
more coagulation factors, bad management of anticoagulation or neutralization during CPB, among other
conditions, can trigger or exaggerate the fibrinolytic
action, thus increasing the bleeding phenomenon.
It is clear, therefore, that most bleeding in cardiovascular surgery is not surgical, it is biological in origin,
essentially the result of DIC in its later phases. Accordingly, the follow-up and treatment of DIC is of the utmost
importance to anticipate and slow down causes of its

leeding is the most frequent complication faced during the implantation of a mechanical cardiac assist
device, both during the operation itself and in the immediate postoperative period, which may continue if there
is hemodynamic instability or multiple organ failure.
Regardless of the type of device, bleeding occurs more
often in case of implantation for recovery than in case of
implantation for bridge to transplant. Indeed, according
to various published series, an average of between 33%
and 73% of patients during implantation for recovery,
and from 29% to 53% receiving ventricular assist devices
or total artificial hearts as bridges to cardiac transplantation, have required reoperation for bleeding [1]. The rate
of bleeding/disseminated intravascular coagulation
(DIC) when undergoing postcardiotomy cardiogenic
shock, as reported in Paes registry [2], is 40% in all
clinical situations. According to the international registry
[3], the rate of bleeding in case of bridge to transplant is
very high, which has a strong influence on survival.
Patients who were discharged after transplantation had a
lower incidence of bleeding (29.4%) compared to those
who died while under device (59.1%), or who were
transplanted but not discharged (50%). The impact of
bleeding on the outcome is clearly demonstrated by two
multivariate analyses: on the postcardiotomy cardiogenic
shock registry [2] the odds ratio predicting weaning in
case of bleeding was 1.43, and in the European registry
Presented at the Fourth International Conference on Circulatory Support
Devices for Severe Cardiac Failure, Houston, TX, Oct 35, 1997.
Address reprint requests to Dr Pavie, Department of Thoracic and
Cardiovascular Surgery, La Pitie Hospital, 47-83 Blvd de lHopital, 75651
Paris Cedex 13, France.

1999 by The Society of Thoracic Surgeons

Published by Elsevier Science Inc

0003-4975/99/$20.00
PII S0003-4975(99)00628-1

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CONTROLLING POSTOPERATIVE BLEEDING

occurrence and prevent further deterioration of the hemostatic systems.

Bleeding and Disseminated Intravascular

Coagulation
Bleeding is a surgeons constant concern, and how he or
she treats it during an operation may make the difference
between success and failure. Above all, he or she must
determine whether it is surgical or biological, and if
biological, must be able to diagnose and treat it correctly.
Biological bleeding, and in particular DIC, is a neglected, little understood phenomenon. Disseminated
intravascular coagulation can be defined as a pathologic
condition in which a generalized activation of the hemostatic systems occurs by one or more triggering pathways, causing widespread thrombin, fibrin, and plasmin
formation and subsequent lysis within the vascular system, which often leads to microthrombosis and consumption of platelets, as well as of clotting and inhibitor
factors.
Disseminated intravascular coagulation can be summarized with one word: hypercoagulability; but this
phenomenon is very difficult to delimit. If biological
hypocoagulability has an evident clinical translation,
bleeding or a bleeding tendency, hypercoagulability does
not always result in thrombosis. This fact has always
troubled the clinician and especially the surgeon, as there
is no distinct parameter of hypercoagulability that can
predict thrombosis. When we analyze the different
phases of DIC, we see that DIC biological hypocoagulability, manifested as hemorrhage, is simply the translation of a state of overt and decompensated hypercoagulability [5]. The DIC thrombophilic condition is a
secondary response to one or more preexisting primary
pathologies, which are mutually enhanced.

Therapeutic Approach
Surgical patients presenting such pathologies suffer a
strong and permanent aggression (continuous injury) at
every level of the coagulation systems, which are always
disturbed. Accordingly, if we want to prevent bleeding,
we must imperatively control all the systems involved
the platelet system, the procoagulant system and its
regulation, and the fibrinolytic system, because all these
systems are tightly interwovenand adapt the treatment
to each individual [6].
The platelet plays an important role in the triggering
and maintenance of a thrombophilic state that can degenerate into DIC and thrombosis. This state must be
controlled and corrected according to the different surgical and clinical conditions to which the patients and their
platelet system are subjected. In patients undergoing
strong and permanent aggression, there is a basic discrepancy between the aggregation curves and those
resulting from the determination of platelet factor 4 (PF4)
and -thromboglobulin (BTG), thus reflecting platelet
hyperactivation. Very few platelets remain intact, explaining the hypoaggregability and possible hemor-

Ann Thorac Surg

1999;68:70510

rhage. The content of the platelet is now external (PF4,

BTG, thrombin), which increases the activation of other
platelets and the formation of circulating aggregates, and
prevents the appropriate use of heparin [6]. Platelets are
permanently activated and morphologically altered
throughout the implantation of any mechanical circulatory support. Because the degranulation phenomenon is
closely related to the change in the intraplatelet level of
cyclic AMP, it is possible to avoid this phenomenon by
increasing the beneficial level of intraplatelet cyclic AMP
by inhibiting phosphodiesterase with appropriate doses
of dipyridamole [7]. The platelet then becomes less
receptive to usual inductors, preventing the release of the
platelets secreted products that can generate endothelial
changes and thus activate other platelets.
Concerning coagulation itself, the goal is to establish a
balance between the different pathways of thrombin
formation and the activity of the most powerful inhibitor
antithrombin III (AT III). Such a balance can be best
evaluated with thromboelastography (TEG) on recalcified whole blood (with the thrombodynamic potential
index; normal value, 6 to 15), the only sensitized test that
allows study of global coagulability and the different
phases of coagulation. This test is able to show the
kinetics, dynamics, syneresis, and structural quality of
the clot [8]. Evaluating hemostasis only in plasma is not
sufficient (especially during the imbalance due to a hemodilution, as in CPB), as the patient performs hemostatic functions on whole blood, including thrombi.
Thromboelastography allows us to assess overall hypercoagulability and appreciate the intensity of an early
lytic-evolving process. Coagulation balance may also be
evaluated by establishing the antithrombin potential index (API), which makes it possible to appreciate the
adaptation capacity of inhibition to global coagulability.
The API is determined by subtracting AT III in serum
from AT III in plasma (normal value, 35 to 45) [6, 8]. And
finally, determining the activated factor X in serum
(normal value, 10% to 20%) indicates the speed of thrombin formation. To obtain a satisfactory balance, the most
appropriate anticoagulant to date is undoubtedly heparin. For CPB, we administer 120 to 200 IU/kg of heparin
and we adapt doses during an operation to reach a
hemochron or activated clotting time of around 450 50
seconds. The neutralization of anticoagulation with protamine at 60% of the total dose of heparin injected during
CPB is sufficient, because the relative excess of circulating heparin left after the intervention is only apparent, as
it is necessary to take into account heparin administered
before intervention and turnover during the operation
[9]. After the administration of protamine, blood recovers
its coagulation potential, although in reality it is not
normal. The patient is actually hypercoagulable as a
result of operation, the existence of thromboplastic material released during the operation, the circulatory arrests and stasis, anoxia, acidosis, and so forth. Huge
amounts of thrombin are generated and subsequent
fibrinogen is activated despite the presence of presumed
adequate heparinization during CPB [10]. Therefore, the
surgeon should be alerted to a possible presence and

Ann Thorac Surg

1999;68:70510

likely imminent occurrence of DIC, especially in the

presence of severe hemodynamic, metabolic, and hepatic
perturbation, with probable sepsis, when a systemic
inflammatory response syndrome is present, during surgical reinterventions, or when CPB has been especially
long, making it necessary to administer heparin to neutralize the thromboplastic material released and break
the vicious circle of a self-sustained coagulation. After
CPB, to maintain appropriate anticoagulation and in case
of DIC, imbalances are corrected by low-dose heparin
(1,000 to 5,000 IU/day). Low-dose heparin has multiple
sites of action, induces endothelial modulation, and releases tissue factor pathway inhibitor. Heparin therapy is
adapted and monitored using TEG to carry out Rabys
transfer test on plasma. We study the TEGs constant
rthe kinetics of the clot formation of a control and
of a mixture patient-control, from which an index is
obtained [8, 11]. The heparin therapy established in our
protocol enables us to obtain an efficient antithrombinic
effect and prophylactic effect. At the same time, it allows
the inhibitory system to function adequately and permits
enough thrombin formation to ensure satisfactory hemostasis, although it is insufficient to bring about a state of
real hypercoagulability.
After having stabilized the platelet function and balanced coagulation, we must stop fibrinolysis. Fibrinolysis
is due to the activation of plasminogen once it has
overcome the effect of the inhibitors of this action. Active
plasmin protease thus formed is physiologically inhibited mainly by 2-antiplasmin. This inhibition can lead to
the systems exhaustion if the activation of plasminogen
is too great or lasts too long. Disseminated intravascular
coagulation in its various phases is a frequent phenomenon. Accordingly, its diagnosis is of considerable interest for the understanding of the patients evolution and
prognosis. Of our first 82 Jarvik total artificial heart
implantations, we found that 63 had DIC, only 17 of
whom could be transplanted. On the other hand, all
patients without DIC were transplanted [9].
Of those patients with immediate postoperative bleeding, tests showed that 91% presented DIC in its later
phases, revealing the close relationship between bleeding and DIC. Perhaps even more important, because less
obvious, the tests also detected DIC in 53% of those
patients who did not bleed, making it possible to give
them an early, and frequently lifesaving treatment [9].
If we focus on patients with DIC in the immediate
postoperative period (65%), 38% presented immediate,
overt bleeding. These patients had gone directly into the
later phases of DIC, requiring an appropriate and vigorous treatment. But the remaining 62% who did not bleed,
yet had biologically proven DIC, were also detected by
our protocol, allowing for early treatment and avoiding
hemorrhage. Finally, it is important to point out that
among total artificial heart patients without postoperative DIC (35%), surgical bleeding was noted in only 7% of
patients [9].
Thus we observe, on the one hand, the strong relationship between DIC and bleeding, and on the other hand,
the need to look for DIC even if there is no bleeding [12].

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CONTROLLING POSTOPERATIVE BLEEDING

Table 1. Phase 1: Compensated Thrombophilia

Laboratory Tests
Factors
Fibrinogen
Reptilase time
Plasma AT III
Serum AT III
API
TEG
TEG
TEG
TEG

r
k
MA
TPI

Profile

Laboratory Tests

Profile

Conserved
Normal

Platelet count
Normal
Platelet aggregation Slightly
2
Moderately 1 Platelet proteins
Slightly
(PF4-TG)
1
Normal or 1 Plasminogen
Normal
2
Alpha-2- antiplasmin Normal
1
FDP
() or
()
5
2
60
75

Treatment: Abstain from treating, but closely monitor the evolution of the
process.
API antithrombin potential index;
AT antithrombin;
FDP
fibrinogen/fibrin degradation products;
k coagulation time;
MA maximal amplitude;
r reaction time;
TPI thrombodynamic potential index;
TEG thromboelastography.

Bleeding is a dynamic phenomenon. The multisystem protocol established by Szefner in our team identifies four
distinct DIC phases [6, 8, 9]: (1) compensated thrombophilic
phase; (2) clot kinetic structure dissociation phase; (3) generalized hypocoagulability phase, with the pinching phenomenon; and (4) secondary fibrinolysis phase.
Each phase has a different biological profile and requires a different therapeutic approach.

Phase 1 (Compensated Thrombophilic Phase)

During the first phase, we can say that the essential
structure appears to be intact: the factors and platelets
are almost normal and fibrinogen is normal or slightly
increased. Nevertheless, TEG indicates structural and
kinetic hypercoagulability, although the inhibitor AT III
is compensating for this excessive solicitation resulting
from greatly accelerated thrombin formation. Solicitation
of the fibrinolytic system is either absent or extremely
weak, the platelet function is relatively intact and there is
no specific clinical profile, except for the cause triggering
this phase (Table 1) [6, 8, 9]. What should we do at this
phase? Little or nothing, other than closely follow the
patients evolution because if the cause or causes persist
in the context of this situation, we may very quickly find
ourselves facing later phases.

Phase 2 (ClotKinetic Structure Dissociation Phase)

In the second phase, the factors are moderately diminished. Fibrinogen may have diminished in quantity and
in quality but it also may have increased (in sepsis, for
example), and reptilase time is longer. Reptilase time
reflects fibrinogen/fibrin degradation products (FDPs)
activity even in the presence of heparin. TEG can best
identify this phase. It reveals whether there is a dissociation between a rapidly forming clot (accelerated kinetics) that is consuming a great deal of raw materials, but
which at the same time is of poor quality (soft clot) and

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CONTROLLING POSTOPERATIVE BLEEDING

Ann Thorac Surg

1999;68:70510

Table 2. Phase 2: Clot KineticStructure Dissociation

Laboratory Tests

Profile

Laboratory Tests

Plasma AT III
Serum AT III

Moderately 2 Platelet count

1 or 2
Platelet aggregation
1
Platelet proteins
(PF4-TG)
2
Plasminogen
2
Alpha-2-antiplasmin

API

Normal or 2 FDP

Factors
Fibrinogen
Reptilase time

TEG
TEG
TEG
TEG

r
k
MA
TPI

Profile
2
2
1
2
Normal
or 2
() or
()

6 10
20
30 35
2.7

Table 3. Phase 3: Generalized Hypocoagulability With

Pinching Phenomenon
Laboratory Tests
Factors
Fibrinogen
Reptilase time
Plasta AT III
Serum AT III
API
TEG r
TEG k
TEG MA
TEG TPI

Profile
22
1 or 2
11
22

Laboratory Tests

Rabys transfer test

Platelet count
Platelet aggregation
Platelet proteins
(PF4-TG)
1
Plasminogen
2or22 Alpha-2-antiplasmin
30 40
FDP

Profile
() (1)
22
22 or ()
11
22
22
()

Treatment: Heparin, 10 to 20 IU/kg per day; dipyridamole, 150 to 200 mg

every 6 hours.

Treatment: Heparin, 5 to 10 IU/kg per day; dipyridamole, 200 to 300 mg

every 6 hours; fresh frozen plasma or fresh whole blood to replace
missing factors.

Abbreviations as in Table 1.

Abbreviations as in Table 1.

which can lyse easily. Plasma AT III is strongly solicited,

although it can still keep up and compensate, providing
a consequent diminution of serum AT III and a normal or
slightly diminished API. We also observe a decrease in
the number of platelets and in their activity, as well as an
early triggering of the fibrinolytic system observed by a
decrease in plasminogen, together with circulating plasmin and thus a drop in 2-antiplasmin (Table 2) [6, 8, 9].
Clinically, we often observe the diffuse presence of isolated or converging petechiae of hematomas. This phase
is very frequent in the immediate postoperative period.
To break the vicious circle (thrombin formationplasmin
formationlysis), we administer high doses of dipyridamole early on to stabilize the platelet function, and low
doses of heparin so as to slow down thrombin formation,
because acceleration of conditions in the second phase
will inevitably lead to the next phase.

counteract the accelerated formation of thrombin, followed by antithrombins exhaustion and later failure.
Both this exhaustion and later failure are expressed by
what we call the pinching phenomenon. The pinching
phenomenon is manifested by a decrease in plasma AT
III and an increase in serum AT III, leading to a reduced
or even nonexistent API, reflecting the total exhaustion of
the inhibitor. The phenomenon is a clear indication of a
seriously disturbed clinical state [6, 8, 9]. It reflects the
inhibitors inability to compensate for growing consumption of procoagulant factors, translated biologically in
TEG by hypocoagulability (of course, with underlying
hypercoagulability) and clinically by hemorrhage. In our
first 56 patients on total artificial hearts, confirmed in all
subsequent patients, it is clear that the pinching phenomenon is a very reliable indicator of the thrombophilic
state that accompanies DIC in its final phases (Fig 1) [9].
In the immediate postoperative period, the pinching
phenomenon is parallel to the last phases of DIC (initial
phases do not present this phenomenon). However, the
presence of the pinching phenomenon in patients with-

Phase 3 (Generalized Hypocoagulability Phase)

As reflected in TEG, the third phase presents a clear
picture of hypocoagulability, including a dramatic decrease in factors and virtual absence of the platelet
function. Fibrinogen, however, is only slightly affected
and Rabys transfer test is positive [11], indicating circulation of great quantities of thromboplastic material, thus
triggering activation of the fibrinolytic system (Table 3)
[6, 8, 9]. This is clinically translated by an aggravation of
the previous phase. In addition, there is a clear tendency
to suffer frequent and profuse hemorrhages at oozing
points and in the mucosae. Treatment administered in
phase 2 should be maintained and consumed factors
should be replaced with fresh frozen plasma (FFP) or
fresh whole blood [13].
A fundamental point should be stressed: as mentioned
earlier, the API obtained by subtracting AT III in serum
from AT III in plasmaallows us to appreciate the
inhibitory systems ability to adapt to global coagulability. In this way, when hypercoagulability is sustained by
large amounts of thromboplastic material, one can verify
in the laboratory the constant effort made by AT III to

Fig 1. Pinching phenomenon and disseminated intravascular coagulation (DIC) (n 56) with total artificial heart. Statistical methods: 2 analysis with Yates correction (for small samples); significantly different when p 0.050.

Ann Thorac Surg

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CIRCULATORY SUPPORT
PAVIE ET AL
CONTROLLING POSTOPERATIVE BLEEDING

709

Table 4. Phase 4: Secondary Fibrinolysis

Laboratory Tests
Factors
Fibrinogen
Reptilase time
Plasma AT III

Fig 2. Pinching phenomenon evolution in patients with total artificial heart (n 56); transplanted (Tx), n 23; nontransplanted
(non Tx), n 33. Statistical methods: 2 analysis with Yates correction (for small samples), significantly different when p 0.05.

out DIC reflects the gravity of the multiple organ failure

that preceded the surgical intervention and that was
corrected by the total artificial hearts. In sepsis, the
correlation is more significantly evident, because of 27
patients with septic DIC, the pinching phenomenon was
present in 26, whereas no patient without septic DIC (n
29) presented it. Similar proportions are found in patients
with both postoperative and later onset septic DIC. The
pinching phenomenon is thus a very reliable indicator of
the thrombophilic state that accompanies DIC. The relationship between the pinching phenomenon and the
probability of being transplanted was also analyzed (Fig
2) [9]. In the immediate postoperative period, 38 patients
presented the pinching phenomenon. Of these, only 35%
could be transplanted, compared to 55% who did not
present the phenomenon. Although there is only a weak
statistical significance due to the small number of patients and the numerous causes of multiple organ failure
before the intervention, the data show a clear tendency
that requires further confirmation. On the other hand,
the relationship is evident in patients presenting late
onset sepsis and the pinching phenomenon of which only
1 (4%) of the 26 patients could be transplanted. And
among patients presenting the phenomenon in both in
the immediate postoperative period and in late onset
sepsis (n 17), no patient could be transplanted. Clearly,
the pinching phenomenon is a valuable prognostic tool
meriting further study to better understand
hypercoagulability.

Profile

Laboratory Tests

222
1or 22
111
222

Serum AT III
API

Rabys transfer test

Platelet count
Platelet aggregation
Platelet proteins
(PF4-TG)
22
Plasminogen
2 or 22 Alpha-2-antiplasmin

TEG r
TEG k
TEG MA
TEG TPI

40

FDP

Profile
() (1)
22
()
111
22
222
or ()
()

Treatment: Aprotinin, 125,000 to 250,000 KIU intravenously, followed by a

drip of 500 KIU/min; heparin, 5 to 10 IU/kg per day; dipyridamole, 200 to
300 mg every 6 hours; fresh frozen plasma, fresh whole blood, cryoprecipitates, fibrinogen, and AT III concentrates, when needed.
Abbreviations as in Table 1.

we must add aprotinin at a dose of 125,000 or 250,000 KIU

administered intravenously, followed by a drip of 500 KIU
per minute. (We should also point out that aprotinin is
administered to some patients in phase 3 when there is a
strong decrease in 2-antiplasmin.) In addition, there
should be a vigorous replenishmentalthough modulated of AT III [14], FFP, and so on, in phase 4 in short, of
everything that is lacking.

Comment
Clear evidence that DIC bleeding can be controlled is
provided by a study carried out by Glauber and colleagues [15] in which they compared early conventional
treatment of bleeding with subsequent reliance on
Szefners multisystem protocol in a series of cardiac
assists over time. In their experience, bleeding and the
need for reoperations were significantly reduced thanks
to the protocol, with a consequent increase in the survival
rate (Fig 3).
We believe it is no exaggeration to say that the classic

Phase 4 (Secondary Fibrinolysis Phase)

In the final phase of DIC, the massive and diffuse hemorrhage is catastrophic, reflecting a breakdown of all systems.
Hypocoagulability appreciated by TEG is accompanied by
an almost complete absence of procoagulant material and
inhibitory activity, together with totally ineffective platelets.
At the same time, and this is of great importance, we
observe that the fibrinolytic system is strongly solicited,
provoking the disappearance of 2-antiplasmin. As a result,
plasmin is able to circulate freely and is self-maintaining,
resulting in a negative Rabys transfer test (Table 4) [6, 8, 9].
According to the treatment applied in the previous phase,

Fig 3. Reduction of hemorrhagic complications with a multisystem

anticoagulation protocol. Statistical methods: 2 analysis and/or unpaired t-test.

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CONTROLLING POSTOPERATIVE BLEEDING

approach to bleeding is to fill up the reservoir, which

results in ever greater consumption of materials. Our
approach adopts a radically different strategy. First,
guided by the biological diagnosis, we ascertain the
patients DIC phase. Second, we stop the bleeding by
treating the biological disturbances of the patient and
only afterward replenish the material that is lacking.
Strict control based on appropriate tests is essential
before the operation, at the end of CPB, and daily after
the operation. More assessments may be necessary in
case of complication [16]. The protocol thus made possible a significant decrease in mean closure time, total
thoracic drainage, reexploration, and blood derivatives
transfusion, thus reducing costs.
Aprotinin is usually applied in large doses during CPB
because of its effect on fibrinolysis and its presumed
effect on the platelet function. In fact, aprotinin has no
direct influence on platelet function [17]. Accordingly, we
stop fibrinolysis with aprotinin, not in large doses systematically during CPB as is usually done, as such an
approach is usually unnecessary and can be dangerous,
but at the end of the operation in modulated doses based
on biological criteria. It should be added that administration of the drug is frequently prolonged at the same
doses in the intensive care unit. Aside from the somewhat excessive procoagulant effects of aprotinin observed in vascular procedures or when controlling CPB
[18], it is worthwhile to draw attention here to bleeding
that resumes shortly after the administration of high
doses of this molecule, in particular when accompanied
by FFP transfusions. Because FFP provides additional
2-antiplasmin (although weakened by previous freezing, conservation, and unfreezing), which then competes with aprotinin. We believe that the adapted doses
recommended in our protocol are sufficient and effective,
while avoiding unnecessary complications.
To be sure, stressing the importance of biological bleeding does not imply underestimating the role of the surgical
team in controlling bleeding. Even relatively minor practices can be effective, such as using adequately preclotted
Dacron tubes, or preclotting tubes with a simple but efficient technique that we use at La Pitie Hospital (fibrinogen
and thrombase). Various types of glue also can be useful.
French glue (gelatin-resorcin-formol) [19] is recommended in reinforcing fragile tissue locally. Fibrin glue can
also be sprayed in case of diffuse bleeding such as in redo
operations, or applied locally in case of localized bleeding,
either alone or in association with French glue.
Bleeding complications may also occur after implantation, particularly in case of infection, which strongly
affects the equilibrium of the different systems of
coagulation. A tamponade can be the first clinical evidence of bleeding in cardiac assist. The tamponade is not
always evident from the echocardiography, therefore, it
is important to monitor modifications in the filling of the
device for earlier indications.
To conclude, bleeding is not a fatality. Quite the
contrary, it must be treated through a multisystem approach, and as early as possible, preferably at a biological
phase before clinical bleeding. In addition, early moni-

Ann Thorac Surg

1999;68:70510

toring and treatment adapted to each patient makes it

possible to better follow a patients evolution and helps
reduce the occurrence of later thromboembolic events.

References
1. Pennington DG, Swartz MT. Bleeding complications in patients requiring mechanical circulatory support. In: Lewis T,
Graham TR, eds. Mechanical circulatory support. London:
Edward Arnold, 1995:293 8.
2. Pae W, Miller C, Matthews Y, et al. Ventricular assist devices
for post cardiotomy shock. J Thorac Cardiovasc Surg 1992;
104:54153.
3. Quaini E, Pavie A, Chieco S, Mambrito B, and the Registry
Committee. The Concerted Action Heart European registry on clinical application of mechanical circulatory support
systems: bridge to transplant. Eur J Cardiothoracic Surg
1997:11;182 8.
4. Murphy PJ, Connery C, Hicks GL, et al. Homologous blood
transfusion as a risk factor for postoperative infection after
coronary artery bypass graft operations. J Thorac Cardiovasc
Surg 1992;104:10929.
5. Szefner J. Apport de letude de la fonction plaquettaire et de la
cinetique coagulo-lytique dans le controle et le traitement des
transplantes cardiaques. In: Laboratoires Sandoz, ed. Transplantation cardiaque. Rueil-Malmaison, France, 1989;80 7.
6. Bellon JL, Szefner J, Cabrol C. Coagulation et coeur artificiel,
1st ed. Paris: Masson, 1989.
7. Teoh KH, Christakis GT, Weisel RD, et al. Dipyridamole preserved platelet and reduced blood loss after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1988;96:33241.
8. Szefner J. Control and treatment of hemostasis in cardiovascular surgery. The experience of La Pitie Hospital with patients
on total artificial heart. Int J Artif Organs 1995;18:633 48.
9. Szefner J, Cabrol C. Control and treatment of hemostasis in
patients with a total artificial heart: the experience of La
Pitie. In: Pifarre R, ed. Anticoagulation, hemostasis, and
blood preservation in cardiovascular surgery. Philadelphia:
Hanley & Belfus, 1993;237 64.
10. Livingston ER, Fischer CA, Bibidakis EJ, et al. Increased
activation of the coagulation and fibrinolytic systems leads
to hemorrhagic complications during left ventricular assist
implantation. Circulation 1996;94(suppl 2):22734.
11. Raby C. Coagulations intravasculaires disseminees et localisees, 2nd ed. Paris: Masson, 1974.
12. Spanier T, Oz M, Levin H, et al. Activation of coagulation
and fibrinolytic pathways in patients with left ventricular
assist devices. J Thorac Cardiovasc Surg 1996;112:10907.
13. Mohr R, Goor DA, Lavee J. Fresh whole blood. In: Mohr R,
Goor DA, Lavee J, eds. Management of bleeding after open
heart surgery. Heidelberg: Springer-Verlag, 1997:11121.
14. Vinazzer HA. Antithrombin III in shock and disseminated
intravascular coagulation. Clin Appl Thrombosis/
Hemostasis 1995;1:625.
15. Glauber M, Szefner J, Senni M, et al. Reduction of haemorrhagic complications during mechanically assisted circulation with the use of a multi-system anticoagulation protocol.
Int J Artif Organs 1995;18:64955.
16. Copeland J, Szefner J. Anticoagulants and the artificial heart.
In: Lewis T, Graham TR, eds. Mechanical circulatory support. London: Edward Arnold, 1995:30611.
17. Wahba A, Black G, Koksch M, et al. Aprotinin has no effect
on platelet activation and adhesion during cardiopulmonary
bypass. Thromb Haemost 1996;5:844 8.
18. Bukhari EA, Krukenkamp IB, Burns PG, et al. Does aprotinin
increase the myocardial damage in the setting of ischemia
and preconditioning? Ann Thorac Surg 1995;60:30710.
19. Cabrol C, Pavie A, Gandjbakhch I, et al. Complete replacement of the ascending aorta with reimplantation of
the coronary arteries. J Thorac Cardiovasc Surg 1981;81:
659 68.