Thromboprophylaxis in microsurgery.
ABSTRACT Microsurgical free tissue transfer has become a gold standard in a wide range of clinical situations. Thrombosis at the anastomotic site is not only the most common cause of failure of microsurgical operations, but it is also one of the factors resulting in microcirculatory intravascular thrombosis in free flaps. All conditions of thrombus formation, defined by Virchow in 1856, are encountered in free flap surgery. This literature review concerns the problem of thromboprophylaxis in microsurgery. All citations published this last ten years (1996-2005) concerning this problem are noted. Data are confronted with other specialties, particularly vascular surgery, or with large retrospective studies. Protocol used in our institution is presented at the end of this lecture.
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ABSTRACT: No consensus exists among microsurgeons regarding the role of intravenous (IV) heparin in digital replantation/revascularization. The current experience of the Provincial Replantation Center in Quebec was reviewed over a 4-year period. An initial retrospective review of all revascularized or reimplanted digits at our Replantation Center from April 2004 to April 2006 was conducted. Then, data of all patients treated at our center from January 08 to September 08 were prospectively collected. The two cohorts were compared with regards to demographics, injury characteristics, postoperative thromboprophylaxis medication as well as complication and success rates. Proportions were compared using χ(2) tests/Fisher's exact tests. Multivariate analysis was conducted with logistic regression. 175 digits were treated from April 2004 to April 2006, including 104 revascularizations and 71 amputations. IV heparin was used in 35.1% of the cases and was associated with a 3.59-fold (95% CI, 1.55-8.31) increase risk of developing a complication compared with cases where heparin was not used (P = 0.001). In 2008, 106 digits were treated. IV heparin was used in 14.6% of the cases and was not significantly associated with a higher complication rate compared with cases where heparin was not used (P = 0.612). Both cohorts' success rates were very similar (P = 0.557). The number of complications decreased from the first period (20.5%) to the second one (12.8%). Routine use of IV heparin following digital replantation and revascularization is not warranted. Surgical technique and type of injury remains the most important predictors for success in these complex procedures.Microsurgery 05/2011; 31(6):421-7. · 1.62 Impact Factor
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ABSTRACT: The effectiveness of heparin for thromboprophylaxis during microvascular free flap transfer is uncertain. The purpose of this meta-analysis was to determine the effect of heparin on the prevention of flap loss in microsurgical free flap transfer.A search of PubMed, Cochrane databases, and Google Scholar using combinations of the search terms heparin, free flap, flap loss, free tissue transfer was conducted on March 15, 2013. Inclusion criteria were: 1) Prospective randomized trials. 2) Retrospective, non-randomized studies. 3) Patients received free tissue transfer. Flap loss rate was used to evaluate treatment efficacy. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated and compared between therapies. Four studies meet the criteria for analysis and were included. Two studiescompared aspirin and heparin, and the ORs of the 2 studies were 1.688 and 2.087. The combined OR of 2.003 (95% CI 0.976-4.109, p = 0.058) did not indicate any significant difference between heparin and aspirin therapies. Two studiescompared high and low doses of dalteparin/heparin therapies, and the ORs of the 2 studies were 4.691 and 11.00. The combined OR of 7.810 (95% CI 1.859-32.808, p = 0.005) revealed a significant difference indicating that high dose dalteparin or heparin therapy is associated with a greater flap loss rate than low dose therapy. Heparin and aspirin prophylaxis are associated with similar flap loss rates after free flap transfer, and high dose dalteparin or heparin therapy is associated with a greater flap loss rate than low dose therapy.PLoS ONE 04/2014; 9(4):e95111. · 3.53 Impact Factor
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ABSTRACT: Prevention of thrombosis in microsurgery was the point of numerous publications without any referenced protocol. The question of this article was to know if it existed, for a patient who needed a microsurgical procedure, any medical treatment used, proved to lower the thrombotic risk. Using principles of evidence-based medicine, we observed that none of the medical treatments proved efficiency on preventing vascular thrombosis, arterial or venous. The low molecular weight heparins (LMWH) could be used on postoperatives to prevent the deep venous thrombosis of lower limbs but not to lower specially the microvascular thrombosis rate. Aspirin did not improve the positive rates and its adjunction to LMWH increased the bleeding. The evidence-based medicine, as we used it here, permits to conclude that the microsurgeon should not wait any miracle of the medical treatments. Until scientific studies prove efficacity of a treatment, the surgeon has to make a personal choice: keeping habits or following evidence-based medicine. The experience of the surgeon, of the anesthetist and of the paramedical team seem to be the main point to decrease the thrombotic risk during the multidisciplinary healing care of the patient.Annales de chirurgie plastique et esthetique 06/2011; 56(3):219-31. · 0.33 Impact Factor
Acta chir belg, 2006, 106, 158-164
Thromboprophylaxis in Microsurgery
Technical advances and refinements in microsurgery
over the past twenty years have led to a high success rate
for free tissue transfers in a wide range of clinical situa-
tions. Simultaneous advances in surgical and anaesthet-
ic management as well as improved perioperative care
have played significant roles in what has become the
standard of care for microsurgical free tissue transfer.
Nonetheless, a significant number of failures, even in the
most skilled hands, still occur.
Thrombosis at the anastomotic site is not only the
most common cause of failure of microsurgical opera-
tions, but it is also one of the factors resulting in circu-
latory failure in free flaps (1). All of conditions resulting
in thrombosis (Virchow, 1856) are encountered in free
flap surgery (Fig. 1).
First, the degree of disruption of the internal elastic
lamina and the presence of sutures appear to contribute
to occlusive thrombus formation following crush injury
and anastomotic suturing.
Secondly, kinking of vessels or compression due to
haematoma, oedema, or excessively tight closure may
also lead to diminished flow. Medical conditions,such as
hypovolemia and hypothermia, can also lead to
decreased blood flow. The quality of per- and post-oper-
ative management may have an important influence,
particularly when surgical conditions are less than opti-
mal (2). Blood stasis at the anastomotic site leads to
local activation of the coagulation system, and also in
the upstream microcirculation in case of arterial occlu-
sion or in the downstream microcirculation in case of
Finally, surgery itself causes changes in haemostasis,
leading to a hypercoagulable state that has been linked
to both arterial and venous thrombotic complications.
The relation between this state and stress hormones is
doubtful (3). These systemic changes are characterized
by activation of coagulation cascade, increased platelet
reactivity, decreased levels of endogenous anticoagu-
lants, and decreased fibrinolysis. Perioperative anaes-
thetic management (especially the use of regional
anaesthesia) may decrease the risk of these thrombotic
complications. Preoperative existence of hypercoagula-
bility (in cancer, or infection) and, locally, pathophysio-
logical changes (particularly the ischemia-reperfusion
phenomenon) in free flaps may often predispose to
It appears obvious that thromboprophylaxis is essen-
tial for the success of this kind of surgery. There has been
much debate regarding the benefit of anti-thrombotic
J. P. Lecoq*, M. Senard*, G. M. Hartstein*, M. Lamy*, O. Heymans**
Dpts of *Anesthesia and Intensive Care Medicine and **Maxillo-Facial, Aesthetic, microsurgery and Hand Surgery,
University Hospital Sart Tilman, University of Liège, Liège, Belgium.
Key words. Thrombosis ; free flap ; microsurgery ; anticoagulation ; microcirculation.
Abstract. Microsurgical free tissue transfer has become a gold standard in a wide range of clinical situations.
Thrombosis at the anastomotic site is not only the most common cause of failure of microsurgical operations, but it is
also one of the factors resulting in microcirculatory intravascular thrombosis in free flaps. All conditions of thrombus
formation, defined by Virchow in 1856, are encountered in free flap surgery.
This literature review concerns the problem of thromboprophylaxis in microsurgery. All citations published this last ten
years (1996-2005) concerning this problem are noted. Data are confronted with other specialties, particularly vascular
surgery, or with large retrospective studies. Protocol used in our institution is presented at the end of this lecture.
Microsuture in free flaps
Prostacyclin is a naturally occurring prostaglandin pro-
duced by the intima of blood vessels. It is the most
potent inhibitor of platelet adhesion known. The effect
on platelets usually disappears within 30 minutes of dis-
continuing the infusion.
A literature search revealed no significant citations
related to use of PGE(1) in terms of thromboprophylax-
is in surgery. The main application is the inhalation of
PGE(1) in the treatment of pulmonary hypertension with
comparable efficacy and haemodynamics effects to
In the microsurgery literature, LEE et al. (7) demon-
strate in an animal study the superiority of this product
over the aspirin, confirmed by histologic analysis. This
product was also used in two case-reports with suc-
cess (8, 9) (2 ng/kg/min or 1200 ngr in 2 hours).
Nonetheless, PGE(1) is currently one of the most
powerful vasodilatators. This side-effect could be dele-
terious to the perfusion pressure of flaps in micro-
surgery. Comparison between this side effect and a
potential antithrombotic effect need more investigations
in microvascular free flap surgery.
Since haemodilution promotes reduction in blood viscos-
ity and in erythrocyte and platelet aggregation as well as
dilution of the coagulation factors themselves, its use
could provide better microcirculatory bloodflow.
However, studies demonstrated the development of
hypercoagulability whenever crystalloids or gelatins are
used for haemodilution to a haematocrit of 10-30%).
Dextran and hydroxyethyl starch (HES) can induce a spe-
cific decrease of von Willebrandt factor, factor VIIIc, and
a natural fibrinolysis, proportional to their molecular
weight. Controversy exist about a possible role of albu-
min in the induction of an anti-aggregating state (10).
Moreover, porcine and human models were able to
demonstrate that acute normovolaemic haemodilution
with HES may be a valid tool to improve the oxygena-
tion of ischemic and hypoxic flaps. The best effect may
be achieved at a haemoglobin concentration of 9 g/dl
(hematocrit slightly < 30%) (11).
Animal studies using HES (12), albumin (13) con-
firm the reduction in venous thrombosis by using this
technique. SIGURDSSON (2) and CONRAD et al. (14), study-
ing pharmacologic optimization in microsurgery, recom-
mended haemodilution (in particular with dextran
0,4 ml/kg/hour) as ideal thromboprophylaxis. In a retro-
spective human study about haematoma formation in
free flap surgery (15), haematoma occurred in 9.2%
(second in frequency after the groups with high dose of
heparin) in the dextran 40 group (25 ml/h), resulting in
a higher thrombosis of the free flap pedicle (31.3%).
therapies versus the risk of complications such as sys-
temic bleeding and haematoma formation with subse-
quent compression of the pedicle.
Unfortunately, pharmacological therapies are often
conceived on the basis of anecdotal experience, with
often marked differences in agents, dosages and timing.
Numerous animal studies and limited prospective clini-
cal studies characterize the literature, with no consensus
on treatment guidelines.
The authors review the literature concerning this
problem and confront literature data with results
obtained in other surgical specialties where thrombopro-
phylactic therapy is usual.
A literature search was carried out using the Medline
(1996-2005) with Ovid Software. Key-words were
“microvascular surgery”, “free flaps”, “microsurgery”
combined with “thrombosis” or “coagulation”. A total of
246 related citations were found. Citations that were not
relevant to the subject were excluded. Abstracts con-
cerning pharmacological thrombolysis in case of free
flaps salvage were also eliminated.
It is obvious that thromboprophylaxis will not be able to
avoid thrombosis in case of poor microsuture quality.
However, the main goal of this kind of approach is to
secure the microsutures performed in normal conditions.
Since success rate reach 95 to 98%, it will be difficult to
establish a definite advantage of thromboprophylaxis in
the success rate.
Numerous pathways will be discussed, that could
play a role in promoting flap success.
Nitric oxide (NO)
Endothelium derived relaxing factor (EDRF), recently
identified as nitric oxide (NO), has been shown to play a
role in vascular tone, platelet aggregation, neurotrans-
mission and immunological response. NO inhibits adhe-
sion and activation of platelets. Since NO is a labile mol-
ecule, it must be administrated by inhalation, or as a pre-
Two animal studies (4, 5) determine the role of NO-
donors (spermine monoate, L-arginine) in local or sys-
temic administration in free flaps. Only NO-inhibitors
decreased arterial patency in animal models.
Further studies are needed to evaluate NO’s role in
microvascular thrombosis. Sodium nitroprusside, known
to promote release of NO. However, the hypotensive
effect associated with this treatment causes a severe
reduction in free flap blood flow with a nocive effect on
flap survival (6).
Thromboprophylaxis in Microsurgery
surgery, in transurethral prostatectomy, in hip and ENT
In microvascular surgery, one retrospective human
study (19) and six animal (7, 20, 21) studies were found.
Significant decrease of arterial or venous thrombosis
compared to placebo group is observed in all works
found. All aspirin groups are associated with hypocoag-
ulable tests. Superiority of aspirin relative to other
products (prostaglandin (7) or inhibitor GpIIb-IIIa –
SR1215661 (21)) is not well established. Same results
are found retrospective study (19) with large cohort of
patients (n = 216) scheduled for head and neck recon-
struction with free flaps. In this observation, the associ-
ation of subcutaneous heparin and aspirin (325 mg/day)
seems to be safe. Comparison with other therapies lacks
in this study. CONRAD et al. (14) recommend aspirin
(1,4 mg/kg the day before and for 14 days after surgery).
Standardised use of aspirin in other specialities leads us
to suggest its wide use in the microsurgery, but it bears
an inherent risk of local haematoma. The bleeding risk
and the absence of reversibility (no antagonist available)
need further study. Many plastic surgeons are reluctant
to the use of aspirin in the immediate post-operative
period. This attitude is in parallel with the few human
data found in the literature.
GpIIb-IIIa receptor blockers and ADP receptor
Inhibition of the GpIIb-IIIa receptor, which is involved
in the platelet aggregation via the fibrin bridge, by
abciximab has been used with success in coronary
angioplasty with stents as well as for myocardial infarc-
tion. Reports of coronary bypass surgery after abcix-
imab administration reveal high rates of bleeding, lead-
ing to the recommendation to delay surgery for more
than 12 to 24 hours.
ADP receptor inhibitors, namely ticlopidine and
clodiprogel, exert their antiplatelet action by inhibiting
the binding of ADP to its platelet receptor and thereby
inhibiting ADP-induced platelet aggregation. This class
of molecules is routinely used for management of the
acute coronary syndrome, peripheral vascular disease,
vascular surgery. Pharmacologic effect persist for 4 to
8 days after drug discontinuation, consistent with the
lifetime of platelets in the circulation, indicating an irre-
versible antiplatelet effect. Three animal studies (21, 22)
showed significant beneficial differences concerning the
antithrombotic effect of these agents (SR121566A (21)
and clodiprogel (22)) at microvascular level in compari-
son with control groups, with few effect on the coagula-
tion profile. These studies support further investigation
into the superiority of these agents, as compared with
other, classical, drugs like aspirin and heparin, including
differences in the haemorragic risk.
The efficacy of the haemodilution on the coagulation
remains questionable and depends on the product used.
The main benefit of this technique is its favourable effect
on the oxygenation of free flaps.
In the anaesthetic literature, an antithrombotic effect of
regional neural blockade is advocated. This effect results
from decreased stress hormone release, probably sec-
ondary to pain attenuation, local fibrinolysis activation
and partial inhibition of platelet activation. Local anaes-
thetics themselves, commonly used in regional neural
blockade, appear to inhibit platelet aggregation by act-
ing on PGE(1), thromboxane, von Willebrandt factor,
the fibrinolysis pathway. A possible anti-inflammatory
effect is also discussed (decreased production of super-
oxyde dismutase, decreased leucocyte adhesion) (16).
Based on this antithrombotic effect, and combined
with peripheral vasodilatation, regional anaesthesia is
recommended in vascular surgery. The main limitation
of this technique is the necessary caution when associat-
ed with use of antithrombotic drugs, with regard to the
risk of neuraxial haematoma.
SCOTT et al. (17) analysed the efficacy of epidural
anaesthesia in a group of 35 human free tissue transfers
and concluded that epidural anaesthesia, with its atten-
dant chemical sympathectomy, is a safe and efficacious
perioperative adjunct for free flap surgery. In this study,
different antithrombotic drugs were associated.
However, regional anaesthetic techniques do not
always improve the perfusion and oxygenation in flap
tissue in relation to autoregulatory mechanisms that
override the sympathic blockade (steal phenomenon), as
demonstrated by ERNI et al. (18).
In the aim to avoid this side effect with regional
anaesthesia, intravenous infusion of local anaesthetic
could be started and replace the local extraluminal appli-
cation, commonly used in microsurgery.
Acetylsalicylic acid and its derivatives
Aspirin imparts its primary antithrombotic effect
through the inhibition of prostaglandin-H-synthetase
(COX) in platelet and endothelial cells. Platelets (char-
acterised by absence of cell nucleus and protein synthe-
sis) cannot generate new COX. So, the effect of aspirin
lasts for the duration of the life of the platelet (8 days).
Until now, there is no currently available antagonist for
aspirin induced platelet inhibition.
Administration of 100 mg or more of aspirin per day
is standard therapy in cardiovascular disease. In cardio-
vascular surgery, aspirin is known to be a guideline. In
other surgery, aspirin was not associated with increased
haemorragic risk, except in posterior segment eye
J. P. Lecoq et al.
In the microvascular literature, UFH is the most
widely used anticoagulant for antithrombotic therapy,
both topically (limited to the operator field) as well as
systemically to prevent anastomotic and microvascular
thrombosis. It is widely considered the reference against
which other drugs or measures should be compared. The
majority of references concerning heparin in micro-
surgery are animal studies.
Although the systemic use of UFH has been proven to
be effective in free flap thromboprophylaxis, studies
using LMWH showed that subcutaneous injection of
these products is safer with similar efficacy (25-27).
Parallelism between animal and human doses is difficult
to determine. A retrospective review (15) of free flaps
failure in microsurgery concluded that low dose intra-
venous UFH (bolus of 2000 to 3000 UI followed by 100
to 400 UI/h) or only an intraoperative bolus (5000 UI) is
safe and effective. The incidence of haematoma was sig-
nificantly greater in high dose UFH group (500 to
1200 UI/h) (20%). Another multivariate analysis (1)
demonstrates the effect of subcutaneous heparin (with no
details of dose) on the prevention of free flap thrombosis.
On the other hand, free flap surgery is characterized
by its long duration, hypothermia, patient’s poor condi-
tion, immobilisation, and is associated with a high risk
of deep venous thrombosis (DVT). The most effective
prophylaxis for DVT, currently is the use of systemic
LMWH. In this conditions, this subcutaneous treatment
must be started early after surgery.
Pre- and post-operative treatment with antithrombotic
drugs is associated with the risk of hemorrhagic compli-
cations. It has been suggested that the ideal system is
local injection of a high concentration of antithrombotic
drug, leading to minimal systemic effects. This literature
review confirms the superiority of local heparin (UFH) on
placebo (28) in animal study. This technique is not asso-
ciated with increased haemorragic events, as demonstrat-
ed by the previous human multi-variate analysis (1).
As conclusion, UFH is useful in local intravascular
irrigation (100 U/ml) prior to vascular unclamping
(50 to 100 U/kg) for preventing thrombosis and the
ischaemia-reperfusion cascade. After surgery, LMWH
should be administrated for prophylaxis of deep venous
thrombosis. This prevention may have also a positive
effect on the patency of the microanastomosis.
Direct thrombin inhibitors, such as hirudin, have been
successfully used for deep venous thrombosis prophy-
laxis and in cardiovascular surgery in patients suffering
In microsurgical animal studies, hirudin is more
effective than heparin, particularly in a prothrombotic
model (29). Hirudin not only counteracts the process of
Nonsteroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) acety-
late and reversibly inactivate cyclo-oxygenase (natural
COX 1 and inductible COX 2). By acting on the
COX-1, NSAIDs decrease platelet aggregation like
aspirin. COX 2 is induced by inflammatory stimuli and
cytokines in migratory and other cells. Drugs with the
highest COX-1 selectivity are the most antithrombotic.
Whether transient and incomplete COX-1 inhibition
with NSAIDs other than aspirin will translate into clini-
cal thromboprophylaxis is unclear. Studies confirm that
NSAIDs lack the protective effect against myocardial
infarction offered by aspirin. Their potent analgesic
effect could also reduce the hypercoagulable state
induced by endogenous catecholamines.
NSAIDs, have analogous advantages in experimental
microsurgery as other drugs in the prevention of
microthrombosis with little effect on the coagulation
profile. Two case- reports with success are presented in
complement with animal work (23). These drugs, with
the exception of selective COX 2 agents, are a suitable
alternative to aspirin, in the first days, when there is a
high risk of bleeding, especially in view of their
reversible inhibition (maximum 24h) compared to
aspirin (7 days).
Unfractionnated Heparin (UFH) and low-molecular-
weight heparin (LMWH)
UFH exerts its main anticoagulant effect after binding to
the serine protease inhibitor antithrombin III in plasma.
The resulting conformational change in the antithrombin
III molecule increases its inhibitory effect on several
coagulation enzymes (factor II and X). Smaller heparin
fractions (LMWH) can still bind to antithrombin III and
can inactivate factor Xa. UFH has a greater potential for
causing bleeding than do its low-molecular weight
derivatives, because of its simultaneous actions on fac-
tors II and X. By acting on antithrombin III, UFH have
an important role in the ischaemia-reperfusion phenom-
enon. These effects have been studied in free flap trans-
fer surgery, with better tolerance to ischaemic injury in
case of heparinized blood (24). Until recently, UFH has
been the drug of choice for the initial management of
deep venous thrombosis and for thromboprophylaxis in
a variety of settings. However, LMWH have been
demonstrated to be similar regarding their efficacy, safer
in terms of haemorrhagic risk, with considerably easier
The use of postoperative anticoagulation with heparin
is common use for patients undergoing vascular proce-
dures, especially in case of extremely poor distal run-off
or with less-than-ideal conduits. In these cases, LMWH
is easier and safer to use, with equal efficacy, in com-
parison to UFH.
Thromboprophylaxis in Microsurgery
J. P. Lecoq et al.
thrombin formation but also promotes vessel recanaliza-
tion. Hirudin could become a promising strategy.
Further study is warranted.
Modulators of the fibrinolytic pathway
Because of the hemorrhagic consequences associated
with this type of treatment, the systemic use of fibri-
nolytic agents is contraindicated in general surgery. In
cardiovascular surgery, local intra-arterial infusion of
rtPA seems to contribute very effectively to restoration
of macro- and microcirculation, with no effect on over-
all coagulation (30).
In animal studies, systemic use of plasminogen acti-
vator –rtPA- (31) in free flap surgery, is associated with
coagulation problems. Local administration is safe. The
sole human phase II study found is the comparison
between rhTFPI (recombinant human tissue factor path-
way inhibitor) (0.05 ng/ml) and heparin (100 U/ml) with
same efficacy but more safety with rhTFPI (32). In ani-
mal models, evaluation of intraluminal irrigation of
other products [(active site-inhibited recombinant
human facor VIIa (33), tissue-type plasminogen activa-
tor (34))] could not reveal significant differences, com-
pared to heparin this last ten years.
Based on the divergent results of animal studies, it
appears illusory to dictate guidelines applicable in
human clinic. The various recommendations are contra-
dictory. However, in animal or human retrospective eval-
uations, pharmacological prevention of microsurgical
thrombosis is associated with less flap necrosis or fail-
ure, without increasing the bleeding risk. Optimal phar-
macological thromboprophylaxis acts on the platelet
aggregation as well as on the coagulation pathway.
Concerning the platelet antiaggregation, low dose
aspirin (max 160 mg/day) seems to be the first choice, as
recommended in vascular surgery and in human retro-
spective studies of microsurgery (19), and significant
number of laboratory results. There still exists some
reluctance of the surgeon to use this medication, because
of its irreversible effect of platelet inactivation. Non-
steroidal antiinflammatory drugs (for example
diclofenac, 75 mg 1 or 2/day or 1 mg/kg 1 or 2/day,
Ketorolac 60 mg/day) seems to be a valuable alternative
with a shorter half-time of platelet inactivation. These
drugs have not been tested in human clinic (only two
case-reports (23)). Other antiaggregating drugs (ADP
Blockers, GpIIb-IIIa inhibitors) are associated with
increased bleeding. These drugs need to be stopped
10 days before surgery. Intake of anti-aggregating drugs
can be resumed cautiously when surgical bleeding risk is
Besides platelet aggregation inhibition, a certain
degree of anticoagulation is mandatory.
To act on the coagulation pathway, heparin has the
double advantage to inhibit the coagulation pathway and
to protect the tissue from the ischemia-reperfusion phe-
nomenon. Peroperative use is safe in local infusion (50
to 100 U/ml). Comparison with other products (modula-
tors of the fibrinolysis pathway, thrombin inhibitors like
hirudin) offers no advantages in term of efficacy, and are
associated with more haemostasis disorders, except for
the human recombinant tissue factor pathway
inhibitor (32) (0.05 ng/ml). Classical systemic postoper-
ative prevention of deep venous thrombosis (subcuta-
neous 40 mg/day of enoxaparin, 0.4 to 0.6 ml/day of dal-
teparin) is sufficient to protect the microanastomoses,
without increasing the bleeding risk.
Normovolemic haemodilution is a classical guideline
in microsurgery, but its main effect is to improve tissue
oxygenation. This technique, when realised with col-
loids, induces a weak hypocoagulable state, insufficient
to prevent the thrombosis of the microanastomoses.
Regional anaesthesia has been associated with
decrease in free flap perfusion, secondary to a steal phe-
nomenon. This technique also limits the use of other
antiaggregating/anticoagulant drugs, in relation with the
risk of neuraxial hematoma. On the other hand, regional
anaesthesia decreases general complications (pulmonary
infections, atelactasis) and their desastrous conse-
quences for the viability of the free-flap. This technique
could be proposed to patients in poor medical condition.
Intravenous infusions of local anesthetics offers numer-
ous advantages (thromboprophylaxis, prevention of
ischaemia-reperfusion phenomenon, improved microcir-
culation) in microsurgery and need further studies.
Results in the microsurgery department of CHU-Liège (Belgium)
Free-flap success Partial necrosisMicrosuture thrombosis Reoperations
Anastomotic revisionsHaemorrhagic problems
412 patients 397 2214249
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24. LI X., COOLEY B. C., FOWLER J. D., GOULD J. S. Intravascular
heparin protects muscle flaps from ischemia/reperfusion injury.
Microsurgery, 1995, 16 : 90-3.
25. MIYAWAKI T., JACKSON I. T., ELMAZAR H., BIER U. C., BARAKAT K.,
ANDRUS L. et al. The effect of low-molecular-weight heparin in the
survival of a rabbit congested skin flap. Plast Reconstr Surg,
2002, 109 : 1994-9.
26. MALM K., DAHLBACK B., ARNLJOTS B. Low-molecular-weight
heparin (dalteparin) effectively prevents thrombosis in a rat
model of deep arterial injury. Plast Reconstr Surg, 2003, 111 :
27. RITTER E. F., CRONAN J. C., RUDNER A. M., SERAFIN D.,
KLITZMAN B. Improved microsurgical anastomotic patency with
low molecular weight heparin. J Reconstr Microsurg, 1998, 14 :
28. HUDSON D. A., ENGELBRECHT G., DUMINY F. J. Another method to
prevent venous thrombosis in microsurgery : an in situ venous
catheter. Plast Reconstr Surg, 2000, 105 : 999-1003.
29. ROESKEN F.,VOLLMAR B., RUCKER M., SEIFFGE D., MENGER M. D. In
vivo analysis of antithrombotic effectiveness of recombinant
hirudin on microvascular thrombus formation and recanalization.
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emergency therapy after early coronary artery bypass thrombosis.
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31. LYKOUDIS E. G., CONTODIMOS G. B., TSOUTSOS D. A.,
FRANGIA K. B., PAPALOIS A. E., STAMATOPOULOS C. N. et al.
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J., ROTH T.,MAGUIRE
Nitric oxyde and prostacyclins could act as antiag-
gregating drugs, but their hypotensive effect compro-
mises the microcircurlation at the level of the free tissue
flap. New or older products (like magnesium, anti-IXa,
anti-Xa, …) are under clinical investigation.
The difficulty to prove the superiority of one product
over another is challenging, since with optimal surgical
and anaethetic management, thrombotic complications
in microsurgery are exceptional. In our department of
plastic surgery (results exposed in table 1), thrombopro-
phylaxis is based on per- and post-operative non-
steroidal antiinflammatory drugs (diclofenac or
Ketorolac), early use of Enoxaparin sc 40 mg/day,start-
ed 4 hours after surgery, and 1000 ml/day of colloids
(Voluven®), eventually associated with peroperative
magnesium (bolus of 50 mg/kg followed by infusion of
500 mg/hour), and/or peroperative intravenous lidocaïne
(1.5 mg/kg followed by 1.5 mg/kg/h). Results in free-
flaps surgery in our department are exposed in the
table 1. Further clinical studies are indicated to evaluate
if heparinisation and platelet inhibition are useful
additional tools to avoid flap necrosis, without increas-
ing the risk of bleeding.
1. KHOURI R. K., COOLEY B. C., KUNSELMAN A. R., LANDIS J. R.,
YERAMIAN P., INGRAM D. et al. A prospective study of micro-
vascular free-flap surgery and outcome. Plast Reconstr Surg,
1998, 102 : 711-21.
2. SIGURDSSON G. H., THOMSON D. Anaesthesia and microvascular
surgery : clinical practice and research. Eur J Anaesthesiol, 1995,
12 : 101-22.
3. DESBOROUGH J. P. The stress response to trauma and surgery. Br J
Anaesth, 2000, 85 : 109-17.
4. CHIANG S., AZIZZADEH B., BUGA G., IGNARRO L., CALCATERRA T.,
BLACKWELL K. Local administration of nitric oxide donor signifi-
cantly impacts microvascular thrombosis. Laryngoscope, 2003,
113 : 406-9.
5. AZIZZADEH B., BUGA G. M., BERKE G. S., LARIAN B., IGNARRO L. J.,
BLACKWELL K. E. Inhibitors of nitric oxide promote microvascular
thrombosis. Arch Facial Plast Surg, 2003, 5 : 31-5.
6. BANIC A., KREJCI V., ERNI D., WHEATLEY A. M., SIGURDSSON G. H.
Effects of sodium nitroprusside and phenylephrine on blood flow
in free musculocutaneous flaps during general anesthesia.
Anesthesiology, 1999, 90 : 147-55.
7. LEE K. S., SUH J. D., HAN S. B.,YOO J. C., LEE S. J., CHO S. J. The
effect of aspirin and prostaglandin E(1) on the patency of microvas-
cular anastomosis in the rats. Hand Surg, 2001, 6 : 177-85.
8. GATELEY D. R., MCANULTY G. R., MARTIN D. L. Intravenous infu-
sion of prostacyclin to prevent platelet thrombus during micro-
vascular anastomoses. Br J Plast Surg, 1996, 49 : 249-50.
9. RENAUD F., SUCCO E., ALESSI M. C., LEGRE R., JUHAN-VAGUE I.
Iloprost and salvage of a free flap. Br J .Plast Surg, 1996, 49 :
10. DE JONGE E., LEVI M. Effects of different plasma substitutes on
blood coagulation : a comparative review. Crit Care Med, 2001,
29 : 1261-7.
11. LANG K., BOLDT J., SUTTNER S., HAISCH G. Colloids versus crystal-
loids and tissue oxygen tension in patients undergoing major
abdominal surgery. Anesth Analg, 2001, 93 : 405-9.
12. ATCHABAHIAN A., MASQUELET A. C. Experimental prevention of
free flap thrombosis. II : Normovolemic hemodilution for throm-
bosis prevention. Microsurgery, 1996, 17 : 714-6.
Thromboprophylaxis in Microsurgery
J. P. Lecoq et al.
32. KHOURI R. K., SHERMAN R., BUNCKE H. J., JR, FELLER A. M.,
HOVIUS S., BENES C. O. et al. A phase II trial of intraluminal
irrigation with recombinant human tissue factor pathway inhibitor
to prevent thrombosis in free flap surgery. Plast Reconstr Surg,
2001, 107 : 408-15.
33. SORENSEN H. B., KRISTENSEN A. T., RAVN H. B., FUGLSANG J.,
HJORTDALV. E. Local application of FFR-rFVIIa reduces thrombus
formation at arterial anastomosis in rats. Microsurgery, 1999, 19 :
34. ROHRICH R. J., HANDREN J., KERSH R., HERGRUETER C. A.,
MAY J. W., Jr. Prevention of microvascular thrombosis with short-
term infusion of human tissue-type plasminogen activator. Plast
Reconstr Surg, 1996, 98 : 118-28.
J. P. Lecoq, M.D.
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