Download Review Article BLEEDING DISORDER AND MINOR ORAL SURGERY

Review Article
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: 02‑09‑14
: 22‑11‑14
: 30‑11‑14
BLEEDING DISORDER AND MINOR ORAL SURGERY: A REVIEW
Hemant Gupta, * Subodh Shankar Natu, ** Sumit Gupta, *** Hemant Mehra, †
Rashmi Agrawal, †† Sujeet Singh †††
* Professor and Head, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India
** Senior Lecturer, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India
*** Reader, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India
† Reader, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India
†† Reader, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh, India
††† Post Graduate Student, Department of Oral & Maxillofacial Surgery, BBD College of Dental Sciences, Lucknow, Uttar Pradesh,
India
_________________________________________________________________________
ABSTRACT
Injury to the blood vessel wall, either by
trauma or surgical intervention, stimulates a
series of reaction that lead to the cessation of
blood loss hence haemostasis is achieved.
Primary haemostasis is achieved by the
platelet plug formation followed by interaction
between exposed subendothelial tissue factor
and circulating blood thereby amplifying the
steps of coagulation cascade resulting in clot
formation and stabilization. Certain drugs and
there preparation, any deficiency in the
coagulation factors or platelet either
qualitative or quantitative leads to deranged
haemostasis.
Prolonged
postoperative
bleeding in such patients could be life
threatening hence surgeons must be aware of
the complication and management strategies
for such patients. This article reviews the
pathophysiology of these disorders and
management considerations.
KEYWORDS: Blood coagulation disorder;
complications; von willebrand’s disease;
anticoagulant regimen (BL)
INTRODUCTION
Haemostasis, a finely balanced process, is
physiology that stops bleeding following injury to
a blood vessel, either surgical or otherwise by the
stimulation of a pair of parallel yet associated
amplification step which result in a clot.[1] Several
drugs, including over the counter preparations,
inherited and acquired abnormalities in these
pathways can seriously compromise haemostasis.
Also, in certain diseases or condition such as
prosthetic heart valves, it is desirable to inhibit
the haemostatic capacity and certain drugs to this
effect are prescribed to such patients. These
IJOCR Jan - Mar 2015; Volume 3 Issue 7
present significant concerns to surgeons
conducting invasive procedures, who must be
aware of the impact of bleeding tendencies. The
surgical treatment of patients with bleeding
tendencies has been widely discussed in the
literatures with an aim of developing guidelines
for the surgery in such patients. Hemostasis
consists of 3 reactions to vessel wall injury: 1)
Primary; 2) Secondary; 3) Tertiary: and is
dependent on three general components: 1)
Vascular wall; 2) Platelets; 3) The coagulation
cascade
Common bleeding disorders [2]
A) Coagulation factor deficiencies
1) Congenital
Hemophilia A and B
von Willebrand’s disease
Other factor deficiencies (rare)
2) Acquired
Liver disease
Vitamin K deficiency, warfarin use
Disseminated intravascular coagulation
B) Platelet disorders
1) Quantitative disorder (thrombocytopenia)
Immune-mediated
Idiopathic
Drug-induced
Collagen vascular disease
Sarcoidosis
Non-immune-mediated
Disseminated intravascular coagulation
Microangiopathic hemolytic anemia
Leukemia
Myelofibrosis
2) Qualitative disorder
 Congenital
Glanzmann thrombasthenia
von Willebrand’s disease
99
Bleeding disorder and minor oral surgery
Platelet
count
(x 109/l)
100-150
50-100
30-50
<30
Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
Table I: Thrombocytopenia and management of surgery[18]
Management in relation to type of oral surgery
Severity of
thrombocytopenia
Dentoalveolar
Maxillofacial
Mild
- No platelet transfusion - Local
haemostatic measures*
- Observe
Moderate
- Platelets may be needed
- Local haemostatic measures*
- Consider postoperative tranexamic
acid mouthwash 25 mg/kg t.i.d for 3
days
Severe
- Platelets needed
- Local haemostatic measures*
Life-threatening
- Platelets needed
- Local haemostatic measures*
- Avoid surgery where possible
- Postoperative tranexamic acid
mouthwash 25 mg/kg t.i.d for 3 days
- Consider platelet transfusion
- Local haemostatic
measures*
- Observe
- Platelets needed
- Local haemostatic measures*
- Postoperative tranexamic acid
mouthwash 25 mg/kg t.i.d for 3
days
- Platelets needed
- Local haemostatic measures*
- Avoid surgery where possible
- Postoperative tranexamic acid
mouthwash 25 mg/kg t.i.d for 3
days
- Platelets needed
- Local haemostatic measures*
- Avoid surgery where possible
- Postoperative tranexamic acid
mouthwash 25 mg/kg t.i.d for 3
days
Table II : Management of patients with coagulation factor deficiencies, who require dental extraction or complex
procedures[1]
Bleeding disorder
vWD, Type 1
vWD, Types 2A and 2B
vWD, Types 2B and 3
Pretreatment for extraction or nerve block
Desmopressin, 0.3 μg/kg (maximum dose 20 μg) IV
over 20–30 minutes or subcutaneously
Desmopressin, as above, if tested response or
Humate-P, 50 IU of vWF:RCoF/kg
Humate-P, 50 IU of vWF:RCoF/kg
Hemophilia A (mild)
Desmopressin, as above, if tested response is
adequate
Hemophilia A (moderate or
severe)
Recombinant Factor VIII concentrate, 20–25 IU/kg
Re-evaluate postprocedure
Hemophilia B (mild, moderate or
severe)
Recombinant Factor IX concentrate, 40–60 IU/kg
Re-evaluate postprocedure
 Acquired
Drug-induced
Liver disease
Alcoholism
C) Vascular disorders
 Scurvy
Purpura
Hereditary hemorrhagic telangiectasia
Cushing syndrome
Ehlers-Danlos syndrome
IJOCR Jan - Mar 2015; Volume 3 Issue 7
Postextraction treatment
for all bleeding disorders
Antifibrinolytic agents
(e.g., tranexamic acid, 25
mg/kg t.i.d.) for 3–5 days
Soft diet for 7 days
Within 24 hours, assess
need for repeat treatment
D) Fibrinolytic defects
Streptokinase therapy
Disseminated intravascular coagulation
GUIDELINES
FOR
PERFORMING
SURGICAL TREATMENT OF PATIENTS
WITH HAEMOSTATIC DEFECTS
The management of bleeding for patients with
haemostatic defects is a challenge to the physician
and surgeons. In patients with coagulopathies,
nerve-blocks are relatively contraindicated unless
100
Bleeding disorder and minor oral surgery
Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
Table III : Flowchart for choice of treatment according to type of anesthesia and severity of the
bleeding disorder [38]
Severe Bleeding Tendencies
General or Local Anesthesia
Replacement Therapy
- Severe or Moderate Hemophilia A
- Severe or Moderate Hemophilia B
- Type 3 Vwd
Desmopressin or Replacement
Therapy
- Type 2 vWD
Non-severe Bleeding Tendencies
General Anesthesia or Nerve Trunk
Local Anesthesia
Infiltration
Replacement Therapy
- Mild
No Treatment
Hemophilia B
- Mild
- Non-responder
Hemophilia B
Hemophilia Amand type 1 vWD
No Treatment or
Desmopressin or Replacement Therapy
Desmopressin
- Mild
- Mild
Hemophilia A
Hemophilia A
- Type 1 vWD
- Type 1 vWD
- Platelet disorders
- Platelet disorders
Table IV : Pharmacological profile of Desmopressin [43]
Chemical composition
Route of administration and dose
Mean factor increase over baseline
Time to peak level
Plasma half-life
1-deamino-8-arginine vasopressin
Intravenous infusion: 0.3 mg/kg diluted in 50 ml saline solution over 30 min
Subcutaneous injection: 0.3 mg/kg
Intranasal spray: 300 mg/kg (concentrated solution)
Factor VIII 3-5 times
vWf 3-5 times
30-60 min after i.v. infusion
90-120 min after s.c. injection
6-8 hours for factor VIII
8-10 hours for vWf
there is no better alternative.[3,4] Loose
connective, non-fibrous, and highly vascularized
tissue is predisposed to the development of a
dissecting hematoma increasing the chance of
morbidity compared to an area where the tissue is
firm and confined. Hence the anatomy of the
injection site plays an important role in
development of hematoma after injection of local
anesthesia. Extravasation of blood in the
oropharyngeal area by an inferior alveolar block
or in the pterygoid plexus can produce gross
swelling, pain, dysphasia, respiratory obstruction
and a resultant risk of death from asphyxia.[2,5-8]
Even lingual infiltration is associated with risk of
developing hematoma since the injection is into
an area with a rich plexus of blood vessels and the
invading needle is not adjacent to bone.
Anesthetic infiltration and intraligamentary
anesthesia are potential alternatives to nerve
block in many cases.[2] Risk of hematoma in case
of inferior alveolar nerve block is reduced by
using the Gow Gate Technique.[1] For commonly
used blocks the minimum concentration of
clotting factors required is 20% - 30%.[2] A buccal
infiltration, intraligamentary or interosseous
IJOCR Jan - Mar 2015; Volume 3 Issue 7
technique can be used without any factor
replacement.[9] Intrapulpal injections can usually
be administered without much concern for
bleeding and rarely require coverage with factor
replacement. There are no restrictions regarding
the type of local anesthetic agent used although
those with vasoconstrictors may provide
additional local hemostatis but following the risk
v/s benefit ratio principle, should be avoided
when contraindicated.[9] Alternative techniques,
including sedation with diazepam or nitrous
oxide-oxygen analgesia, can be employed to
reduce or eliminate the need for anesthesia.[2]
Surgeons must be cautious in prescribing
analgesics at all times in patients with bleeding
disorders as certain agents such as Aspirin,
Phenylbutazone, Indomethacin etc potentiate the
bleeding tendency by altering platelet function.
Cyclooxygenase inhibitors like rofecoxib,
celecoxib appear not to have a significant effect
on platelets or INR.[10,11] Besides these Opiod
analgesics like Codeine, Meperidine, Morphine,
Hydromorphone does not affect platelet function
hence can safely control pain for the bleeding
disorder patients. Acetaminophen, Pentazocine,
101
Bleeding disorder and minor oral surgery
Plain Propoxyphene are weak inhibitors of
platelet function hence can be used safely.[12,13]
PRE-OPERATIVE MEASURES
Platelets have a vital role in hemostasis and are
said to have 4 main functions:
1. Help in maintain the integrity of the
capillaries;
2. From the initial plug in vessel injury;
3. Elaborate various metabolically active
substances such as: Serotonin, adenosine
diphosphate (ADP), and platelet-factor III;
4. Contain thrombasthenin – a contractile protein
involved in clot retraction and consolidation
of a fibrin plug.
Where there is decreased platelet count or
suppressed or altered platelet function platelet
transfusion should be considered. Patients with
severe thrombocytopenia, in which the platelet
count is < 50,000/µl, are candidates for extensive
and prolonged bleeding and definitely require
platelet transfusion.[14] A platelet count of
100,000/µl is desirable for major surgery[15] while
minor surgery resulting in only superficial
wounds can be performed with undue risk with
platelet counts of 30,000/ µl;[14] while Forbes CD
recommend it to be 50,000/µl for minor
surgeries.[16] Because of the relative inability to
control hemorrhage in bony extraction sites by
primarily closure, a platelet count of 100,000/µl is
preferable. Regional local anaesthetic block
injections can be given if the platelet levels are
above 30x109/l.[14] The transfusion of viable,
physiologically active platelets can be achieved
with:[17]
1. Fresh whole blood;
2. Platelet-rich plasma (PRP): contains about
90% of the platelets from a unit of fresh blood
in about half this volume
3. Platelet concentrates (PC): contains about
50% of the platelets from a unit of fresh whole
blood in a volume of only 25 ml.
4. Platelet concentrates is the best source of
platelets.
Theoretically, the patient's body surface area or
blood volume dictates the required number of
platelet units to be transfused. However it should
be determined in a case-specific manner. Certain
systemic condition like splenomegaly lead to
quick sequestration of platelets which further
emphasizes the need for preoperative planning. A
post transfusion platelet count should be obtained
IJOCR Jan - Mar 2015; Volume 3 Issue 7
Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
before surgery. Additional platelets can be
transfused
intraoperatively,
if
necessary,
depending on the expected level of hemorrhage
(Table I).[14] The availability of concentrates of
clotting factors has rendered surgery in
haemophiliacs almost as safe as for normal
subjects. Surgery should be avoided whenever
possible, but when necessary, before surgery, it is
essential to perform in vitro and in vivo tests to
ensure that the patient has developed a specific
level of coagulation factors. Replacement therapy
allows rapid correction of the deficiency of one or
more coagulation factors thereby making surgery
in an individual with coagulation abnormalities
possible, in most cases. Factors may be given in
the form of Fresh whole blood, Fresh frozen
plasma (FFP), Factor VIII concentrates like low
or intermediate potency, cryoprecipitate or high
potency human factor VIII, animal factor VIII,
PPSB (factors II, VII, IX, X), Prothrombinex
(factors II, IX, X), Fibrinogen.[17] Diagnosis of the
bleeding tendency, severity and amount of tissue
damage, coagulation defect, response to therapy
determines the type and amount of blood product,
duration of replacement therapy and rate of
administration.[17] Irrespective of the type of
coagulation abnormality, acute blood loss must
always be replaced with adequate amounts of
blood either as whole blood or appropriate
fractions.[17] In major trauma, including surgery,
greater correction of the coagulation abnormality
is usually required, hence necessary to use
concentrates of clotting factors to avoid fluid
overload.[17] Treatment with concentrates should
be controlled with factor assays, so as to adjust
the amount required. Frequently, a single
transfusion arrests bleeding due to minimal tissue
damage in patients with very severe coagulation
abnormalities but when tissue damage is
extensive, it is usually advisable to repeat the
transfusion at intervals of 24 hours or less for
couple of days.[17] It is essential to continue
correction of the coagulation abnormality before
surgery and until healing occurs following
surgery (Table II). The rate of administration
should be rapid in order to obtain high peak blood
concentrations of the deficient factor and thus
optimum haemostatic effect.[17] Patients diagnosed
with chronic renal failure should be managed the
day after dialysis when heparin has been cleared
from the system and the patient regains his/her
102
Bleeding disorder and minor oral surgery
strength after the dialysis process.[19] Minor
procedures, including tooth extraction, should
also be carried out in hospital that provides
special care for hemophiliacs. In case of patients
lacking vitamin K, because of malabsorption
syndrome, vitamin K supplement should be
administered to restore liver function and the
synthesis of coagulation factors before
performing any surgical procedures. If the patient
has liver failure, the dental management of the
patient should also involve platelet transfusion in
conjunction to transfusion of deficient factors in a
hospital setting.[20] No elective surgery should be
done until the patient has been treated with
antibiotics and is free from acute infection[21] as in
state of the infection patient tends to bleed more.
Patient with deep-vein thrombosis, pulmonary
embolism,
atrial
fibrillation,
mechanical
prosthetic heart valve, valvular heart disease,
cerebrovascular accident, transient ischemic
attacks, and myocardial infarction are on Anticoagulant
regimen.[22-24]
Anticoagulant
medications reduce the risk of embolism but increase the probability of bleeding during and after
the dental procedure. Although persons on
chronic warfarin therapy are often managed by
stopping the anticoagulant for a brief period
before surgery, but this potentiates the risk for the
condition for which they are being treated with
anticoagulant. There are a number of case reports
concerning serious thromboembolic events
developing
after
the
interruption
of
anticoagulation
treatment;[25]
owing
to
hypercoagulability that may ensue after cessation
of anticoagulants, although some recent literature
suggests this concern may not be of practical
clinical significance. In some instances, the
likelihood of a thromboembolic episode in
patients
who
discontinued
taking
the
anticoagulant medications is three times higher of
a bleeding event in patients who remain on the
anticoagulant regimen.[26] Hence detailed risk
assessment should be performed on each patient,
and the possibility of life-threatening situations
should be taken into serious consideration before
discontinuation of anticoagulation therapy. If
warfarin is stopped, the coagulation status for
almost all patients returns to near normal in
approximately 4 days. The decision either
continuation, reduction or withdrawal of
anticoagulant should be based on the international
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Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
normalized ratio value, the invasiveness and
extent of surgical procedure, current illnesses and
medications.[27] The international normalized ratio
is a key component in the treatment of these
patients.
International
normalized
ratio
therapeutic levels for most medical conditions
range between 2.5 and 3.5.[22] Medications
enhancing the effect of coumarin, a diet rich in
vitamin K and/ or compliance reasons may lead to
increased INR values.[27]
When the international normalized ratio is:
 <=3.5, minor surgical procedures can be
carried out on these patients in a dental
office;[20,27] Alteration of anticoagulation
regimen may not be necessary for these
patients.[28-30]
 3.5, the anticoagulation regimen has to be
adjusted.
Detailed surgical procedure and risk for bleeding
should be addressed to medical care provider by
the surgeon so as to adjust the dose of
anticoagulant.[26,31] International normalized ratio
values can be normalized to 3.5 by making minor
adjustments involving the reduction, but not the
discontinuation, of coumarin. Entire withdrawal
of coumarin is not recommended because of the
rebound thrombotic effect noticed especially in
patients with prosthetic cardiac valves.[25,27] A
safe approach entails reduction of the coumarin
dose 2-3 days before the procedure and repetition
of international normalized ratio on the morning
of the procedure to ensure that the value is
<4.[20,23,27] Low-molecular-weight heparin an
alternative substitute for coumarin may be
fruitfull measure for patient on anticoagulant.
Subcutaneous administration of low-molecularweight heparin provides the benefit of
conveniently adjusting the anticoagulation
regimen at the point of care.[23,32] Short half life of
LMWH allow its discontination 4-6 hrs before
surgery.[18] Withdrawal of heparin is adequate to
reverse anticoagulation effect where this is
deemed necessary, or in an emergency, this can
be reversed with intravenous Protamine Sulphate
given in a dose of 1 mg per 100 international
units of heparin.[10] But it is less effective in
reversing LMW Heparin. Interrupting Lowmolecular-weight heparin 4-6 hours before
surgical procedure, substantially minimize the
duration of suboptimal level of anticoagulation
103
Bleeding disorder and minor oral surgery
and subsequently reducing the risk for a
thromboembolic event, following surgical
procedure anticoagulation treatment is resumed
12-18 hours post surgery.[33] If intravenous
unfractionated heparin is used, then appropriate
laboratory testing, a PTT should be done after
discontinuation of the drug and before the
procedure.[34] Patients taking aspirin should
discontinue the medication at least 3 days, and up
to
7
days,
before
the
surgical
procedure.[20,23,24,27,35] However, consultation with
the physician is mandatory. In regard to other
anti-platelet medications, such as ADP inhibitors
and GP IIb-IIIa inhibitors, discontinuation of the
medication 7 days before the procedure gives
adequate time for the level of circulating
functional platelets to be restored.[27,35] The
American heart association and American college
of cardiology scientific statement states that for
patients
undergoing
dental
procedures,
tranexamic acid or EACA mouthwash can be
applied without interrupting anticoagulant
therapy.[36] The sixth American college of chest
physicians (ACCP) consensus conference on
antithrombotic therapy made several limited
recommendations as follows:[37]
 For patients undergoing dental procedures
who are not considered to be at high risk for
bleeding, ACCP recommends that warfarin
therapy not be discontinued. In patients at
high risk of bleeding, ACCP recommends that
warfarin therapy be discontinued.
 For patients undergoing dental procedure in
which local bleeding must be controlled,
tranexamic acid or EACA mouthwash can be
administered
without
interrupting
anticoagulant therapy.
Flowchart for choice of treatment according to
type of anesthesia and severity of the bleeding
disorder (Table III).[38]
INTRA -OPERATIVE MEASURES
Intra-operative measures include a number of systemic and local measures to prevent unlikely
bleeding diathesis. Inherited platelet disorders,
leading to bleeding or increased risk for bleeding,
are managed systemically with platelet
transfusions.[14] Inherited coagulopathies are managed systemically with replacement of
coagulation factors.[39] Intravenous infusion of
deficient, or missing, coagulation factor starts 1
IJOCR Jan - Mar 2015; Volume 3 Issue 7
Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
hour before the procedure in order to achieve a
level that is 30% above the normal plasma
concentration of this particular factor.[40] The
level has to be higher and to reach 50% of the
normal amount when regional block anesthesia is
administered.[40] Proper treatment planning should
be done in accordance with addresses the half life
of coagulation factors, and treatment sessions
should be programmed accordingly. In mild and
moderate inherited coagulopathies, desmopressin
or 1-desamino-8-D arginine vasopressin can be
useful.[41,42] Desmopressin was used for the first
time in 1977 by Mannucci et al., to treat patients
with mild hemophilia A and von Willebrand
disease. Desmopressin, a synthetic analogue of
the antidiuretic hormone vasopressin, raises the
plasma levels of endogenous factor VIII and von
Willebrand factor (vWf). The increase in vWf
results in a shortening of the bleeding time and
the increase in factor VIII results in a shortening
of the activated partial thromboplastin time.[43]
Desmopressin is an alternative to clotting factor
concentrate transfusion[44] and is also efficient in
platelet dysfunction (Table IV).[45] Management
of patients with acquired bleeding disorders is
focused mainly on local hemostatic measures that
apply also to inherited bleeding disorders.[46]
Local infiltration anesthesia with the use of
vasoconstrictive agent is desirable. 1:100,000
epinephrine with Lidocaine 2% or Articaine 4%
provides sufficient anesthesia for surgery in the
mandible. Excessive bleeding can be prevented
by meticulous handling of soft tissues, a
conservative flap design and minimizing flap
elevation. For surgical extractions, tooth
sectioning helps preserving bone and minimizing
the involvement of anatomic spaces around the
surgical site. Mandibular molars should be
approached with a buccal flap and no reflection of
a lingual flap should be attempted. After surgery,
primary closure of the flap accomplished with
either nonresorbable or resorbable sutures
followed by application of pressure for 10
minutes with moistened gauze on the flap has
been suggested.[27] There are a number of
commercially available local hemostatic agents
that enhance clot stabilization. These include:
 Absorbable gelatin[42,47]
 Absorbable collagen[23]
 Microfibrillar collagen[23]
104
Bleeding disorder and minor oral surgery
 Collagen dressings[23]
 Oxidized regenerated cellulose[48]
 Tranexamic acid[49,50]
 Epsilon-amino caproic acid[51]
 Fibrin glue[35,48,49,52]
 Platelet-rich plasma[53]
Gelfoam is an absorbable gelatin sponge material
that provides a stable “scaffold” for clot formation.[54] Collagen, gelatin and cellulose
products provide the scaffold for platelets to
adhere to one another and form the platelet plug.
Fibrin glue consists of:
 Thrombin which converts fibrinogen to fibrin
and this contributes to the formation of the
fibrin clot.
 Fibrinogen,
 Fibronectin - acts as a binding protein for the
blood clot
 Aprotinin - delays the degradation of the
hemostatic clot.
Platelet-rich plasma contains growth factors
released by the platelets that accelerate the
healing process and thus enhance hemostasis.[46]
Electrocautery another useful tool to slow
intraoperative bleeding. However, it must be used
cautiously to avoid excessive tissue necrosis. Not
only will the necrosis delay healing but it may
also become a source of postoperative bleeding
when the necrotic tissue sloughs.[19] Activation of
fibrinolysis is triggered by the presence of fibrin
and tissue-type plasminogen activators at the site
of fibrin formation, a process regulated by
physiologic inhibitors such as α2-antiplasmin,
histidine-rich glycoprotein and plasminogen
activator inhibitor.[55] Plasminogen activator and
plasminogen are present in oral environment in
physiologic conditions whereas fibrinolysis is
triggered after surgery.[56] As early as the 1960’s,
Björlin started studying fibrinolysis in the oral
cavity; Bajoslin G (1984). He considered the local
fibrinolysis in the alveoli the probable cause of
bleeding after dental extraction.[57] Tranexamic
acid, along with epsilon aminocaproic acid,
inhibits plasminogen action and reduces the
fibrinolytic activity of the early formed
hemostatic clot.[46] Epsilon-aminocaproic acid and
tranexamic acid, two synthetic derivatives of the
amino acid lysine, are antifibrinolytic agents
hence help clot stabilization. They bind to
plasminogen at the level of its lysine binding sites
IJOCR Jan - Mar 2015; Volume 3 Issue 7
Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
and competitively antagonize the interaction of
plasminogen with fibrin, thereby preventing
plasmin generation in the fibrin clot.[57]
Tranexamic acid is about 10-fold more potent
than epsilon-aminocaproic acid and has a longer
half-life. It is administered 15–20 mg per kg body
weight
is
given
two
hours
before
surgery/extraction, and then repeated three times
daily for 8-10 days. Mouth rinsing with 10 ml of a
5% solution of TA for two minutes four times
daily for two days may be used. The beneficial
effect of local application of EACA as
mouthwash was first demonstrated by Berry et
al.[58] Sindet-Pedersen advocated the use of TA
mouthwashes
because,
after
systemic
administration, TA was not detectable in saliva in
healthy volunteers who had received 1 g orally as
a single dose. The maximum level in plasma was
reached after approximately 120 minutes. On the
other hand, after rinsing the mouth with 10 ml of
a 5% aqueous solution for two minutes, a high
concentration was achieved in the saliva, while
TA
was
undetectable
in
plasma.[59]
Antifibrinolytic amino acids are effective
adjuvants for the control of mucosal bleeding,
such as nose bleeding, oropharyngeal oozing and
gastroenteric haemorrhages. Mouth washes with
tranexamic acid are effective for bleeding
prevention in patients undergoing dental
extractions during oral anticoagulant therapy.
Antifibrinolytic lysine analogues are useful to
control bleeding in patients with liver cirrhosis, as
hyperfibrinolysis mainly due to impaired hepatic
clearance of tissue-type plasminogen activator
and decreased α2 antiplasmin contributes to the
haemostatic imbalance. Forbes et al., reported
that in patients with hemophilia, treatment for
five days with 1 g of TA three times daily starting
two hours before surgery was associated with
significantly less post-operative bleeding than in a
placebo group.[60] Ramström and Blombäck
reported that factor concentrate requirement and
days spent in hospital could be decreased if TA
and antibiotics were included in the regimen.[61]
Vitamin K, a lipid soluble naphthoquinone
derivative, required as coenzyme for the posttranslational γ-carboxylation of glutamic acid
residues in the N-terminal regions of vitamin Kdependent clotting factors, namely prothrombin,
factor VII, factor IX and factor X. The process of
γ-carboxylation permits such coagulation proteins
105
Bleeding disorder and minor oral surgery
to interact with phospholipid surfaces in the
presence of calcium ions, which act as a bridge
between γ-carbon dioxide of procoagulant factors
and negative charged platelets and endothelial
phospholipids.[43] Slow intravenous injection of
Vitamin K, will reverse the effects of oral
anticoagulants within 12 to 48 hours according to
the dose administered. Vitamin K is generally
ineffective in patients with parenchymal liver
disease, and is of no value in the hereditary
deficiencies of prothrombin, factor VII, factor IX
and factor X. Dental extractions and associated
bleeding are effectively managed with the
insertion of a sponge into the site. The sponge can
be presoaked with an antifibrinolytic agent, such
as tranexamic acid or epsilon aminocaproic
acid.[47] An absorbable gelatin sponge should only
be used in conjunction with thrombin for this
purpose.[23] Fabrication of a surgical splint for
additional pressure, and protection of the site is
recommended.[62,63] Cyanoacrylate has been used
in the past to seal the extraction site.[64]
POST-OPERATIVE MEASURES
Postoperative management is crucial for
preventing bleeding. General recommendations
emphasize the importance of good care of the
surgical area. Rinsing is prohibited on the day of
surgery and the healing site must be left
undisturbed. Specific attention should be given to
tongue movements interfering with healing and
food intake. Liquids and a high-protein diet are
strongly recommended. Philip V & Kent P
(2007): The use of antifibrinolytic mouthwash is
highly recommended the surgery.[46] The regimen
may comprise rinsing with 10 ml of 4.8-5%
tranexamic acid solution, four times a day, for 2
minutes:[40,65] Aframian et al., (2007); Franchini
M et al., (2005). The rinsing can be carried out
over a period of 2-5 days and may be extended up
to 8 days. The dental professional should exercise
caution in prescribing antibiotics and pain
medications. Antibiotics, such as penicillin,
erythromycin,
tetracycline,
metronidazole,
cephalosporin’s, ampicillin and amoxicillin +
clavulanic acid, potentiate the coumarin
action:[24,27,33] Herman WW et al., (1997),
Lockhart PB et al., (2003), Scully C, Wolff A
(2002). Scully C, Wolff A (2002): Clindamycin
should be the antibiotic of choice in these
patients, and a lower dose of acetaminophen for a
short period of time is the regimen recommended
IJOCR Jan - Mar 2015; Volume 3 Issue 7
Gupta H, Natu SS, Gupta S, Mehra H, Agrawal R, Singh S
for postoperative pain control.[27] Lockhart PB et
al., (2003): When other medications are
administered that affect coumarin bioavailability
or metabolism, supplemental international
normalized ratio tests are performed to evaluate
the anticoagulation effect.[20]
Management of Postoperative Hemorrhage: [1]
Techniques for managing postoperative bleeding
episodes are:
 Reapplication of pressure packs. Often
patients do not do this properly. The technique
must be demonstrated to the patient to ensure
that this simple technique is effective.
Pressure packs must be kept in place at least
30 minutes without checking them before the
need for other intervention is determined.
 Packing or repacking sockets with Gelfoam is
usually the second step, with pressure packs
replaced
over
the
fresh
Gelfoam;
Seichshnaydre MA et al., (1994).
 Reinjection of local anesthetic with
epinephrine can help slow hemorrhage and
allow vessel constriction, platelet plug
formation and stable clot formation. However,
after epinephrine rebound, vasodilation can
occur, which may lead to significant
hemorrhage.
 Any large, exophytic clots should be removed
down to the level of the socket as they may
provide a pathway for continued bleeding and
prevent application of adequate pressure to the
site.
 The use of astringents may be considered,
especially on incisions and raw areas. The
“old tea-bag trick” refers to the practice of
using a tea bag as a pressure pack. The tea
contains the astringent tannic acid.
Commercial
preparations
containing
aluminum chloride produce a similar result.
Zanon E et al., (2003).
 Patients should be instructed to limit physical
exertion, to sit or sleep in a semi-sitting
position and to avoid smoking and alcohol
consumption. Ramstrom G, Blomback M
(1974).
CONFLICT OF INTEREST & SOURCE OF
FUNDING
The author declares that there is no source of
funding and there is no conflict of interest among
all authors.
106
Bleeding disorder and minor oral surgery
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