Acquired bleeding and

hyper coagulable
disorders
Dr. Jamil Salman
Oral & Maxillofacial Surgeon
Assit. Prof. Arab American University ,
Palestine

 Definition
• Bleeding disorders are

conditions that alter the ability of blood vessels, platelets, and

coagulation factors to maintain hemostasis.

• Acquired bleeding disorders may occur as the result of

diseases, drugs, radiation, or chemotherapy for cancer in which vascular

wall integrity, platelet production or function, or coagulation factors are
impaired.

 Iatrogenic causes of
bleeding
Most bleeding disorders are iatrogenic.
anticoagulant medication coumarin, antiplatelet medications : aspirin
• prevent recurrent thrombosis, recent myocardial infarction,
• a cerebrovascular accident, or thrombophlebitis.
• Patients who have atrial fibrillation had open heart surgery to correct a
congenital defect,
• replace diseased arteries, or repair or replace damaged heart valves;
• or had recent total hip or knee replacement
• to prevent cardiovascular complications.

ETIOLOGY
• A pathologic alteration of blood vessel walls,

• A significant reduction in the number of platelets,

• Defective platelets or platelet function,

• A disorder of platelet release,

• A deficiency of one or more coagulation factors,

• The administration of anticoagulant or antiplatelet drugs,

• Inability to destroy free plasmin

Classification of Acquired Bleeding and Thrombotic

Disorders

• Nonthrombocytopenic Purpuras
• Vascular Wall Alteration
• Disorders of Platelet Function
• Thrombocytopenic Purpuras
• Primary
• Secondary
• Disorders of Coagulation
• Hypercoagulable States

bleeding problems in patients with normal numbers of

platelets (nonthrombocytopenic purpura)

• Infections, chemicals, collagen

disorders, or certain types of
allergies can alter the structure
and function of the vascular wall
to the point that the patient may
have a clinical bleeding problem.

• A patient may have normal

numbers of platelets, but they may
be defective or unable to perform
their proper function in the control
of blood loss from damaged tissues.

bleeding problems in patients with low numbers of

platelets (thrombocytopenic purpura)

• platelets below 50,000/µL

• Primary or idiopathic thrombocytopenia.

When the total platelet count is reduced by
unknown mechanisms.

• Secondary thrombocytopenia

Chemicals, radiation, and various systemic

diseases (e.g., leukemia) may have a direct
effect on the bone marrow, potentially
resulting in thrombocytopenia

disorders of coagulation,

• Acquired coagulation disorders are the most

common cause of prolonged bleeding.

• may become apparent only after trauma or surgical

procedures.

• usually have multiple factor deficiencies

• The liver produces all of the protein coagulation

factors; thus, any patient with significant liver disease
may have a bleeding problem.

• patient with liver disease who develops portal

hypertension and hypersplenism may be
thrombocytopenic as a result of splenic overactivity,
which leads to increased sequestration of platelets in
the spleen

 • Acquired hemophilia is uncommon, can be caused by autoantibody

inhibitors directed against “self”-clotting, which is mostly commonly factor
VIII.

• About half of cases of acquired hemophilia are associated with autoimmune

diseases, lympho-proliferative disorders, idiosyncratic drug reactions,
pregnancy, and advanced age.

hypercoagulable states

 Pathophysiology
The three phases of hemostasis for
controlling bleeding are
1. vascular,
2. platelet,
3. coagulation.
• The vascular and platelet phases
are referred to as primary,
• The coagulation phase is
secondary.
• The coagulation phase is
followed by the fibrinolytic
phase, during which the clot is
dissolved.

Coagulation Phase.

• The process of the fibrin-forming

(coagulation) system.

• The overall time involved from injury

to a fibrin-stabilized clot is about 9 to
18 minutes.

• Platelets, blood proteins, lipids, and

ions are involved in the process.

• Thrombin is generated on the surface

of the platelets, and bound fibrinogen is
converted to fibrin the end product of
coagulation is a fibrin clot that can stop
further blood loss from injured tissues.

• Coagulation of blood involves many

components.

• Many of the coagulation factors are

proenzymes that become activated in a
“waterfall” or cascade manner—that is,
one factor becomes activated, and it in turn
activates another, and so on in an ordered
sequence. For example, the proenzyme
(zymogen) factor XI is activated to the
enzyme factor XIa through contact with
injury-exposed subendothelial tissues in
vivo to start the intrinsic pathway.

• Coagulation proceeds through two pathways—the intrinsic and the extrinsic.

• Both use a common pathway to form the end product, fibrin.

• The (faster) extrinsic pathway is initiated through tissue factor TF (an integral
membrane protein) and is released or exposed through injury to tissues; this
process activates factor VII (VIIa)7.

• The intrinsic pathway is initiated by contact activation of factor XII. 12

• Thrombin generated by the faster extrinsic and common pathway is used to

accelerate the slower intrinsic and common pathway.

• As a result, thrombin is generated; in turn, fibrinogen is converted to fibrin,

activates factor XIII, enhances factor V and factor VIII activity, and stimulates
aggregation of additional platelets

 (A), The primary (vascular and platelet) system

(B)the secondary (coagulation) system for the
control of bleeding,
(C)and the coagulation cascade.
• The intrinsic coagulation system is triggered
by surface contact,
• The extrinsic system by release of tissue
factor from injured tissues,
• and the common pathway by factor X.

Timing of Clinical Bleeding.

• A significant disorder that may occur in the vascular or platelet phase
leads to an immediate clinical bleeding problem after injury or surgery.

• These phases are concerned with controlling blood loss immediately after
an injury and, if defective, will lead to an early problem.

• However, if the vascular and platelet phases are normal and the
coagulation phase is abnormal, the bleeding problem will not be detected
until several hours or longer after the injury or surgical procedure.

• In the case of small cuts, for example, little bleeding would occur until
several hours after the injury, and then a slow trickle of bleeding would
start.

CLINICAL PRESENTATION

Signs and Symptoms

Signs associated with bleeding disorders may
appear in the skin or mucous membranes or
after trauma or invasive procedures.
with liver disease.
• Jaundice,
• spider angiomas ,
• ecchymoses
• petechiae on the skin and mucosa
• A fine tremor of the hands when held out
• In about 50% of persons with liver
disease, a reduction in platelets occurs
because of hypersplenism that results from
the effects of portal hypertension.

• with abnormal platelets or

thrombocytopenia.

• Petechiae and ecchymoses are the signs

most commonly seen

• Patients with acute or chronic leukemia may

reveal one or more of the following signs:

• ulceration of the oral mucosa,

• hyperplasia of the gingivae,

• petechiae of the skin or mucous

membranes,

• ecchymoses of skin or mucous

membranes,

• and lymphadenopathy.

• A number of patients with bleeding disorders may show no objective signs that
suggest the underlying problem.

• Severe or chronic bleeding can lead to anemia with features of pallor, fatigue, and
so forth.

Laboratory and Diagnostic Findings

Three tests are recommended for use in initial screening for possible bleeding
disorders:
• activated partial thromboplastin time (aPTT),
• prothrombin time (PT),
• platelet count.
• In the absence of clues to the cause of the bleeding problem, an additional test can be
added to the initial screen: the thrombin time (TT).
Patients with positive screening test results should be evaluated further and referred to a
hematologist.

• The Ivy bleeding time (BT)

• for disorders of platelet function and thrombocytopenia.

• The platelet function analyzer (PFA-100),

• measures platelet-dependent coagulation under flow conditions,

• Both tests has been found to be unreliable and is no longer used as a screening test.

Coagulation cascade indicating

• the intrinsic pathway measured by activated partial thromboplastin time (aPTT);
• the extrinsic pathway measured by prothrombin time (PT); and
• the conversion of fibrinogen to fibrin, which is measured by thrombin time (TT).

 MEDICAL MANAGEMENT

• The emphasis is on detection of patients with potential bleeding

problems and management of such patients if surgical procedures
are needed.

• Disorders affecting the vascular, platelet, coagulation, and

fibrinolytic phases

Vascular Defects

Vascular abnormalities may be caused by

• structural malformation of vessels,

• hereditary disorders of connective tissue,

• and acquired connective tissue disorders.

Acquired connective tissue disorders that may be complicated by bleeding include

scurvy,

small vessel vasculitis,

and skin disorders.

• In scurvy, deficiency of vitamin C leads to lack of peptidyl-hydroxylation of

procollagen, resulting in weakened collagen fibers. The abnormal collagen results in
defective perivascular supportive tissues, which can lead to capillary fragility and
delayed wound healing.

• In patients on long-term use of steroids, thinning of connective tissues may result

in bleeding after minor trauma.

• Small vessel vasculitis may be caused by a variety of conditions that produce

inflammation of small vessels, including arterioles, venules, and capillaries.

• Serum sickness can lead to purpura through immune complex deposits into vessel
walls. Drugs such as penicillin, sulfonamides, and thiazide diuretics and hepatitis have
been associated with serum sickness–like reactions.

Platelet Disorders

Disorders of Platelet Function.

• Platelets participate directly in the clotting cascade by

• serving as constituents of factor X and prothrombin-converting

complexes through the release of platelet factor 3 (PF3).

• In some cases, platelets may fail to release of PF3 caused by

defective production of thromboxane, or by a deficiency in the
production of dense-granule ADP.

Defective thromboxane production almost always results from the

administration of anti inflammatory drugs.

• Eg. aspirin, which inactivates COX, the first enzyme of the prostaglandin–
thromboxane synthetic pathway.

• NSAIDs (indomethacin, phenylbutazone, ibuprofen, sulfinpyrazone),

• β-lactam antibiotics;

• calcium channel–blocking drugs (verapamil, diltiazem, and nifedipine),

• phenytoin, nitrates, phenothiazines, and tricyclic antidepressants.

• In healthy people, the impairment of platelet function that is produced

by drugs usually is of no clinical significance.

• However, in patients with coagulation disorders, uremic or

thrombocytopenic patients, and those receiving heparin or coumarin
anticoagulants, drug-induced platelet dysfunction can result in serious
bleeding.

• Platelet function studies often show an absence of secondary wave

aggregation.

• Patients can be screened with standard screening tests; if these results

are normal, surgical procedures can be performed.

• Uremia may interfere with platelet function. This effect can be severe in
patients with grossly abnormal platelet function. Such patients are in
danger of bleeding to death if injury occurs or surgery is performed.

✦ They respond to dialysis, cryoprecipitate, or kidney transplantation

but not to platelet replacement.

• β-lactam antibiotics (penicillin and cephalothins) may cause platelet

dysfunction, usually no treatment is required.

• alcohol may impair platelet function; this effect may be severe enough
to contraindicate surgery unless corrective measures are taken.

Coagulation Disorders

Disseminated Intravascular Coagulation.

• The syndrome is associated with a number of disorders such as infection, obstetric
complications, cancer, and snakebites.

• the most common cause of DIC is snakebite.

• results when the clotting system is activated in all or a major part of the vascular system.

• Despite widespread fibrin production, the major clinical problem is bleeding, not
thrombosis.

• DIC is caused when large quantities of thromboplastic substances are introduced into
the vascular system and “trip” the clotting cascade.

• Acute DIC may be caused by obstetric complications , infection, injuries and burns,
antigen-antibody complexes, sepsis and septic shock, and acidosis.

Clinical Presentation.
Acute DIC

• severe bleeding from small wounds; purpura; and spontaneous bleeding from the
nose, gums, gastro-intestinal tract, or urinary tract.

• Traumatic hemolytic anemia may occur when RBCs are “sliced” by fibrin
strands.

• On rare occasions, bilateral necrosis of the renal cortex has developed.

Chronic DIC

• May occur in association with certain types of cancer. Malignant cells can release
thromboplastic material as they die within the tumor mass.

• Antigen–antibody complexes associated with systemic lupus erythematosus may

cause chronic DIC.

• In the chronic form of the disease, thrombosis is more common than bleeding.

Laboratory and Diagnostic Findings.

• Consumption and inhibition of the function of clotting factors cause prolongation of

the PT, aPTT, and TT.

• Consumption of platelets causes thrombocytopenia.

• Secondary fibrinolysis generates increased titers of FDPs, which can be measured

by latex agglutination or D-dimer assays.

The most difficult differential diagnosis of DIC occurs in patients who have
coexisting liver disease.

In liver failure, the combination of

• decreased synthesis of clotting factors,

• impaired clearance of activated clotting factors,

• secondary fibrinolysis, and

• thrombocytopenia from portal hypertension and hypersplenism may

make the coagulopathy practically impossible to differentiate from DIC

 Medical Management.
Treatment of patients with DIC consists of an attempt to

• reverse the cause,

• control of the major symptom (bleeding or thrombosis),

• a prophylactic regimen to prevent recurrence in cases of chronic DIC.

• Consumed coagulation factors need to be replaced, along with missing platelets.

• Fibrinogen levels must be restored.

• Cryoprecipitate is used if bleeding is the major problem.

• Fresh-frozen plasma (FFP) also may be used.

• If thrombosis is the major problem (early in the process), intravenous (IV) heparin is used.

• Long-term heparin infusion is used for prophylaxis in cases of chronic DIC.

• The use of aminocaproic acid (Amicar), desmopressin, and tranexamic acid preparations is
not recommended because increased bleeding may occur.

Fibrinolytic Disorders
Fibrinolysis and Fibrinogenolysis.

• Primary fibrinogenolysis may develop if active plasmin is generated in the

circulation at a time when the clotting cascade is not in operation.

• It can occur in patients with liver disease, lung cancer, prostate cancer, or
heatstroke.

• Severe bleeding results from the depletion of fibrinogen (split by plasmin)

and the formation of fibrin split products (with their anticoagulant properties)
from fibrinogen.

• Fibrinogenolysis can be treated with ε-aminocaproic acid or tranexamic

acid, which inhibits both plasmin and plasmin activators;

• however, these drugs may be dangerous if used in patients with DIC

because diffuse thromboses may result.

 Thrombosis and Antithrombotic Therapy.

• Thrombosis is the formation, of an abnormal mass within the vascular

system, from components of blood.

• It involves the interaction of vascular, cellular, and humoral factors

within a flowing stream of blood.

• Thrombosis and the complicating emboli that may result are one of the
most important causes of sickness and death in developed countries.

• Thrombosis is of greater overall clinical importance in terms of morbidity

and mortality than are all of the hemorrhagic disorders combined.

• Excessive activation of coagulation or inhibition of anticoagulant

mechanisms may result in hypercoagulability and thrombosis.

• Major factors leading to thrombosis are:

✦ Injury to the vessel wall, alterations in blood flow, and changes in
the composition of blood

• The common causes of acquired venous thrombosis are:

✦ older age, history of thrombosis, immobilization, obesity,
infection, hospitalization, major surgery, and pregnancy.

• Common causes of both venous and arterial thrombosis are:

✦ malignancy, hormonal therapy, and DIC.

• The most common cause of arterial thrombosis is:

✦ atherosclerosis.

• Patients should be considered for laboratory evaluation for inherited

thrombotic disorders if they are younger than 45 years of age and have
recurrent thrombosis.

• In addition, patients who have experienced a single thrombotic event

and have a family history of thrombosis should be tested.

• Atherosclerotic vascular disease associated with platelet thrombi.

• Thrombin is a major mediator in this type of thrombosis.

• Drug therapy for arterial thrombi involves agents with antithrombin and
antiplatelet activity.

• Venous thrombi usually occur in otherwise normal vessel walls; stasis and
hypercoagulability are major predisposing factors.

• Drugs that prevent thrombin

formation or lyse fibrin clots are the
main agents used to treat venous
thrombi.

• Antidotes are available for

overdosing of heparin (protamine)
and warfarin (vitamin K).

• Clot collectors (inferior vena caval filters

[IVCFs]) can be used to prevent large clots
from reaching the lungs.

• The IVCF can be inserted into the vena cava

from an incision in the neck area or in the
groin area.

• The IVCF can be permanent or removed when

the risk of a large clot traveling to the lung is
over.

• Complications have been reported with the use

of IVCFs; these include the breaking off of
pieces of the IVCF and the appliance
becoming attached to the vessel wall and
unable to be removed .

 Anticoagulant Drugs

1. Heparin.
• Heparin is used in high doses to treat thromboembolism in low-dose form for
prophylaxis of thromboembolism.

• Heparin itself is not an anticoagulant. Plasma antithrombin III (ATIII) is the actual
anticoagulant, and heparin serves as a catalyst.

• Low-molecular- weight heparin (LMWH) can be used instead of regular heparin

and is rapidly becoming the treatment of choice.

• Treatment with standard heparin usually consists of an IV infusion in a hospital

setting and requires monitoring with aPTT, Standard heparin has a half-life of 1 to 2
hours.

• LMWH

• is prepared by depolymerization of unfractionated heparin chains,

• LMWH preparations have greater activity against factor Xa than thrombin.

• LMWHs exhibit less binding to plasma proteins, endothelial cells, and

macrophages than is seen with standard heparin. Thus, they have better
bioavailability when administered subcutaneously, longer half-lives, and more
predictable anticoagulant effects.

• LMWHs are administered subcutaneously in the abdomen.

• The dosage is based on body weight, and no laboratory monitoring is needed.

• The half-life of these preparations is about 2 to 4 hours.

• Treatment with LMWHs may be provided on an outpatient basis.

Low-molecular-weight heparin preparations that

are used commonly for the treatment of

deep vein thrombosis (DVT) and

asymptomatic pulmonary embolism (PE)

• Complications with heparin treatment include

thrombocytopenia and thrombosis.

• Overdosing of heparin can cause significant

clinical bleeding

2. Synthetic Heparins.
3. Direct Thrombin Inhibitors.
4. Direct Factor Xa Inhibitors.
 5. Coumarin.
• Warfarin (Coumadin), the most widely used coumarin,
• is an oral anticoagulant that inhibits the biosynthesis of vitamin K–dependent coagulation
proteins (factors VII, IX, and X and pro- thrombin).

• Warfarin is bound to albumin, metabolized through hydroxylation by the liver, and excreted
in the urine.

• PT is used to monitor warfarin therapy because it measures three of the vitamin K–

dependent coagulation proteins: factors VII and X and prothrombin.

• PT is particularly sensitive to factor VII deficiency.

• Therapeutic anticoagulation with warfarin takes 4 to 5 days.
• INR is now used to monitor patients on warfarin therapy.
• The recommended INR goal for a patient on low-intensity warfarin therapy is 2.5, with a
range of 2.0 to 3.0. With a patient on high-intensity anticoagulation therapy, the INR goal is
3.0, with a range of 2.5 to 3.5.

 Antiplatelet Drugs.
• Platelets are an important contributor to arterial thrombi.

• Antiplatelet treatment has been reported to reduce overall mortality rate from
vascular disease by 15% and to reduce nonfatal vascular complications by 30%.

• Aspirin, the prototypical antiplatelet drug, exerts its antithrombotic action by

irreversibly inhibiting platelet COX, preventing synthesis of thromboxane A2, and
impairing platelet secretion and aggregation.

• Aspirin is the least expensive, most widely used, and most widely studied
antiplatelet drug.

• NSAIDs such as ibuprofen and indobufen act as reversible inhibitors of COX and
are used clinically to some extent.

Site of action of antiplatelet drugs.

• Aspirin inhibits thromboxane A2 (TXA2) synthesis by irreversibly acetylating cyclooxygenase-1 (COX-1).
Reduced TXA2 release attenuates platelet activation and recruitment to the site of vascular injury.
• Ticlopidine and clopidogrel irreversibly block P2Y12, a key adenosine diphosphate (ADP) receptor on the
platelet surface. Therefore, these agents also attenuate platelet recruitment.
• Abciximab, eptifibatide, and tirofiban inhibit the final common pathway of platelet aggregation by
blocking fibrinogen binding to activated glycoprotein (GP) IIb/IIIa.

DENTAL
MANAGEMENT
Patient Identification
The four risk assessment methods consist
of the following:
• A thorough history
• Physical examination
• Screening clinical laboratory tests
• Observation of excessive bleeding after
a surgical procedure










Medical Considerations

Patient who is suspected of having a bleeding problem

• Surgical procedures should not be performed

• screened by a dentist

• referred to a hematologist

Absence of Clinical or Historical Clues to Cause a Bleeding Problem.

• The first indication may be prolonged bleeding after a dental surgical procedure.

• For this, local measures should be taken to control the bleeding;

• if these fail, a hematologist may have to be consulted.

• After the problem has been brought under control, the patient should be screened
with the appropriate laboratory tests (PT, aPTT, platelet count, and TT).

History or Clinical Findings (or Both) Suggestive of Possible Bleeding Problem

in the Absence of Clues to Its Cause.

• all four screening laboratory tests should be performed.

• refer the patient to a hematologist for screening and diagnosis.

Antiplatelet Therapy.
✤ Aspirin

• Inhibit platelet thromboxane production and platelet aggregation.

• Although these effects are nonreversible, they generally are not clinically
significant.

• Thus, aspirin use does not usually lead to a significant bleeding problem, and
invasive dental procedures can be performed.

• If major surgery must be performed under emergency conditions, desmopressin

can be used to reduce the risk of excessive bleeding. This should be done in
consultation with the patient’s physician or hematologist.

✤ Non steroidal anti inflammatory drugs

• It inhibit platelet COX, thereby blocking the formation of thromboxane A2.

• These drugs produce a systemic bleeding tendency by impairing thromboxane-

dependent platelet aggregation.

• They inhibit COX reversibly

• Most invasive dental procedures can be performed without adjusting the dose.

• If the patient’s physician recommends stopping the drug, after three half-lives of the
drug have passed, the drug levels will be sufficiently eliminated to allow return of
normal platelet function.

• It should be remembered that the clinical risks of bleeding with aspirin or nonaspirin
NSAIDs are enhanced by the use of alcohol or anticoagulants and by associated
conditions such as advanced age, liver disease, and other coexisting coagulopathies.

✤ The antiplatelet ADP inhibitors, clopidogrel and ticlopidine,

• Commonly used is to prevent thrombosis in arterial stents.

• Clopidogrel (plavix) is used the most often and is given as a single agent or as a dual
agent with aspirin.

• At this time, it appears to be safe for patients taking single ticlopidine or clopidogrel
therapy or dual therapy with aspirin to be maintained on their medication(s) for non
invasive dental procedures , it was found that no episodes of prolonged bleeding occurred

• For major oral surgical procedures that cannot be delayed, the thieno-pyridines may
have to be discontinued until after the surgery.

• Consultation with the patient’s physician is recommended.

✤The fibrinogen receptor inhibitors tirofiban, abciximab, and

eptifibatide

• They are injectable (IV) antiplatelet drugs used in emergency coronary situations,
usually in a hospital setting.

• The dentist is very unlikely to be faced with the management of patients taking these
drugs unless called to the hospital for dental emergency care for a patient with acute
coronary syndrome or myocardial infarction.

• Under these conditions, the dentist should consult with the attending physician regarding
the management of the patient.

• In general, the most conservative dental treatment should be selected to deal with the
dental problem without any changes in the patient’s medications or dosage.

 Coumarin Therapy.

• potential for excessive bleeding.

• if the anticoagulant is discontinued in preparation for the dental procedure, the

major medical concern is thrombosis, which could be life threatening.

• For minor oral surgery and other similarly invasive dental procedures if the INR is
3.5 or less.

• For major oral surgery or If other bleeding problems, such as liver disease and
renal disease, are present or if other drugs (e.g., aspirin, antibiotics, NSAIDs) are
being taken, management of the patient will have to be planned on an individual
basis.

• obtain medical consultation for all patients who are taking warfarin.

• If acute infection is present, surgery should be avoided until the infection has
been treated. When the patient is free of acute infection and the INR is 3.0 or less,
minor surgery can be performed.

• The procedure should be done with as little trauma as possible.

• a tranexamic acid (Cyklokapron) or epsilon aminocaproic acid (EACA)

(Amicar) mouthwash should be applied during the first 2 postoperative days to
help control excessive bleeding.

• The patient is instructed not to “swish” to avoid dislodging a clot. Activities

such as sucking on a straw or candy should be avoided because negative pressure
may dislodge the clot.

>If excessive postoperative bleeding occurs after an

extraction,

• Gelfoam with thrombin may be placed in the socket

to control it.

• primary closure over the socket is desirable.

• Oxycel, Surgicel, or microfibrillar collagen may be

used in place of Gelfoam

• An inhibitor of fibrinolysis (tranexamic acid or

EACA) also can be applied.

>If excessive bleeding cannot be controlled by the local methods listed earlier,

• the dentist should consult the patient’s physician. Available options include

• discontinuation of warfarin, which would take several days before an effect on bleeding would
occur;

• administration of vitamin K; IV route (rapid response but slight risk of anaphylaxis),

subcutaneously (response is unpredictable and sometimes delayed), or orally (predictable response,
effective, convenient, safe, and effect seen within 24 hours).

• administration of FFP (carries a risk of infection)

• a prothrombin concentrate. ( associated with a risk of thromboembolic complications)

• administer recombinant factor VIIa.

If the dosage of anticoagulant must be adjusted,

• the patient’s physician should instruct the patient.

• It will take 3 to 5 days before the effect of the dose reduction is reflected in the lower INR.

• On the day of surgery, the INR should be checked again to determine whether the desired reduction has
occurred.

• If no excessive bleeding occurs on the day after the dental procedure is performed, the patient’s physician
can direct the patient to return to his or her usual warfarin dosage.

Another option for these patients is Coumadin–Lovenox bridging.

One approach is to have the patient’s physician discontinue warfarin therapy 4 days before major oral surgery
and to begin a series of 30-mg subcutaneous enoxaparin (Lovenox and LMWH) injections every 12 hours (at 9
AM and 9 PM) on an outpatient basis, starting 3 days before the surgery is to be performed (referred to as
Coumadin–Lovenox bridging). Through discontinuation of warfarin, the INR is allowed to normalize, and
enoxaparin provides anticoagulation. The last enoxaparin injection is given at 9 PM on the evening before
surgery. The INR should be checked on the morning of surgery and, if within normal values (1.0), the surgery
can be performed. Enoxaparin injections are started again on the evening after the surgery; oral warfarin
therapy is also restarted that evening. After 3 days, the postoperative enoxaparin injections are stopped.
• A potential problem with this approach is that a temporary hypercoagulable state may occur when
warfarin therapy is stopped.

Drugs that will affect the action of warfarin (Coumadin).

• Drugs that potentiate the anticoagulant action of warfarin include

• acetaminophen, metronidazole, salicylates, broad-spectrum antibiotics, erythromycin,

and the new COX-2–specific inhibitors (celecoxib and rofecoxib).

• cimetidine, chloral hydrate, phenytoin, propranolol, and thyroid drugs.

• Drugs that will antagonize the anticoagulant action of warfarin are

• barbiturates, steroids, and nafcillin.

• carbamazepine, cholestyramine, griseofulvin, rifampin, and trazodone.

Postoperative pain control can be attained with

• the use of minimal doses of acetaminophen with or without codeine.

• Aspirin and NSAIDs must be avoided.

• COX-2–specific inhibitors (celecoxib and rofecoxib) they can increase PT and INR in
patients who are taking warfarin; if used, the dosage should be reduced.

Heparin Therapy.

• Most patients treated with standard heparin are hospitalized and will be prescribed
warfarin once discharged.

• Dental emergencies in these patients during hospitalization should be treated as

conservatively as possible, with avoidance of invasive procedures, if possible.

• Patients treated with hemodialysis are given heparin. The half-life of heparin is
only 1 to 2 hours; thus, if they wait until the day after dialysis, these patients can
receive invasive dental treatment.

LMWH or a synthetic heparin.

• These agents are used in patients with recent total hip or knee replacement and for DVT or
asymptomatic PE.

Elective surgical procedures can be

• delayed until the patient is taken off the LMWH or synthetic heparin, which, in most
cases, will occur within 3 to 6 months.

If an invasive procedure must be performed, the dentist has several options.

• The half-life of the LMWHs and fondaparinux is less than 1 day. Thus, the physician could
suggest that the drug be stopped and the surgery be performed within 1 to 2 days.

• The other option is to go ahead with the surgery and deal with any bleeding
complications on a local basis.

Direct Thrombin Inhibitors.

• lepirudin, desirudin, argatroban, and bivalirudin—are injectable drugs used primarily in patients
with a history of HIT (heparin induced thrombocytopenia ).

• They all have very short half-lives of only several hours so only 1 day would be needed without
the drug for more invasive procedure

• The dentist is unlikely to have patients on any of these medications because they are used most
often in a hospital setting.

• However, if the dentist has a patient taking one of these drugs, many invasive dental procedures
can be done without stopping the drug.

• Consultation with the patient’s physician is recommended.

Direct Factor Xa Inhibitors.

• Rivaroxaban (Xarelto) and apixaban (Eliquis) are in common use.

• They are used primarily in patients who need anticoagulation therapy because of cancer.

• Patients taking these drugs will have excessive bleeding with trauma or surgical procedures.

liver Disease.

• Most coagulation factors are produced in the liver; therefore, if enough liver damage has occurred,
the patient could have a serious bleeding problem because of a defect in the coagulation phase.

• about 50% of patients with significant liver disease (with portal hypertension present) will be
thrombocytopenic as a result of sequestration of platelets in the spleen.

• Alcohol also can have a direct effect on homeostasis by interfering with platelet function.

• The PT test can be used to screen for a defect in the coagulation phase in patients with a history that
indicates liver disease.

• A platelet count should be obtained to see if the platelet phase has been affected.

• If both the PT and the platelet count are normal, surgery can be performed on these patients

• If results of both tests are abnormal, then the dentist should consult with the patient’s physician
regarding stabilization of the patient’s bleeding status before surgery.

• Appropriate management may involve vitamin K administration, platelet replacement, or other special
physician-directed procedures.

Malabsorption Syndrome or Long-Term Antibiotic Therapy.

• bacteria in the intestine that produce vitamin K may be adversely affected.

• The liver needs vitamin K for the production and function of prothrombin
(factor II) and related coagulation factors (factors VII, IX, and X).

• The PT test can be ordered to screen for a possible bleeding problem;

• if results are normal, surgery can be performed on these patients without

risk of a bleeding problem.

• The patient’s physician should be consulted regarding the patient’s health

status before surgery because complicating factors may occur in addition to
the possible bleeding problem that would contraindicate surgery.
Parenteral vitamin K may have to be administered in some of these cases.

Vascular Wall Alteration.

• In patients with autoimmune disease, infectious disease, structural

malformation of vessels, scurvy, steroid therapy, small vessel vasculitis, or
deposits of paraproteins, alterations of the vessel wall can result in
excessive bleeding after surgical procedures.

• No reliable screening tests can detect those patients who will be

bleeders.

• The Ivy BT test can be used in an attempt to identify potential bleeders,

but as stated earlier, this is not a reliable test.

• The dentist must rely on the medical history (questions related to

excessive bleeding problems), clinical findings, and consultation with the
patient’s physician to identify these patients.

Thrombocytopenia.

• Patients found to have severe thrombocytopenia may require

• hospitalization and special preparation for surgery, A hematologist should be involved

with the diagnosis, presurgical assessment, preparation, and postsurgical management.

• patients with platelet counts above 30,000/µL. Infiltration and block injections of local
anesthesia can be provided .Also, most routine dental procedures can be performed.

• If the platelet count is below 30,000/µL. routine dental treatment involving minor tissue
injury should be delayed. For urgent or emergency dental needs, platelet replacement is
indicated.

• If the platelet count is above 50,000/µL, extractions and dentoalveolar surgery can be
performed.

• platelet count should be 80,000/µL and 100,000/µL or higher for more advanced surgery,
the Patients with platelet counts below these levels will need platelet replacement before
undergoing the planned procedures.

The need for platelet transfusions can be reduced through the use of

• local measures,

• along with desmopressin and EACA or tranexamic acid to control bleeding.

• Also, topical platelet concentrates can be applied.

Patients who fail to respond to platelet replacement therapy have what

is called platelet transfusion refractoriness.

• This may occur on an immune or a nonimmune basis.

• Platelet transfusion refractoriness presents management problems.

• The hematologist who is involved with the patient will make recommendations on
how to prepare the patient for surgical procedures.

Treatment Planning Modifications

• With proper preparation, most indicated dental treatment can be

provided for patients with various bleeding problems.

• Aspirin and other NSAIDs should not be used for pain relief in
those who have known bleeding disorders or who are receiving
anticoagulant medication.

• Herbal medications that may cause bleeding also should be

avoided.

Oral Manifestations
• Patients with bleeding disorders may experience spontaneous gingival bleeding.

• Oral tissues (e.g., soft palate, tongue, buccal mucosa) may show petechiae, ecchymoses,
jaundice, pallor, and ulcers.

• Spontaneous gingival bleeding and petechiae usually are found in patients with
thrombocytopenia.

• Hemarthrosis of the temporomandibular joint is a rare finding in patients with

coagulation disorders and is not found in patients with thrombocytopenia.

• Enlargement of the parotid glands may be associated with chronic liver disease

• Patients with leukemia may exhibit generalized enlargement and bleeding of the gingiva.

• Patients with neoplastic disease may show osseous lesions on radiographs, as well as oral
ulcers or tumors. These patients also may have drifting and loosening of teeth and may
complain of paresthesias (e.g., burning of the tongue, numbness of the lip) as a result of
neoplasms in the jaw.

“Thank you ”

–Dr. Jamil Salman