The document discusses hemostasis, the process by which bleeding is prevented after vascular injury. It describes the four main mechanisms: vasoconstriction, formation of a platelet plug, coagulation pathways, and fibrinolytic phase. Specifically, it details the roles of platelets, calcium ions, coagulation factors, fibrinogen and thrombin in forming a blood clot via the intrinsic and extrinsic coagulation pathways. It also discusses anticoagulants that prevent unnecessary clotting and plasmin which lyses blood clots.

1. TOPIC : HEMOSTASIS
Presented by : Dr. Astha Kadiyan Guided by : Dr. Munish Ghanghas
MDS 1ST Year (2019) Senior lecturer
Department of OMR Department of OMR

2. CONTENTS
 INTRODUCTION
 Mechansism of hemostasis : a) Vasoconstriction
b) Formation of platelet plug
c) coagulation pathways
d) Fibrinolytic phase
 ROLE OF CALCIUM IONS IN THE INTRINSIC AND EXTRINSIC PATHWAYS
 PREVENTION OF BLOOD CLOTTING IN THE NORMAL VASCULAR SYSTEM – THE
INTRAVASCULAR ANTICOAGULANTS
 LYSIS OF BLOOD CLOTS – PLASMIN
 CLINICAL MANIFESTATIONS
 LABORATORY INVESTIGATIONS
 VESSEL WALL DISORDERS
 PLATELETS DISORDERS

3.  COAGULATION DISORDERS
 ANTICOAGULANT DRUGS
 COAGULOPATHIES—ACQUIRED— DISEASE ASSOCIATED
 IDENTIFICATION OF THE DENTAL PATIENT WITH A BLEEDING DISORDER
 ORAL COMPLICATIONS AND MANIFESTATIONS

4. INTRODUCTION
 The term hemostasis means prevention of blood loss. Whenever a vessel is
injured or ruptured, hemostasis is achieved by several mechanism:
 Vascular spasm
 Formation of a platelet plug
 Formation of a blood clot as a result of blood coagulation
 Eventual growth of fibrous tissue into the blood clot to close the hole in the vessel
permanently.
 Termination and fibrinolytic phase

8. VASCULAR CONSTRICTION
Injured or ruptured
blood vessel
Initiate nervous
reflexes
Local myogenic
spasm
Local humoral
factors
pain

9. Causes vessel to contract
This reduces the flow of blood from ruptured
vessel

10.  Platelets are responsible for much of vasoconstriction by releasing the
vasoconstrictor substance thromboxane A2.
 The more a vessel is traumatized, the greater the degree of spasm.
FORMATION OF THE PLATELET PLUG
Platelets are also known as thrombocytes. They are round or oval discs 1 to 4
micrometers in diameter. They are formed in the bone marrow from
megakaryocytes.

11.  Normal concentration of platelet in blood is between 1,50,000 and 3,00,000
Per microliter. On cell membrane of platelets there is a coat of gylcoproteins
that repulses adherence to normal endothelium and causes adherence to
injured areas of the vessel wall.
 Platelet membrane contains large amounts of phospholipids that play
several activating roles at multiple points in the blood-clotting process.
 Platelet also have two types of cytoplasmic granules : α granules, which express the
adhesion molecule P-selectin on their membranes and contain fibrinogen, fibronectin,
factors V and VIII, platelet factor-4 (a heparin-binding chemokine), platelet-derived
growth factor (PDGF), and transforming growth factor-β (TGF-β)

12.  Dense bodies (δ granules), which contain adenine nucleotides (ADP and ATP),
ionized calcium, histamine, serotonin, and epinephrine
 After vascular injury, platelets encounter ECM constituents (collagen is most
important) and adhesive glycoproteins such as vWF. This sets in motion a series of
events that lead to (1) platelet adhesion, (2) platelet activation, and (3) platelet
aggregation

13. MECHANISM OF THE PLATELET PLUG
When Platelets come in contact with damaged vascular surface, they change their characteristics
drastically. They begin to swell, assume irregular forms with numerous irradiating pseudopods
protruding from their surfaces, their contractile proteins contract forcefully and Calcium and ADP
released from δ granules that are especially important in subsequent events, since calcium is required
by several coagulation factors and ADP is a potent activator of resting platelets. Activated platelets also
synthesize thromboxane A2 (TxA2), a prostaglandin that activates additional nearby platelets and that
also has an important role in platelet aggregation The subtle membrane changes include an increase in
the surface expression of negatively charged phospholipids, which provide binding sites for both
calcium and coagulation factors, and a conformation change in platelet GpIIb/IIIa that permits it to bind
fibrinogen.

14.  After platelet activation there is platelet aggregation. Aggregation is promoted by bridging
interactions between fibrinogen and GpIIb/IIIa receptors on adjacent platelets. The importance of this
interaction is emphasized by a rare inherited deficiency of GpIIb/IIIa (Glanzmann thrombasthenia),
which is associated with bleeding and an Inability of platelets to aggregate. Recognition of the central
role of GpIIb-IIIa receptors in platelet aggregation has stimulated the development of antithrombotic
agents that inhibit GpIIb-IIIa function
 Activation of the coagulation cascade generates thrombin, which stabilizes the platelet plug

16.  There are four processes in the functional response of activated platelets: adhesion, aggregation,
secretion, and procoagulant activity. Platelet adhesion primarily occurs through the binding of
platelet surface receptor GP Ib/IX/V complex to
vWF in the subendothelial matrix. In addition, GP Ia/IIa on platelets bind to collagen fibrils in the
matrix. During platelet aggregation, GP IIb/IIIa binds activated platelets (e.g., activated by
thrombin, collagen, or ADP) through binding of the receptor to fibrinogen. During the secretion
phase, platelets secrete a number of substances to include: ADP and serotonin for platelet
stimulation and recruitment; adhesive proteins bironectin and thrombospondin; fibrinogen;
thromboxane A2 for vasoconstriction and further platelet aggregation; growth factors that
stimulate smooth muscle cell mitosis; and other factors that enhance fibrin and platelet thrombus
formation. In the platelet procoagulant phase, procoagulant phospholipids are exposed and
enzyme complexes for the clotting cascade are assembled on platelet surfaces

17.  Therefore, at the site of any rent in a blood vessel wall, the damaged vascular wall
or extravascular tissues elicit activation of successively increasing numbers of
platelets that themselves attract more and more additional platelets, thus forming
a platelet plug.

18. BLOOD COAGULATION IN THE RUPTURED VESSEL
 The clot begins to develop in 15 to 20 seconds if trauma to the vascular wall has
been severe and in 1 to 2 minutes if the trauma has been minor.
 Substances that promote coagulation – procoagulants
 Substances that inhibit coagulation – anticoagulants.
 In response to rupture of the vessel or damage to blood itself, a complex cascade
of chemical reactions occurs in the blood involving more than a dozen blood
coagulation factors. The net result is formation of a complex of activated
substances collectively known as prothrombin activator.

19.  The prothrombin activator catalyzes the conversion of prothrombin into thrombin.
 The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers, that enmesh
platelets, blood cells, and plasma to form the clot.
CONVERSION OF PROTHROMBIN TO THROMBIN
Prothrombin activator, in the presence of sufficient amounts of ionic ca++,
causes conversion of prothrombin to thrombin.

20.  The thrombin causes polymerization of fibrinogen molecule into fibrin fibers within
another 10 to 15 seconds.
 Prothrombin is a plasma protein present in normal plasma in concentration 15mg/dl. It
is an unstable protein that can easily split into smaller compounds, one of which is
thrombin. It is formed by liver and it is continually being used throughout the body for
blood clotting. Vitamin K is required by liver for normal formation of prothrombin and
other clotting factors. So either lack of Vitamin K or presence of liver disease that
prevents normal prothrombin formation can decrease the prothrombin level and causes
bleeding.
This process of coagulation involves multiple proteins, many of which are synthesised by
the liver (fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII and XIII) and are Vitamin K
dependent ( factor II, VII, IX and X)

21. CONVERSION OF FIBRINOGEN TO FIBRIN- FORMATION OF
THE CLOT
 Thrombin acts on fibrinogen to form fibrin monomer that polymerize with other
fibrin monomer to form fibrin.
 Fibrin is strengthens by a substance, fibrin stabilizing factor that is normally
in small amounts in the plasma globulins. Fibrin stabilizing factor is activated by
thrombin.
Fibrinogen is a high molecular weight protein that occur in plasma in quantities of 100 to
700 mg/dl. Fibrinogen is formed in the liver and liver disease decreases the
concentration of circulating fibrinogen. Because of its large molecular size, little
fibrinogen normally leaks from blood vessel into interstitial fluids, and it is one of
essential factors in the coagulation process, interstitial fluids ordinarily do not coagulate.

23. INITIATION OF COAGULATION : FORMATION OF
PROTHROMBIN ACTIVATOR
 Prothrombin activator is formed by a) trauma to the vascular wall and adjacent tissue.
b) trauma to the blood
c) contact of blood with damaged endothelial cells or with collagen and other tissue
elements outside the blood.
 Prothrombin activator is formed in two ways :
a) by extrinsic pathway that begins with trauma to the vascular wall and
surrounding tissues.
b) by intrinsic pathway that begins in the blood itself.

24. EXTRINSIC PATHWAY
It begins with a traumatized vascular wall or extravascular tissues that come in contact with
the blood.
1) Release of tissue factor : Traumatized tissue releases a complex of several factors known
as tissue factor or tissue thromboplastin. This is composed of phospholipids from the
membranes of tissues plus a lipoprotein complex that functions mainly as a proteolytic
enzyme.
2) Activation of factor X – role of factor VII and tissue factor : The lipoprotein complex of
tissue factor further complexes with blood coagulation factor VII and, in the presence of
Ca++, acts enzymatically on factor X to form activated factor X (Xa).

25. 3) Effect of activated factor X (Xa) to form prothrombin activator – role of factor V :
The activated factor X combines immediately with tissue phospholipids that are
part of tissue factor or with additional phospholipids released from platelets as well
as with factor V to form the complex called prothrombin activator. Within a few
seconds, in the presence of Ca++, this splits prothrombin to form thrombin, and
clotting process proceeds.
First Factor V in the prothrombin activator complex is inactive, but once clotting begins and thrombin
begins to form, the proteolytic action of thrombin activates factor V.
Thus, in final prothrombin activator complex, activated factor X is the actual protease that causes
splitting of prothrombin to form thrombin, activated factor V greatly accelerates this protease activity,
and platelet phospholipids act as vehicle that further accelerates the process.

27. INTRINSIC PATHWAY FOR INITIATING CLOTTING
Intrinsic pathway begins with trauma to the blood itself or exposure of the blood to
collagen from a traumatized blood vessel wall.
1) Blood trauma causes (a) activation of factor XII and (b) release of platelet
phospholipids : when factor XII is disturbed, by coming into contact with collagen it
takes on a new molecular configuration that converts it into a proteolytic enzymes
called “activated factor XII.” The blood trauma also damages the platelets because of
adherence to either collagen or a wettable surface( or by damage in other ways), and
this releases platelet phospholipids that contain the lipoprotein called platelet factor 3.
2) Activation of factor XI : The activated factor XII acts enzymatically on factor XI to
activate the factor XI ( this reaction also requires HMW (high molecular weight)
kininogen and is accelerated by prekallikrein.

28. 3. Activation of factor IX by activated factor XI. The activated factor XI then acts
enzymatically on factor IX to activate factor IX
4. Activation of factor X – role of factor VIII. The activated factor IX, acting with activated
factor VIII and with platelet phospholipids and factor III from traumatized platelets,
activates factor X.
5. Action of activated factor X to form prothrombin activator- role of factor V. This step is
same as in extrinsic pathway. Activated factor X combines to form the complex called
prothrombin activator.
If factor VIII or platelets are in short supply, this step of activation of factor X is deficient.
Factor VIII is missing in person who has classic haemophilia, so it is known as
antihemophilic factor.

30.  Once thrombin is formed, it not only catalyzes the final steps in the coagulation cascade,
but also exerts a wide variety of effects on the local vasculature and inflammatory milieu; it
even actively participates in limiting the extent of
the hemostatic process. Most of these thrombin mediated effects occur through protease-
activated receptors (PARs), which belong to a family of seven transmembrane spanning
proteins. PARs are present on a variety of cell types, including platelets, endothelium,
monocytes, and T lymphocytes. Thrombin activates PARs by clipping their extracellular
domains, causing a conformational change that activates associated G proteins. Thus, PAR
activation is a catalytic process, explaining the impressive potency of thrombin in eliciting
PAR-dependent effects, such as enhancing the adhesive properties of leukocytes.

32.  Once activated, the coagulation cascade must be tightly restricted to the site of injury to
prevent inappropriate and potentially dangerous clotting elsewhere in the vascular tree.
Besides restricting factor activation to sites of exposed phospholipids, clotting also is
controlled by three general categories of natural anticoagulants:
 Antithrombins (e.g., antithrombin III) inhibit the activity of thrombin and other serine
proteases, namely factors IXa, Xa, XIa, and XIIa. Antithrombin III is activated by
binding to heparin-like molecules on endothelial cells— hence the clinical utility of heparin
administration to limit thrombosis.
 Protein C and protein S are two vitamin K–dependent proteins that act in a complex to
proteolytically inactivate cofactors Va and VIIIa. Protein C activation by
thrombomodulin ; protein S is a cofactor for protein C activity.

33.  Tissue factor pathway inhibitor (TFPI) is a protein secreted by endothelium (and other cell
types) that inactivates factor Xa and tissue factor–factor VIIa complexes.

34. THE BLOOD CLOT
The clot is composed of a meshwork of fibrin fibers running in all directions and entrapping
blood cells, platelets, and plasma. The fibrin fibers also adhere to damaged surfaces of blood
vessels; therefore, the blood clot becomes adherent to any vascular opening and therby
prevents further blood loss.
Clotting also sets into motion a fibrinolytic cascade that moderates the ultimate size of the clot.
Fibrinolysis is largely carried out by plasmin, which breaks down fibrin and interferes with its
polymerization. The resulting fibrin split products (FSPs or fibrin degradation products) also can
act as weak anticoagulants. Elevated levels of FSPs (most notably fibrin-derived D dimers) can
be used for diagnosing abnormal thrombotic states including disseminated intravascular
coagulation (DIC), deep
venous thrombosis, or pulmonary thromboembolism

35.  Plasmin is generated by proteolysis of plasminogen, an inactive plasma precursor, either by
factor XII or by plasminogen activators. The most important of the plasminogen activators
is tissue type plasminogen activator (tPA); t-PA is synthesized principally by endothelial
cells and is most active when attached to fibrin. The affinity for fibrin largely confines t-PA
fibrinolytic activity to sites of
recent thrombosis. Urokinase like plasminogen activator (uPA) is another plasminogen
activator present in plasma and in various tissues; it can activate plasmin in the fluid phase.
In addition, plasminogen can be cleaved to its active form by the bacterial product
streptokinase, which is used clinically to lyse clots in some forms of thrombotic disease. As
with any potent regulatory component, the activity of plasmin is tightly restricted. To
prevent excess plasmin from lysing thrombi indiscriminately throughout the body, free
plasmin rapidly complexes with circulating α2-antiplasmin and is inactivated.

36.  Endothelial cells further modulate the coagulation– anticoagulation balance by releasing
plasminogen activator inhibitors (PAIs); these block fibrinolysis and confer an overall
procoagulation effect. PAI production is increased by inflammatory cytokines (in particular
interferon-γ) and probably contributes to the intravascular thrombosis that accompanies
severe inflammation.

37. CLOT RETRACTION – SERUM
 Clot begins to contract and usually expresses most of fluid from the clot within 20 to 60
minutes. The fluid is serum which is devoid of fibrinogen and most of the other clotting
factors.
 Platelets also contribute to clot contraction by activating platelet thrombosthenin, actin, and
myosin molecules, which are contractile proteins in the platelets and cause strong
contraction of platelet spicules attached to the fibrin.
Serum = plasma - fibrinogen and other clotting
factors

38.  As the clot retracts, the edges of the broken blood vessel are pulled together, thus contributing still
further to the ultimate state of hemostasis.
POSITIVE FEEDBACK OF CLOT FORMATION
 Once a blood clot has developed, it extends within minutes into the surrounding blood i.e clot itself
initiate a positive feed back (vicious circle) to promote more clotting.
 It is because of the proteolytic action of thrombin that allows it to act on many of the other blood
clotting factors in addition to fibrinogen.
 Thrombin has a direct proteolytic affect on the prothrombin itself tending to convert this into
thrombin, and it acts on some of blood clotting factors responsible for the formation of prothrombin
activator.

39. Once a critical amount of thrombin is formed, a vicious circle develops that causes still more
blood clotting and more and more thrombin to be formed; thus blood clot continues to grow
until something stops its growth.

40. ROLE OF CALCIUM IONS IN THE INTRINSIC AND EXTRINSIC PATHWAYS
 except for the first two steps in the intrinsic pathway, calcium ions are required for
promotion or acceleration of all the blood- clotting reactions. Therefore, in the absence
calcium ions, blood clotting by either pathway does not occur.
 In the living body, the calcium ion concentration seldom falls low enough to affect
significantly the kinetics of blood clotting. Conversely, when blood is removed from a
person, it can be prevented from clotting by reducing the calcium ion concentration
below the threshold level for clotting, either by deionizing the calcium by causing it to
react with substances such as citrate ion or by precipitating the calcium with substances
such as oxalate ion.

41. PREVENTION OF BLOOD CLOTTING IN THE NORMAL VASCULAR
SYSTEM – THE INTRAVASCULAR ANTICOAGULANTS
Endothelial surface factor : (a) the smoothness of the endothelial surface, which prevents
contact activation of the intrinsic clotting system
(b) A layer of glycocalyx on the endothelium ( glycocalyx is a mucopolysaccharide adsorbed to
the surface of the endothelium), which repels clotting factors and platelets, thereby preventing
activation of clotting.
(c) A protein bound with the endothelial membrane, thrombomodulin, which binds thrombin.
Not only does the binding of thrombomodulin with thrombin slow the clotting process by
removing thrombin, but the thrombomodulin-thrombin complex also activates a plasma
protein, protein C, that acts as an anticoagulant by inactivating activated factors V and VIII.

42. When the endothelial wall is damaged, its smoothness and its glycocalyx-thrombomodulin
layer are lost, which activates both factor XII and the platelets, thus setting off the intrinsic
pathway of clotting. If factor XII and platelet come in contact with the subendothelial
collagen, the activation is even more powerful.
ANTITHROMBIN ACTION OF FIBRIN AND ANTITHROMBIN III
Among the most important anticoagulants in the blood are those that remove thrombin from
the blood. The most powerful of these are (1) the fibrin fibers that
are formed during the process of clotting and (2) an alphaglobulin called antithrombin III or
antithrombin-heparin cofactor.

43. While a clot is forming, about 85 to 90 percent of the thrombin formed from the
prothrombin becomes adsorbed to the fibrin fibers as they develop.
This helps prevent the spread of thrombin into the remaining blood and, therefore, prevents
excessive spread of the clot. The thrombin that does not adsorb to the fibrin fibers soon combines
with antithrombin III, which further blocks the effect of the thrombin on the fibrinogen and then
also inactivates the thrombin itself during the next
12 to 20 minutes

44. Heparin is another powerful anticoagulant, but its concentration in the blood is normally low, so
only under special physiologic conditions does it have significant anticoagulant effects. However,
heparin is used widely as a pharmacological agent in medical practice in much higher
concentrations to prevent intravascular clotting.
The heparin molecule is a highly negatively charged conjugated polysaccharide. By itself, it has little
or no anticoagulant property, but when it combines with antithrombin III, the effectiveness of
antithrombin III in removing thrombin increases by a hundredfold to a thousandfold, and thus it
acts as an anticoagulant.

45. Therefore, in the presence of excess heparin, removal of free thrombin from the
circulating blood by antithrombin III is almost instantaneous. The complex of heparin
and antithrombin III removes several other activated coagulation factors in addition to
thrombin, further enhancing the effectiveness of anticoagulation. The others include
activated Factors XII, XI,
X, and IX
Heparin is produced by many different cells of the body, but especially large quantities
are formed by the basophilic mast cells located in the pericapillary connective tissue
throughout the body.

46. These cells continually secrete small quantities of heparin that diffuse into the circulatory
system. The basophil cells of the blood, which are functionally
almost identical to the mast cells, release small quantities of heparin into the plasma.
Mast cells are abundant in tissue surrounding the capillaries of the lungs and, to a lesser extent,
capillaries of the liver. It is easy to understand why large quantities of heparin might be needed
in these areas because the capillaries of the lungs and liver receive many embolic clots formed
in slowly flowing venous blood; sufficient formation of heparin prevents further growth of the
clots.

48. LYSIS OF BLOOD CLOTS – PLASMIN
The plasma proteins contain a euglobulin called plasminogen (or profibrinolysin) that, when
activated, becomes a substance called plasmin (or fibrinolysin). Plasmin is a proteolytic
enzyme that resembles trypsin, the most important proteolytic digestive enzyme of
pancreatic secretion. Plasmin digests fibrin fibers and some other protein coagulants such
as fibrinogen, Factor V, Factor VIII, prothrombin, and Factor XII. Therefore, whenever
plasmin is formed, it can cause lysis of a clot by destroying many of the clotting factors,
thereby sometimes even causing hypocoagulability of the blood.

49. ACTIVATION OF PLASMINOGEN TO FORM PlASMIN,
THEN LYSIS OF CLOTS.
 When a clot is formed, a large amount of plasminogen is trapped in the clot along with
other plasma proteins. This will not become plasmin or cause lysis of the clot until it is
activated. The injured tissues and vascular endothelium very slowly release a powerful
activator called tissue plasminogen activator (t-PA) that a few days later, after the clot has
stopped the bleeding, eventually converts plasminogen to plasmin, which in turn removes
the remaining unnecessary blood clot. In fact, many small blood vessels in which blood flow
has been blocked by clots are reopened
by this mechanism. Thus, an especially important function of the plasmin system is to
remove minute clots from millions of tiny peripheral vessels that eventually would become
occluded were there no way to clear them.

51. Clinical Manifestations
Clinical manifestations of bleeding disorders can involve various systems, depending on
the extent and type of disease. Individuals with mild disease may present with no clinical
signs, whereas individuals with severe coagulopathies may have definite stigmata. When
skin and mucosa are involved, individuals may present with petechiae, ecchymoses,
spider angiomas,
hematomas, or jaundice. Deep dissecting hematomas and hemarthroses of major joints
may affect severe hemophiliacs and result in disability or death. Disorders of platelet
quantity may result in hepatosplenomegaly, spontaneous gingival bleeding, and risk of
hemorrhagic stroke.

53. Laboratory tests
 Tests to evaluate primary hemostasis involving platelets are the platelet count and platelet
function tests such as bleeding time (BT) and other new platelet function assays.
 Tests to evaluate the status of coagulation function include prothrombin time
(PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT),
thrombin time (TT), FDPs, specific coagulation factor assays (e.g., F VII, F VIII, F IX,
fibrinogen), and coagulation factor inhibitor screening tests (blocking antibodies)

54. Normal platelet counts are 150,000 to 450,000/mm3. Spontaneous clinical
hemorrhage is usually not observed with platelet counts above 10,000 to
20,000/mm3. Many hospitals have established a critical value of 10,000/mm3
platelets, below which platelets are transfused to prevent serious bleeding
sequelae, such as hemorrhagic stroke. Surgical or traumatic hemorrhage is
more likely with platelet counts below 50,000/mm3.

56. TESTS OF PLATELET FUNCTION : a) Bleeding time : Normal range is between 1 and 6
minutes and is considered significantly prolonged when greater than 15 minutes.
b) Platelet Function Analyzer : Closure time (CT), measured by the PFA-100 device, is now
reportable by many clinical laboratories as a possible alternative or supplement to the BT
it is neither specific for nor predictive of any particular disorder (inclusive of vWD).
PROTHROMBIN TIME AND INTERNATIONAL NOMALIZED RATIO : The PT and INR tests
evaluate the extrinsic and common coagulation pathways, screening for the presence or
absence of fibrinogen (F I), prothrombin (F II), and Fs V, VII, and X. The normal range of PT is
approximately 11 to 13 seconds

57. The INR, introduced by the World Health Organization in 1983, is the ratio of PT that adjusts for the
sensitivity of the thromboplastin reagents, such that a normal coagulation profile is reported as an INR
of 1.0, and higher values indicating abnormal coagulation. Its most common use is to measure the
effects of coumarin anticoagulants and reduction of the vitamin K–dependent Fs II, VII, IX, and X. It is
not effective for hemophilia A and B, since it does not measure F VIII or F IX.
ACTIVATED PARTIAL THROMBOPLASTIN TIME : The aPTT is used to evaluate the intrinsic
coagulation pathway, screening for deficiencies in F VIII, F IX, F XI, and F XII, in addition to prekallikrein
and high-molecular-weight (HMW) kiningen. It is performed by calcifying plasma in the presence of a
thromboplastic material (i.e., phospholipid tablet) and a contact activator that is a negatively charged
substance (e.g., kaolin) in the absence of TF.

58. It is considered normal if the control aPTT and the test aPTT are within 10 seconds of each
other. Control aPTT times are usually 15 to 35 seconds. Normal ranges depend on the
manufacturer’s limits as each supplier varies slightly. As a screening test, the aPTT is prolonged
only when the factor levels in the intrinsic and common pathways are less than approximately
30%. It is altered in hemophilia A and B and with the use of the anticoagulant heparin, which
may result in clinical bleeding problems. However, elevated aPTT due to deficiencies in F X II,
prekallikrein, and HMW kiningen do
not correlate with clinical bleeding.
THROMBIN TIME : The TT is used specifically to test the ability to form the initial fibrin clot
from fibrinogen, by adding thrombin to plasma. is considered normal in the range of 9 to 13
seconds, with values in excess of 16 to 18 seconds considered to be prolonged.

59. It is used to measure the activity of heparin, FDPs, or other paraproteins that inhibit conversion of
fibrinogen to fibrin. Fibrinogen can also be specifically assayed and should be present at a level of
200 to 400 mg/dL.
FIBRIN DEGRADATION PRODUCTS : The FDPs are measured using a specific latex agglutination
system to evaluate the presence of the d-dimer of fibrinogen and/or fibrin above normal levels.
Such presence indicates that intravascular lysis has taken place or is occurring. This state can result
from primary fibrinolytic disorders or disseminated intravascular coagulation (DIC).
FACTOR ASSAYS : Inhibitor screening tests are essential when sufficient factor
concentrate to correct the factor deficiency under normal conditions fails to control bleeding.

60. TESTS OF CAPILLARY FRAGILITY : The tourniquet test for capillary fragility is useful for
identifying disorders of vascular wall integrity or platelet disorders. Stasis is produced by
a sphygmomanometer cuff around the arm in the usual manner to a pressure halfway between
systolic and diastolic levels. This moderate degree of stasis is maintained for 5 minutes. At 2
minutes following cuff deflation and removal, a 2.5-cm diameter (size of a quarter) of skin on
volar surface of the arm at 4 cm distal to the antecubital fossa is observed for petechial
hemorrhages. This distal shower of petechiae is called the Rumpel–Leede phenomenon.
petechiae in men do not exceed 5 in number, and in women and children, they do not exceed
in number in the skin region examined. The capillary fragility test is the only test to demonstrate
abnormal results in vessel wall disorders.

62. DENGUE
Dengue is an acute viral illness caused by RNA virus of the family Flaviviridae and spread by
mosquitoes. Presenting features may range from asymptomatic fever to dreaded complications
such as hemorrhagic fever and shock. Acute-onset high fever, muscle and joint pain, myalgia,
cutaneous rash, hemorrhagic episodes, and circulatory shock are the commonly seen symptoms.
Alterations in endothelial microvascular permeability and thromboregulatory mechanisms lead to
an increased loss of protein and plasma
Clinical parameters: Acute-onset febrile phase – high-grade fever lasting from 2 days to 1 week.
Hemorrhagic episodes (at least one of the following forms): Petechiae, purpura, ecchymosis,
epistaxis, gingival and mucosal bleeding, GIT or injection site, hematemesis and/or malena

63. Laboratory parameters: Thrombocytopenia (platelet count <100,000/cu mm)
The hemorrhagic episodes in DHF are associated with multifactorial pathogenesis.
Vasculopathy, deficiency and dysfunction of platelets and defects in the blood coagulation
pathways are the attributed factors. Decreased production of platelets and increased
destruction of platelets may result in thrombocytopenia in DHF. The impaired platelet
function causes the blood vessels to become fragile and this results in hemorrhage. The
condition is usually self-limiting and antiviral therapy is not currently available. Supportive
care with analgesics, hydration with fluid replacement, and sufficient bed rest forms the
preferred management strategy

64. Vessel wall disorders
 due to structural malformation of vessels
 inherited or acquired disorders of connective tissue.
They are :
1. Scurvy
2. Cushing’s Syndrome
3. Ehlers–Danlos Syndrome
4. Rendu–Osler–Weber Syndrome
due to dietary deficiency of vitamin – C. Survy results when dietary vitamin C falls below 10
mg/d. Vitamin C is necessary for the synthesis of hydroxyproline, an essential constituent of
collagen.
SCURVY

65.  Many of the hemorrhagic features of scurvy result from defects in collagen
synthesis. One of the first clinical signs is petechial hemorrhages at the hair follicles and
purpura on the back of the lower extremities that coalesce to form ecchymoses. Hemorrhage
can occur in the muscles, joints, nail beds, and
gingival tissues. Gingival involvement may include swelling, friability, bleeding, secondary
infection, and loosening of teeth. Implementation of a diet rich in vitamin C and
administration of 1 g/d of vitamin C supplements provide
rapid resolution.

66. Cushing’s syndrome, resulting from excessive exogenous
or endogenous corticosteroid intake or production,
leads to general protein wasting and atrophy of
supporting connective tissue around blood vessels.
Patients may show skin bleeding or easy bruising.
Aging causes similar perivascular connective tissue
atrophy and lack of skin mobility. Tears in small blood
vessels can result in irregularly shaped purpuric areas
on arms and hands, called purpura senilis.
Cushing’s Syndrome

67. Ehlers–Danlos syndrome is an autosomal dominant inherited disorder of connective tissue matrix,
generally resulting in fragile skin blood vessels and easy bruising. It is characterized by
hyperelasticity of the skin and hypermobile joints.
Eleven subtypes have been identified with unique biochemical defects and varying clinical
features.
Type I is the classic form, with soft, velvety, hyperextensible skin; easy bruising and scarring;
hypermobile joints; varicose veins; and prematurity
Type VIII, which was recently mapped to chromosome 12q13,44 has skin findings similar to those
in type I, with easy bruising following minor trauma mainly due to the resulting fragility of the
oral mucosa and blood vessels and is characterized by early-onset periodontal disease with
severe loss of alveolar bone and permanent dentition
Ehlers–Danlos Syndrome

68. Children with type VII syndrome may present with microdontia and collagen-related dentinal
structural defects in primary teeth, in addition to bleeding after tooth
brushing. Other oral findings include fragility of the oral mucosa, gingiva, and teeth, as well as
hypermobility of the temporomandibular joint (TMJ) and stunted teeth
and pulp stones on dental radiographs. Oral health may be severely compromised as a result of
specific alterations of collagen in orofacial structures. A number of tissue
responses (mucosa, periodontium, pulp) and precautions (e.g., prevention of TMJ dislocation)
should be considered when planning dental treatment.

70. Rendu–Osler–Weber syndrome, also called hereditary hemorrhagic telangiectasia (HHT), is a group
of autosomal dominant disorders with abnormal telangiectatic capillaries, frequent episodes of nasal
and gastrointestinal bleeding, and associated brain and pulmonary lesions. Perioral and intraoral
angiomatous nodules or telangiectases are common with progressive disease, involving areas of the
lips, tongue, and palate that may bleed upon manipulation during dental procedures. Diagnosis is
facilitated by the history
of nosebleeds and the observation of multiple nonpulsating vascular lesions representing small
arteriovenous malformations. These lesions blanch in response to applied pressure,
unlike petechiae or ecchymoses. Mucocutaneous lesions may bleed profusely with minor trauma or
on occasion, spontaneously. Persistently bleeding lesions may be treated with
cryotherapy, laser ablation, electrocoagulation, or resection.
Rendu–Osler–Weber Syndrome

71. Blood replacement and iron therapy may be necessary following dental extractions in involved
areas. It has also been suggested that antibiotic prophylaxis should be considered before
dental care for patients with HHT and concomitant pulmonary arteriovenous malformation.

72. Platelet disorders

73. CONGENITAL PLATELET DEFECTS
 Bernard–Soulier syndrome results from identified absence in platelet membrane
Ib from the platelet membranes, rendering the platelets unable to interact with vWF.
transfusions are the main treatment modality for Bernard–Soulier syndrome.
 Glanzmann’s thrombasthenia is a qualitative disorder characterized by a deficiency in the
platelet membrane glycoproteins IIb and IIIa. As a result, platelets cannot bind to fibrinogen
and cannot aggregate with other platelets. Clinical signs include bruising, epistaxis, gingival
hemorrhage, and menorrhagia. Treatment of oral surgical bleeding involves platelet
transfusion and use of antifibrinolytics and local hemostatic agents. Treatment of bleeding
episodes in the patient with Glanzmann’s thrombasthenia is usually not warranted unless
hemorrhage is life threatening

75.  Wiskott–Aldrich syndrome is a rare X-linked recessive disease characterized by cutaneous
eczema (usually beginning on the face), thrombocytopenic purpura, and an increased
susceptibility to infection due to an immunologic defect. It is a quantitative and qualitative
platelet disorder. Oral manifestations include gingival bleeding and palatal petechiae.
Thrombocytopenia of Wiskott–Aldrich syndrome
may be managed with platelet transfusions, splenectomy, or bone marrow transplantation.
 May–Hegglin anomaly is a rare hereditary condition characterized by the triad of
thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. Clinical features and
the pathogenesis of bleeding in this disease are poorly defined.

76. Wiskot Aldrich syndrome
May–Hegglin anomaly

77. ACQUIRED PLATELET DEFECTS
1. Idiopathic or immune thrombocytopenic purpura (ITP)
2. Thrombotic thrombocytopenic purpura (TTP)
ITP may be acute and self-limiting (2–6 weeks) in children. In adults, ITP is typically more indolent in
its onset, and the course is persistent, often lasting many years, and may be characterized by
exacerbations of disease. . In severe cases of ITP, oral hematomas and hemorrhagic bullae may be
presenting clinical sign. Most patients with chronic ITP are young women. Intracerebral hemorrhage,
although rare, is the most common cause of death. ITP is assumed to be caused by accelerated
antibody-mediated
platelet consumption.

78. The natural history and long-term prognosis of adults with chronic ITP remain incompletely defined.
ITP may be a component of other systemic diseases. Autoimmune thrombocytopenia associated
with systemic lupus erythematosus is often of little consequence but may be occasionally severe
and serious, requiring aggressive treatment. Immune-mediated thrombocytopenia may occur in
conjunction with HIV disease in approximately 15% of adults, being more common with advanced
clinical disease and immune suppression, although less than 0.5% of patients have severe
thrombocytopenia with platelet counts below 50,000/mm3

79. TTP is an acute catastrophic disease that, until recently, was uniformly fatal. The
causative factors include metastatic malignancy, pregnancy, mitomycin C, and
high-dose chemotherapy. If untreated, it still carries a high mortality rate. In
addition to thrombocytopenia, clinical presentation of TTP includes
microangiopathic hemolytic anemia, fluctuating neurologic abnormalities, renal
dysfunction, and occasional fever. Microvascular infarcts occurring in gingival and
other mucosal tissues are present in about 60% of the cases. These appear as
platelet-rich thrombi. Serial studies of plasma samples from patients during
episodes of TTP have often shown vWF multimer abnormalities.

81. Thrombocytopenia may also be a component of other hematologic disease, such as myelodysplastic
disorders, aplastic anemia, and leukemia. Thrombocytopenia and
thrombocytopathy in liver disease are complicated by coagulation defects, as discussed below.
Alcohol can, itself, induce thrombocytopenia in addition to qualitative platelet defects. Renal disease
can result in qualitative platelet defects resulting from uremia.
Drug-Induced Platelet Defects
Medications can also reduce absolute numbers of platelets or interfere with their function, resulting
in postsurgical hemorrhage. Bone marrow suppression from cytotoxic cancer chemotherapy can
result in severe thrombocytopenia, requiring platelet transfusions for prevention of spontaneous
hemorrhage. Antiplatelet agents are routinely used therapeutically forthromboembolic protection in
patients with ischemic heartdisease, prosthetic heart valves, coronary artery stents, and those at risk
of ischemic cerebrovascular accidents.

82. Antiplatelet therapy reduces the risk of death from cardiovascular causes by about one-sixth and the
risk of nonfatal myocardial infarction and stroke by about one-third for patients with unstable
angina or a history of myocardial infarction, transient ischemia, or stroke.
ASA, also known as aspirin, is an inexpensive and effective drug that is widely used. ASA induces a
functional defect in platelets detectable as prolongation of BT and altered
PFA-100 CTs. It inactivates an enzyme called prostaglandin synthetase, resulting in inactivation of
cyclooxygenase (COX) catalytic activity and decreasing biosynthesis of prostaglandin and
thromboxanes (such as thromboxane A2) that are needed
to regulate interactions between platelets and the endothelium. A single 100 mg dose of ASA
provides rapid complete and irreversible inhibition of platelet COX activity and thromboxane
production. This type of drug-related platelet disorder is compensated for within 7 to 10 days.

83. Most NSAIDs have a similar but less significant antiplatelet effect and therefore
are of mild concern to patients who have other disorders of hemostasis. The COX-2
inhibitors, such as celecoxib (Celebrex, Pfizer, New York, NY), generally do not inhibit
platelet aggregation at indicated doses. Other therapeutic antiplatelet medications work by
different mechanisms affecting platelet adhesion, activation, and aggregation, which include
the inhibition of ADP receptor (e.g., clopidogrel, ticlopidine, and prasugrel); adenosine
reuptake (dipyridamole); phosphodiesterase (e.g., cilostazol); and GP IIb/IIIa (e.g., abciximab,
eptifibatide, tirofiban)

84. Treatment of Platelet Disorders
Treatment modalities for platelet disorders are determined by the type of defect. The
thrombocytopenias are primarily managed acutely with transfusions of platelets to maintain the
minimum level of 10,000 to 20,000/mm3 necessary to prevent spontaneous hemorrhage. This has
been indicated for thrombocytopenias secondary to liver disease, Glanzmann’s thrombasthenia, and
the main therapy for Bernard–Soulier disease. However, repeated platelet transfusions may carry the
risk of development of antiplatelet isoantibodies thereby losing its effectiveness. As a consequence,
transfusions are usually reserved for more acute bleeding episodes or for surgical procedures.
leukocyte antigen (HLA)-matched platelets may be required after antibody development, to reduce
number of platelet transfusions needed for hemostasis. In the absence of satisfactorily compatible
platelets, blood volume and constituents can be maintained with low-antigenicity blood products.
Plasmapheresis to remove circulating isoantibodies is held in reserve for cases of severe
thrombasthenia and lifethreatening bleeding

85. COAGULATION DISORDERS—CONGENITAL
1. von Willebrand Disease
2. Hemophilia A
3. Hemophilia B
4. F XI Deficiency
5. F XII Deficiency
6. F X Deficiency
7. F V Deficiency
8. Fs XIII and I Deficiencies
VON WILLEBRAND DISEASE
It can be due to quantitative or qualitative defects in vWF, a multimeric HMW glycoprotein. This
disorder is usually transmitted as an autosomal dominant trait with varying penetrance.

86. vWD is classified into three primary categories. Type 1 (85% of all vWD) includes partial quantitative
deficiency, type 2 (10%–15% of all vWD) includes qualitative defects, and type 3 (rare) includes
virtually complete deficiency of vWF.
 A rare fourth type is called pseudo- or platelet-type vWD,
and it is a primary platelet disorder that mimics vWD.
 Due to familial genetic variants, wide variations occur
in the patient’s laboratory profile over time; therefore,
diagnosis may be difficult.
 The clinical features of vWD are usually mild and
include mucosal bleeding, soft tissue hemorrhage,
menorrhagia in women, and rare hemarthros

87. Hemophilia A involves a deficiency of F VIII
It is inherited as an X-linked recessive trait. The more common signs include
hematomas, hemarthroses, hematuria, gastrointestinal bleeding, and bleeding from
lacerations or head trauma or spontaneous intracranial bleeding that require factor
replacement therapy. Severe hemorrhage leads to joint synovitis
and hemophilic arthropathies, intramuscular bleeds, and
pseudotumors (encapsulated hemorrhagic cyst)
F IX (Christmas factor) deficiency is found in hemophilia
B. The genetic background, factor levels, and clinical symptoms are similar to those
in hemophilia A. Circulating blocking antibodies or inhibitors to Fs VIII and
IX may be seen in patients with these disorders. These inhibitors are specific for F VIII
or F IX and render the patient refractory to the normal mode of treatment with
concentrates.Catastrophic bleeding can occur, and patients can survive only with
supportive transfusions.
Hageman factor (F XII) deficiency is another rare disease
that presents in the laboratory with prolonged PT and PTT.
Clinical symptoms are non-existent ; therefore, treatment is
contraindicated

88. Plasma thromboplastin antecedent (F XI) deficiency is clinically a mild
disorderit is transmitted as an autosomal dominant trai
Stuart factor (F X)
deficiency, also a rare
bleeding diathesis,
is inherited as an autosomal
recessive trait
Proaccelerin (F V) deficiency, like F XI and F X
deficiencies,
is a rare autosomal recessive trait that presents
with moderate
to severe clinical symptoms
Fibrin-stabilizing (F XIII) deficiency and fibrinogen (F I)
deficiency are very rare, and these diagnoses can be made
only with extensive laboratory tests usually available only
in tertiary care medical centers. Both are autosomal recessive traits

90. Factor Replacement Therapy

91. COAGULATION DISORDERS— ACQUIRED—DRUG INDUCED
1. HEPARIN : treatment for venous thromboembolism. It is typically used for acute anticoagulation. For
acute anticoagulation, intravenous infusion of 1000 units unfractionated heparin per hour, sometimes
following a 5000-unit bolus, is given to increase the aPTT to 1.5 to 2 times the preheparin aPTT.
2. Coumarin Anticoagulant : Coumarin anticoagulants, which include warfarin and dicumarol, slow
thrombin production and clot formation by blocking the action of vitamin K, leading to decreased levels
of vitamin K–dependent factors (Fs II, VI, IX, and X). They are routinely used for anticoagulation to
prevent recurrent thromboembolic events, such as pulmonary embolism, venous thrombosis, stroke, and
myocardial infarction. It is used commonly in patients with atrial fibrillation and in patients with prosthetic
heart valves

92. Daily doses of 2.5 to 7.5 mg warfarin are typically required to maintain adequate anticoagulation.
Coumarin therapy requires continual laboratory monitoring, (i.e., typically every 2–8 weeks) as
fluctuations can occur.
3. New Oral Anticoagulants : New oral anticoagulant medications (e.g., dabigatran,
rivaroxaban, apixaban) have been recently recommended for atrial fibrillation over warfarin mainly due
to its equivalent efficacy, its predictable and stable anticoagulant effect at regular fixed dosages thereby
eliminating the need for regular monitoring. The main drawback to these medications is the lack of
specific antidotes, which are currently in the development stages.

93. COAGULOPATHIES—ACQUIRED— DISEASE ASSOCIATED
Liver Disease : Acute or chronic hepatocellular disease may display decreased vitamin K–dependent
factor levels, with other factors still being normal. In addition, abnormal vitamin K–dependent factor and
fibrinogen molecules have been encountered. Thrombocytopenia due to platelet sequestration in the
spleen and thrombocytopathy are also common in severe liver disease. Liver disease that results in
bleeding from deficient vitamin K–dependent clotting factors (Fs II, VII, IX, and X) may be reversed with
vitamin K injections for three days, either intravenously or subcutaneously. Infusion of FFP may be
employed when more immediate hemorrhage control is necessary, such as prior to dental extractions or
other surgical procedures. Cirrhotic patients with moderate thrombocytopenia and functional platelet
defects may benefit from DDAVP therapy.

94. Renal Disease
Patients with renal disease have thrombocytopathies due to the
effects of accumulated urea on platelets. In uremic patients, dialysis remains the primary
preventive and therapeutic modality used for control of bleeding, although it is not always
immediately effective. Hemodialysis and peritoneal dialysis appear to be equally efficacious in
improving platelet function abnormalities and clinical bleeding in the uremic patient. The
availability of cryoprecipitate and DDAVP offers alternative effective therapy for uremic patients
with chronic abnormal bleeding who require shortened BTs acutely in preparation for urgent
surgery. Conjugated estrogen preparations and recombinant erythropoietin have also been shown
to be beneficial.

95. Vitamin K Deficiency
Vitamin K is a fat-soluble vitamin that is absorbed in the small intestine and stored in the liver. It
plays an important role in hemostasis by activating various coagulation factors. Vitamin K
deficiency is associated with having poorly functioning vitamin K–dependent Fs II,VII, IX, and X.
Deficiency is rare but can result from inadequate dietary intake, intestinal malabsorption, or loss of
storage sites due to hepatocellular disease. Biliary tract obstruction and long-term use of broad-
spectrumantibiotics, particularly the cephalosporins, can also cause vitamin K deficiency. Although
there is a theoretic 30-day store of vitamin K in the liver, severe hemorrhage can result in acutely ill
patients in 7 to 10 days. A rapid fall in F VII levels leads to an initial elevation in INR and a
subsequent prolongation of aPTT. When vitamin K deficiency results in coagulopathy,
supplemental vitamin K by injection restores the integrity of the clotting mechanism within 12 to 24
hours.

96. Disseminated Intravascular Coagulation
DIC is a process that causes both thrombosis and haemorrhage. DIC is triggered by potent stimuli
that activate both F XII and TF to initially form microthrombi and emboli throughout the
microvasculature. The most frequent triggers for DIC are obstetric complications, metastatic cancer,
massive trauma, and infection with sepsis. In acute DIC, it is important to expeditiously identify the
underlying triggering disease or condition and deliver specific and vigorous treatment of the
underlying disorder if long-term survival is to be a possibility. Diagnosis is made by laboratory
studies that confirm increased thrombin generation (e.g., decreased fibrinogen, prolonged PT/INR,
and aPTT) and increased fibrinolysis (e.g., increased FDPs and d-dimer. For chronic DIC, diagnosis is
based on the evidence of microangiopathies on the peripheral blood smear, and creased FDPs such
as d-dimer.

97. The dentist may be called upon to provide a gingival or oral mucosal biopsy specimen for
histopathologic examination to confirm the diagnosis of DIC by the presence of
microthrombi in the vascular bed. Infusion of activated protein C, anti-thrombin III, and
agents directed against TF activity are being investigated
as new therapeutic approaches. Replacement of deficient coagulation factors with FFP and
correction of the platelet deficiency with platelet transfusions may be necessary for
improvement or prophylaxis of the hemorrhagic tendency
of DIC prior to emergency surgical procedures. Elective surgery is deferred due to the
volatility of the coagulation mechanism in these patients.

98. Fibrinolytic Disorders
Primary fibrinolysis typically results in bleeding and may be caused by a deficiency in α2-
antiplasmin or PAIs, natural proteins that turn off activation of the fibrinolytic system. Laboratory
coagulation tests are normal with the exception of decreased
fibrinogen and increased FDP levels. Impaired clearance of tPA may contribute to prolonged
bleeding in individuals with severe liver disease. Patients with primary fibrinolysis are treated with
FFP therapy and antifibrinolytics. Differentiation must be made from the secondary fibrinolysis that
accompanies DIC, a hypercoagulable state that predisposes individuals to thromboembolism.
Dialysis patients with chronic renal failure show a fibrinolysis defect at the level of plasminogen
activation. Activators of the fibrinolytic system
(tPA, streptokinase, and urokinase) are frequently used to accelerate clot lysis in patients with acute
thromboembolism

99. IDENTIFICATION OF THE DENTAL PATIENT WITH A BLEEDING DISORDER
Patient report of a family history of bleeding problems may help identify inherited disorders of
hemostasis. In addition, a patient’s history of bleeding following surgical procedures, including dental
extractions, can help identify a risk. Identification of medications with hemostatic effect (e.g., oral
anticoagulants, heparin, ASA, NSAIDs, and cytotoxic chemotherapy) is essential, in addition to
identification of medications that may enhance their effect (e.g., antibiotics, antifungal medications). In
addition, one must identify medical conditions (e.g., liver disease, renal disease, hematologic
malignancy, cancer patients on chemotherapy, thrombocytopenia) that may predispose patients to
bleeding problems. In addition, a history of heavy alcohol intake is a risk factor for bleeding
consequences. Symptoms of hemorrhagic diatheses reported by patients may include frequent
epistaxis, spontaneous gingival or oral mucosal bleeding, easy bruising, prolonged bleeding from
superficial cuts, excessive menstrual flow, and hematuria.

100. ORAL COMPLICATIONS AND MANIFESTATIONS
Hemophiliacs may experience many episodes of oral bleeding over their lifetime. One report
includes an average 29.1 bleeding events per year serious enough to require factor replacement in
F VIII–deficient patients, of which 9% involved oral structures. The location of oral bleeds was as
follows: labial frenum, 60%; tongue, 23%; buccal mucosa, 17%; and gingiva and palate, 0.5% .
Bleeding occurrences were most frequent in patients with severe hemophilia, followed by moderate
and then mild hemophilia. They
most often resulted from traumatic injury. Bleeding events may also be induced by poor oral
hygiene practices and iatrogenic factors. The frequency of oral hemorrhage by location in people
deficient of F VIII and F IX has been reported as follows: gingiva, 64%; dental pulp, 13%; tongue,
7.5%; lip, 7%; palate, 2%; and buccal mucosa, 1%.167 Many minor oral bleeds, such as those from
the gingiva or dental pulp, can be controlled by local measures.

102. DENTAL MANAGEMENT CONSIDERATIONS
Local Hemostatic Measures
Local hemostatic agents and techniques include pressure, surgical packs,
vasoconstrictors, sutures, surgical stents, topical thrombin, and use of absorbable
hemostatic materials. Microfibrillar collagen fleeces (e.g., Avitene aid hemostasis when
placed against the bleeding bony surface of a well-cleansed extraction socket. It acts to
attract platelets, causing the release phenomenon to trigger aggregation of platelets into
thrombi in the interstices of the fibrous mass of the clot. Surgifoam and Gelfoam are
absorbable gelatin compressed sponges with intrinsic hemostatic properties. A collagen
absorbable hemostat manufactured as a 3 × 4–inch sponge (INSTAT, Ethicon Inc.) or
fabricated as a nonwoven pad or sponge are also useful adjuncts.

103.  Topical thrombin (Thrombogen, Ethicon Inc.), which directly converts fibrinogen in the
blood to fibrin, is an effective adjunct when applied directly to the wound or carried to
the extraction site in a nonacidic medium on oxidized cellulose. Surgical acrylic stents
may be useful if carefully fabricated to avoid traumatic irritation to the surgical site.
 Fibrin sealants or fibrin glue has been used effectively
Susceptibility to Infection
A hematoma form as a result of an anesthetic injection or other dental trauma or
spontaneously, use of a broad-spectrum antibiotic is indicated to prevent infection during
resolution.

104. Pain Control
The use of ASA and other NSAIDs for pain management is generally avoided in patients with
bleeding disorders due to their inhibition of platelet function and potentiation of bleeding
episodes.
Preventative and Periodontal Therapies
Periodontal health is of critical importance for the patient with coagulopathies because
hyperemic gingiva contributes to spontaneous and induced gingival bleeding, and periodontitis
is a leading cause of tooth morbidity, necessitating extraction. Individuals with bleeding
diatheses are unusually prone to oral hygiene neglect due to fear of toothbrush-induced
bleeding; Periodontal probing and supragingival scaling
and polishing can be done routinely. Careful subgingival scaling with fine scalers rarely warrants
replacement therapy. Severely inflamed and swollen tissues are best treated initially with
chlorhexidine oral rinses or by superficial gross débridement with ultrasonic or hand instruments
to allow gingival shrinkage prior to deep scaling.

105. Locally applied pressure and posttreatment antifibrinolytic oral rinses are usually successful in
controlling any protracted bleeding.
Restorative, Endodontic, and Prosthodontic Therapy
Endodontic therapy is often the treatment of choice
over tooth extraction for patients with severe bleeding disorders, due to the higher risk of
hemorrhage from the latter. Instrumentation and filling beyond the apical seal should be avoided.
Application of epinephrine intrapulpally to the apical area is usually successful in providing
intrapulpal hemostasis. Endodontic surgical procedures or implant placement surgeries require the
same factor replacement therapy as do oral surgical procedures.

106. Platelet Disorders
For thrombocytopenic patients (primary or secondary to systemic disease or treatment),
platelet transfusions may be required prior to dental extractions or other oral surgical
procedures with the ideal target of increasing platelet counts above 50,000/mm3.

107. References
1. Glick M. Burket's oral medicine. PMPH USA; 2015
2. Hall JE. Guyton and Hall textbook of medical physiology e-Book. Elsevier Health Sciences;
2015 May 31.
3. Kumar V, Abbas AK, Aster JC. Robbins basic pathology e-book. Elsevier Health Sciences;
2017 Mar 8.
4. Varela D, Tran D, Ngamdu KS, Trullender B, Mukherjee D, Abbas A. Rumpel-Leede
phenomenon presenting as a hypertensive urgency. Proceedings (Baylor University.
Medical Center). 2016 Apr;29(2):200.
5. Hasan S, Jamdar SF, Alalowi M, Al Beaiji SM. Dengue virus: A global human threat: Review
of literature. Journal of International Society of Preventive & Community Dentistry. 2016
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108. Liver factors
Gorlin sign
Dengue
Royal disease