This document discusses various coagulation disorders (coagulopathies) including primary and secondary hemostasis disorders as well as inherited and acquired coagulation disorders. Specific coagulation factor deficiencies are described such as hemophilia A, hemophilia B, von Willebrand disease, and factors VII, IX, and XI deficiencies. Treatment considerations for dental procedures in these disorders and coagulopathies induced by medications like heparin and warfarin are also summarized.

2. BY DR. HARSH VERMA

3. Introduction
 The normal haemostatic system limits blood loss by
precisely regulated interactions between components of
vessel walls, circulating blood platelet and plasma
proteins.
 Coagulation disorders (coagulopathies) are disruptions in
the body's ability to control blood clotting, an essential
function of the body designed to prevent blood loss.

4. Primary hemostasis disorder
1. Defect in platelet adhesion.
1. Von Willebrand disease.
2. Bernard- Soulier sondrome (GpIB/IX defect )
2. Defect in platelet aggeregation.
1. Decrease cyclooxygenase activity
1. Drug induced: Aspirin, NSAIDs
2. Congenital
2. Granule storage pool defects
1. Congenital
2. Acquired.
3. Uremia
4. Platelet coating ( eg. Penicillin or Paraproteins)
3. Defects in platelet coagulation activity
1. Scott’s syndrome

5. Secondary hemostasis disorder
1. Inherited coagulation defects
1. HemophiliaA
2. Hemophilia B
3. von Willebrand’s disease
2. Collagen vascular disorder
1. Ehler-danlos
2. Osler weber randu

6. INHERITED :
1. Defective inhibition of coagulation factor
1. Factor V Leiden (mutation of factor V)
2. Anti thrombin III deficiency.
3. Protein C deficiency.
4. Protein S deficiency.
2. Impaired clot lysis
1. Defibrogenemia
2. Plasminogen deficiency
3. tPA deficiency
4. PAI-I excess
3. Uncertain mechanism
1. Homocysteinuria

7. ACQUIRED
1. Diseases or syndromes
1. Lupus anticoagulant
2. Malignancy
3. Myeloproliferative disorder
4. Thrombotic thrombocytopenic purpura
5. Estrogen treatment
6. Hyperlipidemia
7. Diabetes mellitus
8. Hyperviscosity
9. Nephrotic syndrome
10. Congestive cardiac failure
11. Peroxysymal nocturnal hemoglobinuria

8. 2. Physiologic state
1. Pregnancy (post partum)
2. Obesity
3. Post operative state
4. Immobilization
5. Old age

9. Coagulation disorders
I. Inherited
I. von willebrand’s disease.
II. Hemophillia A (Classical hemophillia)
III. Hemophillia B (Christmas disease)
IV. Hemophillia C (factor IX deficiency)
II. Acquired
I. Liver disease
II. Uremia
III. Hyperglobulinemia

10. Classification according to
Burkit’s
1. Congenital coagulopathies
1. Hemophilia A
2. Hemophilia B
3. Hemophilia C
4. Von willebrand’s disease
5. Factor VII deficiency
2. Anticoagulant related coagulopathies
1. Heparin
2. Coumarin
3. Disease related coagulopathies
1. Liver disease
2. Vitamin K deficiency
3. Disseminated intravascular coagulation disorder.

11. Congenital disorders

12. Hemophilia A
(World Hemophilia Day 17 April)
 Hemophilia or hemophilia A is an inherited coagulation
disorder caused by deficiency of factor VIII.
 This genetic disorder is carried by females but most often
affects male offspring.
 It is characterized by spontaneous musculoskeletal bleeding.
 Most common
 1/10,000 individual

13.  Primary synthesis in liver, endothelial cells.
 Secondary synthesis in spleen, kidney, placenta.
 Plasma half life: 8-12 hrs.
 Non covalently bound to von Willebrand factor (vWF)

14. Genetics
It is X- linked recessive disorder with 36 exons .
a. Single base deletion
a. Potential loss of function with mild – moderate disease
b. Deletion and inversion
a. Severe hemophilia
Mild and severe hemophilia A are inherited through a complex
genetic system that passes a recessive on the female
chromosome.

15.  Women usually do not show signs of hemophilia but are carriers of the
disease.
 Each male child of the carrier has a 50 percent chance of having
hemophilia, and each female child has a 50 percent chance of passing
the gene on.

16. Clinical features
 Numerous large, deep bruises
and painful, swollen joints
caused by internal bleeding.
 Individuals with hemophilia
do not bleed faster, just
longer.

17.  If there is bleeding into the
neck, head, or digestive tract,
or bleeding from an injury,
emergency measures may be
required. Bleeding can be
spontaneous, occurring with
no obvious trauma.
 A person with mild hemophilia may first discover the disorder
with prolonged bleeding following a surgical procedure or
injury.

18. 1. If its congenital : unnoticed till 6 months of life due to
inactivity.
2. Normal level: 50% - 150% (percentage of normal factor
activity in blood) measured by clotting assay.

19. Types of hemophilia:
Sever : Less than 1% : Spontaneous heamarthrosis
Muscle weakness
1-2 bleeds every week
Moderate : 1-5% : Mild trauma / Surgery causes
heamarthrosis
Mild : 5- 40% : Major injury / Surgery causes
heamarthrosis results in
excessive bleeding.

20. 4. Most commonly affects knees , elbows, ankle, and hips.
5. Muscle hematoma generally seen in calf muscle and psoas
muscle.
7. Mild- moderate cases get undiagnosed where as severe
get diagnosed with in 2 year of life.

21. Management
1. Intra venous factor VIII concentrate which can be
obtained by blood donor plasma or by recombinant
technique which is much safer but costly.
2. Factor VIII is freezed and dried stable at 4°C.
3. Complete bed rest or splint.
4. After hemostasis achieved : Patient should be mobilized,
physiotherapy use to restore strength of surrounding
muscle.

22. Complications
Complications due to repeated hemorrhage:
I. Arthropathy of large joints eg. Knee and Elbow
II. Atrophy of muscle secondary to hemartoma.
III. Mono-neuropahthy resulting from pressure by
hemartoma.

23. Complication due to therapy:
I. Anti factor VIII antibody development.
II. Virus transmission
I. Hepatitis A virus – acute self limiting illness
II. Hepatitis B virus – 5-10% becomes chronic Hep B carrier
III. Hepatitis C virus – chronic progressive liver disease.
IV. Hepatitis D virus – only in those with HBsAg
V. Erythro virus – acute self limiting illness.

24. Note:
 Infusion of activated clotting factors eg. Factor VIIa or
factor eight inhibitory by passing activity (FEIBA) an
activated concentrate of factor II, IX, X : May stop
bleeding.
 If the dental extraction is necessary with basal factor VIII
concentrate of 10% - it’s level can be raised 3-5 times by
desmopressin (best I.V / nasal).
Single infusion with 10 days of tranexamic acid with
antibiotic pt can undergo extraction.
In case of othopedic surgery; requires two times daily
therapy for 14 days or longer.

25. HEMOPHILLIA B
(factor IX/ Christmas disease)
 Christmas disease or hemophilia B (factor IX deficiency)
is less common than hemophilia A with similar symptoms.
 Factor IX is produced in the liver and is dependent on
interaction with vitamin K in order to function properly.
Deficiency in the vitamin can affect the clotting factor's
performance as well as deficiency in the factor itself.
 Plasma half life is 18-24 hrs

26.  The severity of Christmas disease varies from mild to
severe, although mild cases are more common.
 The severity depends on the degree of deficiency of factor
IX.
 Hemophilia most often occurs in families with a known
history of the disease, but occasionally, new cases occur in
families with no apparent history.

27. Hemophilia B symptoms are similar to those of hemophilia
A, including
 numerous, large, and deep bruises and
 prolonged bleeding.
The more dangerous symptoms are those that represent
possible internal bleeding, such as
 swelling of joints
 bleeding into internal organs upon trauma.

28. Following oral surgical intervention:
 Canadian clinical practice guidelines recommend
replacement factor levels of 40 to 50% of
 Factor VIII (dose 20–25 U/kg) and
 Factor IX (dose 40–50 U/kg), used in conjunction with anti-
fibrinolytics.
 Gingival or dental bleeding unresponsive to anti-
fibrinolytics requires 20 to 30% clotting Factor VIII or
Factor IX.

30. Factor XI deficiency (Hemophilia
C)
 It is the second most common bleeding disorder among
women.
 1 in 100,000 people.
 Some factor XI deficiencies may result in bleeding long
after an injury, and some women experience prolonged
bleeding after childbirth.
 It occurs more frequently among certain ethnic groups,
with an incidence of about one in 10,000 among
Ashkenazi Jews.
 Nearly 50 percent of individuals with this disorder
experience no symptoms, but others may notice blood in
their urine, nose bleeds or bruising.

31. Von willebrand’s disease (vWD)
 von Willebrand's disease, a hereditary autosomal
dominant. disorder with prolonged bleeding time, is due to
a clotting factor deficiency and impaired platelet function.
 It is caused by a defect in the von Willebrand clotting
factor, often accompanied by a deficiency of factor VIII as
well.
 It is the most common inherited coagulation disorder.
 Mild disorder.
 Due to defect in chromosome no. 12
 In rare cases, it may be acquired.

32. Types
von Willebrand disease has been classified into 3 types:
Type 1 vWD: characterized by mild reduction in vWF
(partially quantitative deficiency) autosomal dominant
Type 2 vWD: loss of high molecular weight multimers
(qualitative defects). autosomal dominant
Type 3 vWD: characterized by severe reduction in vWF.
(virtually complete deficiency of vWF) autosomal
recessive.
Type 1 is most common type of disorder.
Type
3
vWD

33. Features
1. Easy bruising,
2. Bleeding from small cuts that stops and starts,
3. Abnormal bleeding after surgery, and
4. Abnormally heavy menstrual bleeding.
5. Nose bleeds and
6. Blood in the stool with a black, tarlike appearance are
also signs of von willebrand's disease.

35. Oral manifestations
1) Angina bullosa hemorrhagica
1) (Angina bullosa hemorrhagica (ABH) is the term used to
describe acute, benign, and generally subepithelial oral
mucosal blisters filled with blood that are not attributable to a
systemic disorder or hemostatic defect)
2) Oral hematoma
3) Tongue and palatal purpura
4) Ecchymotic lesions on lips, tongue and oral mucosa
5) Epistaxis
6) Spontaneous or post traumatic gingival hemorrhage
7) Post extraction hemorrhage.
8) TMJ heamarthrosis and arthropathy
Hemophilia C (Tmj heamarthrosis not seen)

36.  Von Willebrand's disease is diagnosed by ordering
laboratory tests that reveal a prolonged bleeding time,
absent or reduced levels of factor VIII, and a normal
platelet count. Other tests are likely be done to conform a
diagnosis.

38. Treatment

39. Factor VII deficiency
 Also called Serum Prothrombin Conversion Accelerator
(SPCA) Deficiency.
 One in 500,000 people may be affected
 It is often diagnosed in newborns because of bleeding into
the brain as a result of traumatic delivery.
 A deficiency of factor VII may cause varying levels of
bleeding severity in those affected.

40. Features
1. Women may experience heavy menstrual bleeding,
2. Bleeding from the gums or nose,
3. Bleeding deep within the skin,
4. And episodes of bleeding into the
stomach, intestines, and urinary tract.
Bleeding into the joints is rare but may also occur in some
individuals.

41. Hypo-prothrombinemia
Hypo-prothrombinemia is a congenital deficiency of clotting
factors that can lead to hemorrhage.
 Hypo-prothrombinemia is an inherited or acquired
deficiency in prothrombin, or factor II, a glycoprotein
formed and stored in the liver.
 Prothrombin, under the right conditions, is converted to
thrombin, which activates fibrin and begins the process of
coagulation.

42. Features
 Some individuals may show no symptoms, and others may
suffer severe hemorrhaging.
 Easy bruising,
 Profuse nose bleeds,
 Postpartum hemorrhage,
 Excessively prolonged or heavy menstrual bleeding, and
 Postsurgical hemorrhage may also result.
Acquired hypo-prothrombinemia usually arises from a vitamin
K deficiency caused by liver disease, newborn hemorrhagic
disease, or other causes.

43. Oral surgical procedure
 Pre operative factor levels at least 40%-50%.
 On out patient basis the aim is to increase level to
50-100% when using single bolous infusion.
 For post operative : factor concentrate with
desmopressin acetate , cryopercepitate or fresh
frozen plasma.
 3-5 days post surgical bleeding due to fibrinolysis
usually controlled by local measures.

44.  Continuous ooze from the socket: unstable fibrin
clot:- remove the clot and repack with an anti
fibrinolytic and hemoststic agent.
 Deficient factor activity level required for post
extraction hemostasis:
 3.5-25% for deciduous tooth.
 5.5- 20% for the permanent teeth.

45.  Factor levels can be raise in three ways:
 Intermittant
 Contineous I.V. infusion
 Single pre- operative factor concentratewith anti
fibrinolytic mouth wash
 anti fibrinolytic mouth wash:
 E-aminocaproic acid(Amicar) 250mg /ml 3 times daily
for 7-10 days.
 Tranexamic acid mouth wash : 4.8% is 10 times more
patent than E-aminocaproic acid

46.  Factor VIII can be sufficiently raised by
desmopressin acetate in mild to moderate cases of
hemophilia and VWD.
 Fibrin glue:
 cryoprecipitate with 10,000units
 Topical thrombin powder
 10ml normal saline (syringe)
 10ml of calcium chloride (syringe)
 Cryoprecipitate with calcium chloride forms gelatinous
glue.

47. Anticoagulant related
coagulopathy
1. Heparin
2. Coumarine (warfarine )

48. Heparin
 Heparin is a potent anticoagulant that binds with anti-
thrombin III to dramatically inhibit activation of Factor IX,
X, and XI, thereby reducing thrombin generation and fibrin
formation.
 The major bleeding complications from heparin therapy are
bleeding at surgical sites and bleeding into the retro-
peritoneum.
 Heparin has a relatively short duration of action of 3 to 4
hours, so is typically used for acute anticoagulation,
whereas chronic therapy is initiated with coumarin drugs.

49.  For acute anticoagulation, intravenous infusion of 1,000
units un-fractionated heparin per hour, sometimes
following a 5,000-unit bolus, is given to raise the aPTT to
1.5 to 2 times the pre-heparin aPTT .
 Alternatively, subcutaneous injections of 5,000 to 10,000
units of heparin are given every 12 hours.

50.  Newer biologically active low-molecular-weight heparins
administered subcutaneously once or twice daily are less
likely to result in thrombocytopenia and bleeding
complications.
 Protamine sulfate can rapidly reverse the anticoagulant
effects of heparin.

51. Coumarine
 Coumarin anticoagulants, which include warfarin and
dicumarol are used for anticoagulation to prevent
recurrent thrombotic phenomena (pulmonary embolism,
venous thrombosis, stroke, myocardial infarction), to treat
atrial fibrillation, and in conjunction with prosthetic heart
valves.
 They slow thrombin production and clot formation by
blocking the action of vitamin K.

52.  Levels of vitamin K–dependent Fs II, VI, IX, and X
(prothrombin complex proteins) are reduced.
 The anticoagulant effect of coumarin drugs may be
reversed rapidly by infusion of fresh frozen plasma, or
over the course of 12 to 24 hours by administration of
vitamin K. PT/INR is used to monitor anticoagulation
levels.

53. Disease related coagulopathy
 Liver disease
 Vitamin K related deficiencies
 Renal disease
 Disseminated intravascular coagulation.

54. Liver disease
 Hepatic 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
3 days, either intravenously or subcutaneously.
 However, infusion of FFP may be employed when
more immediate hemorrhage control is necessary,
such as prior to dental extractions.

55.  Cirrhotic patients with moderate thrombocytopenia
and functional platelet defects may benefit from
desmopressin acetate therapy.
 Antifibrinolytic drugs, if used cautiously, have
markedly reduced bleeding and thus reduced need for
blood and blood product substitution.

56. 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.
 Vitamin K deficiency is associated with the production of
poorly functioning vitamin K–dependent Fs II, VII, IX,
and X.
 Deficiency is rare but can result from inadequate dietary
intake, intestinal mal-absorption, or loss of storage sites
due to hepato-cellular disease.
 Biliary tract obstruction and long-term use of broad-
spectrum antibiotics, particularly the cephalosporins, can
cause vitamin K deficiency.

57.  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 Factor 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.

58. Renal disease
 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.

59.  The availability of cryoprecipitate and Desmopressin
acetate offers alternative effective therapy for patients
who require shortened bleeding times acutely in
preparation for urgent surgery.
 Conjugated estrogen preparations and recombinant
erythropoietin have also been shown to be beneficial
for uremic patients with chronic abnormal bleeding.

60. Disseminated intravascular
coagulation
 Disseminated intravascular coagulation, also known as
consumption coagulopathy, is not a disease in itself but a
clinical emergency that occurs as a result of other diseases
and conditions.
 This condition accelerates clotting, which ironically can
result in hemorrhage when the clotting factors are
exhausted.

61.  Disseminated intravascular coagulation (DIC) occurs
when the malfunction of clotting factors causes platelets
to form clots in small blood vessels throughout the body.
This action leads to depletion of clotting factors and
platelets, which are then not available at a site of injury
where clotting is needed.
 When DIC occurs, the individual bleeds abnormally even
though there is no history of coagulation abnormality.

62. Symptoms may include
minute spots of hemorrhage on the skin, and purple
patches or hematomas caused by bleeding under the skin.
Bleeding may occur at a surgical site or intravenous
injection (IV) sites.
Related symptoms include
 vomiting ;
 seizures;
 shortness of breath;
 severe pain in the back, muscles, abdomen, or chest; and,
 if prolonged or uncorrected can lead to shock and coma or
death.

63.  Not inherited and not a disease, DIC results from vascular
complications during pregnancy or delivery, surgery,
overwhelming infections, acute leukemia, metastatic
cancer , extensive burns , liver disease, pancreatitis,
trauma, snakebites, and other causes.
 For example, uterine tissue can enter the mother's
circulation during prolonged labor, introducing foreign
proteins into the blood, or the venom of some exotic
snakes can activate one of the clotting factors.

64.  Severe head trauma can expose blood to brain tissue.
Regardless of the specific cause of DIC, the results are a
malfunction of thrombin (an enzyme) and prothrombin (a
glycoprotein), which activate the fibrinolytic system,
releasing clotting factors in the blood.
 DIC can alternate from hemorrhage to thrombosis, and
both can exist, which further complicates diagnosis and
treatment.

66. References
 Harrison text book of medicine
 Burkits oral medicine