BLEEDING AND CLOTTING DISORDERS

BLEEDING AND CLOTTING
DISORDERS
Presented by-
Dr. SHILPY JAIN

CONTENTS
• INTRODUCTION
• HAEMOSTASIS
• PLATELETS
• COAGULATION FACTORS
• FIBRINOLYTIC SYSTEM
• BLOOD INVESTIGATIONS
• CLASSIFICATION OF BLEEDING DISORDERS
• DISORDERS OF VESSEL WALL ABNORMALITY
• DISORDERS OF PLATELETS
• COAGULATION DISORDERS
• SUMMARY
• REFERENCES

INTRODUCTION
• Blood must be maintained in a fluid state in order to
function as a transport system, must also able to solidify
to form a clot following vascular injury.
• Hemostasis is a complex process, involves interactions
between blood vessel wall, platelets and coagulation
factors.
Colledge, N. R., Walker, B. R., Ralston, S., & Davidson, S. (2010). Davidson's principles and
practice of medicine. Edinburgh: Churchill Livingstone/Elsevier.

HAEMOSTASIS
• The term haemostasis is derived from the
Greek word haem= blood and stasis=halt.
• Haemostasis is defined as “ stoppage of
bleeding by fibrin clot plugging”
• It is a complex natural physiological response.
CL.Ghai.A Textbook of Practical Physiology 8th Edition.Jaaypee
Publishers

STEPS IN HAEMOSTASIS
Injury to the vessel wall
Early haemostatic response
Platelet plug
Platelet Aggregation
Fibrin clot formation
Fibrinolysis
Colledge, N. R., Walker, B. R., Ralston, S., & Davidson, S. (2010). Davidson's principles
and practice of medicine. Edinburgh: Churchill Livingstone/Elsevier.

Kumar, Abbas, Aster (2013) Robbins Basic Pathology, 9th Edition

Colledge, N. R., Walker, B. R., Ralston, S., & Davidson, S. (2010). Davidson's principles and practice of medicine.
Edinburgh: Churchill Livingstone/Elsevier
PLATELETS

COAGULATION SYSTEM
• Coagulation system consists of a cascade of soluble
inactive zymogen proteins designated by Roman
numerals.
• When proteolytically cleaved and activated each is
capable of activating one or more components of the
cascade.
• The end point of clotting mechanism is formation of
fibrin
CL.Ghai.A Textbook of Practical Physiology 8th Edition.Jaaypee Publishers

SN Chugh. A Textbook of Clinical Medicine 2nd Edition. Arya Publications
SCHEMATIC
REPRESENTATION
OF PATHWAYS OF
COAGULATION
SYSTEM AND
FIBRINOLYTIC
SYSTEM

FIBRINOLYTIC SYSTEM
• Fibrinolysis is a process of dissolution of fibrin clot and
thrombus by activating tissue thrombo plasminogen
activator released from endothelial cells.
Plasmin

PRIMARY
HAEMOSTASI
S
SECONDARY
HAEMOSTASIS

DISTINGUISHING FEATURES BETWEEM DISORDERS OF
PLATELETS , VESSEL WALL AND COAGULATION
FINDINGS DISORDER OF
PLATELETS OR VESSELS
DISORDER OF
COAGULATION
Petechiae Characteristic Rare
Deep dissecting Hematoma Rare Characteristic
Superficial ecchymoses Characteristic, usually small
and multiple
Common, usually large and
solitary
Haemarthrosis Rare Characteristic
Delayed Bleeding Rare Common
Bleeding from superficial cut
and scratches
Profuse Minimal
Sex of patient
Positive family history
Relatively more common in
females
Rare
80-90% males
Common
SN Chugh. A Textbook of Clinical Medicine 2nd Edition. Arya Publications

Srivathsa SH. Oral Ecchymosis in elderly: Senile purpura. J Indian Acad Oral Med Radiol 2015;27:331-3
PETECHIAE PURPURA ECCHYMOSES

TESTS FOR HAEMOSTASIS:
• Bleeding time
• Platelet count
• Clotting time
• Prothrombin time.
• Activated Partial thromboplastin time

BLEEDING TIME
• The bleeding time test is a useful tool to test for platelet plug formation
• Prolonged bleeding time
Platelet count below 50,000/µl
• Four procedures are currently in use for determining the bleeding time:
1. The Duke method.
2. The Ivy Method.
3. The Mielke Method.
4. The Simplate or Surgicutt Method.
John P. Greer et al, Wintrobe’s Clinical Haematology, 12th edition

CLOTTING TIME
It is the time taken from the puncture of the blood vessel to the formation of fibrin
thread.
A)Capillary glass tube method: Here the blood is collected in capillary tube and
total time is noted to form fibrin threads on breaking tube every 30 seconds
Normal – 3-8 minutes
B) Lee & White method: Here venous blood is collected in 8mm diameter glass
tube, rocked in a water bath at 37° C & time is noted from the time of venous
puncture till blood stops flowing
Normal – 6-12 minutes
John P. Greer et al. Wintrobe’s Clinical Haematology, 12th edition

HESS TEST or RUMPEL-LEEDE TEST
• Used to assess capillary fragility.
• Pressure is applied to the forearm with a blood pressure cuff inflated to
between systolic and diastolic blood pressure for 10 min.
• After removing the cuff, the no. of petechiae in 5 cm diameter circle of
the area under pressure is counted.
• Normal- less than 15 petechiae are seen.
• More than 15- indicates poor platelet function
• Thrombocytopenia, scurvy.

PROTHROMBIN TIME
• Measures the activity of certain clotting factors (Extrinsic
pathway)
• Monitor patients on blood thinner medicines like
Coumadin
• Prolonged :
Liver diseases
Congenital deficiency of coagulation factors
• Normal: 9-12 seconds

ACTIVATED PARTIAL THROMBOPLASTIN
TIME (APTT)
• Kaolin Cephalin Clotting time
• Screening test to evaluate bleeding disorders
• Number of seconds taken for a fibrin clot to form in blood
sample
• Measures efficacy of both intrinsic and common coagulation
pathway
• High in long term antibiotic use and viral illness
• Normal- 26-36 seconds

Investigation Normal range Situations in which tests
maybe abnormal
Platelet count 1,50,000-4,40,000/mm3 Thrombocytopenia
Bleeding time 1-6 min Thrombocytopenia
Abnormal platelet function
Von willebrand disease
Vascular and connective
tissue abnormalities
Prothrombin time 9-12 sec Deficiencies of factors
II,V,VII or X.
Activated partial
thromboplastin time (APTT)
26-36 secs Deficiencies of factor
II,V,VIII,IX,X,XI,XII.
Fibrinogen concentration 1.5-4.0g/L Hypofibrinogenemia.
TEST FOR ASSESSMENT OF A CASE WITH BLEEDING

CLASSIFICATION OF DISOREDRS
BLEEDING DISORDERS:
1.Vascular abnormalities disorders
2. Platelet disorders.
CLOTTING DISORDERS:
1. Congenital : Hemophilia A, Hemophilia B, Von willebrand’s disease.
2. Acquired: Vitamin K deficiency
3. Fibrinolytic disorders.
4. Drug induced

BLEEDING DISORDERS
• Bleeding disorders are due to altered ability
of blood vessels and platelets to maintain
haemostasis.
• May be inherited due to genetic transmission
or acquired secondary to diseases.
Colledge, N. R., Walker, B. R., Ralston, S., & Davidson, S. (2010). Davidson's principles and practice of
medicine. Edinburgh: Churchill Livingstone/Elsevier.

BLEEDING DISORDERS
1. Disorder of vessel wall abnormalities
2. Qualitative disorders of platelets
3. Quantitative disorders of platelets

DISORDER OF VESSEL
WALL ABNORMALITIES

BLEEDING DISORDER DUE TO VASCULAR ABNORMALITIES ( NON
THROMBOCYTOPENIC PURPURA)
I AUTOIMMUNE
1. Allergic purpura
2. Drug- induced vascular purpura
3. Purpura fulminans
II INFECTIONS
1. Bacterial ( meningococcemia and septicaemia , typhoid fever,diphtheria, tuberculosis, endocarditis, bacterial
products)
2. Viral ( smallpox, influenza, measles)
3. Rickettsia
4. Protozoal ( Malaria, toxoplasmosis)
III STRUCTURAL MALFORMATIONS
1. Hereditary hemorrhagic telangiectasia
2. Hereditary disorders of connective tissue ( Ehlers- Danlos syndrome, osteogenesis imperfecta)
3. Acquired disorders of connective tissue ( Scurvy, corticosteroid purpura, senile purpura)
IV MISCELLANEOUS
1. Autoerythrocyte sensitization and related syndromes
2. Paraproteinemias
3. Purpura simplex and related disorders
4. Purpura in association with certain skin diseases Shafers textbook of Oral Pathology. 5th Edition.

STRUCTURAL MALFORMATIONS:
1. Hereditary hemorrhagic Telangiectesias
2. Hereditary disorders of the connective
tissue: Ehlers-Danlos syndrome.
3. Acquired diseases of the Connective tissue:
Scurvy
Shafers textbook of Oral Pathology. 5th Edition.

HEREDITARY HEMORRHAGIC TELANGIECTASIA
(Osler-weber-rendu-syndrome,Rendu-osler-Weber syndrome, heredofamilial
angiomatosis, familial hemorrhagic angiomatosis, osler’s disease)
• Autosomal dominant disorder.
• Effects 1 in 5000 to 18,000 people.
• Mucocutaneous disorder.
• Characterised by Arteriovenous malformations
1.Brad .W. Neville. Textbook of Oral and Maxillofacial Pathology .South Asian Edition.
2. Shafers textbook of Oral Pathology. 5th Edition.

ETIOPATHOGENESIS:
Mutation of either one or two different genes at two
separate loci is responsible for the condition.
• 9q33-q34
• 12q
HHT 1- mutation of endoglin ( ENG) gene on
chromosome 9.
HHT 2- mutation of activin receptor-like kinase-1
(ALK1-ACVRLI) gene on chromosome 12.
Encoding
for:
Homodimeric
integral
membrane
glycoprotein
Surface receptor
Transforming
growth factor
betaShafers textbook of Oral Pathology. 5th Edition.

Factor Role
Transforming growth factor beta Tissue repair and angiogenesis
Mutations in the genes:
Development of Abnormal
vasculature
Defect in endothelial cell junctions
Endothelial cell degeneration
Weakness of the perivascular
connective tissue
Dilation of the capillaries and post
capillary venules
Telangiectases
Arteriovenous Malformations
Aneurysms

CLINICAL FEATURES
• One of the earliest sign of the disease : epistaxis and bleeding
from the oral cavity
• Involvement of oral mucous membrane
• Further examination- nasal and oropharyngeal mucosae
exhibiting numerous scattered red papules 1 to 2 mm in size.
• Spider-like telangiectasias are present .
• Associated with CREST syndrome.

 Systemic involvement:
Hand , neck , chest and feet
Gastrointestinal mucosa, genitourinary tract,
conjunctival mucosa.
 Oral manifestations:
Sites-vermillion zone of lips, tongue, and buccal
mucosa , palate, floor of the mouth.
Scattered red papules.

Seung-Tae Lee et al, Clinical Features and Mutations in the ENG, ACVRL1, and SMAD4 genes in Korean Patients with Hereditary Hemorrhagic TelangiectasiaJ
Korean Med Sci. 2009 Feb;24(1):69-76

Lee HE, Sagong C, Yeo KY, Ko JY, Kim JS, Yu HJ. A Case of Hereditary Hemorrhagic Telangiectasia. Annals of
Dermatology. 2009;21(2):206-208. doi:10.5021/ad.2009.21.2.206.

DIAGNOSIS AND LABORATORY FINDINGS
• Criteria for diagnosis:
Recurrent spontaneous epistaxis
Telangiectasias of mucosa and skin
AVM’s involving lungs, liver.
Family history.
• BT & CT are normal.
• With severe bleeding, Mild anemia & Thrombocytopenia
Shafers textbook of Oral Pathology. 5th Edition

TREATMENT
• Spontaneous haemorrhage – Pressure packs
(nasal bleeding)
• Angiomatous and telangiectatic areas -
Cauterized, treated with X ray radiation or
surgically excised

EHLERS-DANLOS SYNDROME
(Tenascin-X deficiency syndrome, lysyl hydroxylase
deficiency, Cutis hyper elastica)
• Inherited connective tissue disorder.
• Genetic defect of collagen synthesis
• Affect skin, joints and blood vessels
• Autosomal dominant.
• Type IV associated with arterial rupture and visceral
perforation Shafers textbook of Oral Pathology. 5th Edition

ETIOPATHOGENESIS
• Subtypes caused by
1.Mutations in genes coding for collagens type I,III and V.
2. Mutations in genes encoding for enzymes involved in the
post translational modification of I,III and V collagens.
Type I and II-Mutation in COL5A1, COL5A2 and Tenascin – X
genes
Type IV-Decreased amount of type III collagen
Type V and VI - Deficiency of hydroxylase and lysyl oxidase

• Hyperelasticity of skin
• Hyperextensibility of the joints
• Fragility of the skin and blood vessels
Young patient is often mistaken for a victim of child abuse.
Life expectancy is reduced because of aortic aneurysm
formation and rupture.
CLINICAL FEATURES:
Easy bruising
Defective
healing of
skin

Type Feature
EDS I and EDS III Hyperextensibility of skin and
joints
EDS IV Ecchymotic type (rupture of
large arteries and intestine)
• Hypertelorism
• Wide nasal bridge
• Epicanthic folds
• Protruding ears
• Frontal bossing
• Bilateral bleeding in
cheeks

ORAL MANIFESTATIONS
• Gorlin sign – patients (50%) touch the tip
of the nose with their tongue.
• Easy bruising and bleeding and bleeding
during minor manipulations of the oral
mucosa.
• Hypermobility of the TMJ , repeated
dislocations of the jaw

LABORATORY FINDINGS
• Normal BT & CT.
• Abnormal capillary fragility test
(Hess test) Rumple-leede test.

SCURVY
• Vitamin C also called as L-ascorbic acid.
• Water soluble vitamin.
• Richest sources are : vegetables , citrus fruits ( lemon, guava,
orange , grapes)
• Dietary intake : According to National Health and Nutrition
examination survey ( NHANES)-
• Infants: 35mg/day
• Adults: 60mg/day. Shafers textbook of Oral Pathology. 5th Edition.

• Deficiency of Vit C causes – Scurvy.
• Scurvy was first described in the 5th century BC by
Hippocrates.
• Scurvy occurs with a deficiency of < 10mg/day .
• Severe deficiency of Vit C causes – Scorbutic Gingivits

ROLE OF VIT C:
• Collagen synthesis
• Vit C is a cofactor in diverse biological processes
• Highest tissue concentration of Vit C is found in
pituitary and adrenal glands.
Agarwal, Anil et al. Scurvy in pediatric age group – A disease often forgotten?
Journal of Clinical Orthopaedics & Trauma, Volume 6, Issue 2, 101 - 107

Sandhu SV et al. Collagen in health and disease. J Orofac Res 2012; 2(3); 153-159

Agarwal, Anil et al. Scurvy in pediatric age group – A disease often forgotten?
Journal of Clinical Orthopaedics & Trauma, Volume 6, Issue 2, 101 - 107

ORAL MANIFESTATIONS
• Interdental and marginal gingiva- swollen, bright red
• In severe cases, Gingiva is boggy , ulcerates and bleeds
• Foul breath
• Loss of bone and loosening of teeth

.
LABORATORY FINDINGS:
• Increased bleeding time.
• Abnormal capillary fragility test (Hess test)
Rumple-leede test.
• Infants and children are usually treated with vitamin C 100–
300 mg daily and adults 500–1000 mg daily for 1 month
TREATMENT :

THROMBOCYTOPE
NIA
THROMBOCYTOSIS
1) Idiopathic/Immune
thrombocytopenic
purpura*
1) Benign or reactive
process
2) Thrombotic
thrombocytopenic
purpura*
2) Myeloproliferative
disorders
3) Wiskoff aldrich
syndrome*
4) Heparin induced
thrombocytopenia
QUANTITATIVE
CLASSIFICATION OF PLATELET DISORDERS
QUALITATIVE
CONGENITAL ACQUIRED
1) Glanzmann’s
Thrombasthenia*
1) Drug induced*
2) Bernard- Soulier
syndrome*
2)Acute or chronic
leukemias
3) Storage granule
abnormalities
3) Haemorrhagic
thrombocythaemia
4)Myelofibrosis
5)Anaemia
J Ochei, A Kolhatkar. Medical Laboratory Science Theory and Practice, 2000

IMMUNE THROMBOCYTOPENIC PURPURA(ITP)
(Werlhof’s disease, Idiopathic purpura)
• Autoimmune disorder characterized by antibody-mediated platelet destruction
and decreased platelet production.
• Paul Gottlieb Werlhof in 1735 wrote initial report of the purpura of ITP.
Shafers Textbook of Oral Pathology.5th edition.
ACUTE CHRONIC
Self limited Common
Children Adults (Female predilection) (20-40years)
Viral infections Unknown
Spontaneous resolution in 2
months
Longer than 6 months

PATHOPHYSIOLOGY OF ITP
Hirokazu Kashiwagi , Yoshiaki Tomiyama .Pathophysiology and management of primary immune thrombocytopenia. Int J Hematol (2013)
98:24–33

CLINICAL FINDINGS
• Spontaneous purpuric or hemorrhagic lesions (petechiae to ecchymosis).
• Bleeding from nose ( Epistaxis).
• Bleeding in urinary tract (Hematuria).
• Bleeding in GIT (melena or hematemesis)
• Complication- Intracranial hemorrhage
• According to Wintrobe, 80% before 30 years
Shafers Textbook of Oral Pathology.5th edition

ORAL MANIFESTATIONS
• Severe and profuse gingival
hemorrhage
• Petechiae on the palate
• Contraindicates many surgical
procedures

LABORATORY FINDINGS
• Platelet count- below 60,000platelets/cu.mm.
• Prolonged BT ( 1hr or more)
• CT is normal.
• Tourniquet test- Strongly positive

TREATMENT:
Hirokazu Kashiwagi , Yoshiaki Tomiyama .Pathophysiology and management of primary immune thrombocytopenia.
Int J Hematol (2013) 98:24–33

THROMBOTIC THROMBOCYTOPENIC PURPURA
(Moschcowitz disease)
• Uncommon form
• Life-threatening multisystem disorder.
• First described by Eli Moschcowitz in 1924.
• Common in adults
• Associated with pregnancy, HIV, cancer, bacterial infection
and vasculitis, bone marrow transplantation and drugs.

J Evan Sadler Pathophysiology of thrombotic thrombocytopenic purpura. BLOOD, 7 SEPTEMBER 2017 x VOLUME 130, NUMBER 10

• Deficiency of a protease enzyme ADAMTS 13.
• TTP and Haemolytic uremic syndrome are thrombotic
microangiopathies characterized by microvascular lesions with
platelet aggregation
• HUS distinguished from TTP by absence of neurologic symptoms,
acute renal failure and occurrence in children

CLINICAL FEATURES
• Occurs in young adults.
• More common in females than males..
• Thrombocytopenia
• Hemolytic anemia
• Fever
• Transitory neurologic dysfunction
• Renal failure
PENTAD OF
SYMPTOMS

LABORATORY FINDINGS
• Reduced platelet count.
• PTT and aPTT normal.
• Urine analysis show
proteinuria and microscopic
hematuria

TREATMENT
• Corticosteroids*
• Platelet aggregation inhibitors*
• Splenectomy
• Blood transfusions

WISKOTT-ALDRICH SYNDROME
• X-linked recessive .
• Severe congenital Immunoglobulin M deficiency.
• Exclusively in Boys
• Deficiency of X-linked genetic defect in a protein termed
Wiskott-Aldrich syndrome protein (WASp).

Davis BR, Candotti F. Revertant somatic mosaicism in the Wiskott-Aldrich syndrome. Immunol Res. 2009;44(1–3):127–131
WASp FUNCTIONS
• Actin polymerization
• Cytoskeletal
arrangement
• Signaling

CLINICAL FINDINGS
• Thrombocytopenic purpura.
• Eczema
• Increased susceptibility to infection due to cellular and humoral
immunodeficiency.
• Petechiae, purpuric rash, ecchymoses - Early signs

• Patients unable to form antibody against
polysaccharide containing organisms such
as pneumococci , H. influenza and
coliform bacilli
• T and B cell abnormalities

ORAL MANIFESTATIONS:
• Spontaneous bleeding of the gingiva.
• Palatal petechiae

LABORATORY FINDINGS
• Reduced platelet count- 18,000-
80,000/cumm.
• Prolonged Bleeding time
TREATMENT
• Platelet transfusions
• Bone marrow transplantation
• Transfer factor

THROMBOCYTOSIS
(Thrombocythemia)
PRIMARY SECONDARY
• Essential
• Unknown etiology
• Reactive
• Traumatic injury
• Inflammatory conditions
• Surgical procedures
• Overproduction of
proinflammatory cytokines IL-
1, IL-6 and IL-11 (Chronic inf)
• Elevated C-reactive protein, G-
CSF, GM-CSF ( Reactive
conditions)

CLINICAL FEATURES
• Bleeding tendency
• Epistaxis
• Bleeding into GIT, GUT, CNS
• Haemorrhage into skin
ORAL MANIFESTATIONS
• Spontaneous gingival bleeding
• Prolonged bleeding after dental extractions

LABORATORY FINDINGS
• Platelet count may increase upto 14,000,000 cells / cumm
• Bleeding time prolonged
• Clotting time , prothrombin time , tourniquet test - normal
TREATMENT
• Aspirin
• Corticosteroids

GLANZMANN THROMBASTHENIA
(Familial thrombasthenia)
• Hereditary chronic hemorrhagic disorder
• Autosomal recessive trait.
• First identified in 1918 by a pediatrician from Switzerland, Dr.
Eduard Glanzmann
PATHOGENESIS:
• Abnormality in the genes for glycoproteins IIb/IIIa
• Defect in platelet aggregation

CLINICAL FEATURES:
• Spontaneous bleeding.
• M=F.
• Purpuric hemorrhages of skin are common.
• Epistaxis
• GIT bleeding.
• Hemarthrosis
• Menorrhagia
Shafer’s Textbook of Oral PATHOLOGY.5th edition.

• Spontaneous bleeding from
the gingiva.
• Palatal petechiae.

• Prolonged BT.
• Clot retraction is impaired*
• Platelet count, CT are normal.
TREATMENT
• Microfibrillar collagen preparation with
fibrinolytic inhibitors
• Recombinant factor VIIa

THROMBOCYTOPATHIC PURPURA
(Bernard-Soulier syndrome ,Thrombocytopathia)
• Rare disease
• Unknown etiology
• Qualitative defects( functional defect )in the blood
platelets.
PATHOGENESIS :
• Abnormality in the genes for glycoprotein Ib.
• Defect in platelet adhesion

CLINICAL FEATURES:
• Spontaneous ecchymosis
• Epistaxis
• Bleeding into GIT.
• Gingival bleeding
• Mucosal ecchymoses

LABORATORY FINDINGS
• Prolonged BT and CT.
• Platelet count is normal.
TREATMENT

DRUG INDUCED
DRUGS EXAMPLES SIDE EFFECTS
Antiplatelet drugs Asprin,
Dipyrimadol,Clopidogre
l
Increased bleeding
Anticoagulant drugs Heparin,Low mol.wt.
Heparin, Warfarin
Increased CT
Heparin induced
Thrombocytopenia
Thrombolytics Amistreplase,
Urokinase, Reteplase
Bleeding and
allergic reactions.
Padmaja Udaykumar.Textbook of Pharmacology for Dental and allied Health Sciences.3rd
edition.Jaypee Publishers.

COAGULATION FACTOR DEFICIENCIES
CONGENITAL:
• Hemophilia A and B
• Von Willebrand’s disease
• Other factor deficiencies (rare)
ACQUIRED:
• Liver disease
• Vitamin K deficiency
• Disseminated intravascular coagulation
J Ochei, A Kolhatkar. Medical Laboratory Science Theory and Practice, 2000

ACQUIRED COAGULATION
DISORDERS

LIVER DISEASE
• Liver plays a major role in the clotting process.
• Site for the synthesis of clotting factors and their
inhibitors.
• Liver disease causes impaired hemostatic
function
• Most common finding of liver disease is
thrombocytopenia.

CLINICAL FINDINGS
• No abnormal bleeding
• Gastrointestinal haemorrhage
ORAL MANIFESTATIONS
• Recurrent ecchymosis
• Epistaxis
• Severe generalized bleeding

• Decreased platelet count.
• Increased levels of PT , aPTT
TREATMENT:
• Fresh frozen plasma
• Cryoprecipitate
• Recombinant factor VIIa
• Thrombopoietins ( Eltrombopag)

VITAMIN-K DEFICIENCY:
• Hemorrhagic disease of newborn
• Now uncommon due to administration of vitamin k at birth
• Vitamin-K ( Koagulation vitamin), Fat soluble vitamin.
• Noticed by Dam in the year 1929.
• Involved in both intrinsic and extrinsic pathway of clotting.

ROLE OF Vit –K:
• Necessary for post-translational
carboxylation of glutamic acid
necessary for calcium binding to
proteins like prothrombin, factor
II,VII,IX and X.
• SOURCE: green leafy vegetables, butter
,liver, milk , vegetable oils.
• REQUIREMENTS:
1-2mcg/kg.

CLINICAL FEATURES
• Bleeding is severe
• Melena
• Large cephalohematomas
• Bleeding from umbilical stump
ORAL MANIFESTATIONS
• Gingival bleeding.
• PT levels < 35% - bleeding immediately after tooth
brushing.
• PT< 20 % - spontaneous gingival hemorrhage.

LABORATORY DIAGNOSIS
• Increased Prothrombin time, partial
thromboplastin time
TREATMENT
• Vitamin K1 ( 0.5 -1.0 mg IM)
• Transfusion of plasma

DISSEMINATED INTRAVASCULAR COAGULATION
• DIC is an acquired syndrome
characterized by the systemic activation
of coagulation and results in the
formation of thrombi throughout the
microcirculation

ETIOLOGY
• Obstetric complications
• Infections
• Neoplasms
• Disorder of the hematopoietic
• Vascular disorders
• Massive tissue injury
• Snake bite
• Trauma

PATHOPHYSIOLOGY

ACUTE CHRONIC
Generalized ecchymoses
Petechiae
Bleeding from previous
venepuncture site
Extensive ecchymoses of
extremities
Without petechiae
Haemorrhagic skin lesions Renal impairment, neurologic
symptoms
Geographic acral cyanosis Trousseau sign
Epistaxis Recurrent episodes of epistaxis
Gastrointestinal bleeding
Pulmonary haemorrhage
Hematuria
Serious internal mucosal bleeding
Thrombosis
CLINICAL FEATURES

LABORATORY FINDINGS
• Prolonged aPTT, PT.
• platelet count less than 50,000/cu.mm.
• Increased fibrin split products*
TREATMENT
• Anticoagulants (Heparin)
• Fresh frozen plasma

CONGENITAL COAGULATION
DISORDERS

HEMOPHILIA
Bleeder’s disease , disease of the Hapsburg, the disease of Kings.
• Hereditary disorder
• Defect carried by X chromosome and transmitted as a gender linked
Mendelian recessive trait
• Broadly divided into
1. Hemophilia A or classic hemophilia.( def of factor VIII)
2. Hemophilia B or christmas disease ( def of factor IX)
3. Hemophilia C or Rosenthal syndrome ( def of factor XI)
Kumar ,Abbas,Fausto. Acute and Chronic Inflammation:Robbins and Cortan Pathologic Basis Of Diseases, 6th edition; 2005.p
50-87.

GENETICS
Hemophilia A Hemophilia B Hemophilia C
Genetic abnormalities
include deletions ,
abnormalities with stop
codons, frame shift
defects.
Partial and total
deletions ,missense
mutations result in
decrease in or absence
of factor IX.
Mutations of factor XI
causes failure, reduced
production of active
protein and rarely
production of
abnormal molecule.
• Genes for factor VIII and factor IX are located on the long arm of the X
chromosome in bands q28 and q27
• Genes for factor XI located on chromosome 4

Hemophilia A
• 80-85% of hemophiliacs.
• Occurs due to deficiency of factor
VIII
• X-linked recessive.
• Females are carriers and affects
males.
• Gilchrist in 1961- reported a case in
a female patient.
• Effects 1 in every 10,000 patients.
• Positive family history.
• Seen in the Great Britain’s Queen
Victorias’s family-Royal disease.

STRUCTURE AND FUNCTION OF FACTOR VIII–VON
WILLEBRAND FACTOR (VWF) COMPLEX
Kumar ,Abbas,Fausto. Acute and Chronic Inflammation:Robbins and Cortan Pathologic Basis Of Diseases, 6th
edition; 2005.p 50-87.

Hemophilia B
• Also called as Christmas disease
(named after the 1st patient in whom it
was described)
• X linked disorder.
• 14% of the patients.

CLINICAL FEATURES
• Persistent bleeding , either spontaneous or
following slight trauma.
• Hemorrhage into the subcutaneous tissues,
internal organs, and joints is a common
feature.
• Usually present from birth but becomes
clinically apparent after several years.

Classification of hemophilia( ISTH criteria)
Degree
of
severity
Factor
activity
percentage
Clinical presentation
Severe <1 Severe Spontaneous
bleeding and muscle
hematomas, hemarthrosis.
Moderat
e
1-5 Moderate bleeding with
minimal trauma or surgery
Mild >5 Major injury or surgery
results in mild bleeding.
ISTH- International Society on Thrombosis and Haemostasis

ORAL MANIFESTATIONS
• Hemorrhage from any site in the oral cavity is a common
finding.
• Gingival hemorrhage may be massive and prolonged.
• Tooth eruption and exfoliation shows severe prolonged
hemorrhage
• Mandibular ‘pseudotumor’ reported by Stoneman and Beirl- a
condition in which there is subperiosteal bleeding , with reactive
new bone formation causing tumor – like expansion of bone.

LAB FINDINGS
• Prolonged coagulation time.
• BT is normal
• PT and platelet aggregation is normal.
• aPTT is prolonged.

MANAGEMENT
• Pre-operative transfusion of whole
blood.
• Administration of factor VIII
concentrate by IV infusion

VON WILLEBRAND’S DISEASE
(Pseudohaemophilia, vascular hemophilia, vascular purpura)
• Hereditary bleeding disorder first described by
Erik Adolf Von Willebrand in 1926.
• Autosomal dominant disorder.
• Manifested in both males and females.
• Characterized by prolonged bleeding time.

QUANTITATIVE AND QUALITATIVE ABNORMALITY OF THE VWF.

CLASSIFICATION OF vWD
• Type 1: characterized by a partial quantitative
decrease of normal vWF and factor VIII.
• Type 2: vWD is a variant of the disease with primarily
qualitative defects of vWF . It is either autosomal
dominant or recessive.
• Type 3: most severe and rarest form of vWD ,
characterized by marked deficiency of both vWF and
factor VIII.

CLINICAL FEATURES
• Prevalence rate is 0.9-1.3 per cent.
• Many children are asymptomatic and are
diagnosed as a result of positive family history.
• Excessive bleeding.
• Sites: nose ,skin and gingiva.

ORAL MANIFESTATIONS
• Gingival bleeding in 39 per cent of the
cases.
• Some instances there is spontaneous
bleeding and other cases bleeding
occurs as a result of brushing.

LABORATORY FINDINGS
• Increased bleeding time (BT)
• PT , CT ,aPTT are normal
• Positive tourniquet test in 50%
cases

MANAGEMENT
• Transfusion of plasma and / or
antihemophilic factor
• Desmopressin

Disease Deficiency Role
Parahaemophila Factor V
(Proaccelerin)
Conversion of
prothrombin to
thrombin
Afibrinogenemia
Hypofibrinogene
mia
Fibrinogen Helps in blood
clotting

FIBRIN – STABILIZING FACTOR DEFICIENCY
• Recognized by Duckert in 1960
• Autosomal recessive disease
• Mutations in gene encoding the catalyst α subunit located on
chromosome 6
• Activated factor XIII cross links fibrin or stabilizes it by
transamidation

CLINICAL FEATURES:
• Severe postsurgical bleeding episodes
• Hemarthrosis
• Defective wound healing
• Bleeding from the stump of umbilical cord
within first days to weeks of life * (seen in 80%)
• Bleeding from mouth and gums during teething

LABORATORY FINDINGS
• Measurement of clot stability- commonly used
screening test ( Clot Solubility test )
• Factor XIII α and Factor XIII β antigen levels
by means of ELISA techniques

TREATMENT:
• Plasma , cryoprecipitate and factor
XIII concentrate

SUMMARY
BLEEDING DISORDERS CLOTTING DISORDERS
VESSEL WALL
ABNORMALITIES
Autoimmune
Infections
Structural
malformations
QUALITATIVE
DISORDERS OF
PLATELETS
Congenital:
• Glanzmann’s
Thrombasthenia
• Bernard Soulier
syndrome
• Storage granule
disease
Acquired :
• Drug induced
• Acute / chronic
leukemia
• Myelofibrosis
• Anemia
QUANTITATIVE
DISORDERS OF
PLATELETS
Thrombocytopenia:
• ITP
• TTP
• Wiskoff Aldrich
syndrome
Thrombocytosis:
• Benign or reactive
process
• Myeloproliferative
disorders
CONGENITAL
Hemophilia A & B
Von Willebrand’s
disease
Other factor
deficiency (Rare)
ACQUIRED
Liver disease
Vitamin k
deficiency
DIC

REFERENCES
• Shafer’s Textbook of Oral PATHOLOGY.5th edition.
• Brad .W. Neville. Textbook of Oral and Maxillofacial Pathology .South Asian Edition.
• John P. Greer et al, Wintrobe’s Clinical Haematology, 12th edition
• Kumar, Abbas, Aster (2013) Robbins Basic Pathology, 9th Edition
• J Ochei, A Kolhatkar. Medical Laboratory Science Theory and Practice, 2000
• CL.Ghai.A Textbook of Practical Physiology 8th Edition.Jaaypee Publishers.
• SN Chugh. A Textbook of Clinical Medicine 2nd Edition. Arya Publications

• Colledge, N. R., Walker, B. R., Ralston, S., & Davidson, S. (2010). Davidson's principles
and practice of medicine. Edinburgh: Churchill Livingstone/Elsevier.
• Agarwal, Anil et al. Scurvy in pediatric age group – A disease often forgotten?
• Journal of Clinical Orthopaedics & Trauma, Volume 6, Issue 2, 101 – 107
• Srivathsa SH. Oral Ecchymosis in elderly: Senile purpura. J Indian Acad Oral Med
Radiol 2015;27:331-3
• Sandhu SV et al. Collagen in health and disease. J Orofac Res 2012; 2(3); 153-159
• Seung-Tae Lee et al, Clinical Features and Mutations in the ENG, ACVRL1,
and SMAD4 genes in Korean Patients with Hereditary Hemorrhagic TelangiectasiaJ
Korean Med Sci. 2009 Feb;24(1):69-76

• Kerstin Jurk Beate E. Kehrel (2007) Inherited and Acquired Disorders of
Platelet Function, Transfus Med Hemother 2007;34:6–19
• Hirokazu Kashiwagi , Yoshiaki Tomiyama .Pathophysiology and
management of primary immune thrombocytopenia. Int J Hematol (2013)
98:24–33
• J Evan Sadler Pathophysiology of thrombotic thrombocytopenic purpura.
BLOOD, 7 SEPTEMBER 2017 x VOLUME 130, NUMBER 10
• Davis BR, Candotti F. Revertant somatic mosaicism in the Wiskott-
Aldrich syndrome. Immunol Res. 2009;44(1–3):127–131

BLEEDING AND CLOTTING DISORDERS

BLEEDING AND CLOTTING DISORDERS

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to BLEEDING AND CLOTTING DISORDERS

Similar to BLEEDING AND CLOTTING DISORDERS (20)

Recently uploaded

Recently uploaded (20)

BLEEDING AND CLOTTING DISORDERS