Coag disorder

1. COAGULATION
DISORDERS
Presented by
DR. NEHA
JR 1 Pathology

2. HEMOSTATIC PROCESS
1.
2.
3.
3 Main steps -
Primary hemostasis: Local
vasoconstriction & platelet plug
formation.
Coagulation cascade
Fibrinolysis

4. PLATELET PLUG FORMATION
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Vascular Injury
Release and binding of vWF to exposed
blood vessel collagen
Glycoprotein IB on platelet surface
membrane binds to vWF
TxA2 – vasoconstriction & platelet
adhesion
Platelet Factor 3 (PF3) phospholipid layer
(procoagulant)

5. PLATELET ACTIVATION &
AGGREGATION
Exposed endothelial surface
Platelets exposed to collagen
“activated”
Release content of cytoplasmic granules
Adenosine diphosphate
(ADP)
Accelerates platelet
Aggregation/activation

6. COAGULATION CASCADE

8. INVESTIGATIONS OF COAGULATION
DISORDERS
1.
2.
3.
Screening tests
Platelet Count
PT
APTT
Special Tests
Coagulation factor assays

9. PROTHROMBIN TIME (PT)
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Measures the activity of certain clotting
factors (Extrinsic pathway)
Monitor patients on blood thinner medicine
like Coumadin
Prolonged:
Liver Diseases
Congenital deficiency of coagulation
factor V, VII, X Prothrombin or
Fibrinogen
Normal Values: 10-14 seconds

10. ACTIVATED PARTIAL PROTHROMBIN
TIME (APPT)
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Test for intrinsic and common pathways
Dependent on activity of all coagulation
factors, except VII and XIII
Normal Values: 30-40 seconds
Monitors heparin tx & screen for
hemophilia

11. PLATELET COUNT

12. Laboratory test Components
Measured
Normal Values
Bleeding time Platelet function
Vascular Integrity
3-10 Minutes
PT I, II, V, VII, IX, X 10-14 Seconds
PTT I, II, V, VII, IX, X, XI, XII 30-40 Seconds
Thrombin
Time
I, II 12-20 Seconds

13. DISORDER OF COAGULATION
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CONGENITAL
Either quantitative or
qualitative defect in single
coagulation factor
Haemophilia A
Haemophilia B
VWD
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ACQUIRED
Deficiencies of Multiple
coagulation factors
Vit. K Def
Liver Disorders
Fibrinolytic defects
DIC

14. HEMOPHILIA
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Bleeder’s disease, disease of Hapsburg,
the disease of kings
Hereditary disorder
Defect carried X chromosome and
transmitted as a gender linked Mendelian
recessive trait

15. BROADLY DIVIDED INTO

16. HEMOPHILIA A
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It is the most common hereditary coagulation disorder with
life threatening bleeding
Occurs in approximately 1:10,000 individuals.
Caused by hereditary deficiency or dysfunction of factor VIII.

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In India about 1300 hemophiliacs are born
every year & currently there are about 50,
000 patients with severe disease.
In heritance of Hemophilia is X-linked
recessive is located on the X chromosome
The disease manifests only in males
because they lack the complementary
normal X chromosome.
Female are carriers but don’t manifest the
disease

19. • Severity of disease is based on the amount
of Factor VIII C activity

20. •
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CLINICAL FEATURES
Hemarthrosis
Acute excruciating pain in the affected
joint ex. Knee, Elbow or wrist joint.
Prolonged bleeding following trauma, tooth
extraction or surgery
Bleeding from mouth, gums and tongue is
common.
CNS bleeding is the most common serious
complication

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Patients present with headache, vomiting,
irritability, confusion and drowsiness.
Wound healing is delayed because of
continued bleeding at the site of injury
Petechiae are characteristically absent
LABORATORY INVESTIGATIONS
Prolonged PTT and a normal PT.
These tests point to on abnormality of the
intrinsic coagulation pathway

24. HEMOPHILIA B
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CHRISTMAS DISEASE, FACTOR IX
DEFICIENCY
Severe factor IX deficiency produces a
disorder clinically indistinguishable from
factor VIII deficiency (Hemophilia A)
PTT is prolonged and PT is normal
Treated with infusions of recombinant
factor IX

25. VON WILLEBRAND DISEASE
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M.C inherited bleeding disorder
Bleeding tendency is mild and often goes
unnoticed until some hemostatic stress,
such as surgery or a dental procedure.
Spontaneous bleeding from mucous
membranes ex. Epistaxis
Excessive bleeding from wounds,
menorrhagia.

26. •
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Prolonged bleeding time in the presence of
a normal platelet count
It is usually transmitted as an autosomal
dominant disorder, but rare autosomal
variant have been described.
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

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Type 3: Most severe and rarest form of
vWD, characterized by marked deficiency
of both vWF and factor VIII.
Prevalence rate 0.9-1.3 percent
Many children are asymptomatic and are
diagnosed as a result of positive family
history
Excessive Bleeding
Site : Nose, Skin and Gingiva

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LABORATORY FINDING:
Increased bleeding time
PT, CT, APPT are normal
MANAGEMENT
Transfusion of plasma and / or
antihemophilic factor (VIII)
Desmopressin

30. ACQUIRED
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VITAMIN K DEFICIENCY
Hemorrhagic disease of newborn
Now uncommon due to administration of
vitamin K at birth
Vitamin K fat soluble vitamin
Noticed by Dam in the year 1929
Involved in both intrinsic and extrinsic
pathway

31. •
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ROLE OF VITAMIN K
Necessary for post-translational
carboxylation of glutamic acid
Calcium binding to proteins like
Prothrombin factor II, VII, IX, X
SOURCE
Green leafy vegetables
Liver
Milk
Vegetable oils

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LABORATORY DIAGNOSIS
Increase Prothrombin time
Partial thromboplastin time
TREATMENT
Vitamin K 0.5 – 1.0 mg IM
Transfusion of Plasma

35. DISSEMINATED INTRAVASCULAR
COAGULATION
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Is an acute, Subacute or chronic thrombo-
hemorrhagic disorder.
Coagulation and results in the formation of
thrombi throughout the microcirculation.
ETIOLOGY
OBSTETRIC COMPLICATIONS:
Amniotic fluid embolism
Eclampsia
Premature separation of placenta
Retained dead fetus placenta

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INFECTIONS:
Meningococcal septicemia
Septic Abortion
Gm –ve sepsis E•Coli and Psedomanas
MALIGNANCIES:
Metastatic Mucus secreting
adenocarcinoma
Lymphoproliferative disorder
Fat Embolism
Vascular Disorder
Massive Tissue injury
Severe burn
Hepatic Failure
Post Surgery Massive Trauma

38. PATHOPHYSIOLOGY
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Two major mechanism trigger DIC
Release of tissue factor or thromboplastic
substances in to the circulation
Wide spread injury to the endothelial cells

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ACUTE
Generalized ecchymoses
Petechiae
Bleeding from previous
Venipuncture site
Haemorrhagic Skin
lesions
Geographic acro cyanosis
Epistaxis
Gastrointestinal bleeding
Pulmonary haemorrhage
Hematuria
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CHRONIC
Extensive ecchymoses
of extremities
Without petechiae
Renal impairment,
Neurologic symptoms
Trousseau sign
Recurrent episodes of
epistaxis
Serious internal
neucosal bleeding
Thrombosis

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LABORATORY FINDINGS
Prolonged aPPT, PT
Platelet count less than 50,000 /cu mm
Increase fibrin degradation products
Low level of coagulation inhibitors – AT III, Protein C
Low level of coagulation factors V, VIII, X, XIII
TREATMENT
Supportive therapy
No specific treatments
Anticoagulants (Heparin)
Fresh Frozen plasma

42. LIVER DISEASE
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Liver plays a major role in 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.

43. 
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CLINICAL FINDINGS
No abnormal bleeding
Gastrointestinal haemorrhage
ORAL MANIFESTATION
Recurrent ecchymosis
Epistaxis
Severe generalized bleeding
LABORATORY FINDINGS
Decreased platelet count
Increase level of PT, aPTT

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TREATMENT
Fresh frozen plasma
Cryoprecipitate
Recombinant factor VIII A
Thrombopoietins (Eltrombolpag )