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Download MBBS Pathology PPT 1 Coagulation Pathology Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pathology PPT 1 Coagulation Pathology Lecture Notes

This post was last modified on 07 April 2022


Approach to Bleeding

Disorders

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? Primary haemostasis involves the

binding of platelets to exposed

collagen in the sub endothelium of

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damaged vessels.

? Secondary haemostasis is the process

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of activation of coagulation factors

leading to the production of

thrombin.

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2


(A) After vascular injury, local neurohumoral

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factors induce a transient vasoconstriction.

(B) Platelets bind via glycoprotein Ib (GpIb)
receptors to von Willebrand factor (vWF) on exposed
extracellular matrix (ECM) and are activated,

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undergoing a shape change and granule release.
Released ADP & thromboxane A2 (TxA2) induce
additional platelet aggregation through platelet GpIIb
-IIIa receptor binding to fibrinogen, and form the
primary hemostatic plug.

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Platelet adhesion and aggregation-

Von Willebrand factor functions as an
adhesion bridge between subendothelial

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collagen and the glycoprotein Ib (GpIb)
platelet receptor. Aggregation occurs by
fibrinogen bridging GpIIb-IIIa receptors on
different platelets.
Congenital deficiencies in the various

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receptors or bridging molecules lead to
different diseases.


(C) Local activation of the coagulation cascade

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(involving tissue factor and platelet phospholipids) results
in fibrin polymerization, "cementing" the platelets into a
definitive secondary hemostatic plug.

(D) Counterregulatory mechanisms, mediated by

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tissue plasminogen activator (t-PA, a fibrinolytic product)
and thrombomodulin, confine the hemostatic process to
the site of injury

SIMPLIFIED DIAGRAM OF COAGULATION CASCADE:-

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PROCOAGULANT FACTORS :-

PROCOAGULANT FACTORS. Cont'd. :-

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ANTICOAGULANT FACTORS:-


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Bleeding disorder

Bleeding disorders can be due to

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Blood vessel anomalies

Platelet abnormalities

Coagulation disorders

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DISORDERS OF VESSEL WALL:-

HEREDITARY:-

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1) Hereditary hemorrhagic telangiectasia (Osler?Weber?Rendu disease )

2) Ehler Danlos Syndrome

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ALLERGIC:-

1) Henoch?Sch?nlein purpura (HSP)

2) Leucocytoclastic angitis

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ATROPHIC:-

1) Senile purpura

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2) Scurvy

MISCELLANEOUS:-

1) Simple easy bruising

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2) Amyloidosis

3) Infections

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PLATELET DISORDERS.. Cont'd:-


DISORDERS OF COAGULATION:-

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INHERITED

ACQUIRED

HEMOPHILIA A

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DIC

HEMOPHILIA B

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LIVER DISEASE

vWD

HDN

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DISORDERS OF FIBRINOGEN-

Nephrotic Syndrome

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HEREDITARY AFIBRINOGENAEMIA

HYPOFIBRINOGENAEMIA

DYSFIBRINOGENAEMIA

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FXIII deficiency

APLS

FV deficiency

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HEPARIN OR ORAL ANTICOAGULANT

THERAPY
VIT K DEFICIENCY

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MASSIVE TRANSFUSION OF STORED

BLOOD

Clinical evaluation.. Cont'd:-

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.

Petechiae <3 mm, Purpura 0.3?1 cm (3?10 mm), ecchymoses >1 cm.

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Clinical evaluation.. Cont'd:-

Hemarthrosis in a case of Hemophilia

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Purpura in a case of ITP

Von willebrand Disease


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? One of the Most Common inherited disorders of bleeding
? AD disease with gene located on 12 th chromosome
? vwf synthesize in endothelium, platelet and megakatyocytes
? vwf facilitate platelet adhesion to subendothelial collagen

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C/F ? Spontaneous bleeding from mucus membrane,

Excessive bleeding from wounds / gums

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Menorrhagia

>20 variants reported

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Type1(50% activity) & 3(no activity)

Type 2

Reduced vWF

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Qualitative defects

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Lab Findings

? Prolonged BT
? (Normal) platelet count

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? Deficient Ristocetin aggregation
? Prolonged PTT

Treatment
? cryoprecipitate

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HEMOPHILIA ? A

(F ? VIII deficiency)

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Most Common hereditary disease

Reduced activity of F ? VIII

X ? linked recessive trait

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30% of patients have no positive family history

<1% of normal F-VIII activity ? Severe disease

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2 ? 5% of normal F-VIII activity ? Moderate disease


6 ? 50% of normal F-VIII activity ? Mild disease

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Clinical /Features:

normal hemostasis require 25% factor VIII activity

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Symptomatic patients mostly have < 5% factor VIII activity
Easy bruising
Massive Hemorrhage after mild trauma / operation
Joint bleeding ? Haemarthrosis ? Deformities

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Lab Features

? Bleeding Time - Normal

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? Prothrombin Time - Normal
? Platelet Count - Normal
? APTT - Increased
? Diagnosis can be confirmed by F-VIII assay.

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Therapy
F-VIII Infusion
15% of severely affected patients ?developed Antibodies against F - VIII
HEMOPHILIA ? B

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Severe Factor - IX deficiency

X ? linked recessive

PT ? Normal

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APTT ? Increased

Factor assay is must to differentiate between Hemophilia A & Hemophilia B

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Screening tests for primary hemostasis are -

I. Bleeding time- Assesses adequate functioning of platelets and blood vessels

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II. Peripheral blood smear examination
III. Platelet count
IV. Mean Platelet volume
V. Reticulated platelets

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VI. Platelet function analysis
VII. Tests for Vessel wall disorder
Tests for Vessel wal disorder

HESS` CAPILLARY FRAGILITY TEST:

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Cuff is wrapped in upper arm and pressure is maintained midway b/w systolic and

diastolic BP for 15 minutes, 4 cm below the elbow joint, a circle of 2.5 cm diameter is

drawn on the anterior aspect of forearm.

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Upto 10 new hemorrhagic spots are normal. But >20 new spots are always

pathological.

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This is positive in increased capillary fragility, ITP.

Screening tests for secondary hemostasis are -

I. Clotting time

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II. Prothrombin time (PT) and Activated partial thromboplastin time (aPTT)
III. Thrombin Time (TT)
Col ection of blood for coagulation studies

The anticoagulant used for coagulation studies is trisodium

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citrate (3.2%), with anticoagulant to blood proportion being 1:9.

Clotting Time

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This is a crude test and is now replaced by activated partial thromboplastin time.
Prolongation of clotting time only occurs in severe deficiency of a clotting factor and is

normal in mild or moderate deficiency.
PROTHROMBIN TIME(PT)

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PT assesses coagulation factors in extrinsic pathway (F VII) and

common pathway.

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Principle:- Tissue thromboplastin and calcium are added to

platelet poor plasma and clotting time is determined.

CONCEPT OF INR

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1.The international normalized ratio (INR) was introduced in an attempt to standardize the

PT.
2.Calculation ~ INR = [ PT (patient) / PT (Control) ]ISI

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The INR has no units (it is a ratio)

**ISI, or international sensitivity index is a function of the thromboplastin reagent.

** NORMAL RANGE PT 11-16 seconds

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INR 0.9 ? 1.1.
Uses of PT
1. To monitor patients who are on oral anticoagulant

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therapy

2. To assess liver function
3. Detection of vitamin K deficiency
4. To screen for hereditary deficiency of coagulation

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factors

Causes of prolongation of PT
1.Treatment with oral anticoagulants

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2.Liver disease
3.Vitamin K deficiency
4.Disseminated intravascular coagulation
5.Inherited deficiency of factors in extrinsic and

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comm

ACTI on

V pat

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ATEhwa

D Pys.

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ARTIAL THROMBOPLASTIN TIME (APTT)

Significance
Reflects efficiency of Intrinsic and Common pathway.

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Principle

The test measures the clotting time of plasma after the activation of contact

factors (Kaolin/Silica/El agic acid) and the addition of phospholipid and

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CaCl2, but without added tissue thromboplastin.

So it indicates the overal efficiency of the Intrinsic pathway.

Normal range

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26 to 40 seconds.
Uses of APTT:-

1. Screening for hereditary disorders of

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coagulation

2. To monitor heparin therapy
3. Screening for circulating inhibitors of

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coagulation

aPTT is prolonged in:-

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1.Inherited deficiencies of factor VIII (Hemophilia A) and Factor IX (Hemophilia B)
2.Non specific inhibitor antibodies against F VIII e.g. Lupus inhibitor (Don't act directly
but block interaction of FVIII with other clotting factors)
3.DIC
4.Heparin

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( Inhibits factor XII, XI and X through antithrombin III & Heparin therapy is monitored
through aPTT)
5. Vit K deficiency
6.Massive transfusion of plasma depleted stored blood.
THROMBIN TIME(TT)

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Significance:-

Asses the final step of coagulation i.e. conversion of fibrinogen to fibrin in presence of

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thrombin.

Bypasses Extrinsic & Intrinsic pathway.

Causes of prolonged TT

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1. Disorders of fibrinogen-

i) Afibrinogenaemia
ii) Hypofibrinogenaemia

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3. Chronic liver disease
FXIII Qualitative assay (Urea clot lysis test)

Done when all other tests for hemostasis are normal.

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FXIII provides stability to clot formed.

Method:-

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Summary of Approach to Bleeding Disorders