blood cagulation disorder

7/27/2019 Blood Cagulation Disorder

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Blood Coagulation and

Haemostasis

Dr. Ahlam AL-Buhairan

Basic clinical haematology (241 CLS)


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Haemostatic System

Definition:

A physiological mechanism wherebybleeding is stopped from sites of vesselinjury.

Maintains a balance between procoagulantand anticoagulant processes.


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Haemostatic System

Five major components are involved

in this mechanism:

1.Platelets

2.Coagulation Factors

3.Coagulation Inhibitors4.Fibrinolysis

5.Blood vessels


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Platelets

Plts are produced in the B.M.

The precursor cells are the

megakaryoblast.

The megakaryocytes mature by

endomitotic synchronous nuclear

replication.


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Platelets

Each megakaryocyte results in

production of ~4000 plts.

Plts production takes ~ 10 days


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Plts production

Plts production is regulated mainly by

Thrombopoietin.

It is produced by the liver and kidney

and its level is high in thrombocytopenia.

Another factor is interleukin-11.


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Plts production

The normal plts count range is150- 400X109/l.

Plts life span is 7-10 days.

~30% of plts may be trapped in thespleen at any one time of theirproduction.


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Plts function

The main function is the formation of

mechanical plug during vascular injury.

This is achieved through:

1. Plts adhesion

2. Plts release reaction

3. Plts aggregation

4. Plts procoagulant activity


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Blood coagulation cascade

This involves a cascade of circulating

precursor proteins called coagulation

factors.

They form what is known as intrinsic and

extrinsic pathways.


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Blood coagulation cascade

They result in the generation of thrombin

which converts plasma fibrinogen into

fibrin leading to a firm and stable

haemostatic plug.


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Inherited Bleeding Disorders

Abnormal bleeding result from

vascular disorders,

thrombocytopenia,

plt dysfunction, or

defective coagulation


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Thrombocytopenia

Occurs when plts are lost from thecirculation faster than they can be

replaced by the B.M.

This result from a failure of plts

production, an increased rate of removalfrom the circulation or a combination ofboth mechanisms.


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The Blood Platelets

Abnormal bleeding associated with

thrombocytopenia is characterized by

spontaneous skin purpura, haemorrhage and

prolonged bleeding after trauma.

Causes of thrombocytopenia can be classified

under 2 main categories; defective plt

production and diminished plt survival.


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Causes of thrombocytopenia

Failure of plt production:

Part of general B.M failure e.g

aplastic anaemia, leukaemia, M.A, cytotoxicdrugs.

Selective megakaryocyte depression e.gchemicals, viral infections and drugs.


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Causes of thrombocytopenia

I ncreased consumption of plts:

Immune e.g autoimmune, SLE, CLL,infections (HIV, malaria..)

Disseminated intravascular coagulation (DIC)

Thrombotic thrombocytopenic purpura.


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Chronic autoimmune

thrombocytopenic pupura

(ITP)

The commonest cause of

thrombocytopenia without anaemia orneutropenia.

The highest incidence in women aged 15-

50 years. Idiopathic and may be associated with

SLE, HIV, CLL.etc.


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Chronic autoimmune

thrombocytopenic pupura (ITP) Plt sensitization with auto-antibodies (IGg)

leads to premature removal from the

circulation by the macrophages in the spleenand liver.

The normal lifespan of plts is reduced to onlyfew hours.


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Clinical features

Petechial haemorrhage, easy bruising

and menorrhagia.

Mucosal bleeding in severe cases.

The spleen is not palpable.


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Diagnosis

Plt count is 10-50X109 .

Hb is normal.

WBC is normal. Blood film shows reduced plts (large).

B.M shows normal or increased plts.

Sensitive tests will demonstrateantiplatelet IgG on the platelet surface orin the serum in most patients.


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Treatment

Aim: reducing the level of autoantibodyand reducing the destruction rate of

sensitized plts.

Steroids.

Splenectomy.


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Inherited Bleeding Disorders

Recent advances in protein chemistry and

recombinant DNA technology haveproduced a comprehensive account both of

normal coagulation and of the molecular

genetics of some bleeding disorders.


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Haemophilia A

Occurs due to FVIII being deficient ordefective.

Almost all patients are male.

An X-linked recessive disorder.

The gene for FVIII is localized near the

tip of the long arm of the X chromosome.


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Haemophilia A

The cDNA for FVIII has been cloned.

This lead to the identification of many

genetic defects including gene deletionsand point mutations.


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Clinical features

The patients suffer mainly from recurrent

painful haemarthroses and muscle

haematomas with progressive crippling. Prolonged bleeding is frequent after dental

extractions.

Haematuria. Operative and post traumatic haemorrhage

are life-threatening in affected patients.


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Clinical features

Spontaneous intracerebral haemorrhage

(a cause of death in many severe

haemophilics).

Haemophilic pseudotumours in the long

bones, pelvis and fingers may occur

Infections e.g hepatitis B, C, HIV ..etc..due

to infusions of blood products.

In general the severity correlates with FVIII

level.


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Disease severity and FVIII

activity FVIII activity (%)


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Lab findings

B.T is normal.

P.T is normal.

Platelet count is normal.

Ristocetin-induced platelet.

APTT is prolonged.

FVIII is low.


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Treatment

Specialized haemophilia centers.

Bleeding episodes are treated with FVIII

replacement therapy (FVIII concentrates)

or desmopressin (DDAVP).


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Factor IX deficiency

(Haemophilia B) Also called Christmas disease.

FIX is coded by a gene near the tip of the

long arm of the X chromosome.

The inheritance and clinical picture are

identical to those of haemophilia A.

They can be distinguished by specific

coagulation factor assays.


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Lab findings

B.T is normal.

P.T is normal.

APTT is prolonged.

FIX clotting assay is low.


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Treatment

Similar to the approach of haemophilia A.

FIX concentrates (has longer half- life than

FVIII).


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von Willebrand disease

von Willebrand disease (VWD) is themost frequent inherited human bleeding

disorder.

It occurs due to a deficiency and/or

abnormality of von Willebrand factor

(VWF).

The inheritance is autosomal dominant.


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VWD

Patients who have reduced or

abnormal VWF suffer mainly from

mucosal bleeding (epistaxis,

menorrhagia), operative and post-

traumatic haemorrhage and

excessive blood loss from superficial

cuts.


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VWD types

VWD is a very heterogeneous disorder

that has been classified into :

Type 1 VWD (partial deficiency of VWF)

Type 2 VWD (qualitative abnormality)

Type 3 VWD (total deficiency of VWF)


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VWF function

VWF performs two essential functions in

primary haemostasis:

1.Binds to and stabilises blood clotting

factor VIII in the circulation

2. Mediates the adhesion of platelets at sites

of vascular damage


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Lab findings

P.T is normal.

Plt count is normal.

Prolonged B.T. APTT is normal or prolonged.

FVIII:C is low (FVIII activity).

VWF level is low. Ristocetin- induced plt aggregation is

defective.

VWF:RCo is low (VWF activity).


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Treatment

Bleeding episodes are managed by

intermediate- purity FVIII concentrates

(contain both FVIII and VWF) or

DDAVP.


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blood cagulation disorder

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