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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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