Hemostasis Part -1-

BY:
DR. ZAHRAA AL-ZUHAIRI
 Hemostasis

 Is the physiological arrest of hemorrhage at sites

of vascular leakage.
 There are mainly 5 COMPONENTS which
interact together to ensure hemostasis, namely :
1) Blood vessels
2) Platelets
3) Coagulation factors
4) Coagulation inhibitors
5) Fibrinolytic system: Later it involves
dissolution of the clot after repairing the vessel.
 RESPONSE
TO VASCULAR INJURY
Platelet
Leakage Plug

Vessel
Constriction
Primary hemostasis

Fibrin
reinforced
Platelet
Plug

Remodelling & Secondary hemostasis

Return to
Fibrinolysis
normal
Coagulation pathways-
Old version
 Relation between vonWillebrand’s Factor
(vWF) and Factor VIII

vWF serves two unique functions in haemostasis, as a carrier

for FVIII and as the bifunctional ligand mediating platelet
GPIb α adhesion to collagen.
Coagulation pathways - new version

VIIIa

Va

Act. Plat.

Factor I Fibrin
Natural Coagulation pathway inhibitors

TFPI

Activated Protein C

Antithrombin
VIIIa
Va
Act. Plat.

Factor
Fibrin
I
Activated Protein C
 Basic Screening tests for Hemostasis
1. Platelets count (Normal range 150 000 – 450 000/mm2): a
reduced platelets count is associated with increased liability to
bleeding.
2. Bleeding time (NR 2 – 10 minutes) : is prolonged if there is
reduced platelets count or number, or if there is a vascular
defect.
3. Prothrombin Time (PT): this is a test which tests the
extrinsic and the common pathway of the coagulation (PT will be
prolonged by deficiencies in FVII,FX, FV, FII or fibrinogen).
4. Activated Partial Thromboplastine Time (APTT): This
test is used to test for intrinsic and the common pathway (APTT
will be prolonged by deficiencies of FXII,FXI, FIX, FVIII, FX, FV,
FII, fibrinogen)
5. Thrombin time (TT): this tests the last step in the
coagulation pathway i.e. the conversion of Fibrinogen (factor I)
to fibrin.
 Activated Partial
Thromboplastin Time
Prothrombin Time
 T.T.

Thrombin Time
 Bleeding tendency

 Dry purpura: cutaneous purpura (petechiae,

ecchymosis, easy bruising).
 Wet purpura: mucosal bleeding (oozing gums, blood
blisters in mouth, epistaxis, hematuria, menorrhagia,
melena, bleeding per rectum), fundal hemorrhages.
There are 2 main causes are:
1. Platelets disorders: May either be due to reduced
platelets count (thrombocytopenia) or function
2. Coagulation Disorders: caused by deficiency of
clotting factors and lead to defects in normal clot
formation process.
Bleeding tendency : dry Purpura

Petechiae < 3mm

Bleeding tendency: dry Purpura

Ecchymosis > 3mm

Platelets disorders
 Causes of Thrombocytopenia
Reduced production of platelets .
1. Acute leukemia.
2. Aplastic Anemia .
3. Cytotoxic drugs.
4. Marrow infiltration by malignant disease.
5. Myelofibrosis.
Increased platelets consumption (with normal or
increased production)
1. Autoimmune Thrombocytopenic Purpura (AITP).
2. Alloimmune thrombocytopenia.
3. Drug induced immune Purpura.
4. Hypersplenism (increased consumption of platelets by
hyperactive enlarged spleen).
5. Dissaminated Intravascular coagulation (DIC) .
 Autoimmune Thrombocytopenic purpura

 A relatively common hematological disorder, the main

feature of which is bleeding tendency due to
thrombocytopenia, and could be classified into:
1. Idiopathic thrombocytopenic purpura (ITP):
Immune (autoimmune, idiopathic) thrombocytopenic
purpura is a common acquired autoimmune disorder
defined by a low platelet count secondary to accelerated
platelet destruction by antiplatelet antibodies. usually
affecting young or middle aged adults, without
precedent or associated illness
2. Secondary autoimmune thrombocytopenia:
resembles ITP clinically, but associated
Autoimmune disorder, or malignancy (SLE, CTD,
LPD, Solid tumors, AIDS etc).

3. Acute Post-viral auto-immune

thrombocytopenia: acute usually self-limiting
thrombocytopenic purpura, typically seen in
children following acute viral infection or
immunization.
 Clinical features of AITP

Clinical parameter Acute Chronic

Peak age (yr.) 2-8 20-40

Sex distribution F=M 3F:1M
Onset Sudden Insidious
Duration usually often
weeks months/years.
Associated disorders post-viral 1. Idiopathic.
2. Secondary.
N.B.: Splenomegaly is not a feature of AITP, except if
secondary
 Hematological findings
 Blood Picture :
Main feature reduced platelets (<80x109/L).
Normal or reduced Hb.
Leucocytes often normal.
 Bone marrow shows :
Usually normal cellularity.
Mainly increased or normal no. of Megakaryocytes.
Normal erythropoiesis and granulopoiesis.
No excess blasts or foreign cells.
 Diagnosis is confirmed by demonstration of platelets
auto-antibodies.
Bone marrow Aspirate in AITP
Increased Megakaryocytes
 Management of AITP

 Traditionally, treatments have been grouped into

first line, second line, third line
 First-line therapies comprise corticosteroids, IV
Ig and anti-D. These three treatments work fairly
quickly (within 24–48 hours) and their efficacy rates
are high at around 70–80%.
 If patients fail to respond to first-line treatment they
may then be given a second-line drug, such as
azathioprine, mycophenolate mofetil or a TPO
receptor agonist in some cases splenectomy may
be indicated.
 In Acute Post-viral ITP : majority recover
spontaneously within 3 months. The recommended
treatment is IV Immunoglobulin.
 In chronic ITP : management includes steroids,
followed by splenectomy if necessary
Coagulation Disorders

DR. ZAHRAA
ALQAISI
 MUSTAFA GHENI

Coagulation Disorders
 Classification

1) Hereditary Coagulation Disorder

These inherited plasma coagulation disorders are due to
qualitative or quantitative defect in single coagulation factor.
A. Sex Linked (X) Disorders : e.g. Classical haemophilia or
haemophilia A, Christmas disease or haemophilia B
B. Autosomal Disorders : e.g. von Willebrand’s disease
2) Acquired Coagulation Disorder
These are characterized by deficiency of multiple coagulation
factor.
A. Vitamin K deficiency
B. Coagulation disorder of liver disease
C. Disseminated intravascular coagulation DIC
D. Fibrinolytic defects
 Inherited Coagulation Disorders

 Most important is Hemophilia A: Due to inherited

deficiency of Factor VIII.
 Probably the most frequent, but clinically less significant
is von-Willebrand’s Disease, due to deficiency of
vonWillebrand’s factor.
 Next in importance is Hemophilia B (Christmas
Disease) due to sex-linked inherited deficiency of
Factor IX.
 Other inherited coagulation defects are much less
frequent and include : Fibrinogen(Factor I) Deficiency,
Factor VII, Factor X etc.
 Hemophilia A
 It is the second most common cause, sex linked
inherited disorder characterized by deficiency of factor
VIII.
 Caused by either:
 Quantitative reduction in factor VIII (in 90% of
cases) OR
 Qualitative defect: Normal or increased level of
factor VIII with reduced activity (in 10% of cases).
 Factor VIII is synthesized in hepatocytes. In the
intrinsic coagulation pathway factor IXa complexes with
factor VIIIa, this complex in the presence of platelets,
PL and Ca2+ activates factor X to Xa.
 HAEMOPHILIA A

I IXa
X

VIII
a
PL
Ca2+

X Xa

Disruption of the Intrinsic Coagulation Pathway

(Due to the absence of activated Factor VIII)
 Clinically:
 Males are affected.
 Features start usually when the infant starts to crawl
or walking.
 Symptoms are appear when factor VIII activity is
reduced to less than 25%.
 Patient suffers bleeding for hrs. to days and severity is
based on plasma concentration of factor VIII activity
 One of the main features is Hemarthrosis (bleeding
into joints).
 Bleeding into muscles, S/C tissue, after any
injury or surgery, painless hematuria, GI
bleeding also may be seen.
Hemophilia (Hemarthrosis)

Knee Joint
 Hematomas

Hemophilia
Hematoma
S/C Hematoma
 Bleeding into biceps
muscle - Pseudotumor
Long term sequels of hemophilia: Deformities due to
recurrent hemarthrosis and permanent joint damage
and muscle atrophy
 Haemophilia A: X‐ray of the knee joints shows
destruction and narrowing of the left joint space.
 Long-term sequels of Hemophilia:
Permanent damage to knee and elbow joints.
 Lab Diagnosis:
A. Bleeding time: N
B. PT: N
C. TT: N
D. aPTT: prolonged; and corrected by mixing with normal
plasma.
E. Functional factor VIII coagulant activity is measured by
one-stage clotting assays based on aPTT: low level of
factor VIII but the Ag may be normal.

 Treatment:
Factor VIII replacement therapy : infusion of factor VIII
derived from human plasma OR recombinant FVIII (50–100
units/kg twice daily) to achieve FVIII levels of 1.0 unit/mL.
Hemophilia A:
PT : normal.
APTT : Prolonged.
TT : normal
F VIII : reduced.
 HAEMOPHILIA B
 X linked recessive disease.
 Rarer than haemophilia A.
 Incidence Ratio is 1: 100000 male birth.
 Inheritance pattern and clinical features are similar to
classical haemophilia.
 Lab Diagnosis:
Assay of factor IX level which is lowered. Other lab
findings are similar to haemophilia A.
 Treatment:
recombinant FIX concentrate, Infusion of fresh frozen
plasma or plasma enriched with factor IX.
 Von-Willebrand’s Disease

 VonWillebrand’s factor is present in both plasma and

platelets and acts as :
1. A carrier protein of Factor VIII.
2. It is also plays an important role in platelets
adhesion to sub-endothelium.
 The VW Disease represent a most common inherited
coagulation disorder, due to deficiency of vonWillebrand’s
factor.
 This disorder is inherited mostly as autosomal dominant
 Disease classified to type 1 ,type 2 and type 3 according to the
type of defect quantitive or qualitative
 Clinically

 Mucous membrane bleeding, particularly

epistaxis and menorrhagia.

 Bruising and bleeding after trauma or during

surgery are also common.

 Haemarthrosis unlikely.
 Lab Diagnosis
 Prolonged bleeding time.
 PT: normal
 PTT: prolonged especially in type 2N & 3 but may be
normal in mild cases.
 Platelet count: normal except in type 2B & type 3
(reduced).
 Reduced plasma vWF concentration.
 Defective platelet aggregation with ristocetin .
 Reduced factor VIII activity.
 Treatment:
Cryo-precipitates or Factor VIII concentrates
 ACQUIRED COAGULATION DISORDERS

Vitamin K Deficiency
 Vitamin K serves as a cofactor in the formation of 6
prothrombin complex proteins (Vitamin K
dependent coagulation factors) synthesized in the
liver: Factor II, VII, IX, X, Protein C and Protein S.
 Causes of Vitamin K deficiency:
 Obstructive jaundice.

 Chronic diarrhoea.

 Liver disease.

 Haemorrhagic states in infants.

 Lab Diagnosis:

Prolonged PT.

 Treatment:

Parenteral administration of Vitamin K causes

complete recovery in 48 hrs
COAGULATION DISORDER IN LIVER DISEASE

 Liver is the site of synthesis and metabolism of Coagulation

Factors.
Factors promoting Factors inhibiting
coagulation coagulation
1) Synthesis of Coagulation 1) Synthesis of Anti-
Factors. thrombin 3, Protein C and
Protein S
2) Clearance of Fibrinolytic 2) Clearance of Activated
enzymes Factors

 Liver disease leads to hypercoagulability and predispose to

develop DIC and systemic fibrinolysis.
 Liver disease may be associated with bleeding

tendency or may be with hypercoagulability

state or may be both as in DIC.

 Lab Diagnosis:

Prolonged PT and a PTT, mild thrombocytopenia,

decrease fibrinogen level and decreased hepatic
stores of Vitamin k.
DISSEMINATED INTRAVASCULAR COAGULATION

 Also called as defibrinate syndrome or

consumption coagulopathy is a complex
thrombo-haemorrhagic disease occurring as
secondary complication of some systemic disease.
 Major disorders associated with DIC:
 Obstetrics Complications- Abruption
placentae, retained dead foetus, septic abortion,
amniotic fluid embolism, toxaemia.
 Infections- Gram negative sepsis,
meningococcemia, rocky mountain spotted fever,
malaria.
  Neoplasms- Carcinoma of pancreas, prostate,
lung and stomach.
 Massive Tissue Injury- Traumatic, burns,
extensive surgery.
 Miscellaneous- Acute intravascular haemolysis,
snake bite, giant haemangioma, shock, heat stroke.
 Pathogenesis:
All the etiological factor act via 2 mechanisms-a.
Release of tissue factor in the circulation. b.
Widespread injury to endothelial cell.
PATHOPHYSIOLOGY OF DISSEMINATED
INTRAVASCULAR COAGULATION
 Clinical Features

A. Widespread fibrin deposition within

microcirculation leading to ischemia of organs
like kidney and brain.

B. Bleeding diathesis - ensues as the platelets and

clotting factors are consumed and there are
secondary release of plasminogen activator but also
digest Factor V and VIII there by reducing their
concentration further.
 Lab Diagnosis

A. Reduced platelet count.

B. Blood film shows microangiopathic haemorrhagic
haemolytic anaemia.
C. PT, TT,APTT are prolonged.
D. Plasma fibrinogen level is reduced.
E. Fibrin Degradation Products are raised.

 Treatment:
Anticoagulants like heparin or coagulants contained in
fresh frozen plasma, underlying disorder must be
treated simultaneously.
 Management
1. Central venous catheter inserted to :
 facilitate blood product
 adm. of chemotherapy and antibiotics
 frequent blood sampling

2. Blood support:
 platelet con. for bleeding episodes or if the platelet count is
<10 x 109/L with fever .
 Fresh frozen plasma if the coagulation screen results are
abnormal.
 packed red cell for severe anemia (caution: if white cell
count is extremely high).
 Management

3. Prevention and control infection

 barrier nursed

 Intravenous antimicrobial agents if there is a fever

or sign of infection
4. Physiological and social support
Treatment of acute leukemia
Outcome in adult acute leukemia
M1
M2
M2
M3
M3 - Classical
M3 - Classical
M3 - Variant
M3 - Variant
M4
M4
M5 a

M5 b
M5 a
M5 b
M6
M6
M7
M7
M7
ALL
ALL
L1
L2
L3
CML
CML
CML
CML
CML
 CLL
cll
CLL
PV
ETC
ETC
MF
mf
MF
MF