The micrograph shows activated
platelets adhering to some damaged
cells
Hemostasis
Content
•
•
•
•
•
Defination
Normal vessel wall
Stages of haemostasis
Anti clotting mechanism
Applied
Defination
• Term haemostasis means prevention of blood
flow.
• It is a process of forming clots in the walls of
damaged blood vessels and preventing blood
loss while maintaining blood in a fluid state
within the vascular system.
HEMOSTASIS
• Normal hemostasis is a consequence of
tightly regulated process that maintain
blood in a fluid state in normal vessels, yet
also permit the rapid formation of a
hemostasis clot at the site of a vascular
injury.
HEMOSTASIS
The process of hemostasis can be divided into two distinct stages namely:
1. Primary hemostasis – platelet plug formation
2. Secondary hemostasis – coagulation cascade
• The goal of both primary and secondary hemostasis is to arrest bleeding from
damaged blood vessels (hemo = blood, stasis = standing)
• Is counter-balanced by reactions, which prevent blood coagulation in uninjured
vessels and maintain the blood in a fluid state
– Balance between procoagulants and anticoagulants
• 4 overlapping processes or stages
– Local vasoconstriction
– Formation of a platelet plug
– Formation of a web of fibrin proteins that penetrate and surround the platelet
plug – blood coagulation or clotting
– Clot retraction.
6
LOCAL VASOCONSTRICTION
• Results from
– Release of vasoconstrictor substances (paracrine & autocrine agents)
from
• Platelets (i.e., serotonin & thromboxane A2)
• Traumatized tissue
– Local myogenic spasm initiated by direct tissue damage
– Reflex vasoconstriction initiated by activation of nociceptors and
other sensory endings
• Effects
– ↓ blood flow and Pressure in the damaged area
 Last for many minutes or even hours,
 during this time the ensuing processes of platelet plugging and blood
coagulation can take place
7
FORMATION OF A PLATELET PLUG (temporary hemostatic plug, white plug)
Factors that prevent/limit
formation of a plug
1. Prostacyclin
(prostaglandin I2).
Inhibits platelet
aggregation;
vasodilator
2. Nitric oxide* (NO).
Inhibits platelet
adhesion, activation and
aggregation and
stimulates local
vasodilation
Damaged blood vessel wall
Intact blood
vessel wall
Collagen fibers are exposed
to the blood and coated
with WF*
Secretion of
prostacyclin
& nitric oxide
-
+ stimulation
- inhibition
* Von Willebrand factor, a protein synthesized by endothelial
cells and megakaryocytes, enhances platelet adherence by
forming a bridge between cell surface receptors and collagen
in the subendothelial matrix.
Adhesion of the
platelets
Platelet release
reaction &
activation
Platelet
aggregation &
plug retraction
Temporary
hemostatic
(platelet) plug
+
+
Local
vasoconstriction
FORMATION OF A PLATELET PLUG (cont.)
Stage 1. Platelets adhesion
A. vWF - von Willebrand
factor (soluble plasma
protein) binds to collagen of
subendothelial matrix
Failure of this step may be due to:
- Absence of von Willebrand factor
- Malfunction of collagen - Scurvy
B. vWF exposes multiple intrinsic binding sites
for the platelet specific membrane
glycoprotein Ib (GPIb)
vWF binds to glucoprotein Ib receptors of
platelets and to collagen
9
FORMATION OF A PLATELET PLUG (cont.)
Stage 2-3 Platelets release reaction
and activation.
Binding of the platelets to the collagen
→ Release of agents from secretory
granules (degranulation) – serotonin,
adrenaline, several clotting factors,
thromboxane A2, tissue factor and
ADP
Serotonin, adrenaline and ADP act
locally → changes in the
metabolism, shape, and surface
proteins of the platelets.
Serotonin and
thromboxane A2 stimulate
local vasoconstriction
10
Primary Hemostatsis
Step 1: Transient vasoconstriction
(endothelin)
Step 2: Platelet adhesion - von
willebrand factor bind to the
disrupted blood vessel via GpIb
Step 3: Platelet release ADP and
thromboxane A2 which stimulate
adhesion of the next layers of
platelets (recruitment) through a
positive feedback mechanism and
formation of a platelet plug inside
the vessel ADP induces platelet to
express GpIIB-IIIa which is needed to
platelets aggregation via fibrinogen
Step 4: Platelet aggregation (Platelt
plug)
Deficiency:
Bernard-Soulier
syndrome
Deficiency:
Glanzmann
thombasthenia
GpIb
Platelet
GpIIb-IIIa
complex
GpIb
Endothelium
Von willebrand factor
Subendothelium
FORMATION OF A PLATELET PLUG (cont.)
Stage 4: Recruitment and loose platelets aggregation
Platelet
• ADP and thromboxane A2
stimulate adhesion of the
next layers of platelets
(recruitment) through a
positive feedback
mechanism and formation
of a platelet plug inside the
vessel
GpIIb-IIIa
complex
Failure of this step:
- Insufficient number of platelets
- Dysfunctional platelets (prior activation
occurs during cardiopulmonary
bypass, storage, exposure to aspirin,
uraemia and acute and chronic alcohol
exposure)
12
12
Normal Blood Vessel
Injured blood vessel
Attracts more
platelets
Aggregate into
platelet plug
Release of
Platelet factors
Exposed collagen
binds and activates
platelets
Secondary Hemostasis
This involve the conversion of the fibrinogen
(solube) in the platelet plug to fibrin (insoluble).
Fibrin is then cross-linked to yield a stable
platelet-fibrin thrombus.
Secondary hemostasis involve the activation of
coagulation cascade factors in both intrinsic and
extrinsic pathways
BLOOD COAGULATION (CLOTTING)
• Is the transformation of the blood into a solid gel (a clot or thrombus)
• Occurs locally around the platelet plug; supports and reinforces the
plug
• Requires 12 plasma clotting factors and platelets
• Involves a cascade of biochemical reactions in which each factor that
is activated in turn activates the next factor
• The fundamental reaction is conversion a soluble protein, fibrinogen
to an insoluble protein, fibrin
 In coagulation a series of plasma proteins called blood-clotting factors play
major roles.
 Most of these are inactive forms of proteolytic enzymes.
 When converted to the active forms, their enzymatic actions cause the
successive, cascading reactions of the clotting process.
17
Coagulation System
Consists of a cascading system of proteins
– Primarily originating from liver (except factor III)
– Circulate in inactive form
– System includes:
•
•
•
•
•
Enzymatic factors
Non-enzymatic factors
Tissue thromboplastin (factor III)
Calcium (factor IV)
Platelet phospholipid (PF 3) - structural component; accelerates factor
activation
• Anticoagulant factors
The coagulation system consists of three pathways (intrinsic,
extrinsic and common)
PLASMA CLOTTING FACTORS
Scientific Name
Common Name
Main Function
Factor I
Fibrinogen
Converted to fibrin
Factor II
Prothrombin
Enzyme
Factor III
Tissue thromboplasm
Cofactor
Factor IV
Calcium
Cofactor
Factor V
Proaccelerin
Cofactor
Factor VII
Proconvertin
Enzyme
Factor VIII
Antihemophilic factor
Cofactor
Factor IX
Christmas factor
Enzyme
Factor X
Stuart factor
Enzyme
Factor XI
Plasma thromboplatin antecedent
Enzyme
Factor XII
Hageman factor
Enzyme
Factor XIII
Fibrin stabilizing factor
Enzyme
3 PHASES OF BLOOD COAGULATION
•
Formation of a complex of activated substances prothrombinase (prothrombin activator)
•
Formation of active thrombin from prothrombin
– Is catalyzed by prothrombin activator
•
Formation of insoluble fibrin from soluble fibrinogen
– Is catalyzed by thrombin
20
PHASE 1 – FORMATION OF PROTHROMBINASE
INTRINSIC PATHWAY
XII
EXTRINSIC PATHWAY
XIIa
XIa
XI
IX
Ca2+
III
Ca2+
VIIa
VII
IXa
PF-3
Ca2+
VIII
Xa
PF-3
Ca2+
V
X
II
X
XIII
Thrombin
XIIIa
Fibrinogen
Fibrin
Stable fibrin
polymer
PHASE 3 – FORMATION OF FIBRIN
• Thrombin catalyses release of 2
pairs of polypeptides from each
fibrinogen molecule and
formation of fibrin monomers
– Ca++ and platelet factors are
also required
• Monomers join together to form
insoluble fibrin polymers – a loose
mesh of stands
• Stabilization of fibrin – formation
of covalent cross-bridges, which is
catalyzed by factor XIII (+ Ca++)
22
FINAL EVENTS OF HEMOSTASIS
•
Fibrin forms a meshwork, which supports
the platelet plug
•
Clot occludes the damaged blood vessel and
↓ or stops bleeding
•
Retraction of the clot due to contraction of
fibrin fibers and contractile proteins of the
platelets
– ↑ clot density
– Occlusion of the damaged vessel
– Bringing the edges of wound together →
facilitation of wound heeling
•
Fate of the blood clot
– Invasion by fibroblasts → formation of
connective tissue through the clot
– Fibrinolysis and destruction of the clot
23
Dissolving the Clot
Figure 16-14: Coagulation and fibrinolysis
Clot Dissolution
• Plasmin (fibrin-digesting enzyme) is made from activating
plasminogen (blood protein)
– Presence of the clot causes endothelial cells to release
tissue plasminogen activator
– Fibrinolysis begins within 2 days and continues slowly
over several days until the clot is dissolved.
ra
Plasminogen
Activator (e.g. t-PA)
Fibrin
Plasmin
soluble fragments
Fibrinolysis Clinical applicationHuman t-PA is produced by recombinant DNA
technology and available for clinical use.
lyses clots in the coronary arteries if given to
patients soon after the onset of myocardial
infarction.
Streptokinase (from bacteria-streptococcci) and
urokinase are also fibrinolytic enzymes
used in the treatment of early myocardial infarction
26
Clot retraction & repair
• Clot retraction occurs within 30-60 minutes.
• Platelets contain actin & myosin
• As clot is compacted fibroblasts (stimulated by plateletderived growth factor -PDGF) rebuild the wall while
endothelial cells (stimulated by vascular endothelial
growth factor -VEGF) multiply to restore the lining
Overview of Hemostasis and Tissue Repair
Damage to
wall of blood
vessel
Collagen exposed
Tissue factor exposed
Platelets adhere
and release
platelet factors
Vasoconstriction
Coagulation
cascade
Thrombin
formation
Platelets aggregate
into loose platelet plug
Reinforced platelet plug
(clot)
Temporary
hemostasis
Fibrin slowly dissolved by
plasmin
Cell growth and
tissue repair
Clot dissolves
Intact blood
vessel wall
Converts
fibrinogen to
fibrin
ROLE OF VITAMIN K IN CLOTTING
•
Vitamin K acts as a cofactor of the enzyme γ-glutamyl carboxylase
•
Is required for γ carboxylation in the liver of
– Prothrombin and factors VII, IX and X
– Proteins S and C (natural anticoagulants)
Vit K is activated by epoxide reductase in the liver
•
•
γ carboxylation (introduction of a carboxylic acid group) of certain glutamate
residues in target clotting factors → binding sites for Ca++ and PF3
most of clotting factors are synthesized by the liver. Therefore, liver diseases
(i.e., hepatitis, cirrhoses, atrophy) depress the clotting system. Decreased
dietary intake of vit K has limited consequences on blood clotting because Vit
K is continuously synthesized by the intestinal flora. Note that Vit K is fat
soluble and requires fats for absorption. Lack of the bile decreases fat
digestion and absorption.
30
ROLE OF Ca++ IN COAGULATION
• Ca++ is required for all steps of coagulation (except first 2 steps of
the intrinsic pathway)
• ↓ in the plasma [Ca++] below the threshold level for clotting → ↓
blood clotting by both pathways
31
ROLE OF THE PLATELETS IN COAGULATION
Activated platelets
• Display specific plasma membrane receptors that bind several of
the clotting factors → several cascade reactions take place on the
surface of activated platelets
• Display phospholipids (platelet factors), which act as cofactors of
the bound clotting factors
32
ROLE OF THE LIVER IN BLOOD COAGULATION
• Synthesis of the plasma clotting factors
• Synthesis of the bile salts, which are required for intestinal
absorption of lipid soluble vitamin K
33
Anti clotting mechanism
Anti clotting mechanism
1.
2.
3.
4.
5.
6.
7.
8.
Smoothness of endothelium (glycocalyx)
Thrombomodulin
Fibrin fibers and anti thrombin III
Heparin
Plasmin
Prostacyclin
2 macroglobulin
Circulating blood
• Antithrombin III – inhibits factor X and
thrombin
• Fibrin acts as an anticoagulant by binding
thrombin and preventing its:
• Heparin – a natural anticoagulant,potentiates
effects of antithrombin III (together they
inhibit IX, X, XI, XII and thrombin
• Antithromboplastin (inhibits „tissue factors” –
tissue thromboplastins)
• Protein C and S – degrade factor Va and VIIIa
NATURAL ANTICOAGULANTS (cont.)
Thrombin/thrombo-modulin/protein C pathway
Endothelial cell
Thrombomodulin is a thrombin-binding
endothelial cell receptor
Thrombomodulin
Thrombin
Binds thrombin and inactivates it
Protein C
Complex of thrombin+thrombo-modulin binds
protein C and activates it
Activated Prot C
Protein S
Protein C in collaboration with
protein S inactivates factors Va and
VIIIa and activates plasminogen and
fibrinolysis
ViIIa
Note: Mutated factor V cannot be inactivated
(switched off) by activated protein C, and this
will lead to hypercoagulable state
VIII
Inactivation of
inhibitors of
plasminogen
activator
Plasminogen
Thrombin
Va
V
Plasmin
Fibrinolysis
37
DRUGS THAT INHIBIT BLOOD CLOTTING
(ANTICOAGULANTS)
• Heparin: Heparin binds to the enzyme inhibitor antithrombin III
(AT), causing a conformational change that results in its
activation. The activated AT then inactivates thrombin and
other proteases involved in blood clotting such as XIIa, XIa, Xa
and IXa
• Coumarin derivatives (i.e., warfarin)
– Block stimulatory effects of vitamin K on synthesis of clotting
factors II, VII, IX, and X by the liver (inhibit epoxide reductase
which activates vit K in the liver: K → K1)
• Aspirin
– Low doses inhibit prostaglandins and thromboxanes synthesis by
the platelets → inhibition of platelet release reaction and platelet
aggregation
– Is effective in preventing of heart attack and reduction of the
incidence of sudden death
38
IN VITRO INHIBITION OF BLOOD CLOTTING
•
Keeping of blood in seliconized containers – prevention of contact activation of
platelets and factor XII
•
Substances that bind ionized calcium to produce un-ionized calcium compound or
to form insoluble salts with calcium
– Sodium citrate or oxalate
– Ammonium or potassium citrate
– EDTA (ethylenediaminetetraacetic acid)
• Is ability to "sequester" di- and tricationic ions (Ca2+ & Fe3+)
• Is widely used as an anticoagulant for blood samples for complete blood
count/full blood examination
•
Heparin
39
Bleeding time



This is a test that measures
the speed in which small blood vessels close off
(the condition of the blood vessels and platelet
function)
This test is useful for detecting bleeding tendencies
The bleeding stops within 1 to 4 minutes. This may vary
from lab to lab, depending on how the test is measured



The time taken for blood
to clot mainly reflects the
time required for the
generation of thrombin
The surface of the glass
tube initiates the clotting
process. This test is
sensitive to the factors
involved in the intrinsic
pathway
The expected range for
clotting time is 4-10 mins.
Whole blood
clotting time
Tests of coagulation
"Intrinsic" and "extrinsic"
coagulation pathways
Activated Partial
Thromboplastin Time
N: 25-35 sec
Prothrombin Time
N: 9.9 – 13 sec
PROTHROMBIN TIME (protime, PT test)
• Measures the clotting time of
plasma from the activation of
factor VII, through the formation
of fibrin clot
• Assesses the integrity of the
extrinsic/tissue factor pathway
and common pathways of
coagulation (factors VII, X, V, II, I)
• The PT test is widely used to
monitor patients taking
anticoagulants as well as to help
diagnose clotting disorders
44
Prothrombin Time
Factors
Thromboplastin
and Calcium
Patient’s
Plasma
Diagnostica Stago training, 2005
I
II
V
VII
X
45
Prothrombin time (PT) test – norm 11 -15 sec
evaluates extrinsic system (VII, X, V, II, fibrinogen)
•
prolonged PT indicates a deficiency
in any of factors VII, X, V,
prothrombin (factor II), or fibrinogen
(factor I).
• Prolonged PT:
- a vitamin K deficiency (vitamin K is a
co-factor in the synthesis of
functional factors II (prothrombin),
VII, IX and X)
- liver disease
- Warfarin therapy
- DIC
- excesive heparin
PROTHROMBIN TIME (cont.)
•
Depends on [prothrombin] in the blood
•
Normal range 12 – 14 sec
•
Increased
– ↓ prothrombin (less than 10% of normal)
– Deficiency of fibrinogen or factors V, VII, or X
– Therapeutic anticoagulants (i.e., heparin,
warfarin, aspirin), some drugs (i.e.,
antibiotics, anabolic steroids, estrogens, etc.)
– Liver diseases
– Vit K deficiency
– Disseminated intravascular coagulation
•
Decreased
– Vit K supplementation
– Thrombophlebitis
47
ACTIVATED PARTIAL THROMBOPLASTIN TIME
(aPTT)
• Assesses the integrity of the intrinsic and common pathways
of coagulation
• Measures the clotting time of plasma, from the activation of
factor XII by a reagent through the formation of fibrin clot
• Normal range 25 – 38 sec
• Prolonged time
– Use of heparin
– Antiphospholipids antibodies
– Coagulation factors deficiency (intrinsic and common pathways; i.e.,
hemophilias)
48
Activated Partial
Thromboplastin Time
Factors
Ca++
Phospholipid
and Activator
Patient’s
Plasma
Diagnostica Stago training, 2005
I
II
V
VIII
IX
X
XI
XII
49
Activated Partial Thromboplastin Time test
(aPTT) – norm: 25-35 s; evaluates intrinsic system
(VIII, IX, XI, XII, X, V, II, fibrinogen)
• an isolated prolongation of the
aPTT (PT normal) suggests
deficiency of factor VIII, IX, XI
or XII
• prolongation of both the APTT
and PT suggests factor X, V, II
or I (fibrinogen) deficiency, all
of which are rare
• aPTT is normal in factor VII
deficiency (PT prolonged) and
factor XIII deficiency
Most common case of prolonged aPTT – heparin!!!
Thrombin Clotting Time
Low concentration
of thrombin
Screens for
effects of
• Heparin
• FDPs
Undiluted patient’s
plasma
Diagnostica Stago training, 2005
52
Thrombin time (TT) – norm: 14-15 sec
Prolonged TT:
• Heparin (much more sensitive to heparin
than aPTT)
• Hypofibrinogenemia
Selected causes of abnormal
coagulation tests
Partial
Thromboplastin
Time (aPTT)
Prothrombin
Time (PT)
Thrombin Time
(TT)
Bleeding Time
(BT)
Factor deficiency
(except VII)
VII, X, V, II,
fibrinogen
deficiency
Low or absent
fibrinogen
Thrombocytopenia
Antibodies to
clotting factors
Antibodies
Dysfibrinogenemia,
Von Willebrand’s
disease
Heparin
Warfarin; Vit K
defficiency (mild to
severe)
Heparin
Drugs (Aspirin,
NSAIDs, high dose
penicillins, etc.)
Excessive Warfarin
Excessive Heparin
hypofibrinogenemia
Cirrhosis, Uremia,
PLTs dysfunction
2 TYPES OF ABNORMALITIES OF HEMOSTASIS
• Excessive bleeding (hemorrhagic disease) caused by
deficiency of a clotting factor/s or platelets
• Excessive clotting: thrombosis, embolism, disseminated
intravascular coagulation
56
CONDITIONS THAT CAUSE EXCESSIVE BLEEDING
• Vitamin K deficiency
• Deficiency of clotting factors (i.e., hemophilia)
• Deficiency of thrombocytes – thrombocytopenia
• Deficiency of von Willebrand factor
57
VITAMIN K DEFICIENCY
• Results from
– ↓ intestinal absorption of fats due to ↓ bile secretion (i.e., liver
disease or obstruction of the bile ducts)
– ↓ dietary intake of vit K (limited importance)
• Results in
– ↓ hepatic gamma carboxylation of
• Prothrombin (II)
• Factors VII, IX and X
• Protein C and S
– Bleeding tendency
• Prolonged prothrombin time and partial thromboplastin time
• Normal platelets count and serum fibrinogen split products
58
HEMOPHILIA
• Is a hemorrhagic disease that results from deficiency
of
– Factor VIII (the smaller component) - hemophilia A
or classical
– Factor IX – hemophilia B, Christmas disease
– Factor XI – hemophilia C
• Is a genetic disease
– Hemophilia A and B are sex linked (X chromosome)
• Occur in males
• Females are hemophilia carriers
• Results in ↑ aPTT (PT, thrombocytes count, fibrin split
products are normal)
59
Hemophilia A
(lack of F VIII; 85%)
• Spontaneous or
traumatic subcutaneous
bleeding
• Blood in the urine
• Bleeding in the mouth,
lips, tongue
• Bleeding to the joints,
CNS, gastrointestinal
tract
Mild hemophilia after
injection in buttock
HEMOPHILIA
Deficienc Clinical Syndrome
y Factor
Cause
Factor I
Afibrinogenemia
Depletion during pregnancy with premature
separation of placenta: Congenital
Factor II
Hypoprothrombinemia
(Hemorrhagic tendency in
liver diseases
Decreased hepatic synthesis (secondary to
vitamin K deficiency)
Factor V
Parahemophila
Congenital
Factor VII Hypoconvertinemia
Congenital
Factor
VIII
Hemophilia A (classical
hemophilia)
Congenital recessive sex-linked defect due to
abnormalities of the gene that codes for factor
VIII (X chromosome)
Factor IX
Hemophilia B (Christmas
disease)
Congenital recessive trait carried on X
chromosome
Factor X
Stuart-Prower factor
deficiency
Congenital
Hemophilia C (PTA
deficiency
Congenital
Hageman trait
Congenital
THROMBOCYTOPENIA
• Low thrombocytes count (below 50 000/m l) → poor plug formation,
deficient clot retraction, deficient platelet phospholipids, poor constriction
of ruptured vessels → bleeding tendency from many small venules and
capillaries
• Multiple hemorrhages in the skin and mucous membranes –
thrombocytopenic purpura
– Petechiae – small punctate hemorrhages(1-3 mm)
– Echymoses - large hemorrhages (bruises)
• Other causes of purpura
– ↓ plasma level of 1 or more clotting factors
– ↑ fragility of capillary walls (congenital, Vit C deficiency,
adrenal failure, toxins, drugs, allergic reactions)
62




Severe reduction in the
number of PLTs thrombocytopenia
this causes spontaneous
bleeding as a reaction to
minor trauma
in the skin - reddish-purple
blotchy rash
it may result from:
-
decreased production (toxins, radiation,
infection, leukemias)
-
increased destruction (autoimmune
processes)
-
increased PLTs consumption (DIC)
Thrombocytopenia
Hemorrhagic spots (petechiae)
von Willebrand’s disease
• Is the most common genetic bleeding disorder
• Results from defect in vWF ( quantitative or functional)
• Results in combination of
– Platelet function abnormality (vWF) - impaired adhesion
– Clotting factor deficiency (factor VIII) - ↑ aPTT (PT is normal)
64
THROMBO-EMBOLIC CONDITIONS
•
Thrombosis - blood clotting within the CVS which obstruct the blood flow through
the CVS (Should be distinguished from extravascular clotting, clotting in wounds
and clotting that occurs in the CVS after death). Thrombosis is rather a
pathological condition.
•
Common causes
– Roughened endothelial surface (i.e., atherosclerosis, infections, traumas)
– Slow blood flow
– Hypercoagulobility
– Acquired refers to transient or acquired conditions that increase the tendency
to clot. This might include antiphospholipid antibodies or a temporary
hypercoagulable state such as pregnancy. Also, advanced carcinomas of the
pancreas or lung may produce a hypercoagulable state.
– Congenital refers to hereditary conditions that increase the tendency to clot.
These include Factor V Leiden, prothrombin ,protein C, protein S and
antithrombin deficiencies
65
Consequences
Formation of emboli (thromboembolism) – braking down
of the thrombus and spreading of its particles particles
throughout the CVS
Thrombosis in the left side of the heart and large
arteries → emboli in the brain, kidneys, etc
Thrombosis in the venous system and in the right side
of the heart → emboli in the pulmonary circulation
Disseminated intravascular
coagulation (DIC)
• Widespread coagulation 
thrombosis in small blood vessels
 increased fibrinolysis,
and depletion of coagulating
factors  generalized bleeding
• It may result from:
- bacterial infections
damage)
- disseminated cancers
(release of procoagulants)
- complications of pregnancy
- severe catabolic states
(endothelial
Disseminated cervical
cancer metastases (PET
imaging)
DESSIMINATED INTRAVASCULAR COAGULATION
• Reasons
– Large areas of necrotic tissue (release of tissue factors into the blood)
– Septicemia (activation of clotting by circulation bacteria and bacterial
toxins)
• Consequences
– Consumption coagulopathy
• ↓ fibrinogen, thrombocytopenia
• ↑ fibrin split products
• ↑ PT and PTT
68
CHALENGE YOURSELF
1/5
A baby is born prematurely at 28 weeks gestational
age with a birth weight of 1200 g. A few weeks after
birth his mother noticed a bleeding tendency in the
infant. Blood test revealed a low prothrombin level.
Which vitamin can be given to the baby to reduce or
to prevent the bleeding tendency?
a. Vitamin B12
b. Vitamin B6
c. Vitamin K
d. Folic acid
e. Vitamin A
Answer is C
69
CHALENGE YOURSELF
2/5
• A 72-year-old African-American man undergoes hip surgery.
On his third hospital day he experiences chest pain,
tachycardia, dyspnea, and a low-grade fever. The man goes
into cardiac arrest, and efforts to resuscitate him are
unsuccessful. On autopsy a massive pulmonary embolus is
discovered. Which of the following, if present, would most
likely predispose the patient to this event?
(A) Factor VIII defi ciency
(B) Low serum homocysteine levels
(C) Mutation in the Factor V gene
(D) Overproduction of protein C
(E) von Willebrand factor defi ciency
Answer is C
CHALENGE YOURSELF
3/5
Taking aspirin every day can reduce the risk of heart
disease because
a.it is a powerful vasodilator
b it stimulates fibrinolysis
c. it prevents atherosclerosis
d.it loosens atherosclerotic plaque on arterial walls
e. it prevents platelet aggregation
Answer is E
CHALENGE YOURSELF
5/5
• A 65-year-old man presented with history of acute
chest pain that radiates to his left arm. Coronary
angiography demonstrates more than 75% occlusion of
his coronary artery. He was administered a
thrombolytic agent for reestablishment of blood flow to
the dying myocardium. The thrombolytic agent
activates:
The Answer is C
A. Heparin
B. Throbin
C. Plasminogen
D. Kininogen
E. Prothrombin
Fill in the gap please
PT
Hemophilia A
Hemophilia B
vWF disease
Vit K Def
Liver Disease
N
PTT
Platelet
Count
Bleeding
Time
Reticulo
cyte
Megakyr D-Dimer
yocyte
Schicocy
te
N
N
N
N
No
No
What is the proper pathway for the extrinsic clotting pathway?
A) Contact of blood with collagen, formation of prothrombin
activator, conversion of prothrombin into
thrombin, conversion of fibrinogen into fibrin threads
B) Tissue trauma, formation of prothrombin activator,
conversion of prothrombin into thrombin,
conversion of fibrinogen into fibrin threads
C) Activation of platelets, formation of prothrombin
activator, conversion of prothrombin into thrombin,
conversion of fibrinogen into fibrin threads
D) Trauma to the blood, formation of prothrombin
activator, conversion of prothrombin into thrombin,
conversion of fibrinogen into fibrin threads
What condition leads to a deficiency in factor IX
that can be corrected by an intravenous
injection of vitamin K?
A) Classic hemophilia
B) Hepatitis B
C) Bile duct obstruction
D) Genetic deficiency in antithrombin III
A patient suffers from a congenital deficiency in
factorXIII (fibrin-stabilizing factor). What would
analysis of
his blood reveal?
A) Prolonged prothrombin time
B) Prolonged whole blood clotting time
C) Prolonged partial thromboplastin time
D) Easily breakable clot
A 2-year-old boy bruises easily and has previously
had bleeding gums. The maternal grandfather has a
bleeding disorder. His physical examination shows
several small bruises on the legs. Of which
coagulation factor would you suspect this patient to
be deficient?
A) Prothrombin activator
B) Factor II
C) Factor VIII
D) Factor X
An 11-year-old premenstrual female presents with a painful knee
after mild trauma. Upon further evaluation you observe soft tissue
bruises. The child is an orphan and there is no family history. The
foster mother reports no other problems. The aPTT is prolonged
and the PT is normal. A complete hematologic workup would yield
A) decreased plasma Ca21
B) elevated plasmin
C) lack of factor VIII
D) decreased platelet number