POINTERS TO REVIEW
Terminologies
o Thrombosis
Pathologic counterpart, Thrombus within intact
vessels
o Hematoma
masses of clotted of Blood that form when a
blood vessel breaks.
o Hemoconcentration
o Thrombophlebitis  o
A thrombus is a clump of blood cells (i.e.,
platelets, clotting factors, fibrin, etc.)
Thrombi also occur the superficial veins in the
legs (superficial thrombophlebitis).
o Primary hemostasis
Primary hemostasis depends upon the response
of the platelet and blood vessel wall to the
injury.
When the small blood vessels are injured, blood
platelets adhere and aggregate at the site of
injury, reducing and finally arresting bleeding.
􏰔 Patelet adherence and activation
􏰔 Dramatic shape change
􏰔 Release of secretory granules
􏰔 Recruit additional
platelets (aggregation) to form a hemostatic plug
􏰕primary hemostasis
o Secondary hemostasis (What are those things
that happen in primary and secondary
hemostasis)
starts when the cascade system of Coagulation is
activated by substances released at the time of
blood vessel injury.
􏰔 Membrane-bound procoagulant
glycoprotein synthesized by endothelial
cells
􏰔 Exposed at the site of injury
􏰔 With factor VII, in vivo initiator of the
coagulation cascade
􏰔 Thrombin generation
􏰔 Cleavage of fibrinogen into insoluble
fibrin
􏰔 Creation a fibrin meshwork
􏰔 Further platelet recruitment and
activation
o Von willebrand factor
HEREDITARY PLATELET DISORDER
􏰔 Most common congenital bleeding disorder
􏰔 Quantitative or qualitative abn. Of vWF (By
mediating adhesion of platelets to the injured
endothelium)
􏰔 VWF plays role in both formation of platelet as
well as fibrin clot ( By functioning as a Protective
carrier of Factor VIII)
1 – most common
2 - Qualitative alterations in the vWF structure and
funtion
3 - Least common and most severe
Bernard soulier syndrome
Inherited as an autosomal recessive trait.
Bruising and moderate to severe bleeding.
Giant Platelets (20 um in diameter) Coarse
granulation and vacuoles, Mild
thrombocytopenia
o The drugs that involved in platelet
cyclooxygenase
o Prothrombin time
Deficiency or inhibition of one or more of the
following coagulation factors: VII, X, V, II,
fibrinogen
therefore the time required for the plasma to clot
after an excess of thromboplastin and an optimal
concentration of calcium have been added.
Modified by Brown, Stanley and Bancroft
􏰔 Measures Effectiveness of the Extrinsic
Pathway
􏰔 Measures the activity of V, VII, X, II, I
Normal Value: 11-16 Seconds
o Partial thromboplasin time
(PT) test is ordered to help diagnose unexplained
bleeding, often along with a partial
thromboplastin time (PTT) test.
Partial thromboplastin time (PTT) to measure
the functioning of factors VIII, IX, XI, XII, and
von Willebrand factors
o APTT
Activated partial thromboplastin time (aPTT) is
an assay used to screen for abnormalities of the
intrinsic clotting system. It is also used to
monitor the anticoagulant effect of circulating
heparin.
Normal: 30-40 seconds

o Thrombin time
Deficiency or abnormality of fibrinogen or
inhibition of thrombin by heparin or FDPs.
Thrombin time (TT) the time required for
plasma fibrinogen to form thrombin,
measured as the time for clot formation after
exogenous thrombin is added to citrated plasma.
o Bleeding time
-Platelet function -Vascular integrity. 3-10 mins
o Findings/results (normal PTT with prolonged
PT and so on)
o Mild bleeding
Hemophilia A
o Situation problem about Laboratory findings
and interpret or select
o Autohemolysis test
o Glucose-6-phosphate dehydrogenase test
o Thrombocytopenia (causes)
>platelet count <100,000 or rapidly Declining.
low platelet count.
o Causes of platelet destruction
Both the drug and Ab must be present in the
system at the same time for platelets destruction
o Condition associated to platelet distraction
Increased splenic pooling is differentiated from
destruction of platelets
o Primary ITP (pathophysiology)
o Pathophysiology thrombotic
thrombocytopenic purpura
blood disorder that results in blood clots forming
in small blood vessels throughout the body. This
results in a low platelet count, low red blood
cells due to their breakdown, and often kidney,
heart, and brain dysfunction.
o Heparin induced thrombocytopenia
o DIC
Disseminated intravascular coagulation (DIC is
a pathological activation of coagulation) blood
clotting) mechanisms that happen in response to
a variety of disease.
DIC leads to the formation of small blood clots
inside the blood vessels throughout the body.
The small clots also disrupt normal blood flow
to organs (such as the kidney), which may
malfunction as a result
o different types of hemophilia
Mutations in the factor VIII gene results in
HEMOPHILIA A.
􏰡 CLASSICAL HEMOPHILIA, an X-linked recessive
coagulation disorder.
Factor IX Deficiency cause Hemophilia B or Christmas
disease.
o Hematoma petechial purpura hemadioma
o Erlichdone syndrome
o Senile purpura
o Solar actinic purpura
Solar purpura (also known as "Actinic purpura," and
"Senile purpura") or Purpura Senilis is a skin condition
characterized by large, sharply outlined, 1- to 5-cm, dark
purplish-red ecchymoses appearing on the dorsa of the
forearms and less often the hands.
Easy skin bruising in older people. As people age, their
skin becomes thinner and more fragile.
􏰟 Bruises (senile purpura) tend to form easily as the
blood vessels in the skin are also more fragile
􏰟 The bruising does not mean that the person is
necessarily deficient in any vitamins or minerals nor
does it mean that they have a bleeding
disorder.
o Afibrinogenemia; Hypofibrinoginemia;
Dysfibrinogenemia (classical findings of the
lab tests)
INHERITED DISORDERS (MUTATIONS IN
FIBRINOGEN) INCLUDE:
1. Afibrinogenemia, when fibrinogen is absent
2. Hypofibrinogenemia, when some protein with
normal structure is present but below levels needed for
normal clotting.
3. Dysfibrinogenemia is a qualitative disorder in which
normal amounts of fibrinogen are produced by the liver,
but they function properly.
o D-dimers test Petechiae are tiny, usually measuring less than
Uses: an eighth of an inch (about 3 millimeters).
1. Deep Vein Thrombosis Larger varieties of these types of spots are called
2. Pulmonary embolism Purpura and Ecchymoses
3. DIC
4. Efficacy of treatment in MI
􏰿 A more rapid detection of fibrinolytic o Laboratory test of investigation of
􏰿 activity, especially hyperfibrinolysis, is coagulation disorders (which are hereditary
possible with thromboelastometry (TEM) in and which are acquired disorders)
whole blood, even in patients on heparin.
􏰿 In this assay, increased fibrinolysis is assessed o Sex-linked recessive disorders
by comparing the TEM profile in the absence or
presence of the fibrinolysis
inhibitor aprotinin. (Protease inhibitor).
􏰿 Clinically, the TEM is useful for near real-
time measurement of activated fibrinolysis
for at-risk patients, such as those experiencing
significant blood loss during
surgery.

o Anti-thrombogenic; thrombogenic

o In general, what is bleeding disorders?

􏰔 Acquired platelet function defects.
􏰔 Congenital platelet function defects.
􏰔 Disseminated intravascular
􏰔 coagulation (DIC)
􏰔 Prothrombin deficiency.
􏰔 Factor V deficiency.
􏰔 Factor VII deficiency.
􏰔 Factor X deficiency.
􏰔 Factor XI deficiency (hemophilia C)
􏰔 XII deficiency

o Coagulation disorders?
1. Hereditary coagulation disorders
ii. von Willebrand disease
iii. afibrinogenemia or
dysfibrinogenemia
2. Acquired coagulation disorders
i. Vit- K def.
ii. Liver disease
iii. Intravascular clotting
iv. Anticoagulant therapy

o The manifestation of bleeding (petechia,

chymosis purpura and others)
Petechiae, Purpura and Ecchymoses (Blue or
purple ) the three terms that refer to bleeding
that occurs in the skin. The term petechiae refer
to smaller lesions. Prpura and ecchymoses refer
to larger lesions. In all situations, petechiae,
ecchymoses, and purpura do not blanch when
pressed.
 Hemophilia A or Factor VIII or Christmas
disease (factor IX deficiency)
o Mutation of the genes
autosomal recessive pattern, meaning both
parents must carry the mutated gene in order for
their children to be affected. In some cases,
􏰟 FXI deficiency can also be inherited in
an autosomal dominant pattern, meaning children with
only one affected parent may inherit the condition.
􏰟 However, people with only one copy of the mutated
gene rarely exhibit severe symptoms.
􏰟 Men and women are affected by FXI deficien
o Major causes of death in haemophiliacs
o Impairment of platelet functions
o Evidence of bleeding
o Fibrinolysis  o
The last stage of coagulation is fibrinolysis, which is the
dissolution and localization of a fibrin clot. These
functions are carried out by enzymes and their inhibitors.
A disruption or breach of the fine balance of this
fibrinolytic system can result in bleeding or thrombosis.
o What are those that involved in bleeding
o Pathological situations that disturb the
balance of hemostasis
􏰔 Surgery or anesthesia or any other invasive
procedure.
􏰔 Trauma,
􏰔 Cytokines
􏰔 Infectious agents
Pre-operative period is at high risk for both
prohaemorrhagic and prothrombotic
abnormalities.
o Procoagulants and anticoagulants
PAI-1 Antiplasmi Tissue Factor Clotting Factors
–P
Prot. S Prot. C TFPI Fibrinolytic System ATIII -
A factor X deficiency.
o Haemophilia A
o Mutations in the factor VIII gene results in
HEMOPHILIA A.
o 􏰡 CLASSICAL HEMOPHILIA, an X-linked
recessive coagulation disorder.
o Deficiency clotting factor VIII and others
o What elevated fdp is suggesting
Fibrinogen degradation products (FDP) are the
products of fibrinogenolysis and are detected by
the FDP assay
􏰖 Fibrin degradation products (fdp) (fsp) are the
product of fibrinolysis.
o Agrigonometry test (platelet adhesiveness
test)
o Laboratory results of DIC and other clotting
factors deficiency
Lab Results- Prolonged BT, PTT
o Function of vWD
o Component of PTT
Most common inherited bleeding disorder
o Which one will have the normal PTT
o Haemophilia B
o Classification of vWF deficiency
o Factor V, VII, X deficiency
o Treatment, mutations, nonherited forms of
factor X
o Stypven time
Stypven time test a prothrombin test similar to
the (one-stage) prothrombin time, but performed
with Russell's viper venom
􏰺 Stypven) as the thromboplastic agent; useful
in defining deficiencies of blood coagulation
factor X. Called also Russell's viper venom t. or
time and Stypven time.
􏰺 Stypven activates factor X directly, thus the
Stypven time is normal in factor VII deficiency,
but abnormal in factor V, II and most cases of
o Rosenthal syndrome
FACTOR XI DEFICIENCY (Hemophilia C,
Plasma Thromboplastin Antecedent (PTA)
Deficiency, Rosenthal Syndrome)
o Reptilase coagulation time
 􏰺 Reptilase time (RT) is a blood test used to
detect deficiency or abnormalities in fibrinogen
especially in cases of heparin contamination.

􏰺 The reptilase time measures the conversion

of fibrinogen to fibrin clot by reptilase
(Batroxobin, Atroxin), a thrombin-like enzyme
derived from the venom of the fer- de-lance
(barba amarilla,Bothrops atrox) a poisonous
snake of South and Central America and the
West Indies.

􏰺 In contrast to thrombin, which cleaves

fibrinopeptides A, AP, and B from the
fibrinogen molecule

􏰺 Reptilase only cleaves fibrinopeptides A and

AP.

􏰺 The resulting fibrin monomers polymerize

end to end to form a fibrin clot.

􏰺 Reptilase has no fibrinolytic activity, does not

activate plasminogen, and is not inhibited by
antifibrinolytics or heparin.

􏰺 The reptilase time is used in the evaluation of

a prolonged APTT, specifically to exclude the
presence of dysfibrinogenemia.

o Fibrinostrand (the crosslinking)

o Common pathway of coagulation

o Final common coagulation pathway

o Plasmin function in hemostasis

o Lupus anticoagulant

o Heparin as anticoagulant

o Tests for fibrinogen