HEMATOLOGY 2 2NDSem (FINAL)
After plasmin removes the first layer of lysine residue it
Fibrinolysis
As know, our primary and secondary hemostasis focuses on
the creation of blood clots, and in order to maintain balance
in our blood vessels there should be fibrinolysis.
A stage we clot dissolution is visible.
The last phase of the normal clotting process
After we achieve the stabilize fibrin clot, we will need to
dissolve the clot because normally we don’t have a clot in our
blood vessels.
FIBRINOLYTIC SYSTEM
Keeps blood vessels clear and is important in clot dissolution.
Has many similarities that exist between our coagulation and
fibrinolytic system.
As there as checks and balances in the formation of clot there
are also similar mechanisms for the dissolution of the clot to
promote wound healing.
( In short kaylangan madissolve yung clots in order to
promote repair and healing sa ating mga blood vessels)
It is important that bleeding does not reoccur because of
premature lysing of blood clots
- Our “FIBRIN CLOT “is formed by its precursor
“FIBINOGEN”. This fibrinogen is activated by
“THROMBIN” to help in the formation of fibrin clot.
- To stabilize our clot we will be needing our factor XIII
- Note that upon stabilizing our fibrin clot it does not stop
there after this we need to dissolve the clot to maintain
balance.
FIBRINOLYSIS
• Fibrinolysis is a “Process by which cross-linked fibrin is
systematically and gradually dissolved as the vessel heals
in order to restore normal blood flow”
• This is also the body's defense against occlusion of blood
vessels
• It is systematic in accelerating hydrolysis of our fibrin which
is bound by our plasmin
• During this process plasminogen is activated into plasmin
COMPONENTS OF FIBRINOLYSIS:
PLASMINOGEN
PLASMIN
FIBRINOLYSIS ACTIVATORS
INHIBITORS
PLASMINOGEN
• A single chain Glycoprotein which is called 5
glycosylated group (also known as “kringles”)
• Normally present in Plasma
• Synthesized by the liver
• Stored and transported in Eosinophils
• INCREASED CONC. IN INFLAMMATION
NOTE:
Kingles serves as a binding site, which allows our plasminogen
to bind to our fibrin clot.
Example:
our PLASMINOGEN --→ meron siyang KINGLES ---→
which tends to bind to our FIBRIN CLOT --→ specifically
a clot with LYSINE RESIDUE --→ UNDERSTAND that
this kringles binds to our lysine in order to be ACTIVATED
--→ of course it is with the help of our ACTIVATORS --→
specifically our TPA and UPA.
PLASMIN
Serine protease – PROTEASE means it is a
PROTEOLYTIC ENZYME which HYDROLYSES the
FIBRIN CLOT
Helps digest FIBRIN, FIBRINOGEN , FACTOR V & VIII
– specifically our FREE PLASMIN
Active form of plasminogen which removes lysine residue
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exposes another layer of lysine residue at kapag may
exposed nanaman na layer of lysine residue magbabind ule
ang ating plasminogen which will be activated into plasmin
which will again remove that layer of lysine residue until all
the clots has degraded which will result (Product will be) to
FIBRIN DEGRAGATION PRODUCTS or X AND
YFRGMENT or D-DIMER FRAGMENTS.
Once again our free plasmin usually binds with our factor
V,VIII and our fibronectin and fibrinogen and try to digest
those substances, so very helpful talaga ang ating plasmin in
our fibrinolysis
This is the MOST POWERFUL ENZYME in our
fibrinolysis and is a NON-SPECIFIC PROTEASE
PLASMINOGEN ACTIVATORS
This plasminogen activators helps in the activation of our
plasminogen to became an active enzyme which is the
plasmin.
1. Intrinsic Activators- CONTACT FACTORS: FACTOR
XIIa, kallikrein, HMK (high molecular weight kininogen)
2. UPA (urokinase-like plasminogen activator)
- secreted by the kidney, activates plasminogen
- a proteolytic enzyme which found in our body fluids
specifically secreted by our kidneys and vascular cells
- a purified form of our urine
- “urok” coming from the word kidney
- Involved in tissue remodeling and cell migration.
3. Therapeutic activators such as treatment for
thromboemboli
a. STREPTOKINASE – isolated from our beta-
hemolytic streptococci and it functions like the
activators of human origin but is more of an
antigenic type.
- Used for the treatment of
THROMBOEMBOLISM
b. STAPHYLOKINASE - isolated from
Staphylococcus aureus it also functions like the
activators of human origin but is more of an
antigenic type.
- Useful in the treatment of acquired
tromboembol
c. TPA- Tissue plasminogen activator
d. UPA- urokinase-like plasminogen activator
These acquired therapeutic agents are usually monitored by
our THROMBIN TIME
The Therapeutic range – 1.5 -5 x the reference range
4. TPA (Tissue plasminogen activator)
- a serine protease which is synthesize by our
ENDOTHELIUM which is usually regulated by our
PROTEIN C but exact mechanism of our TPA is still
unknown.
Inhibitors of Fibrinolysis
Why do we have inhibitors?
- Kasi nga in order to prevent excessive formation of
plasmin, kasi pag mas subra na plasmin it tends to cause
bleeding so dapat meron tayung inhibitors and activators
to balance the work with in our blood vessels.
Alpha 2 antiplasmin
o a major/principal inhibitor in our
fibrinolysis
o The first to bind with our plasmin
o It irreversible binds with our free plasmin and
renders as a non-functional form ibig sabihin it
neutralizes our plasmin
o Inhibits the clot promoting activities of our
plasma kallikrein and also inhibits our serine
proteases which are activated factor XII, XI,
activated factor II AND Xa
o HEREDITARY DEFICIENCIES has been
associated with EXCESSIVE CLOTTING
because of DECREASED PLASMIN / NO
PLASMIN that causes EXVESSIVE
FIBRINOLYSIS
1
 HEMATOLOGY 2
o Directed to plasmin
o Rise to compete with lysine residue of the clot
so plasminogen will not be converted to
plasmin
o Another action of alpha 2 antiplasmin is that it
tends to digest our plasmin
Alpha 2 macroglobulin
o Serves as the secondary to bind sa ating
plasmin
Alpha 1 antitrypsin
o The last major naturally occurring defense
against our plasmin
o THIRD MOST IMPORTANT
NATURALLY OCCURING INHIBOTOR
OF OUR FIBRINOLYTIC SYSTEM
o This inactivates our plasmin slowly and does
not bind plasmin until both alpha 2 anti-
plasmin and alpha 2 macroglobulin is already
saturated
o It also inhibit our coagulation by its potent
inhibitory effects sa ating factor XIa which is a
contact factor
Thrombospondin
PA (plasminogen activator) inhibitor 1 and 2 or
(PAI-1 and PAI-2)
o PAI-1
- Main inhibitor in our fibrinolysis
- inhibits our plasminogen activators (TPA,UPA,
STREPTOKINASE)
- produced by our endothelial cells, megakaryocytes
and other vascular cells in the body.
- stored as a component of Alpha granules
- Wala tayung plasmin na naproproduce kapag ang
inhibitpr natin ay ang PAI 1, because main action
ng ating PAI 1 is inhibiting (TPA, UPA,
STREPTOKINASE) and alam naman natin that
these and other activators nayan helps activate ang
ating plasminogen into its active form so kung wala
yung mga yan walang plasmin
o PAI-2
NOTE:
TOO MUCH/INCREASE INHIBITORS CAUSES
THROMBOUS FORMATION
BAKIT?
- So alam naman natin plasminogen will not be converted
into plasmin, So yung plasmin is the one that digest that
clot at dahil di siya naform walang madadigest na clot
which causes increase THROMBOUS FORMATION
DEFICIENCIES/DECREASE INHIBITORS TENDS
TO CAUSE BLEEDING
BAKIT?
- Kapag deficient ang ating inhibitors there will be a
continuous activation of plasminogen kasi nga walang
inhibitors, puro nalang siya activate ng activate walang
nagiiinhibit, so there will be a production of too much
plasmin which causes bleeding because walang healing
or repair sa ating vessels na magaganap kasi nga always
madadigest yung clots.
Fibrinogen Degradation Products
• So now let’s talk about our fragment X. Itong fragment X
natin it represents the original structure of our fibrinogen
which contains yung ating mga degragation products or the
fragments D-E-D which is the original structure, it has both
the D fragments in both terminal ends and merong E
fragment in the middle.
X=D–E–D
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2NDSem (FINAL)
*** For our Y fragment naman it only has the D fragment in one
end and E fragment sa kanyang tabe. This represents the removal
of the D fragment on one end which results to our D – E
structure. Yung structure is parang nacut siya on one end. Which
removes our D fragment on the end of the original structure.
Y=D–E
*** For our D fragment naman or the Dimer Fragment is caused
by a crossed linked structures.For example: one original structure
is D – E – D then another structure of fibrinogen D – E – D is
seen and kapag yung ating factor XIII binds this two D fragments
it will become a D – dimer.
D – E – D Crossed linked by our factor XIII
D–E–D
= D dimer
D- Dimer – represents two domains of D fragments that is
crossed linked by our factor XIII. In other terms it is the
combination of two fibrinogen factors that is attached by our
Factor XIII.
So ano nga aa tong mga D- dimer?
- This are what you call the fibrin degradation products
• X &Y – represents the early degradation products
• D & E – represents the late degradation products
❖ This degradation products will later be removed by the RES
(reticuloendothelial system) and other organs such as the liver
which serves as a filter sa ating katawan removes yung ating
FDP and fibrin split products.
FRAGMENT X
- Is the first and the largest fragment that is formed during
fibrinolysis
- The result of plasmin cleavage of the terminal portion of
the alpha chains sa ating fibrin monomer and this further
cleaves yung ating intermediate complexes which is yung
ating original structure na D – E – D which will be later
on degraded like yung ating next degradation products
like Y fragments and etc.
❖ Pathologic effects of FDP – very significant inside our blood
vessels because of their hemostatic effect which includes
antithrombin activity, interference sa ating polymerization of
fibrin monomer, interference platelet activity.
FIBRIN SPLIT PRODUCTS
- May act as a circulating anticoagulants because they
inhibits the process of our fibrin polymerization until
cleared by our liver and other reticuloendothelial system.
❖ X & Y- anticoagulant activity
❖ Y & D- Inhibits fibrin polymerization
❖ E- powerful inhibitor of thrombin
PATHOLOGIC FIBRINOLYSIS
- THE DISORDERS OF FIBRINOLYSIS
Primary Fibrinolysis
• Involves “Degradation of Fibrinogen”
• Negative in the Protamine sulfate test is one of
fibrinolytic test that we are performing in the lab.
• Is the excessive activation of the activators due to a
damage or the presence of a malignant cell inside the
body example is our prostate cancer.
• No fibrin monomer formed, polymer and D-dimer in
short there were no fragments formed.
• Converts plasminogen to plasmin in the absence of
fibrin formation
Secondary Fibrinolysis
• Associated with the inappropriate formation of fibrin
• A result of Degradation of Fibrin
• Positive in the protamine sulfate test
• Associated with DIC (Disseminated intravascular
coagulation) – the uncontrolled or the inappropriate
formation of fibrin within the blood vessels, where there
is a mass consumption of platelets in this condition.
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 HEMATOLOGY 2 2NDSem (FINAL)
• Contains fibrin monomer formed, polymer and D-dimer Monoclonal antibodies to D-dimers are attached to latex
so merong nabuong fibrin at the same time meron siyang particles causing agglutination if D-dimers are present
fragments nadegrade. In here yung d-dimer Ag + microlatex particle coated with
• Associated with infections, snake bites neoplasm and etc anti- D-dimer will produce a reaction kapag meron presence
of D-dimer merong (+) turbidimetry or meron agglutination
na magaganap.
LABORATORY TESTS FOR
FIBRINOLYSIS DIFFERENT TEST THAT ARE PERFORMED IN OUR
PRIMARY AND SECONDARY FIBRINOLYSIS:
WHOLE BLOOD CLOT LYSIS TIME TEST PRIMARY SECONDARY
➢ Whole blood (No Anticoagulant) should remain clotted and WHOLE <48 HRS <48 HRS
should not show significant lysis for 48 hours at 37 o c BLOOD CLOT REACTION LYSIS
➢ Positive in severe fibrinolysis LYSIS REACTIN
➢ NORMAL VALUE OF WHOLE BLOOD CLOT LYSIS EUGLOBULIN < 2 HOURS < 2 HOURS
TIME: MORE THAN 48 HRS DOON LANG LYSIS TEST
MAGIISTART ANG ATING LYSIS PROTAMIN NEGATIVE POSITIVE
➢ ABNORMAL: LYSIS IS ALREADY VISIBLE WITHIN SULFATE REACTION REACTION
LESS THAN <48 HOURS. DILUTION (-) (+)
EUGLOBULIN LYSIS TIME: TEST
➢ Is used as a screening test for fibrinolytic activity. ETHANOL NEGATIVE POSITIVE
➢ The euglobulin fraction of plasma consists of Fibrinogen, GELATION REACTION REACTION
plasminogen, and fibrinolytic activators (-) (+)
➢ IN HERE WE MEASURE WHEN THE D- DIMER NEGATIVE POSITIVE
EUGLOBULIN WILL LYSE REACTION REACTION
➢ The euglobulin fraction is precipitated with 1% acetic acid (-) (+) – because
and resuspended in a borate solution. Euglobulins are clotted d-dimer is only
by the addition of thrombin (5 units/mL). The resulting clot specific in
is incubated and the time of lysis is obtained. 2ndary
➢ Monitor euglobulin lysis fibrinolysis
➢ The clot should remain intact for 2-4 hours
Interpretation: FIBRIN DEGRADATION PRODUCTS
✓ NORMAL VALUE: >2HRS ➢
Latex particles are coated with antibodies to FSPs.
✓ Clot lysis in < 2hours is indicative of abnormal fibrinolytic ➢
If significant level of the fragments are in the serum,
activity and decrease in fibrinogen agglutination will occur.
✓ A prolonged time > 4 hours is caused by a decrease in • DIC
plasminogen or activator. • Pulmonary embolism
PROTAMINE SULFATE DILUTION TEST • DVT (Deep vein Thrombosis)
This test will identify the presence of FIBRIN • Myocardial infarction
MONOMER
• Pre-eclampsia
When protamine is added in plasma, it displaces the
NORMAL VALUE OF FDP = <2ng/uL sa ating plasma
secondary (smaller) degradation products from fibrin
> 100ng/uL would mean association
monomer and primary (larger) FDP will polymerize
spontaneously (parcoagulation)
TEST FOR FDP
Process:
- identified with immunoassay
- We add plasma with our protamine sulfate and we
1. Semiquantitative Agglutination immunoassay
observe for precipitin
Polysteryne latex particle+ Monoclonal Anti E antibody
- (+) -→ precipitation
- An example of the detection different fragments after
✓ So kapag merong precipitation ibig sabihin merong
our plasmin dissolution of clots.
presence ng fibrin monomers
*** THIS TEST IS USUALLY HELPFUL IN DIC, - Example: If we want to detect fragment E we just add
PULMONARY EMBOLISM AND THROMBOLYTIC polysteryne latex particles + monoclonal anti-E antibody
THERAPHY *** and the result will be agglutination then if there is a
Normally, no gel formation presence of agglutination then is a presence of fragment
(+) result : gel formation = DIC, pulmonary embolism, E.
thrombolytic therapy +) result will be agglutination
Ethanol Gelation Test - If you want to detect fragment D we just add polysteryne
o Also a test for fibrin monomer but is Less sensitive but latex particles + monoclonal anti-D antibody and the
more specific than protamine result will be agglutination and the result will be
o In here we use plasma as specimen plus our NaOH plus the agglutination then if there is a presence of agglutination
addition of ethanol. then is a presence of fragment D.
o 50% solution ethanol will polymerize any fibrin monomers +) result will be agglutination
resulting to gel formation CHROMOGENIC (CHANGE OF COLOR) SUBSTRATE
Positive result (+) result is PRECIPITATION ASSAY
– Presence of precipitation also identifies the presence of fibrin ➢ SUBSTRATE: p-Nitroanilide (which is a colorless
monomer. substrate so upon activation, if there is a color reaction
D-DIMER ASSAY: it will give rise to YELLOW COLOR)
THIS TEST IS SPECIFIC FOR D- DIMER ➢ (+) YELLOW COLOR
PRINCIPLE OF THE TEST: FIBRINOLYSIS DEFICIENCY
- It is an immunoassay, means the antigen and antibody - Kapag merong decrease sa ating activators there will be
complex reaction. thrombus formation.
Cross-linked D-dimer fragments when stabilized fibrin
clots are degraded by plasmin.

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 HEMATOLOGY 2 2NDSem (FINAL)
• If there is no residual TPA as a result of reaction, means
super dami ng inhibitor.
PLASMINOGEN DETERMINATION TEST
• If there is too much residual TPA as a result of
reaction, means super less ng inhibitor.
PLASMINOGEN CHROMOGENIC ASSAY: • Plasminogen gives off to activated plasmin
- Chromogenic or fluorogenic substrate allow functional • The substrate p-Nitroanilide reacts or give off to color
quantitation of plasminogen. reaction if there is a presence of plasmin.
PRINCIPLE: plasminogen = activator will result to plasmin. • Intensity of color is inversely proportional to the
With addition to substrate (p-Nitroanilide) + plasmin, there will presence of TPA
be a color reaction. YELLOW COLOR • CONFIRMATORY TEST: SERUM NOT
- Will be measured by spectrophotometry. PLASMA
- (+)= intensity of yellow color o If there is decrease PAI 1 in serum= it will
- This color is directly proportional to the concentration of signify PAI 1 deficiency
plasminogen.
- The more color are intensified, the higher the presence of
plasminogen concentration.
PLASMINOGEN HALF PLASMA
ACTIVATORS LIFE CONCENTRATION

TPA (release by EC) 3 mins 5ng/ml

UPA (release by 7 mins 2-4ng/ml

kidneys and vascular
cells)

TPA- more commonly tested

- Done in a chromogenic substrate assay
TPA Determination
• also a chromogenic substrate assay.
• Specimen used: PPP (platelet poor plasma)
• Specimen collection (should know all of these before
extraction)
1. Increase in Exercise
2. Diurnal Variation- increase concentration in
the morning
3. Patient Should be at rest
4. Minimal tourniquet application
5. immediately acidify- to preserve TPA
principle: plasminogen + activator (TPA)== active plasmin
- if ever there’s a presence of plasmin, the substrate p-NA
will have yellow reaction
- This color is directly proportional to the concentration
of plasminogen.
- The more color is intensified, the higher the TPA
concentration
PLATELET POOR PLASMA- specimen used. And
should be frozen at -70C until it is ready for test.
PAI-I assay
• Plasminogen activator 1 is inhibitor of fibrinolysis.
• We perform the test to know if we have the presence of
this inhibitor.
• Specimen collection
1. Increase in Exercise
2. Diurnal Variation- increase concentration in
the morning
3. Patient Should be at rest
4. Minimal tourniquet application
5. immediately acidify- to preserve TPA
• Same with TPA
- Blood should be centrifuged immediately and plasma is
seperated to avoid in vitro released of PAI-I with platelets.
1. Enzyme immunoassay
• PRINCIPLE: PAI 1+ Urokinase (activator)→ PAI
1 complex + monoclonal anti PAI 1 antibody
- we measure anti-urokinase immunoglobulin
complex
2. Chromogenic substrate assay
• There is a color reaction
• We use TPA as activator
• Principle: PAI 1 + TPA → TPA– PAI 1
COMPLEX+ residual TPA

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 HEMATOLOGY 2
Disease of Hemostasis
Basic terminologies
CONDITION DESCRIPTION
PETECHIAE Purplish red pinpoint
hemorrhagic spots in the
skin caused by loss of
capillary ability to
withstand normal blood
pressure and trauma. Size :
1 mm or less than 3mm
PURPURA Hemorrhage of blood
into small areas of the skin,
mucous membranes, and
other tissue. Size:3mm
ECHIMOSIS Form of purpura in
which blood escapes
into large areas of skin
and mucous
membranes, but not into
deep tissues. Size: >1cm
EPISTAXIS Nosebleed
- Found in bleeding
tendencies
HEMARTHROSIS Leakage of blood into
joint cavities
HEMATEMESIS Vomiting of blood
HEMATOMA Swelling of tumor in the
tissue or a body cavity
that contains clotted
blood
HEMATURIA PRESENCE of RBC in
urine
HEMOGLUBINURIA Presence of
Hemoglobin in urine
MELENA Stool containing dark
red or black blood
MENORRHAGIA Excessive menstrual
bleeding
PLATELET DISORDERS
QUANTITATIVE PLATELET DISORDERS
A. THROMBOCYTOPENIA
➢ decrease in circulating platelets
1. Decreased platelet production
• Decreased megakaryocyte in the bone marrow.
(megakaryocytes is the precursor of platelets so if there
is a ↓ megakaryocytes, there is also↓ number of
platelets produces )
• Congenital hypoplasia
• Aplastic anemia pancytopenia is a decreased of RBC,
WBC and platelets in the circulation
• Fanconi syndrome
• Ineffective thrombopoiesis
• Infiltration of the bone marrow by malignant cells
• TAR syndrome (Thrombocytopenia with absent radii)
• Acquired hypoplasia of megakaryocytes due to drugs,
radiation, chemotherapy, or infectious agents
• Hereditary macrothrombocytopenia (e.g Alport's
syndrome)
2. Decreased platelet survival time due to increased or
decreased consumption
➢ Increased platelet destruction: Immunologic:
Idiopathic thrombocytopenic purpura
(ITP)(autoantibody that is direct against platelet) - own
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2NDSem (FINAL)
cells destroy platelets that is why there is dec. Plt survival
time and causes thrombocytopenia
- majority cases is due to viral infection ( example: dengue)
➢ Drug induced immunologic thrombocytopenia-
antibiotics, hypnotics, analgesics, heavy metals,
diuretics, etc. Generally both the drugs and the
antibody must be present in the system at the same time
for destruction of platelets
➢ Post transfusion purpura - occurs 7 to 10 days after
transfusion, due to anti-PIA or anti HPA-1a(platelet
antibodies). The recipient's plasma is found to contain
alloantibodies to antigens on the platelets or platelet
membranes of the transfused blood product, directed
against an antigen the recipient does not have.
➢ Isoimmune neonatal thrombocytopenia/Neonatal
autoimmune thrombocytopenia - rare hemolytic
disease of newborn. Result of transplacental transfer of
maternal antiplatelet antibodies produced in response to
fetal antigen inherited from the father. It is associated to
a mother with ITP or SLE.
➢ Increased platelet consumption: Non immunologic:
Thrombotic thrombocytopenic purpura (TTP) -
rare disorder, the exact cause is unknown. The
development of TTP seems to be directly related to the
accumulation of ultra-large von Willebrand factor
(ULVWF) multimers in the plasma due to deficiency of
the von Willebrand factorcleaving protease known as a
disintegrin and metalloproteinase with a
thrombospondin type 1 motif, member 13 (ADAMTS-
13).
➢ DIC - disseminated intravascular coagulation
➢ HUS - hemolytic uremic syndrome
3. Increased platelet sequestration on the spleen
Spleen is the one that stores our platelets so ang ating
spleen holds the 20 to 30% platelets population. Kapag
may increased platelet sequestration, may decreased
number of platelets in the circulation kasi nga mas
dumadami yung mga platelets na nasstored inside the
spleen instead na andon sila sa circulation)
4.Dilution of platelet count by multiple blood transfusions
or Extensive blood transfusion often is accompanied by
thrombocytopenia, the degree of which is directly
proportional to the number of units transfused
(the more blood transufusion that is done sa isang tao,
the more na malelessen yung number of platelet
because madadilute yung ating platelet count because
of multiple blood transfusion)
B. THROMBOCYTOSIS
➢ increase number in circulating platelet
*** The number of platelets in the circulation is usually
up to 70% to 80%. Kai 20% to 30% nasa spleen.
*** Normally 2/3 of platelet population is nasa
circulation
1. Reactive (secondary) thrombocytosis
• Moderate increase, usually asymptomatic
• Generally responds when the underlying disorder is
treated like recovery from major surgery like
splenectomy (removal of spleen, spleen store 20-30%
of platelet kapag natanggal ang spleen the 20-30% will to
the circulation that is why it caused thrombocytosis or
increased In number of circulating plt.), after childbirth
and acute blood loss
splenomegaly - enlargement of spleen, decreased
number of plt in circulation. Mas lumalaki yung spleen
mas more yung space ng plt storage
Splenectomy is the removal of spleen and our spleen is
the one that stored the 20 – 30% of platelets. So kapag
natanggal yung spleen the 20 to 30% na nastore sa spleen
ay pupunta sa circulation that is why it cause increases of
5
 HEMATOLOGY 2 2NDSem (FINAL)
platelet is the circulation.
Splenomegaly lumalaki yung spleen, so there will be a
decrease of platelet in the circulation.Kapag lumalaki 3.Platelet Secretion problems
yung spleen the more na malaki ang space for platelet - storage pool effects
storage Alpha granules Dense/Delta granules
• The term reactive thrombocytosis is used to describe an deficiency deficiency
elevation in the platelet count secondary to GREY PLATELET *Wiskott Aldrich
inflammation, trauma, or other underlying and SYNDROME - large and syndrome - Triad
seemingly unrelated conditions. gray appearance of thrombocytopenia,
• Reactive thrombocytosis is not associated with platelets in Wright's stain recurrent infections, and
thrombosis, hemorrhage, or abnormal thrombopoietin eczema
levels. QUEBEC PLATELET *Hermansky pudlak- triad
DISORDERS- an of thyrosinase positive,
2. Autonomous thrombocytosis autosomal dominant occulutination abinism,
• Marked increase, associated with uncontrolled bleeding disorder that and accumalation of serud
proliferation of platelet thrombotic/ hemorrhagic results from a deficiency like pigment in the
complication of multimerin (a macrophages, and
• Primary or autonomous thrombocytosis is a typical multimeric protein that is bleeding tendencies
finding in four chronic myeloproliferative disorders stored complexed with *Chediak Higashi
(CML, Polycythemia vera, Essential thrombocythemia, factor V in a-granules) syndrome - albinism,
and Primary Myelofibrosis recurrent infections and
QUALITATIVE PLATELET DISORDERS giant lysosomes in all
granules contain cell
➢ Can be attributed in adhesion, aggregation or secretory
*Thrombocytopenia with
defects
absent Radius
➢ Release defects are the largest group of platelet function
(TAR syndrome)
disorders and this condition are caused by abnormalities of
signal transductase membrane and normal metabolic
pathway or abnormal release mechanism ➢ B. ACQUIRED PLATELET PROBLEMS

1. Uremia - accumalation of toxic metabolites

➢ A.HEREDITARY/ INHERITED PLATELET
2. Paraproteinemias - coating the platelet membrane with
PROBLEMS
abnormal proteins (example: Multiple myeloma and
1. PLATELET ADHESION Waldenstrom macroglobulinemia)
3. AML - accosiated with bone marrow
Von ✓ with five ✓ normal with 4. Myeloproliferative disorders such as CML
Willebrand major ADP, 5. drugs - such as aspirin (inhibits cyclooxygenase)
’s disease subtypes COLLAGE 6. Chronic liver disease - abnormal function of liver
(VwD) ✓ Inherited as N AND
- lack of both an EPINEPH VASCULAR DISORDERS (PRIMARY HEMOSTASIS
vwf autosomal RINE DISORDERS
- treated dominant ✓ Abnormal
with cryo types and aggregation
precipitate autosomal with 1. Hereditary hemorrhagic telangiectasia /Osler-Weber-
recessive RISTOSCE Rendu Syndrome
trait TIN
➢ most common inherited vascular disorder
BERNAR ✓ Autosomal ✓ Normal with
D - recessive ADP, ➢ Characterized by blood vessel walls that are thin and lacks
SOULIER trait COLLAGE smooth muscle
SYNDRO ✓ Platelets lack N AND
ME gp1b or the EPINEPH ➢ Inherited as autosomal dominant trait
- Lacks gp I/X/V RINE
gpid complex ✓ Abnormal ➢ Localized dilation of the walls of the small blood vessels of
Receptor ✓ Presence of aggregation skin and mucous membranes; walls of the affected blood
giant with vessels are thin and lack of smooth muscle.
platelets RISTOSCE
TIN ➢ Telangiectasias are thin, dilated vessels. With a lesi

* GPID - rececptor for vwf 2. Hereditary Hemangioma / Kasabach - Meritt syndrome

2.Platelet Aggregation problems
➢ GLANCE MAN THROMBASCEMIA - lacks gpIIB-IIIa,
autosomal recessive trait
➢ Decrease or absence or abnormality of GP IIb-IIIa
complex (receptor for fibrinogen)
➢ Platelet aggregation: normal restocetin
➢ Abnormal with: epinephrine, collagen, and ADP
➢ Abnormal clot retraction results
➢ Heterozygotes are clinically normal, whereas homozygotes
have serious bleeding problems
➢ Disorder associated withblood vessel tumors composed of
blood vessels that commonly swell and bleed at the surface
3. Ehlers Danlos Syndrome
➢ Increased vascular fragility
➢ Characterized with hyperextended joints and hyper plastic
skin

➢ Inherited as autosomal dominant

➢ The defect may lie in a peptidase enzyme that converts

procollagen to collagen

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 HEMATOLOGY 2 2NDSem (FINAL)
4. Marfan syndrome ✓ Acquired prothrombin deficiency

➢ increased vascular fragility ✓ It is commonly found in vitamin K Deficiency

➢ Inherited as autosomal dominant ✓ it is related to a defective utilization or absorption of

vitamin k such as in the following;
➢ long extremities (long arm and legs)
✓ Gastrointestinal diseases
5. Psuedoxanthoma elasticum ✓ Obstructive jaundice
➢ Autosomal recessive ✓ Coumadin therapy
➢ Connective tissue elastic fibers in small arteries are 3.Factor V Deficiency
structurally and calcified abnormal
➢ Inherited: congenital form known as parahemophilia
➢ Subarachnoid and gastrointestinal bleedingare the most
common causes of death This manifests the following;
✓ Mucosal membrane bleeding
✓ Easy bruising
6. Senile Purpura
✓ Git bleeding
✓ Excessive bleeding following dental or surgical
➢ Loss of elasticity of the skin
procedures
➢ Usually due to aging, (elderly persons) Acquired Factor V Deficiency
➢ It is associated with DIC and Liver disease
➢ The aging process brings about a degeneration of collagen,
elastin, and subcutaneous fat
4. Factor VII Deficiency
7. Scurvy
✓ Inherited: Congenital form
➢ Deficiency of ascorbic acid ✓ It is associated with mild bleeding

➢ Acquired defect in the synthesis of collagen and hyaluronic

Acquired Factor VII Deficiency
acid
➢ It occurs in same condition as that of Factor II Deficiency
➢ Causes bleeding in gums
5. Factor VIII Deficiency
8. Henoch-Schonlein purpura
✓ Hereditary
➢ Immunologic damage to endothelial cells (specific allergic
purpura) ✓ It may manifest in Hemophilia A and in Von willebrand
disease
➢ Gastrointestinal hemorrhage and joint swelling occur with
a.1. Hemophilia A
purpuric rash
➢ It is the result of a deficiency or dysfunctional factor VIII:C
➢ Most common in children and often follows upper component of the Factor VIII molecule
respiratory infections
It is characterized:
COAGULATION DISORDERS ✓ GIT Bleeding

✓ GUT bleeding
A. CLOTTING FACTOR DEFICIENCIES
✓ Epistaxis
1. Factor I Deficiency
✓ Excessive bleeding after dental extractions
➢ It is a rare coagulation disorder that is associated with severe
hemorrhages
✓ Hemarthrosis
➢ It can be acquired or inherited:
✓ Hematoma
Inherited Deficiency of Fibrinogen: Congenital form is
✓ Intracranial bleeding (death)
classified into 3 categories:
✓ a.1. Afibrinogenemia Hereditary form is associated
with hemorrhage and menorrhagia 6. Factor IX Deficiency
✓ a.2. Hypofibrinogenemia
✓ a.3. Dysfibrinogenemia ✓ Congenital Form: Christmas disease
Acquired Deficiency of Fibrinogen: It is more common than
the congenital form. It may occur as a result of; ✓ It is also referred to as Hemophilia B
✓ b.1. Excessive fibrinogen utilization
✓ It is associated with mild bleeding tendencies
✓ b.2. Increased fibrinogen destruction
✓ b.3. Impaired fibrinogen production Acquired
✓ It is associated with;
2.Factor II Deficiency
Hereditary: congenital deficiency of prothrombin ✓ Liver disease
✓ It is the rarest factor deficiency. It is associated with mild
bleeding ✓ Coumadin therapy

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 HEMATOLOGY 2 2NDSem (FINAL)
✓ Vitamin k deficiency b. non-specific inhibitors such as the LUPUS INHIBITOR
- anti phospholipid antibody, Paraproteins and FDP's.
7. Factor X Deficiency
D. DIC/ Consumptive coagulopathy/ Defibrination
✓ Congenital form syndrome

✓ Associated with bleeding having a severity dependent ✓ A complication or intermediary phase of many
on the pattern of inheritance diseases such as liver disease, renal disease, and
lymphoproliferative disorders
Acquired
✓ It is commonly seen in; ✓ It can also be triggered by infections, trauma, shock,
hypothermia, AMI, and eclampsia.
✓ Liver disease ✓ There is a continuous activation of both coagulation and
fibrinolytic system
✓ Vitamin k deficiency
✓ Decrease platelet count, prolong all coagulation test
✓ Coumadin therapy ✓ Positive for D-Dimer assay (most specific test)

8. Factor XI Deficiency

➢ It is also referred to as hemophilia C which has a milder

bleeding tendencies Compared to Hemophilia A and B

9. Factor XII Deficiency

➢ It is not associated with any clinical manifestations though
minor bleeding may happen

10. Factor XIII Deficiency

➢ It is associated with hemorrhage

➢ CNS bleeding is more common in this type of coagulation

factor deficiency

11. Prekallikrein deficiency

➢ It is related from little to no bleeding tendencies

➢ aPTT is moderately prolonged due to slow contact

activation time

12. HMWK deficiency

➢ More often, this coagulopathy is asymptomatic though

aPTT is prolonged.

B.LIVER DISEASE
✓ Associated with multiple factor deficiency without
the presence of D-dimer

✓ Liver is one of the major site for coagulation factor

synthesis

✓ Factor VII is the first coagulation factor to exhibit

decreased activity in liver disease

✓ A more specific marker of liver disease because it is not

affected by Vitamin K deficiency
✓ Prothrombin time (PT) Serves as a sensitive early
marker for mild liver disease that can detect
✓factor VII deficiency and Vitamin K deficiency
✓ In end-stage liver disease, the fibrinogen level may fall to
less than 100mg/dl which is a mark of liver failure

C. CIRCULATING ANTICOAGULANTS AND

INHIBITORS
✓ Prolonged APTT and PT and NOT CORRECTED
by the addition of normal fresh serum or plasma
✓ Inactivate an activated coagulation factor or block
interaction between coagulation factors and platelet
✓ They can be IgM, IgG, or IgA
Two group:
a. the specific inhibitors against specific coagulation factors
and

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