PLATELET DISORDERS

QUANTITATIVE AND
QUALITATIVE DISORDERS

QUALITATIVE
PL ATELET
DISORDERS
THROMBOCYTOPENIA
THROMBOCYTOSIS

THROMBOCYTOPENIA
MOST COMMON CAUSE OF ABNORMAL
BLEEDING AND GENERALLY
ATTTRIBUTED TO THE FF. CAUSES:
1. Decrease platelet production
2. Decreased platelet survival time due to increase
destruction and/or consumption
3. Increased platelet sequestration by the spleen, &
4. Dilution of the platelet count by multiple blood
transfusions.

DECREASED PLATELET
PRODUCTION
1. CONGENITAL HYPOPLASIA OF THE
MEGAKARYOCYTES IN THE BM
a) FANCONI SYNDROME- d/t pancytopenia
b) TAR SYNDROME- thrombocytopenia w/ absent radii
c) NEWBORNS AS A RESULT OF INTRAUTERINE
EXPOSURE TO DRUGS (THIAZIDES) AND VIRAL
INFECTIONS (RUBELLA)

2. ACQUIRED HYPOPLASIA OF MEGAKARYOCYTES

)DUE TO THERAPEUTIC AGENT ACTIONS
THIAZIDE DIURETICS, ESTROGEN HORMONE AND
ALCOHOL SELECTIVELY DECREASES
MEGAKAYOCYTE PRODUCTION

3. INFILTRATION OF THE BM BY MALIGNANT CELLS

Thrombocytopenia associated to such oncogenic conditions is
due to marrow replacement or
toxin inhibitors of
thrombopoiesis produced by the abnormal cells.
4. INEFFECTIVE THROMBOPOIESIS
Characterize by normal to increased marrow megakaryocytes
in association with decreased circulating platelets.
Due to defective platelet formation, abnormal marrow release of
platelets, or destruction of platelets in the BM.
Found in Px w/:
a) Megaloblastic Anemia
b) DiGuglielmos Syndrome
c) Paroxyxmal nocturnal hgburia
d) Myelodysplastic syndromes and leukemia

 HEREDITARY CONDITIONS ASSTD W/ INFFECTIVE

PLATELET PRODUCTION
a) Autosomal dominant thrombocytopenia
b) May-Hegglin anomaly
c) Wiscott-Aldrich syndrome
5. DISORDERS OF THE CONTROL OF
THROMBOPOEISIS
)Not common; Result from an impairment in the
mechanism that control platelet production.
)Cyclic Thrombocytopenia is a condition in which
thrombocytopenia and normal platelet counts alternate
at regular intervals

DECREASE PLATELET SURVIVAL TIME

INCREASE PLATELET DESTRUCTION: IMMUNOLOGIC
THROMBOCYTOPENIA
1. IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)
THROMBOCYTOPENIA OCCURS IN THE ABSENCE OF ANY
DISEASE ASSOCIATED WITH DECREASE PLATELET OR
TOXIN EXPOSURE.
a) Acute ITP 2-6 years old; after recovery from viral infection; self
limiting
i.

STAINED BLOOD SMEAR presents: young, large platelet w/

abnormal shapes
ii. Dec. Platelet survival time- due to destruction by immune complexes or
foreign Ag adsorbed by platelets as a result of an infection
iii. Spontaneous remission

b) Chronic ITP- adult; mostly 20-40 years women

Circulating platelet are young w/ short lifespan and IgG
are elevated.
iii. Thrombocytopenia is due to clearing of the Ab coated
platelets by slpeen and liver.
iv. Tx is costicosteroid therapy or splenectomy
v. Rare remission
ii.

c) Recurrent ITP- found in Px that does not experience

permanent remission ff the CITP Tx.
Characterized by alternating intercals of thrombocytopenia
and normal platelet count.
iii. Tx Immunosuppressive drugs and plasmapheresis
ii.

d) Neonatal ITP- transplacental passage of antiplatelet Ab

and occurs most freq when mother is thrombocytopenic
at the time of delivery

2. DRUG INDUCED IMMUNOLOGIC

THROMBOCYTOPENIA
a) Antibiotics, hypnotics, analgesics, heavy metals,
diuretics, chloroquine, digitoxin, heparin and
tolbutamide
b) Both the drug and Ab must be present in the system
at the same time for platelets destruction.
c) Thrombocytopenia will occur after 12 hour of drug
intake but the time can be still delayed
d) Megakaryocyte in the BM is normal
e) Removal of the fending drug is usually curative to
normalize platelet

3. IMMUNOLOGIC
THROMBOCYTOPENIA
Condition that is
indistinguishable to
chronic ITP
4. POST TRANSFUSION
PURPURA
Occurs 7-10 days after blood
transfusion containing
platelets.
Result from sensitization of
individuals negative for the
platelet Ag PIA 1 . This Ag is
found 97% in normal
population.
Primary immunization occurs
during pregnancy.

5. ISOIMMUNE NEONATAL
THROMBOCYTOPENIA
Analogous to HDN
Non-immunologic since
thrombocytopenia is due
to increase platelet
consumption
Occurs as a result of
maternal antiplatelet Ab
produces in response to
fetal Ag inherited from the
father.
Usually affects the first
child and platelet Ag PIA1
has most often been asstd.

6. Inc. platelet consumption; nonimmunologic thrombocytopenia

Thrombotic thrombocytopenic
purpura (TTP)- unknown exact
cause; serious dse
a) Hemolytic anemia- trauma to
RBC
b) Changing neurologic Sx
c) Fever &
d) Renal abnormalities
e) DIC-When progress
*caused by thrombi in the capillaries
and arterioles through out the body.
Peripheral blood smear:
poikilocytosis and normoblasts
*most commonly found in women
(40 yrs. Mean age)

7. Hemolytic uremic
syndrome

Resembles TTP
Primary in children
Intravascular clotting is
confined to kidney
Tx- dialysis, plasma
transdusion or exchange
& antihypersensitive
therapy

7. NONIMMUNOLOGIC THROMBOCYTOPENIA
Thrombocytopenia may be present in a number of
rickettsial, bacterial, viral or malarial infections- due
to Increase consumption of platelets and less commonly
as a result of decrease production.
Thrombocytopenia related to cardiopulmonary
bypass can result from DIC, dilution, sequestration,
platelet destruction in the oxygenerator and increase
fibrinolysis.

INCREASED PLATELET SEQUESTRATION

An abnormal distribution of platelets may also
cause thrombocytopenia.
Normally the spleen pools approximately onethird of the total spleen (splenomegaly).
An increased percentage of the platelets will be
found in the spleen, thereby producing
thrombocytopenia.
Increased splenic pooling is differentiated from
destruction of platelets

thrombocytopenia

DILUTION OF THE PLATELET COUNT

Multiple transfusions

Splenic pool

Transfusion

THROMBOCYTOSIS
A platelet count increased above normal will be
found as a result f a variety of circumstances.
Reactive thrombocytosis

REACTIVE
THROMBOCYTOSIS
Generally responds when the lying
disorder is treated.
Following splenectomy, the platelet count
will generally rise during the first
postoperative week, peak at about 2 to 3
weeks, and return to normal over a
period of several months.

 Thrombocytosis following major surgery

usually occurs during the first postoperative
week, with the platelet count generally
decreasing to normal levels within about 2
weeks.
Within about a day or so following acute
blood loss, a reactive thrombocytosis may
occur as a result of increased bone marrow
stimulation.

AUTONOMOUS
THROMBOCYTOSIS

Marked increase in the platelet count

Associated with thrombotic and /or hemorrhagic

complications.
Common in myeloproliferative disorder that includes:
Essential thrombocytosis
Chronic Myelogenous Leukemia
Polycythemia Vera
Myeloid Mataplasia

AUTONOMOUS
THROMBOCYTOSIS

bleeding or thrombosis with bleeding

episodes predominating
(Gastrointestinal hemorrhage)
Splenom
egaly is
a
frequent
finding

Thrombocythemi
a
Middle age
patients (both
male and
female)

Bleedin
g in
arterial
and
venous
circulati
on

Platelet
Adhesion

Platelet
Aggregation

QUALITATIVE
PLATELET
DISORDER
Functional
Platelet Disorder

Platelet
Secretion
or
Release
Reaction

Hereditary Qualitative Platelet

Disorder
Acquired Qualitative Platelet
Disorder

PLATELET ADHESION
DEFECTS
Bernard-Soulier Syndrome
Inherited as an autosomal recessive trait
Bruising and moderate to severe bleeding
** CHARACTERISTICS **
Giant Platelets (20 um in diameter)
Coarse granulation and vacuoles
Mild thrombocytopenia

PLATELET

Lack glycoprotein 1b
(GP1b)

Lack glycoprotein V
AND IV

Function as
Receptor in
vonWillebrand
factor

Do not bind
coagulation
factor XI
normally

Unable to adhere
normally to
vascular
endothelium

CHARACTERISTICS
o MEGAKARYOCYTE (in BM) = Normal to slightly
increased
o PLATELET
- Bleeding time is PROLONGED but clot refraction is
NORMAL
- Platelet aggregation is NORMAL with ADP,
epinephrine and collagen, but ABNORMAL ristocetin
and thrombin
- DECREASED platelet retention in glass beads column

vonWillebrands Disease
- ABSENT or ABNORMAL form of
vonWillebrand factor = impaired platelet adhesion
- NORMAL in Aggregation studies with ADP,
collagen and epinephrine
- ABNORMAL ristocetin-induced aggregation

PLATELET AGGREGATION
DEFECTS
An aggregation disorder is when platelets do not bind with
fibrinogen and other proteins in order to stick to other platelets.
As a result the platelets cannot form a plug to stop the bleeding
from a damaged blood vessel.
A defect of platelet aggregation associated with an abnormal
distribution of glycoprotein IIb-IIIa complexes within the platelet:
the cause of a lifelong bleeding disorder.
platelet aggregation studies show a defective primary response in
the presence of collagen, epinphrine, ADP, and thrombin but
normal response with ristocen

Diagnose:

platelet retention is markedly increased

platelet count is generally normal but may
occasionally be slightly decreased.
clot retraction is decreased to absent
bleeding time is prolonged
Blood tests show: that bleeding time is much longer than
normal that the platelets do not clump together at all
(platelet aggregation is absent).
Wright stain blood smear: it appear as morphologically
normal and show aggregating agents.

Also called Glanzmanns thrombosthenia

-is major inherited bleeding disorder characterized by the
failure of platelets to aggregate when stimulated with adenosine
diphosphate (ADP) or other physiologic agonists.
It is inherited or passed down from a child's parent(s). This
disorder causes moderate to severe bleeding symptoms:
Bleeding from the mouth
Bleeding with dental procedures
Nose bleeds
Bruising or small purplish red dots under the skin
Bleeding for a long time after an injury or surgery
Girls or women may have heavy periods
Infant boys may have bleeding after circumcision

PLATELET SECRETION DEFECTS

A secretion disorder is when the damaged blood vessel takes
more time for the bleeding to stop due to missing chemicals that
signals the platelets to stick together. As a result, it takes a lot
longer for the bleeding from a damaged blood vessel to stop. This
is the most common platelet disorder.

Two groups:
1.Storage pool disorder
defective platelet release reaction due to a lack of dense
bodies and/or granules.
mild to moderate bleeding tendency, and easy bruising
Abnormalities of the dense bodies or a granules

2. Aspirin-like defects
platelets have normal granules but defective release
deficiency of the enzyme cyclo-oxygenase or
thbormalrombozane synthetase
have a prolonged bleeding time and abnormal
aggregation with ADP, epinephrine, and collagen.

Three platelet function disorders involve platelet secretion:

1. Alpha Granule Deficiency, called Gray Platelet Syndrome, there
is a lack of important proteins within the alpha granule inside the
platelet. This problem slows down normal platelet adhesion,
aggregation and repair of the blood vessel
2. Dense Granule Deficiency, called Delta Storage Pool Deficiency,
there is a lack of storage granules for certain substances needed
for normal platelet activation. Their absence slows down platelet
activation and blood vessel constriction.
3. Abnormalities of the granule secretory mechanism occur when the
normal granules fail to release their contents when platelets are
activated.

HEREDITARY FORMS OF PLATELET

DYSFUNCTION
- Very large platelets & abnormalities in platelets adhesion
& aggregation
*Ehlers-Danlos Syndorme
Hereditary Afibrinogenemia
- prolonged bleeding time
- abnormal platelet aggregation with ADP
*glycoprotein storage disease type 1 (G-6-PD
deficiency)
- bleeding time is also prolonged
- platelet defects may be secondary to the metabolic
defect

ACQUIRED QUALITATIVE
PLATELET DISORDERS
- Acquired disorders of platelet function are associated
with a number of conditions & with the ingestion of
certain drugs.
Uremia- metabolites that are toxic to the platelets
accumulate in the plasma.
- Platelet release reaction, aggregation, retention are all
abnormal & bleeding time is prolonged.
- Platelet dysfunction & abnormal platelet-vessel wall
interaction
- Dialysis is of temporary therapeutic value; the
administration of cryoprecipitates will aid in controlling
major bleeding episodes.

 Platelet dysfunction & bleeding disorders will

be present in the various paraproteinemia.
Multiple myeloma & Waldenstroms
macroglobinemia
-abnormalities of the platelet aggregation &
reduced platelet retention are thought to be due
to:
- coating of the platelet membrane
- vessel walls with the abnormal proteins

Acute myeloblastic leukemia

Megakaryocyte in the BM may be small &
somewhat abnormal
Resultant platelets abnormal
- defective platelet aggregation
- defective release mechanism

Myeloproliferative disorders
(polycytothemia vera, chronic myelogeneous leukemia, myeloid
metaplasia, & essential thrombocythemia)
-Display fuctional abnormalities in addtion to thrombocytosis
-Common complications:
-bleeding and/or thrombosis
Myeloid metaplasia
-bleeding time is prolonged
-defective platelet adhesion, aggregation, & storage pool deficiencies
Abnormal platelet aggregation- polycythemia vera
Thrombocythemia- platelets appear in large & morphologically
abnormal
Prolonged bleeding time & defective aggregation- chronic
myelogenous leukemia

 Inc. amounts of fibrinogen degradation

products
- Present in DIC, fibrinogenolysis, & liver disease
- Inhibit ADP induced platelet aggregation
Fragments D & E
-absorb onto the platelet surface, interfere with
platelet function & will inhibit thrombin
induced platelet aggregation

Platelet associated antibodies

Iodiophatic thormbocytopenia purpura
Autoimmune disorders
-systemetic lupus erythromatosis
- Antibodies have been shown to cause platelet lysis,
platelet aggregation & serotonin release

Drugs

Inhibit platelet function

Aspirin:
- inhibit release reaction & secondary wave of the aggregation
- Direct result of aspirins ability to inactive the enzyme cyclooxygenase
- Effect of aspirin : lasts for the life of the platelet
- Presence of aspirin: defective platelet aggregation with ADP,
epinephrine & collagen
- Other drugs that induce qualitative platelet abnormalities:
-antihistamines, antidepressants & antibiotics, heparin dextran
& other plasma expanders, ethanol & certain local anesthetics