3. 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.
4. 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
5. 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) DiGuglielmo’s Syndrome
c) Paroxyxmal nocturnal hgburia
d) Myelodysplastic syndromes and leukemia
6. 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
7. 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
8. b) Chronic ITP- adult; mostly 20-40 years women
ii. 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
c) Recurrent ITP- found in Px that does not
experience permanent remission ff the CITP Tx.
ii. Characterized by alternating intercals of
thrombocytopenia and normal platelet count.
iii. Tx Immunosuppressive drugs and plasmapheresis
d) Neonatal ITP- transplacental passage of
antiplatelet Ab and occurs most freq when
mother is thrombocytopenic at the time of
delivery
9. 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
10. 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 PIA1 .
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.
11. 6. Inc. platelet consumption;
non-immunologic
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
12. 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.
13. An abnormal distribution of platelets may
also cause thrombocytopenia.
Normally the spleen pools approximately
one-third 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
17. A platelet count increased above normal
will be found as a result f a variety of
circumstances.
Reactive thrombocytosis
18. 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.
19. 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.
20. 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
21.
22. Thrombocythemia
Middle age
patients (both
male and
female)
bleeding or thrombosis with
bleeding episodes
predominating
(Gastrointestinal hemorrhage)
Bleedin
g in
arterial
and
venous
circulati
on
Splenome
galy is a
frequent
finding
24. 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
25. PLATELET
Lack glycoprotein
1b (GP1b)
Lack glycoprotein V
AND IV
Function as
Receptor in
vonWillebrand
factor
Unable to adhere
normally to
vascular
endothelium
Do not bind
coagulation
factor XI
normally
26. 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
27. vonWillebrand’s Disease
- ABSENT or ABNORMAL form of
vonWillebrand factor = impaired platelet
adhesion
- NORMAL in Aggregation studies with
ADP, collagen and epinephrine
- ABNORMAL ristocetin-induced
aggregation
28. 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
29. 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.
30. Also called Glanzmann’s 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
31. 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.
32. 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
33. 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.
34. 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.
35. - 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
36. - Acquired disorders of platelet function are
associated with a number of conditions & with the
ingestion of certain drugs.
• - 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.
37. Platelet dysfunction & bleeding disorders
will be present in the various
Multiple myeloma & Waldenstrom’s
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
38. Megakaryocyte in the BM may be small &
somewhat abnormal
Resultant platelets abnormal
- defective platelet aggregation
- defective release mechanism
39. (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
40. Inc. amounts of
- 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
41. Iodiophatic thormbocytopenia purpura
Autoimmune disorders
-systemetic lupus erythromatosis
- Antibodies have been shown to cause
platelet lysis, platelet aggregation &
serotonin release
42. Inhibit platelet function
Aspirin
- inhibit release reaction & secondary wave of the
aggregation
- Direct result of aspirin’s ability to inactive the enzyme
cyclo-oxygenase
- 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
Notas do Editor
2. CHEMOTHERAPHY, RADIATION, DRUG ACTIONS
Radii- bone in the arm