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MLS12A

MODULE 3: PLATELET DISORDERS

FRANCISCO

STUDY QUESTIONS & REVIEW

Q1
...

b
...
What are the two major quantitative platelet disorders? What are their distinguishing characteristics?
a
...


Thrombocytosis: >450,000/ uL or 450x10 9/L
Thrombocytopenia: <100,000/uL or 100x109/L

Q3
...


INCREASED PROGRESSIVE RISK for bleeding

Q3
...
HIGH RISK for severe spontaneous bleeding
Q4
...


INVERSELY PROPORTIONAL:
▪
INCREASED/HIGH platelet concentration = DECREASED/LOW risk of severe bleeding
▪
DECREASED/LOW platelet concentration = INCREASED/HIGH risk of severe bleeding

Q5
...
MPNS
b
...
What are the conditions related to thrombocytopenia?
a
...

c
...

e
...
What happens when there is an increased sequestration?
a
...
So, because there is an increased sequestration, platelets stay on the
spleen and are not released in circulation
...

Q8
...
Thrombocytopenia: same as with the sequestration but this time, it is caused by dilution
...

Q9
...


Thrombocytopenia: Since platelets are used/consumed during clot formation, especially in secondary hemostasis,
if the bone marrow cannot keep up with the production of platelets
...

Q10
...


b
...

d
...
Platelet counts that reaches 1-2 million/uL is rarely seen
...
During reactive thrombocytosis,
platelet function, megakaryocyte, and morphology are normal
...

Sidenotes: In this condition, platelet production remains responsive to TPO [the normal regulatory stimuli,
hormone that is produced chiefly in the liver parenchyma and secondarily in kidney] and morphologically normal
platelets are produced at a moderately increased rate
...
HEMATOLOGY 2
...
STUDY QUESTIONS

Page | 1

e
...

Q11
...


A persistent reactive thrombocytosis is a hallmark of myeloproliferative disorders such as polycythemia vera,
chronic myelogenous leukemia, and myelofibrosis with myeloid metaplasia primary myelofibrosis
...

Q12
...


Platelet count is low for 2-6 days if there is no platelet transfusion done but typically rebounds to elevated levels
for several days before returning to pre-hemorrhage level (normal level) 10-16 days after blood loss
...
What happens to your platelet level after splenectomy? How long will it take to return to its normal level?
a
...


POSTSPLENECTOMY THROMBOCYTOSIS: removal of spleen results to an increased platelet count that can reach
or exceed 1million/uL regardless of the reason for splenectomy
...
After splenectomy, there would be an expected initial increase in the platelet count
approximately 30%-50%, however, far exceeds levels that could result from rebalancing of the circulating platelet
pool to incorporate the splenic platelet pool
...
In some patients who undergo splenectomy for treatment of
anemias, the platelet count can remain elevated for several years
...
What would be the level of platelets in patients that are associated with IDA? What is the importance of iron in the
regulation of platelet production?
a
...


Thrombocytosis: 50% of mild IDA cases is associated with thrombocytosis
...
In some cases of IDA, platelet count may reach up to
2million/uL if there is no iron therapy
...

Iron: plays an important role in regulating thrombopoiesis [same as with TPO] because treatment of iron
deficiency with iron replacement has resulted in a normalization of the platelet count in thrombocytopenic
patients
...


Q15
...
THROMBOCYTOSIS: serves as an indication of inflammation and related diseases such as rheumatoid arthritis,
rheumatic fever, osteomyelitis, ulcerative colitis, and acute infections
...
Rheumatoid arthritis: presence of thrombocytosis can be correlated with activation of inflammatory processes
...
Tumor (Hodgkin disease) and various carcinomas: thrombocytosis could be an early evidence of these two
...
Hemophilia: patients with elevated platelet count greater than normal limits (>450,000/uL) indicates hemophilia,
even in the absence of active bleeding
...
What is Kawasaki disease? How it affects your platelet level?
a
...

c
...

e
...

g
...

i
...


Kawasaki disease is an inflammation of the walls of small and medium-sized arteries throughout the body
...

Acute febrile stage: 2 weeks or longer
Subacute stage: additional 10 weeks; during this phase the platelet level reaches 2millions/uL
In infants and young children: it is an acute febrile illness
...

Highest incidence rate was reported from Japan
...

Other substances that are elevated during inflammation includes: C-reactive proteins, fibrinogen, VWF
...


Q17
...


Strenuous exercise is a well-known cause of relative thrombocytosis due to the release of platelets from the splenic
pool or hemoconcentration by the transfer of plasma water to the extravascular compartment or both
...


MLS12A
...
MODULE 3
...

c
...


Like WBC: platelet shift from marginal pool to the circulating pool
...

EPINEPHRINE = PLATELET ACTIVATION =PLATELET LEVEL IN CIRCULATION [due to shifting]
Platelet level returns to its pre-exercise baseline level 30 minutes after completion of exercise
...
In phlebotomy, why is it important to let the patient take a rest first before collecting blood sample?
a
...


Q19
...
Rebound thrombocytosis happens 10-17 days after withdrawal of offending drugs such as alcohol or
methotrexate(medication for certain cancer), therapy for underlying conditions with which thrombocytopenia is
associated (vitamin B12 deficiency)
...
After withdrawal, of course there is already an underlying thrombocytopenia, therefore
thrombocytosis would rapidly increase (sudden increase of platelet) as a compensation
...
If a patient is an alcoholic person, what do you think would happen to his/her platelet level?
a
...
TPO is a stimulating hormone for platelet production, therefore if liver is damaged, then it would not
produce TPO properly
...
What happens during Myeloproliferative neoplasm?
a
...
Whether TPO decreases or increases, it will neither
affect the thrombocytopoiesis
...
What are the four major myeloproliferative disorders?
a
...
Chronic myelogenous leukemia
c
...
Chronic idiopathic myelofibrosis
Q23
...

b
...

d
...

f
...


A chronic myeloproliferative neoplasm in which the peripheral blood platelet count exceeds 1million/uL due to an
uncontrolled proliferation of marrow megakaryocytes because it is unresponsive to TPO
...

ET is caused by the clonal proliferation of megakaryocytes induced by a mutation in the Janus-associated kinases
(JAK1 & JAK2)
Clinical symptoms: Hemorrhage, platelet dysfunction, and thrombosis
Although you have millions of platelets, upon injury, you would still bleed out because they are dysfunctional
...

Blood picture: Heterogenous size, bizarrely shaped platelets; hypogranular or agranular with a clear, light blue
appearance on Wright stain
...
What the 5 major conditions that are related to thrombocytopenia?
a
...

What is the effect of chemotherapy to the platelet concentration?
▪
Chemotherapy: this procedure is toxic towards cells especially the progenitor cells and stem cells which is
why there would be thrombocytopenia or decreased
What is the effect on platelet concentration if a patient has aplastic anemia?
▪
Aplastic anemia: this is a total absence or decrease of stem cells in
What do TAR means?
▪
Thrombocytopenia with Absent Radius/Radii
MLS12A
...
MODULE 3
...

So platelet concentration decreases
...

Knowing this, we could also say that not only RBCs and WBCs are affected but so are the platelets
...

▪
TAR syndrome: Thrombocytopenia with Absent Radius
...

▪
Associated with a mutation in the RBM8A gene located in the long arm of chromosome 1
...

▪
Platelet count usually increase over time, with normal levels usually achieved by the time these children
reach school age
...
= DECREASED
PLATELET PRODUCTION = DECREASED PLATELET COUNT
Explain May-Hegglin Anomaly
...

▪
Large platelets are present in peripheral blood films
▪
Dohle bodies are present in neutrophils and occasionally in monocytes
...

▪
Platelet function in response to platelet-activating agents is usually normal
...

▪
Mutation in the MYH9 gene that encodes for non-muscle myosin heavy chain have been reported and is
believed to be responsible for the abnormal size of platelets in this disorder
...

▪
Caused by mutations in MPL gene on chromosome 1 (1p34
...

▪
Affected infants: platelet count is less than or equal to 20,000/uL at birth, petechiae and evidence of
bleeding at or shortly after birth
...
1)
▪
Mutation in ANKRD26 gene lead to incomplete megakaryocyte differentiation and resultant
thrombocytopenia
...

▪
Bleeding is absent or mild, because platelet function is still normal
...
23) or
mutations in GATA1 gene also on the X chromosome at Xp11
...
HEMATOLOGY 2
...
STUDY QUESTIONS

Page | 4

What is Neonatal Thrombocytopenia?
▪
Platelet count <150,000/uL [present in 1%to 5% of infants at birth
...

▪
Common causes: TORCH [Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes syndrome
infections]
What is the most common infectious agent causing congenital thrombocytopenia? What is its mechanism?
▪
Cytomegalovirus: mechanism is not well understood but reports state that it inhibits megakaryocytes and
their receptors, which results to impaired platelet production
...

▪
Bone marrow examination would usually show marked decreased or absence of megakaryocytes
...

▪
Recovery usually occurs within a few weeks after birth
...

▪
TAGLINE: INHIBITED megakaryocytes and their precursors leads to IMPAIRED PLATELET PRODUCTION
leading also to DECREASED PLATELET COUNT (THROMBOCYTOPENIA)
What are the effects of chemotherapeutic agents on platelet concentration?
▪
Chemotherapeutic agents used for treatment hematologic and nonhematologic malignancies suppresses
bone marrow megakaryocyte production and production of other hematopoietic cells which as a result
can cause thrombocytopenia
...
This condition is called Drug-induced Hypoplasia, the doselimiting factor for many chemotherapeutic agents
...
This drug is used for treating thrombocytosis in
patients with essential thrombocythemia and other myeloproliferative disorders
...

What happens to the platelet concentration in case of long-term ingestion (like months to years)?
▪
ETHANOL: can cause persistent, severe thrombocytopenia
...

▪
Platelet counts usually returns to normal level weeks after alcohol withdrawal, but thrombocytopenia
may persist for longer periods
...

When a patient undergoes an interferon therapy, what would be the expected result on his/her platelet
concentration?
▪
A mild thrombocytopenia would be expected because interferon-alpha and interferon-gamma inhibits
stem cell differentiation and proliferation in the bone marrow
...
The best course of
action to avoid this, is to do it in moderation or follow the doctor’s prescription
...

▪
Antibacterial agents, tranquilizers, and anticonvulsants also have been reported to cause
thrombocytopenia since these can also suppress the bone marrow
...
So, megakaryocytes tend to form lobules resulting to decreased formation of platelets
...
HEMATOLOGY 2
...
STUDY QUESTIONS

Page | 5

b
...

Increased platelet destruction
What are the common causes of increased platelet destruction?
▪
Immunologic responses
o ITP
o DIT
o HIT
o NAIT
o PTP
▪
Non-immunologic responses
o Thrombocytopenia in pregnancy and preeclampsia
o Thrombocytopenia in HDN
▪
Mechanical damage, consumption, and sequestration
What is ITP? What is the expected level of platelet counts in this condition?
▪
ITP stands for Immune Thrombocytopenic Purpura
...

▪
Platelet counts is decreased [<100x109/L]
▪
There is an autoantibody mediated platelet destruction in which autoantibodies such as IgG, IgA, and IgM
binds to platelets leading to enhanced platelet removal from circulation by the reticuloendothelial cells of
the spleen
...

o Viral antigen absorption to platelet surface, meaning if an antigen binds to platelet surface, the
antibody will target the platelet and eventually lysing it
...

o Platelets that are bound to antibodies will be directly phagocytized, meaning the Fc region of the
antibody that is bound to the platelet will bind to the Fc receptor of the macrophage/monocyte
and this macrophage will phagocytize the platelet and because of that, platelet level would
decrease
...

▪
DECREASED platelet counts
▪
After 1 to 2 weeks of exposure from a new drug, three drug-dependent antibodies occur in the circulation
including:
o Drug-dependent Ab
✓ Platelet count falls rapidly (<10,000/uL)
✓ In the presence of drug, Fab region of an antibody binds directly to platelet membrane
constituent, GPIb/IX/V complex or the GPIIb/IIIa complex
...
Therefore, this could result to decreased
platelet count in circulation
...

✓ Patient may experience an abrupt onset of bleeding
...

o Hapten-induced Ab
✓ Platelet count of <10,000/uL and sometimes <1,000/uL
✓ Drug molecules are too small to trigger an immune response, therefore, they would act
as hapten in which they would try to combine with a larger carrier molecule (could be a

MLS12A
...
MODULE 3
...
Once bounded to a
larger carrier molecule, it will be targeted by the antibody causing the destruction of
platelets
...

o Drug-induced AutoAb
✓ In this case, drugs stimulate the formation of an autoantibody that binds to a specific
platelet membrane glycoprotein with no requirement for the presence of free drug
...
Autoantibodies
would directly bind to the platelet membrane without the attachment of the drug to the
platelet membrane
...
The Fab region of the IgG will then bind to the exposed PF4 neoepitope while
Fcy of the IgG will also bind to the FcyIIa receptor of the platelet membrane, thereby, resulting to platelet
activation and aggregation
...

▪
In case of heparin therapy, PF4 that is normally present on the surface of endothelial cells or released in
small quantities from the circulating platelets, will bind to the heparin forming PF4-heparin complex
...
IgG will then bind to the Fc
receptors of the circulating platelet forming PF4-heparin and IgG complex
...
Because more PF4 were released, therefore,
more heparin molecules will be bound to the PF4 and the cycle goes on
...

▪
HIT could damage the endothelial cells in the endothelial lining
...

What is NAIT? What would be the expected platelet count in this condition?
▪
NAIT stands for Neonatal Alloimmune Thrombocytopenia
...
Fetal platelet antigens are inherited as codominant genes and may pass from the fetal to the
maternal circulation as early as the 14th week of gestation through the mother’s placenta
...

These IgG antibodies that are attached to the antigen-bearing fetal platelets will cross the placenta
resulting to thrombocytopenia in the fetus because these antigen-bearing fetal platelets will be
phagocytized by the macrophages resulting to platelet destruction
...

▪
By the term alloimmune, meaning the fetus does not produce its own antibodies or autoantibodies
...

What is the difference of NAIT to HDN?
▪
In NAIT, instead of coating RBC they destroy the platelets
...

▪
Manifestations: Rapid onset severe thrombocytopenia, moderate to severe hemorrhage that may be lifethreatening
...

▪
Mostly found in multiparous middle-aged women and almost all have history of blood transfusion
...
HEMATOLOGY 2
...
STUDY QUESTIONS

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Rarely seen on men who do not have history of blood transfusion and in women who have never been
transfused or pregnant
...

What would be the expected platelet counts in pregnancy and preeclampsia?
▪
Incidental thrombocytopenia of pregnancy is also known as pregnancy-associated thrombocytopenia or
gestational thrombocytopenia
...

▪
Thrombocytopenia in pregnancy are associated with hypertensive disorders including preeclampsia,
preeclampsia-eclampsia, pre-eclampsia with chronic hypertension, chronic hypertension, and gestational
hypertension
...

▪
Pregnant women have lower platelet counts than nonpregnant women
...

Increased sequestration
▪
Related conditions: HYPERSPLENISM & HYPOTHERMIA
▪
Hypersplenism: an enlarged spleen, meaning; there would be a large enough space for the platelets to be
store in which instead of being in the circulation, they would settle in the large space of the spleen
...

▪
Delayed intrasplenic transit because of liver problems by alcoholic and post hepatic cirrhosis
...

▪
There is an increased platelet production but there is no proper transit in the circulation or delayed transit
resulting to thrombocytopenia
...

What happens when there is hypothermia?
▪
Hypothermia: <25 degrees Celsius
▪
When there is low body temperature, therefore, there would also be a mild or transient thrombocytopenia
secondary to platelet sequestration in the spleen and liver and transient defect in the function
...

▪
Surgery involving extracorporeal circulatory devices includes:
✓ Damage and partial activation of platelets in the pump
✓ Severe thrombocytopenia
✓ Marked impairment of platelet function
✓ Activation of fibrinolysis
✓ Intravascular coagulation
Abnormalities of distribution or dilution
▪
Distribution: spleen
▪
Dilution: false decrease due to increased plasma volume?
Increased platelet consumption
▪
Related conditions:
✓ TTP
✓ HUS
✓ DIC
What is TTP? What happens here? What would be the expected platelet counts?
▪
TTP stands for Thrombotic Thrombocytopenic Purpura
▪
Aka Moschcowitz syndrome
▪
Platelet counts of <30,000/uL
▪

c
...


e
...
HEMATOLOGY 2
...
STUDY QUESTIONS

Page | 8

There is a formation of microthrombi in microvasculature because there is a lot of clot formation and the
platelets involved in the clot therefore decreasing its concentration in the circulation, that’s why
thrombocytopenic
...

▪
Thrombocytopenia with schistocytes because there is an absence or dysfunction of ADAMTS13 which
normally digests or cuts the ultralarge VWF from the endothelial cells into smaller multimers
...

▪
The absence or dysfunction of ADAMTS13 allows the UL-VWF multimers to remain in circulation
...

How TTP develops?
▪
TTP development in most cases are directly related to the accumulation of ultralarge VWF (UL-VWF)
multimers in the plasma/circulation
...
UL-VWF that are stored in the
Weibel-Palade bodies of endothelial cells, will be secreted into the subendothelium and plasma
...
The loss of ADAMTS13 activity would
result to the accumulation of ultralalarge (high molecular weight) VWF multimers
...
So, once RBCs passes the circulation
where there is thrombi, they are damaged and lysed resulting the presence of fragmented RBCs or
schistocytes
...

Why there is MAHA, Thrombocytopenia, Neurologic abnormalities and renal dysfunction?
▪
MAHA: resulted due to the narrowing of blood vessel space because of the formation of microthrombi
...

▪
Neurologic abnormalities: results due to the accumulation/blocking of blood in the vasculature, thus,
blood cannot pass through properly to the brain and are fragmented in shape
...

What is the significance of cleaving UL-VWF multimers into smaller VWF multimers?
▪
VWF-cleaving protease or ADAMTS13 is responsible for regulating VWF in which it cuts or cleaves ULVWF multimers into smaller VWF multimers
...
But, if VWF as larger and longer, therefore, there would be more platelet adhesion that would
result to accumulation or formation of plate-rich thrombi that would also block the passage of blood in
the circulation since the vascular space is narrow
...

▪
Cases is approximately 10 cases per 1 million
...
Most common in women 30 to 40 years of age
...

What are the three (3) causes of TTP?
1
...
Secondary
3
...

▪

MLS12A
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MODULE 3
...

If a person do have an Inherited Upshaw-Shulman, he/she is high risk for developing what type of condition?
▪
Inherited Upshaw-Shulman is also known as ADAMTS13 deficiency and dysfunction
...

What is HUS?
▪
HUS stands for Hemolytic Uremic Syndrome
▪
It is the formation of hyaline thrombi in the renal vasculature that leads to the development of renal
failure, thrombocytopenia and MAHA
...

In what conditions that HUS is usually seen?
▪
HUS is usually seen in bacterial infections of S
...
coli (0157:H7)
that is also capable of releasing shigella-like toxin 1 and 2
...
RBC
fragmentation is not as usually as severe like in the TTP
...
MAHA; is
reflected by elevate reticulocyte count, less than 10mg/dL of Hb, and presence of schistocytes in the
peripheral blood
...

What is the difference between HUS and TTP?
▪
Basically, HUS and TTP have the same mechanism, in which, both forms thrombi but the difference is that
in TTP, thrombi is formed in the arterial or capillary vasculature; while in HUS, the thrombi is formed in
the renal vasculature
...

▪
Also, in HUS, the thrombocytopenia is mild to moderate because it occurs in the renal vasculature; while
in TTP, thrombocytopenia is most severe because it occurs in the arterial and capillary vasculature
...

What is Atypical HUS?
▪
Atypical Hemolytic Uremic Syndrome is associated with the defects in the regulation of complement
activation
...
Rather, AHUS is associated with the defects in the regulation of complement activation, in
which, there are mutations in the complement regulatory proteins
...

What are the causes of HUS?
▪
Shigella dysenteriae serotypes – shigan toxin
▪
Enterohemorrhagic Escherichia coli-shiga-like toxins
▪
Exposure to immunosuppressive agents or chemotherapeutic agents or both (in adults)
▪
Postpartum period
What is a Disseminated Intravascular Coagulation?

MLS12A
...
MODULE 3
...

What are the similarities and difference of DIC with TTP?
▪
Just like in TTP, there is presence of MAHA and deposition of thrombi in the arterial circulation of most
organs
...

▪
DIC is one of the problems in the Secondary Hemostasis, because of coagulation cascade that results in
consumptive coagulopathy that entraps the platelets in the intravascular fibrin clots
...

▪

PATHOPHYSIOLOGY OF DIFFERENT PROBLEMS WITH PLATELET
▪
TTP: VWF-Platelet thrombosis leading to microvascular stenosis
...

▪
If there is thrombus, then there would always be thrombocytopenia and RBC fragmentation
...

Instead, manual checking will be furtherly performed
...
That’s why we need to recheck
the automated result for us to confirm
...

▪
But if there is none, then we need to perform bone marrow examination
...
If megakaryocytes are decreased, then we examine, marrow for infiltrative disease, aplasia,
etcetera, because may be there is problem in the lineage but if increased, then we still need to proceed for further
confirmation
...
So, if abnormal, then we
have to evaluate for primary hematologic disease but if normal then we can say that there is peripheral platelet
destruction so there could be ITP or things like that
...


STEM CELL POOL
▪

▪

▪

HYPOPLASIA, what happens here?
If there is hypoplasia meaning there is an impaired regulation of stem cell pool
...

What if there is a decreased in TPO concentration?
TPO is a regulating hormone which is very essential in the production of platelets, therefore, magdecline sya, then
there would also be thrombocytopenia
...


MLS12A
...
MODULE 3
...
Like for example, if there is an increased
sequestration in the spleen especially in cases of big spleen syndrome, there are more platelets that stays in the
spleen rather than in the circulation, which results to low platelet concentration in the circulation
...

PART 3: QUALITATIVE PLATELET DISORDERS
Q1
...
When can we say, if a platelet disorder is either qualitative or quantitative?
▪
If the excessive bruising or the superficial bleeding in a patient is associated with normal platelet count, then, it
already suggests that is an either acquired or congenital, generally, a qualitative disorder
...
If a patient has qualitative platelet disorder, does it mean that the disorder is due to platelet function?
▪
As discussed previously, qualitative platelet disorders are disorders in which there is a normal platelet count
...
A normal
platelet count is only suggestive that a platelet disorder is either inherited or acquired, because we could also have
other defects aside from platelet function
...
Defects in platelet-vessel wall interaction (adhesion defetcts)
2
...
Disorders in platelet secretion and abnormalities of granules
▪
Important proteins and non-proteins are contained in the platelet granules
▪
Defect in the secretion leads to abnormalities of granules
4
...
Defects in cytoskeletal regulation
▪
Sol-gel zone or the structural zone of the platelet
▪
Problem with the microtubules, microfilaments, and intermediate filaments
6
...

EXAMPLES OF ACQUIRED FUNCTIONAL DEFECTS (AAACD)
1
...
Antiplatelets antibodies, autoimmune
3
...
Cardiopulmonary bypass surgery
5
...
Liver diseases
2
...
Myeloproliferative disorders
4
...
What are the two substances that are involved in platelet adhesion?
▪
GP 1B/V/IX complex
▪
vWF
Q5
...
This glycoprotein is very essential in platelet adhesion through binding to the VWF on the
MLS12A
...
MODULE 3
...
Defects in the GP1b/V/IX complex affects both platelet production and
structure resulting to thrombocytopenia
...
In what cases BSS is commonly seen?
•
BSS is a rare disorder of a platelet adhesion that usually manifest in infancy or childhood with hemorrhage
characteristics of defective platelet function including ecchymoses, epistaxis, and gingival bleeding
...

Q7
...
What would be the laboratory findings for the aggregation tests?
▪
Normal aggregation test with all agonists (AACE) EXCEPT for Ristocetin and Thrombin
...
What would be the effect of this syndrome to the platelet structure?
▪
Platelet size could be similar to RBC or larger
...

Q10
...
As a result, platelets and large VWF multimers with their associated Factor VIII are
removed in the circulation resulting to thrombocytopenia and reduced factor VIII clot activity or the platelet clot
formation
...
Since this binding will consume the VWF, there would be thrombocytopenia and reduced
VWF and Factor VIII clot activity
...
TYPE 1: partial quantitative deficiency of VWF
2
...

3
...
Glanzmann’s thrombasthenia
2
...
Hereditary Hypofibrinogenemia
Q11
...
GPIIb/IIIa is a membrane receptor in which has the ability to bind with fibrinogen to initiate
an clot formation or platelet aggregation
...

▪
This condition is also associated with an abnormal in vitro clot retraction due to lack of
thrombosthenin/actomyosin
...
What the other substances that are capable of binding to fibrinogen?
▪
Fibronectin, vWF, and other adhesive ligands
...
What are the clinical manifestations seen in Glanzmann’s Trombasthenia?
▪
Occasional bleeding following circumcision
▪
Frequent epistaxis and gingival bleeding
▪
Hemorrhagic manifestations include petechiae, purpura, menorrhagia, GI tract bleeding and hematuria
▪
Severity of bleeding episodes decrease with age
...
What would be the laboratory findings in patients with GT?
▪
A normal platelet count and morphology
▪
Abnormal aggregation tests with all agonists except ristocetin
...
How would you differentiate GT from BSS?
▪
DEFECT: In BSS, there is defect in GP1b/V/IX complex, whereas, in GT there is defect in GPIIb/IIIa complex
▪
AGGRE-TEST: In BSS, NORMAL with all agonist except Ritocetin and thrombi, whereas, in GT, ABNORMAL with
all agonist except to Ristocetin
...
HEMATOLOGY 2
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STUDY QUESTIONS

Page | 13

Q16
...

INHERITED GIANT PLATELET SYNDROME
Q17
...

▪
In May Hegglin, there an abnormal microtubule distribution, whereas, in Epstein Syndrome the platelets are
spherical in shape and has a prominent surface-connected canalicular system
...

GIANT PLATELET SYNDROMES
1
...
MHA
3
...
Fechtner PS
5
...
Macrothrombocytopenia
7
...

CHEDIAK-HIGASHI SYNDROME
Q18
...

▪
Give rise to disorder in generalized cellular dysfunction involving fusion of cytoplasmic granules leading to
secretion difficulty
...
23
▪
Mutations is WASP gene
▪
WASP plays a crucial role in actin cytoskeleton remodelling
...

▪
Movement and attachment to other cells and tissues platelets impairs their developments reading to reduced size
and early cell death
...

A-DENSE STORAGE POOL DEFICIENCY
▪

▪

Both a-granules and dense granules are deficient

MLS12A
...
MODULE 3
...

Inhibits cyclooxygenase
...


SCOTT SYNDROME
▪
Rare autosomal recessive disorder of a calcium-induced membrane phospholipid scrambling and thrombin
generation on platelets
...

▪
Phospholipid asymmetry is maintained by the enzyme aminophospholipid translocase
...

▪
In conclusion, if there is scramblase defect, there would be flipping out of phosphatidylserine resulting to the
inhibition of secondary hemostasis continuation
...

▪
This is a condition in which platelets are always in an “activated state” and expresses phosphatidylserine on the
out leaflet of the platelet membrane without prior activation
...

▪
Defect in aminophospholipid translocase may result to:
✓ Overactivation of enzyme scramblase, not regulation
✓ Overexpression of phosphatidylserine leading to an abnormal number of fibrin (red) clots)
ACQUIRED-QUALITATIVE PLATELET DISORDERS
1
...
Antiplatelelet antibodies
3
...
CBSurgery
5
...
Dysproteinemia and Paraproteinemia
7
...
MM & Waldenstrom macroglobulinemia
9
...
Uremia
UREMIA
UREMIA is a bleeding caused by platelet dysfunction
1
...
Altered prostaglandin metabolism
▪
GSA is an NO donor (Nitric oxide)
▪
NO is present in the circulation at higher than normal levels
...
HEMATOLOGY 2
...
STUDY QUESTIONS

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✓ Prostaglandin synthesis: inhibition of cyclooxygenase
✓ Phosphodiesterase activity
Ibuprofen and Related Compounds
▪
▪

Competitive inhibitors of cyclooxygenase
As the blood concentration of the drug decreases, platelet function is recovered
...


What are the other effects of drugs?
Drugs can also inhibit the transmembrane receptors thus no further activation of platelets
...

HYPERAGGREGABLE PLATELETS
▪

▪
▪
▪

Aka Sticky platelet syndrome
Happens due to emotional stress
If there is an increased emotional stress then there would also be increased ADP, epinephrine or both resulting to
overactivation and aggregation of platelets
...
HEMATOLOGY 2
...
STUDY QUESTIONS

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