[TRANS] LECTURE UNIT 11: PLATELET DISORDERS

QUANTITATIVE PLATELET DISORDERS o Ecchymosis

• Bleeding disorders resulting from platelet abnormalities ▪ Irregular
whether they may be quantitative or qualitative, may ▪ 1 cm
usually manifest as bleeding into the skin or mucous
membranes or both (mucocutaneous bleeding). • Small vessel bleeding can
• Common presenting symptoms include: be seen in skin, mucous
membranes of nose and
o Petechiae mouth, GI, urinary and resp.
o Purpura tracts (common sites)
o Ecchymoses • Hemorrhage in CNS most serious site
o Epistaxis • severity of bleeding is related to the degree of
o Gingival bleeding thrombocytopenia
▪ These similar findings are also seen in vascular o > 50,000/uL - unusual for clinical significant
disorders (e.g., Ehlers-Danlos syndrome) which bleeding to occur
are relatively rare o < 60 x 109/L: significant bleeding
• Deep tissue bleeding, such as hematoma and o severity of bleeding = degree of thrombocytopenia
hemarthrosis, is associated with clotting factor o < 20 x 109/L spontaneous bleeding into skin and
deficiencies mucous membrane
o < 10 000 uL platelet counts – high risk of developing
• Quantitative Platelet Disorders
spontaneous bleeding (Rodak’s)
o Thrombocytopenia
o Thrombocytosis • Laboratory Findings
o Prolonged Bleeding Time
Thrombocytopenia
o Abnormal Clot retraction
• Platelet count of fewer than 100,000/μL Etiologies
• Most common cause of clinically important bleeding
o True thrombocytopenia has to be differentiated from • Generalized BM suppression
the thrombocytopenia artifact that can result from:
o Aplastic Anemia
▪ poor specimen collection o Acquired: toxic chemical or physical agents (e.g.,
▪ poorly prepared blood films ionizing radiation or chemotherapeutic agents)
▪ automated cell counts
• Selective suppression of megakaryocyte
▪ platelet clumping or platelet satellitosis
o Associated with an intake of diuretic agents such as
I. Decreased Production chlorothiazide but the mechanism is still unclear
• Abnormalities in platelet production can result from • Myelophthisic process
megakaryocyte hypoplasia in the bone marrow or o it is a space occupying lesion such as tumor, fibrosis
ineffective thrombopoiesis. or leukemia
• Factors causing decreased platelet production can be o the thrombocytopenia in this condition is related to
congenital or acquired. the abnormal cells that are crowding out the normal
• Small-vessel bleeding in the skin attributed to bone marrow elements
thrombocytopenia manifests as hemorrhages of
different sizes. It may include the following: • Ineffective thrombopoiesis that could be associated
with:
o Petechiae
o Ethanol abuse with or without malnutrition
▪ small, pinpoint o Megaloblastic states wherein there is an impairment
hemorrhages of DNA synthesis
▪ 1 mm in o Could be due to severe iron deficiency anemia
diameter
▪ iron is essential in platelet synthesis
o Purpura
o Paroxysmal nocturnal hemoglobinuria
▪ round
▪ 3 mm in diameter ▪ wherein the stem cell is abnormally sensitive to
C3b
o Due to viral infections such as in HIV

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 LECTURE UNIT 11: PLATELET DISORDERS

II. Dilutional Loss o Analogous to Rh Hemolytic Disease

• Patients’ refractory to Platelet transfusion
• Extensive blood transfusion
o Alloimmunization
o The degree of thrombocytopenia is also directly
o Characterized by failure to achieve adequate
proportional to the number of units that has been
increments in the circulating platelet count after
transfused
several transfusions
o There are two mechanisms for thrombocytopenia.
o Alloantibodies are directed against the HLA antigens
Could be due to:
o Patients resists the treatment
▪ Dilution of own platelet pull
▪ Can be observed in patients who have received
▪ Acute blood loss
long-term platelet support
III. Non-Immune Destruction Autoimmune
• Artificial surfaces can induce platelet adherence and
• Primary Autoimmune Thrombocytopenia
platelet microaggregates in cases of:
o Cardiovascular prosthetic devices o E.g., Immune Thrombocytopenic Purpura (ITP)
o Prosthetic vascular grafts • Acute Immune Thrombocytopenic Purpura (ITP)
o Dialysis membranes
o Can also induce platelet adherence and platelet o Primarily a disorder of children
microaggregates ▪ there is a similar condition seen occasionally in
• Activation of the coagulation System adults

o In diffuse intravascular coagulation there is an o Characterized by an abrupt onset of bruising,

activation of coagulation system that will lead to: petechiae and mucosal bleeding (sometimes) in a
previously healthy child
▪ intravascular thrombin generation platelet o Primary Hematologic Feature: Thrombocytopenia
aggregation
▪ Often occurs one to three weeks after an
 thrombin mediated reaction will trap platelets infection
in the fibrin networks and will eventually
destroy them. o Acquired and self-limiting
o Preceded by various infections or vaccinations in
▪ consumption of Factors I, V, VIII and XIII. more than half of pediatric patients in the 4 weeks
• Hemolytic Uremic Syndrome (HUS) and Thrombotic before the diagnosis
Thrombocytopenic Purpura (TTP) ▪ Measles Mumps Rubella (MMR) vaccine
• Pathophysiology for thrombus formation: ▪ Diphtheria Tetanus and Pertussis (DTP)
o Intravascular aggregation (e.g., Endothelial ▪ Other vaccines: Polio, Hepatitis A and B
prostacyclin deficiency) o Observation: Often follows a viral illness or
o Endothelial Injury (e.g., Endotoxins) vaccination suggests that some children will produce
antibodies and immune-complexes against the viral
IV. Immune Platelet Destruction
antigens
• Associated with IgG or complement on platelet surfaces ▪ Platelet destruction results from the binding of
o Previously called as “Idiopathic thrombocytopenic these antibodies or immune complexes to the
purpura” because it describes the cases of platelet surface
thrombocytopenia arising without apparent reasons. • Immune Thrombocytopenic Purpura
o Since acute and chronic ITP are immunologically
mediated, the word idiopathic has been replaced o Enhanced platelet consumption
with immune. o Idiopathic

• Causes: ▪ Causes appear to be related to antibodies

against platelets
o Isoimmune (alloantibodies)
o Autoimmune (autoantibodies) • Drug-Induced Thrombocytopenic Purpura
o Drugs o Certain drugs can stimulate production of
Isoimmune immunoglobulin that will bind to platelet membrane
antigen
o Heparin-induced Thrombocytopenia
• Post-transfusion (Isoimmune) Purpura
▪ Patients develop antibodies that appear to bind
o Rare complication of post transfusion characterized
by their Fab region to platelet factor 4 (PF-4)
by a sudden profound self-limiting thrombocytopenia
o Certain drugs can stimulate formation of
• Neonatal Isoimmune Thrombocytopenia autoantibodies that will bind to specific platelet
o Caused by transplacental passage of maternal IgG membrane glycoprotein with no requirement for the
directed against fetal platelet antigens presence of free drug

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 LECTURE UNIT 11: PLATELET DISORDERS

▪ Gold salts ▪ In severe cases with clinical bleeding,

▪ Procainamide transfusion with platelets is necessary.
▪ Levodopa
• Other Conditions
o Certain drugs induce antibodies which is analogous
o Fetcher syndrome
to drug-induced hemolytic anemia
o Epstein syndrome
▪ Quinidine o Sebastian syndrome
▪ Quinine o Bernard-Soulier syndrome
▪ Sulfa antibiotics o Velocardiofacial/DiGeorge syndrome
▪ Sulfonamides o Paris-Trousseau Thrombocytopenia
▪ Chloroquine o Mutation in transcription factor GATA1
▪ Rifampicin
Small platelets
V. Secondary Autoimmune Thrombocytopenia
• Wiskott-Aldrich Syndrome
• 5-10% of px with chronic lymphocytic leukemia (CLL)
o X-linked thrombocytopenia
and 14-26% of px with SLE
o Due to mutations in WASp gene
VI. Drug-Induced Immune Thrombocytopenia o Characterized by:
▪ Abnormal immune system function
• Can be divided to several types based on mechanisms ▪ Immune deficiency
underlying the interaction of antibodies with the drug ▪ Eczema
and platelets ▪ Inflammatory skin disorders
• Like quinidine
 Patches of red irritated skin
VII. Splenic Sequestration ▪ Reduced ability to form blood clots
• In splenomegaly, either there is o Primarily affects MALE
o increased phagocytosis and destruction of damaged Normal size platelets
platelets
o Increased sequestration of normal undamaged • Familial Platelet Disorder
platelets.
o Predisposition to AML
• Sequestration can be seen in Gaucher disease, o Secondary to mutations in the CBFA/AML1 gene
sarcoidosis, and Felty’s syndrome o Platelets may look paler
o Felty’s syndrome is the adult type of Rheumatoid o Reduce platelet aggregation with collagen
arthritis with splenomegaly. o PLT count may not be always reduced
▪ Uncertain if it has qualitative PLT effect
VIII. Congenital Thrombocytopenia
o Symptoms may vary
Increased platelet size
▪ There are patients with no symptoms of easy
bruising or bleeding
• Arise from mutations in the MYH9 gene encoding the ▪ Some patients have bleeding
nonmuscle myosin heavy chain II
• This is a rare autosomal dominant disorder o Hemoglobin and WBC may be elevated
• May-Hegglin Anomaly Other causes
o Abnormal genetic
condition that is an Dohle body • Congenital Amegakaryocytic Thrombocytopenia
autosomal dominant
disorder whose exact o Autosomal recessive disorder associated with
frequency is unknown. mutations in the thrombopoietin receptor MPL
o It is characterized by • Gray Platelet Syndrome
the presence of Dohle
bodies like inclusions Giant platelets o Rare congenital disorder in which platelets are large
in eosinophils, and have grey appearance on light microscopy due
neutrophils, and to the absence of alpha granules
monocytes. o Lifelong bleeding disorder
o Abnormal giant platelets measuring 20mm in
diameter
o Thrombocytopenia frequently coexists
o Platelet function in response to platelet activating
agents is usually normal.
o In some patients, the number of megakaryocytes is
increased and ultra-structure is abnormal
o Most patients are asymptomatic unless there is a
severe thrombocytopenia

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 LECTURE UNIT 11: PLATELET DISORDERS

IX. Thrombotic Thrombocytopenic Purpura • Clinical picture: resembles thrombocytopenia but

platelet count is within the normal range
• Related to deficient activity of a plasma vWF-cleaving • Clinical manifestations:
metalloproteinase (now known as ADAMTS-13)
o Epistaxis
• Large vWF molecules that are capable of binding to o Menorrhagia
platelets and producing platelet thrombi in the o Easy bruising
microcirculation o Postoperative bleeding
o There is microangiopathic hemolytic anemia
secondary to platelet aggregation in the small blood
vessels
Thrombocytosis

• An increase in number of circulating platelets

• Transient increase: physiologic stress or epinephrine
infusion
• Classification:
o Primary (Autonomous thrombocytosis)
o Secondary (Reactive thrombocytosis)

I. Primary (Autonomous Thrombocytosis)

• Uncontrolled platelet proliferation

o Increased platelet counts and megakaryocyte
numbers and volumes
• Myeloproliferative disorders
o Polycythemia vera Inherited Defects
o Essential thrombocytosis
I. Platelet Vessel Wall Interaction - Disorders of Adhesion
▪ Persistent elevation of platelet 3x the normal
value
• Platelets fail to adhere on exposed subendothelial
o Chronic granulocytic leukemia components such as collagen and basement membrane
o Myelofibrosis
o Chronic Myelogenous leukemia

II. Secondary (Reactive Thrombocytosis)

• Usually transient and benign

o May be a reactive process
o Thrombocytosis is not as pronounced as the primary
• Result from acute or chronic disorders
o Iron deficiency anemia
o Inflammatory diseases
o Malignancy Von Willebrand Disease
o Drugs
o Redistribution of platelets • Deficiency or abnormality in plasma vWF
o Rebound thrombocytosis • Von Willebrand Factor
o Hemolytic anemias
o Acute blood loss o pivotal protein and plays key roles in both primary
o Major surgical procedure, splenectomy hemostasis and secondary hemostasis
o Other pathological conditions o secreted by endothelial cells, specifically the Weibel-
Palade bodies, and alpha granules of platelets
▪ Weibel-Palade bodies – elongated secretory
QUALITATIVE PLATELET DISORDERS
organelles specific to endothelial cells
• excessive bruising and superficial bleeding in patients o It serves as an adhesive platelet ligand that ties the
whose platelet count is normal suggests an acquired or platelet to the exposed collagen at sites of vascular
a congenital disorder of platelet function injury
Thrombocytopathy o Gene is located on chromosome 12
o Partial but nonfunctional duplication – chromosome
• Refers to the platelets with functional defects 22 (vWF pseudogene)
• Inherited or acquired
• Primary or secondary

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 LECTURE UNIT 11: PLATELET DISORDERS

▪ Important consideration in the design of primers o Patients tend to do better if platelet apheresis is
for amplification of vWF gene used for transfusion because it limits the number of
donors to which the patient is exposed.
• Platelet is functional but incapable of adhering to BV
wall ▪ Therefore, the rate of alloimmunization is lower
• Spontaneous bleeding from mucous membranes,
• Treatments:
excessive wound bleeding
• Laboratory findings: o desmopressin acetate (DDAVP), a synthetic
analogue of ADH.
o Prolonged bleeding time, normal platelet count
o More recently, the recombinant factor VIIa or the
o Decreased Factor VIII – increased PTT
activated factor 7.
▪ vWF plays a role in secondary hemostasis as it
• Laboratory Findings
serves as a carrier protein for Factor VIII
▪ Absence of vWF will rapidly clear Factor VIII o Bleeding Time (BT) is markedly prolonged.
from the plasma o Platelet Count (PC) moderately decreased and
increased in size (peripheral smear)
o Normal aggregation: epinephrine, collagen and ADP
o Normal aggregation: Epinephrine, Thrombin,
o Fails to aggregate at ristocetin
Collagen and ADP (ECA)
▪ The rate and extend of their aggregation are o Fails at: ristocetin
measured by the standard platelet aggregometer
▪ There is a decreased or absence of aggregation
and ELISA
• Von Willebrand Disease Classification II. Platelet-Platelet Interaction - Disorders of Aggregation
o Type 1 - Partial quantitative deficiency of vWF Congenital Afibrinogenemia
▪ Most common variant that occurs in about 80%
of the patients • Deficiency of plasma fibrinogen (Factor I)
• Not a truly platelet function disorder
o Type 2 - Qualitative deficiency of vWF
o Type 2A - Decreased platelet-dependent vWF o Platelet do not exhibit normal function in the
function w/ selective deficiency of HMW multimers absence of fibrinogen
o Type 2B - Increased affinity for platelet glycoprotein
• Laboratory Findings
Ib
o Type 2M - Decreased platelet-dependent vWF o Prolonged PT, aPTT, and Thrombin Time
function with HMW multimers present o Cryoprecipitate or fibrinogen concentrates can be
o Type 2N - Markedly decreased binding of Factor VIII used to treat bleeding episodes.
to vWF
o Type 3 - Complete deficiency of vWF ▪ Some patients develop antibodies to fibrinogen –
ineffective treatment
▪ Absence of the vWF antigen and vWF activity
Glanzmann’s Thrombasthenia
▪ Very low levels of Factor VIII
Bernard-Soulier Syndrome (Giant Platelet Syndrome) • Originally described as a bleeding disorder associated
with abnormal in-vitro clot reaction and normal platelet
• Rare autosomal recessive count
platelet function resulting from • Autosomal recessive
an abnormality in platelet GP • Frequently seen in populations with high degree of
Ib/IX/V complex consanguinity
o The glycoprotein Ib/IX/V • Platelet: Normal size and morphology
complex is missing from • Quantitative and qualitative defect in the GP llb/llla
the platelet surface or exhibits abnormal function. complex

▪ Mediates the binding of vWF to platelets o Genetic mutations are distributed widely over ITG
▪ For platelet adhesion to the subendothelium A2B and ITGB 3 genes (Chromosome 17)
o Fibrinogen binding to platelets on activation and
• There is an inability to bind to the vWF, which accounts aggregation are impared
for the inability of the platelet to adhere to the exposed
subendothelium → bleeding characteristics of this • Treatment: Transfusion of normal platelet
disorder o The defective platelets may interfere with the normal
• Patients with this type of syndrome usually manifest in transfused platelet and it may be necessary to
infancy or childhood with hemorrhage characteristic of infuse more donor platelets (control the bleeding)
defective platelet function such as ecchymosis, o Patients may become alloimmunized.
epistaxis, and gingival bleeding.
• There is no specific treatment, but platelet transfusions ▪ To reduce alloimmunization:
are the therapy of choice.  single donor platelet apheresis products
o However, some patients develop alloantibodies so  HLA match donor platelets
that further platelet transfusion is no longer possible.  ABO match donor platelets

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 LECTURE UNIT 11: PLATELET DISORDERS

• Laboratory Findings • Prothrombinase activity (Platelet procoagulant) that is

induced upon activation is reported to be impaired in
o Prolonged bleeding time
association with an inability to maintain elevated
o Impaired clot reaction
intracellular calcium ion levels
o Platelet count is normal in number, with normal size,
morphology, and life span, but without platelet- • In association with other inherited disorders
platelet clumping o Hermansky-Pudlak Syndrome (HPS)
o Absence or marked decrease of platelet aggregation
in the presence of ADP, Collagen, Epinephrine and ▪ aka Oculocutaneous albinism
Thrombin – diagnostic hallmark o Chediak-Higashi Syndrome
o Normal platelet agglutination in the presence of o Wiskott-Aldrich Syndrome
ristocetin o Thrombocytopenia-Absent Radii Syndrome
o Criscelli Syndrome
III. Platelet Secretion and Abnormalities of Granules -
Storage Pool Deficiency Hermansky-Pudlak Syndrome (HPS)

• Deficiencies in: • Tyronase-positive

oculocutaneous albinism
o Dense granules (delta-SPD) or Alpha granules • Defective lysosomal function in
(alpha-SPD) or both (alpha/delta-SPD) a variety of cell types
• Clinical Manifestations: • Accumulation of ceroid-like
pigments in macrophages
o Mucocutaneous hemorrhage and hematuria,
epistaxis, and easy and spontaneous bruising o Lipofuscinosis – ceroid-
o Petechiae are less common than in other qualitative like deposition in the cell of
platelet disorders the reticuloendothelial system

• Laboratory Findings ▪ A neurodegenerative disorder that results from

excessive accumulation of lipofuscin in the
o Prolonged bleeding time body’s tissue
o Platelet count = normal
o Response to ADP and epinephrine – absent or • Profound platelet dense granule deficiency
blunted • Due to the mutation of Chromosome 19
o Collagen response – markedly impaired • Clinical manifestations

Delta-Storage Pool Deficiency o Bleeding tendency associated with abnormal platelet

function
o Defective lysosomal function
• The dense granules are the storage site for serotonin o Bleeding associated with most dense granule
nucleotides such as ATP and ADP, Calcium and deficiencies is rarely severe
Pyrophosphate o Causes an abnormally pigmentation of the hair, skin,
• In this disorder, there is a diminished platelet and eyes
aggregation during the second phase o A person can have a higher chance or risk of skin
• Due to the decrease in dense granules materials and damage and skin cancers caused by long-term sun
other abnormalities reported in this disorder exposure
o There is a decreased in synthesis (in platelets o Vision problems
activated with collagen and epinephrine, but not ▪ Reduced vision rapid, involuntary eye
arachidonate) movements, and increased sensitivity to light are
▪ Prostaglandins common
▪ Thromboxane-2 ▪ Remain stable after early childhood
▪ Malondialdehyde Chediak-Higashi Syndrome (CHS)
• Dense granule deficiencies can be subdivided into • Rare autosomal recessive disorder characterized by
deficiency states associated with Albinism and those
normal individuals (non-Albinos) o Partial oculocutaneous albinism
o frequent pyogenic bacterial infections
o In the platelets for non-Albinos, there is evidence for o giant lysosomal granules in cells of hematologic and
the presence of dense granule membranes in nonhematologic origin
normal to near normal numbers o platelet dense granule deficiency
▪ Which suggests that this disorder arises from the o hemorrhage
inability to package the dense granule contents • Defective cytotoxic T cells and NK cells
• addition of arachidonic acid to platelet-rich plasma, fails • Arises from the mutations in the lysosomal trafficking
to induce aggregation response regulator or the LYST gene on Chromosome 1
o This is due to the impaired liberation of arachidonic o Protein coded by the gene interacts with protein
acid from the membrane phospholipids including the SNARE complex protein, HRS, and the
signalling proteins
• Enhanced ADP but not thrombin-induced rise in o Participates in the intracellular membrane fusion
cytoplasmic calcium ion levels reaction and vessel trafficking

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 LECTURE UNIT 11: PLATELET DISORDERS

• Decreased platelet count and a defective platelet o Impaired thrombin-induced calcium ion mobilization
function & increased calcium ions transport reported in some
patients
o Prolonged bleeding time
o Abnormal platelet aggregation studies with any • Heterogenous disorder
aggregating agents used associated with
abnormalities in α-
▪ Abnormal relase of the granule contents with a
granule formation and
decrease ADP and serotonin
maturation
• Defect in parts of Chromosome 1 • Platelets are large with
• During the accelerated phase, thrombocytopenia can discrete gray color
also contribute to a prolonged bleeding time
o Almost the same
o Bleeding episodes vary from mild to moderate but size with RBCs
worsen as platelet count decreases
Quebec Platelet Disorder

• Autosomal dominant disorder

• Delayed bleeding and abnormal proteolysis of alpha-
granule proteins
o due to increased amounts of platelet urokinase type
plasminogen activator
• Consequently, stored platelet plasminogen is converted
to plasmin
o Plasmin – play a role in degrading a number of
proteins stored in platelet α-granules
▪ Proteins – Factor V, Von Willebrand factor,
Fibrinogen, Thrombospondin I, and Osteonectin
• There is also a quantitative deficiency in platelet protein
Multimerin I
Alpha-Storage Pool Deficiency
• Upon platelet activation of Quebec platelet disorder,
urokinase type plasminogen can be released into
Gray Platelet Syndrome forming blood clots and accelerate clot lysis resulting in
a delayed onset of bleeding
• Platelet α-granules are the storage site for proteins: • Characterized by:
o produced by the megakaryocyte o Normal to reduced platelet counts
▪ e.g., platelet-derived growth factor, o Proteolytic degradation of soluble and membrane
thrombospondin, and platelet factor 4 proteins of alpha granule
o Deficiency of an alpha-granule Factor V binding
o present in the plasma and taken up by plate lets and protein – multimerin
transported to α-granules for storage o Selective defective aggregation with epinephrine
▪ e.g., albumin, IgG, and fibrinogen o Platelet Factor-V is degraded along with other
alpha-granule proteins, fibrinogen, vWF,
• Inherited in an autosomal recessive fashion thrombospondin, osteonectin, fibronectin, and P-
o A mutation in the region of Chromosome 3 selectin
involving the gene NBEAL2 that is crucial for the • Patients suffer from mucocutaneous bleeding which is
development of α-granules often delayed by 12 to 24 hours following injury
• Clinically, it is characterized by: o Patients are unresponsive to platelet transfusion but
o Lifelong mild bleeding tendencies will respond to fibrinolytic inhibitors.
o Prolonged bleeding time
o Moderate thrombocytopenia IV. Defects in Cytoskeletal Regulation
o Fibrosis of the bone marrow Wiskott-Aldrich Syndrome
o Large gray platelets in wright-stained smear
• Laboratory Findiings • An X-linked inherited
disorder affecting T-
o Variable platelet aggregation responses
lymphocytes and platelets
▪ ADP and Epinephrine – Normal • Characterized by
▪ Thrombin and collagen – Impaired thrombocytopenia,
immunodeficiency, and
eczema

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 LECTURE UNIT 11: PLATELET DISORDERS

• Patients with this syndrome lacks the ability to make o Chronic Idiopathic Myelofibrosis (Myelofebrosis with
anti-polysaccharide antibodies which results in the myeloid metaplasia)
propensity for pneumococcal sepsis
• Platelet dysfunction is the common finding in patients
• Platelet abnormalities in Wiskott-Aldrich Syndrome:
with this disorder
o Deficiency in dense granules • Increased platelet count but they have a functionally
o Deficiencies of platelet GP1b, GP IIb/IIIa, and GP Ia abnormal platelet
o Platelets are small – feature of diagnostic
improtance o Platelets are defective in any or all platelet functions
whether it is adhesion, aggregation, release or
• This syndrome arises from mutation WAS protein of contraction
502 amino acids that binds to several other signaling
proteins Acute Leukemias and Myelodysplastic Syndromes
o link between cytoskeleton and signaling pathways • Major cause of bleeding in these conditions is
o these proteins are key regulators of the cytoskeletal thrombocytopenia
assembly
o However, in patients with normal or elevated platelet
▪ Cdc42 (GTPase) counts, bleeding complications may be associated
▪ P47nck (SH3-containing adapter protein) with platelet dysfunction

V. Platelet Coagulant-Protein Interaction - Membrane • Acquired platelet defects associated with clinical
Phospholipids Defects bleeding are more common in:
o AML, ALL, Acute myelomonoblastic leukemias,
• Platelets play an important role in the blood coagulation
HCL, myelodysplastic syndromes
by providing the surface on which several specific key
enzymatic reactions occur ▪ Reduced aggregation response to ADP,
• In resting platelets, asymmetry is seen in the distribution epinephrine, and collagen along with a
of some of the phospholipids (e.g., phosphatidylserine & diminished nucleotide secretion
phosphatidylethanolamine) that are located
• Platelets may be morphologically abnormal
predominantly on the inner leaflet
o Decreased microtubules
o Phosphatidylcholine has the opposite distribution
o Reduced number
• Platelet activation results in the redistribution with o Abnormal size of dense granules
expression of phosphatidylserine on the outer surface o Excessive membranous system
o Mediated by phospholipid scramblase • Megakaryocytes exhibit dysplasia
• The exposure of phosphatidylserine on the outer Dysproteinemias
surface is an important event in the expression of the
platelet procoagulant activities • Bleeding appears to be related to:
Scott Syndrome o Platelet dysfunction
o Specific coagulation abnormalities
• In SCOTT syndrome, platelet contribution to blood o Hyperviscosity
coagulation is impaired but the aggregation and o Alterations in blood vessels due to amyloid
secretion responses are normal. deposition
• SCOTT Syndrome is a very rare autosomal recessive
disorder • Qualitative platelet defects also occur in some patients
• Laboratory Findings: o Attributed to the coating of platelet by the
o bleeding disorder but they have a normal bleeding paraproteins
time and platelet aggregation responses
Uremia
o normal PT and APTT result
o diminished platelet Factor Xa binding sites and • Platelet dysfunction and impaired platelet-vessel-wall
binding of Factors IXa and VIIIa interaction
▪ Associated with decrease surface expression of o Major cause of hemostatic defects in uremia
phosphatidylserine following platelet activation
Acquired Storage Pool Disease
Acquired Defects
• Dense-granule Storage Pool Disease
Myeloproliferative Disorders
o Reflects the in vivo release of platelet dense granule
• These are chronic myeloproliferative neoplasms which contents due to activation or production of abnormal
include: platelets by the bone marrow
o Polycythemia vera (PCV) • Observed in patients with:
o Chronic Myelogenous Leukemia (CML)
o Essential thrombocythemia (ET) o Antiplatelet antibodies
o Systemic Lupus Erythematosus (SLE)
o Chronic Idiopathic Thrombocytopenic Purpura (ITP)

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 LECTURE UNIT 11: PLATELET DISORDERS

o Hemolytic Uremic Syndrome (HUS) and

Disseminated Intravascular Coagulation (DIC)
o Renal transplant rejection
o Multiple cavernous hemagioma
o Myeloproliferative Disorder (MPD)
o Acute and chronic leukemias
o Severe valvular disease
o Patients undergoing Cardiopulmonary bypass
o Platelet concentrates stored for transfusion
Drugs that Inhibit Platelet Function

• Numerous drugs may affect platelet function and cause:

o Platelet dysfunction
o impaired platelet-vessel-wall interaction
o interefere with platelet factor receptor
o inhibit Prostaglandin pathways
• Nitrofurantoin - interfere with platelet factor receptor
• Theophylline - interfere with platelet
phosphodiesterase activity
• Aspirin - inhibit cyclooxygenase synthesis in platelets
• Penicillin-type antibiotics (Carbenicillin)
• Alcohol (Ethanol)
o Impair the platelet factor III release and reduces
secondary aggregation
o Impair prostaglandin synthesis
o Inhibit thromboxane A2 release
• Nonsteroidal anti-inflammatory agents
(Indomethacin, Ibuprofen, Butazolidin, and Dextran)
o Used as plasma expanders
• Foods – can also inhibit platelet function
o Fish that is rich in omega-3 fatty acids
▪ Result in the replacement of the arachidonic acid
and production of inactive prostaglandin
o Onion
o Garlic
o Ginger
o Cumin
o Turmeric
o Cloves
o Black fungus
o Gingko biloba – inhibit platelet aggregation
• Excessive intake of Vitamin E
o Can cause defects in the prostaglandin synthesis

TOLO. ERESE. DE LEON. LIM. FLORES. IGARI. ANIBAN. PIENCENAVES. CENA. BOLDIOS. SARMEINTO. MACAVINTA. BSMLS 3 9
ADVINCULA. POSIA. GALAGALA. SUBANG. TING. MONTEROSO. DACALOS