DISORDER OF PRIMARY HEMOSTASIS

PLATELET DISORDER
A.QUANTITATIVE
B. QUALITATIVE
Chapter 40
713
WEEK 14
A. QUANTITATIVE PLATELET DISORDER

• Pathophysiologic Process that result in

Thrombocytopenia

1. Decreased Platelet Production

2. Increased Platelet Destruction
3. Abnormal Platelet Distribution
 1. Impaired or Decreased Platelet
Production

• 2 Categories in Abnormal Platelet Production

• 1. Megakaryocyte Hypoplasia
• 2. Ineffective Thrombopoiesis
Inherited / Congenital Thrombocytopenia:
Autosomal Dominant Thrombocytopenia
MYH9- related Thrombocytopenia
Syndromes
• Caused by mutations in the MYH9 gene
• These include May-Hegglin anomaly, Sebastian syndrome
and its variant, Epstein syndrome and Fechtner syndrome.
• Affected patients have triad of thrombocytopenia,
macrothrombocytes and Dohle body-like inclusions in the
leukocytes except with Epstein syndrome which lacks the
inclusion
• Mild to moderate thrombocytopenia
• PBS revealed enlarged platelets with frequent giant platelets
 MYH9- related Thrombocytopenia Syndromes
Syndrome Macrothr Dohle-like Nephritis Deafness Cataracts
ombocyto bodies
penia

May- Yes Yes No No No

Hegglin

Sebastian Yes Yes No No No

Fechtner Yes Yes Yes Yes Yes

Epstein Yes No Yes Yes No

Congenital Thrombocytopenia:
Autosomal Recessive Thrombocytopenia
Thrombocytopenia with Absent Radius (TAR)

• Associated with the mutation in the RBM8A – CH 1

• Rare disease, first identified in 1959
• Platelet count is , approximately 10-30 X 103/uL
• Serum TPO levels are normal, and marrow cellularity is
normal or increased.
• Megakaryocytes are low in number, absent or appear
immature
• Can be managed by platelet transfusion
Thrombocytopenia with Absent
Radius (TAR)
 Congenital Thrombocytopenia:
Autosomal Recessive Thrombocytopenia

Congenital Amegakaryocytic Thrombocytopenia

(CAMT)
• Mutation in the MPL gene –ch 1 – loss of TPO
receptor
• Presence of severe thrombocytopenia, absence of
megakaryocytes in the bone marrow
• Family history is negative, both parents having normal
platelet counts and function
• Markedly elevated serum thrombopoietin
• Patients develop progressive marrow aplasia
 Congenital Thrombocytopenia:
Autosomal Recessive Thrombocytopenia
Congenital Amegakaryocytic Thrombocytopenia
(CAMT)

 Group CAMT I- more severe type of

thrombocytopenia with constantly low platelet count
and an early onset of pancytopenia..

 Group CAMT II- transient increased in platelet counts

during the first year of life and a later or no
development of pancytopenia.
Congenital Thrombocytopenia:
Autosomal Dominant Thrombocytopenia
 Mutation on ANKRD26 –Ch 10- incomplete
megakaryocyte differentiation
 Mild thrombocytopenia characterized by a normal
platelet survival and normal number of bone
megakaryocytes
 Thrombocytopenia (counts 20,000 to 100000/uL) or
a history of increased bruisability is apparent on
early life.
 PBS shows platelet macrocytosis
 Abnormal platelet aggregation, normal platelet
membrane glycoproteins.
Congenital Thrombocytopenia:
X-Linked Thrombocytopenia
Wiskott-Aldrich Syndrome
• Originally described in 1937, is now known as X-
linked hereditary disorder associated with
combined immunodeficiency thrombocytopenia,
small platelets, eczema and an increased risk to
autoimmune disorders and cancer
• Microthrombocytopenia is the most consistent
feature of WASP-associated disease.
Neonatal Thrombocytopenia
• Platelet count less than 150,000 /ul
• Cause of Neonatal Thrombocytopenia :
• Infection with toxoplasma , rubella, cytomegalovirus,
herpes
• Thrombocytopenia may be severe plt count of
70 ,000 /ul
• CMV most common infectious agent
2. Increased Platelet Destruction
2.1 Immune Mechanism of Platelet
Destruction

Acute and Chronic ITP

Drug Induced immunologic
Heparin Induced Thrombocytopenia
Neonatal Alloimmune ( isoimmune neonatal)
thrombocytopenia
Posttransfusion isoimmune thrombocytopenia
Secondary autoimmune thrombocytopenia
Idiopathic Thrombocytopenic Purpura

• A.K.A immune thrombocytopenic purpura (ITP)

• One of the most common disorders causing severe
isolated thrombocytopenia
• Caused by an autoantibody to the patient’s platelet
• No specific test to confirm presence of ITP rather
diagnosis of exclusion
• Can be present in children and adults
Idiopathic Thrombocytopenic Purpura:
Acute / Childhood ITP
• Young children may present with an immune
thrombocytopenia that typically develops acute
with a 1 to 3 weeks duration, usually with bruising
or petechiae.
• Present an initial platelet count of less than 20 X
109/L
• Self-limiting, spontaneous remissions with or
without therapy in majority of the patient
• IgG and corticosteriods are often used to decrease
the period of thrombocytopenia
Idiopathic Thrombocytopenic Purpura:
Chronic / Adult ITP
 Commonly presents in the 20-50 year old groups, chronic
disease process with a greater predilection for women
 Occasionally, patients will have immune thrombocytopenia
after a viral illness or exposure to drugs
 Platelet counts are typically less than 30 X 109/L in patients
who present with bleeding manifestations
 Patient present with mucosal bleeding typical of a primary
hemostatic defect, such as menorrhagia, epistaxis, easy
bruisability, or petechiae
 Does not usually remit spontaneously
 IVIG treatment of choice
Common Clinical Findings

• BM is characterized by an increased or normal numbers

of megakaryocytes
• Platelet lifespan is shortened and circulating platelets
are morphologically large on the smear
• Bleeding time may not be as prolonged as the bleeding
time in other disorders associated with the same degree
of thrombocytopenia
• Measurement of antibodies (IgG) specific for platelet
surface GP IIb//IIIa and Ib/IX may provide greater
specificity but still are not diagnostic.
• Splenectomy and cortocosteroids are the conventional
therapies.
 Clinical Picture of Acute and Chronic ITP
Characteristic Acute Chronic
Age at onset 2-6 yr 20-50 yr
Sex predilection None Female
Prior Infection Common Unusual
Onset of Bleeding Sudden Gradual
Platelet count < 20,000/ul 30,000-80,000 /ul
Duration 2-6 weeks Months - years
Spontaneous 90 % of pts Uncommon
remission
Therapy
Steroids 70% response rate 30% response rate
Splenectomy Rarely required < 45 y/o 90% response
> 45 y /o 40 % response
rate
Drug-induced Immune Thrombocytopenia
 Quinine has been recognized as one of the most
frequent causes of drug-induced
thrombocytopenia; where it act as a hapten
 Drug most frequently cited: quinine, quinidine,
salicylates, thiazides and sulfa drugs
 Appears more frequently in the elderly due to
increased usage of medication
 Purpura occurs approximately 7 days after initial
use of the drug but may occur within 3-5 days
owing to anamnestic response.
Neonatal alloimmune /
Isoimmune Neonatal Thrombocytopenia
• It result to from immunization of the mother by fetal
platelet antigen and placental transfer of maternal
antibody
• It is most often caused by maternal alloantibodies to
the P1A1 antigen
• It is uncommon disorder, generally affecting the first-
born child
• Infants who develop this disorder appear normal at
birth but within a few hours develop scattered
petechiae and purpuric hemorrhages, with platelet
counts below 30 X 109/L
Neonatal Autoimmune
Thrombocytopenia
• Neonatal Autoimmune Thrombocytopenia –
passive transplacental transfer of abs from mother
with ITP or SLE.
• Maternal disease severity and/or platelet count
during pregnancy can be used to predict the
neonatal platelet count in most cases, but the
clinical manifestations are less severe than in NAITP.
• Affected newborns – normal – decreased platelet
numbers at birth ( 1 week) dec.
Neonatal Autoimmune
Thrombocytopenia

• Neonatal Thrombocytopenia persist for 1-2 weeks-

months .
• Requires no treatment
• If severe Thrombocytopenic infants– IVIG tx
• Bleeding – Plt Transfusion IVIG tx and
corticosteroid.
Post Transfusion Purpura
• Rare disorder
• Develops after 1 week after transfusion of
plt containing products.
• Manifested by rapid onset of severe
thrombocytopenia---- bleeding
• Plasmapheresis-----effective in resolving
bleeding
• IVIG ----Tx of choice
• Quantitative Platelet Disorder
Secondary (Non immune)

Thrombocytopenia in Pregnancy
HIV Infection
HDN
TTP
DIC
Drug induced
 1. Thrombocytopenia in
Pregnancy and Preeclampsia
• Incidental Thrombocytopenia of Pregnancy
Pregnancy Associated Thrombocytopenia
Gestational Thrombocytopenia
• Platelet count : 100,000 -150,000/ul
• Maternal Platelet returns to normal within several
weeks
 Preeclampsia- defined by hypertension and
proteinuria; usually becomes evident during second
trimester and is a major contributor to maternal
and fetal morbidity and mortality
 Eclampsia- defined by the occurrence of acute
neurologic abnormalities in a preeclamptic woman
during peripartum pariod
 Connection with thrombocytopenia, in an manner
that blood coagulation is activated and is detected
by elevated FDG and thrombin-antithrombin
process
 Low level of ADAMTS13 is detected
HELLPS Syndrome
 Disorder related to preeclampsia/eclampsia and is
seen in the peripartum period and defined by the
presence of microangiopathic HA, elevated liver
enzymes, and low platelet count
 HELLP (hemolysis, elevated liver enzymes, low
platelet count)
 HELLP is difficult to differentiate from :
 TTP
 DIC
 HUS
Gestational Thrombocytopenia
• Mild thrombocytopenia with platelet counts of 50-
80 X 109/L
• Commonly develops in the 3rd trimester of
pregnancy and does not cause bleeding in the
mother or infant
• Low platelet count returns to normal after deliver
HIV Related Thrombocytopenia

• Appears to be correlated between CD4+ T cell

depletion, viral load in plasma and the occurrence
of thrombocytopenia
• Viral infection of hematopoietic cells, altered
marrow microenvironment of dysfunction of the
RES contribute to ineffective thrombopoiesis in HIV-
related thrombocytopenia.
• Development of marrow fibrosis and marrow
involvement by AIDS-related lymphoma may also
lead to thrombocytopenia.
HIV Related Thrombocytopenia

• Antiretroviral therapy is often effective course

of action
• Intravenous IgG and anti-D globulin are found
to be effective treatment
• Corticosteroids may be effective but have the
potential to increase the risk of infection in
immunocompromised individuals
• Splenectomy may also be effective
Thrombotic Thrombocytopenic Purpura

• First described as a pentad of signs and symptoms

that include: thrombocytopenia, microangiopathic
hemolytic anemia, fever, neurologic abnormalities
and renal dysfunction
• Hyaline microthrombi are the characteristic
pathologic feature and are found in multiple organs
• Coagulation screening tests and D-Dimer assay are
NORMAL in TTP, in contrast to DIC which they are
abnormal
• Two types of TTP: acquired and hereditary
Acquired Thrombotic Thrombocytopenic Purpura

• Thrombi found most extensively in the heart,

pancreas, spleen, kidney, adrenal gland and brain
and are composed mainly of platelets and vWF
• Associated with ADAMTS13 deficiency (a
disintegrin-like and matalloprotease with
thrombospodin motifs) and is found in most cases.
• ADAMTS13 is also decreased in sepsis, DIC, and
liver disease
Acquired Thrombotic Thrombocytopenic Purpura :
Laboratory Findings

• Thrombocytopenia and hemolysis, with the blood

smear showing polychromasia, basophilic
stippling, nucleated cells, schistocytes
• Platelet counts below 20 X 109/L at first
presentation
• Reticulocyte count increased
• Bone marrow studies reveal erythroid hyperplasia,
increased number of megakaryocytes and
occasionally microvascular hyaline thrombi
• Screening tests are usually normal and FDP may
be slightly increased
Acquired Thrombotic Thrombocytopenic Purpura :
Laboratory Findings

• Serum lactic dehydrogenase (LDH) and

unconjugated concentrations are common but
invariably increased.
• Hemolysis is of the intravascular type: haptoglobin
levels are reduced and hemoglobinuria and
hemosiderinuria usually are present
• LDH levels and platelet counts are sensitive indices
of the response of the disorder to therapy;
• Proteinuria and microscopic hematuria are present
in most cases
Acquired Thrombotic Thrombocytopenic Purpura :
Laboratory Findings

• Blood urea nitrogen (BUN) and creatinine are

normal or slightly elevated
• Liver function tests are usually normal
• Analysis of the cerebrospinal fluid is rarely indicated
but may reveal an increased protein concentration
and xanthochromia
• ADAMTS13 binding IgG is detectable enzyme-
linked immunoabsorbent assay (ELISA) in 97-100%
TTP cases
Hereditary Thrombotic Thrombocytopenic
Purpura
A.k.a Schulman-Upshaw syndrome or Chronic
Relasping TTP
Rare disorder believed to < 1% of the TTP cases
In the typical cases, the affected neonate is born with
meconium stain or presents within a few hours after
birth with neonatal distress, jaundice and
thrombocytopenia
Hemolysis with schistocytes on blood smears may be
noted
Hereditary TTP responds to 10-15 mL of FFP per
kilogram of body weight administered every 2 to 3
weeks.
 Disseminated Intravascular Coagulation

• DIC appears to be accelerated platelet destruction in

combination with coagulation factors consumption

2 Forms of DIC
1.Acute - rapid platelet consumption
2.Chronic – low grade consumptive coagulopathy
 Disseminated Intravascular Coagulation

• Caused by many illnesses, sepsis, obstetric

emergencies and severe trauma, and may cause
bleeding
• Chronic form may be seen in cancer and may result in
thrombosis rather than bleeding
• Thrombocytopenia is usually seen in acute DIC
• Platelet count may be normal or elevated in chronic
DIC
• DIC appears to be accelerated platelet destruction in
combination with coagulation factors consumption
3. Abnormalities in Distribution
or Dilution
• Splenic sequestration
• Kasabach Meritt syndrome
• Hypothermia
• Loss of Platelets : massive blood
transfusion
Thrombocytopenia Resulting from Abnormal Platelet
Distribution: SPLENOMEGALY

• May lead to thrombocytopenia by inducing a

reversible pooling up to 90% of total body
platelets
• Platelet production is usually normal
• Chronic liver disease with portal
hypertension and congestive splenomegaly
• Most common disorder causing
thrombocytopenia
Thrombocytopenia Resulting from Abnormal Platelet
Distribution: HYPERSPLENISM

• It is distinguished from uncomplicated

splenomegaly in that pooling is
accompanied by increased destruction
of platelets, leukocytes and
erythrocytes in association with
increased marrow precursors of the
deficient and correction of the
cytopenia by splenectomy
Thrombocytopenia Resulting from Abnormal Platelet
Distribution: KASABACH-MERRITT SYNDROME

• Profound thrombocytopenia related to platelet

trapping within a vascular tumour, either a Kaposi-
like hemangioendothelioma or a tufted angioma
• Thrombocytopenia is usually severe and associated
with DIC
• Contributing factors include “platelet trapping” and
platelet consumption associated with DIC.
• Platelet trapping demonstrated by
immunohistochemical staining of the tumours with
anti-CD61 antibodies.
Quantitative Platelet Disorder:
THROMBOCYTOSIS
II. Thrombocytosis
- is characterized by an increase in the circulating platelet counts
greater than 450,000/uL.
A. Primary/ Essential Thrombocytosis
- The result of primary bone marrow disorder. It is characterized by
an increase number of platelets which is a result of clonal
proliferation that affects all hematopoietic cells. Patients have
bleeding tendencies because of platelet function abnormalities. It
is most commonly seen in patients with the following disorders:
1. Hodgkin’s disease
2. Polycythemia vera
3. Myelofibrosis
4. CML
5. Thrombocythemia
Quantitative Platelet Disorder
B. Reactive/ Secondary thrombocytosis
- a secondary response most associated with the following
disorders:
1. IDA associated with chronic blood loss
2. Chronic inflammatory disease may be associated with high
platelet counts.
3. Splenectomy-associated thrombocytosis
4. Rebound thrombocytosis, which may occur after a platelet
depletion through a massive blood loss.
- TPO levels in plasma are decreased
- Promoted by different types of drug like epinephrine,
recombinant IL11 (Oprevelkin)
 QUALITATIVE
PLATELET DISORDER
Qualitative abnormalities :Changes in Platelet
Function ( Thrombocytopathy)

• Disorder of Platelet Aggregation

• Glanzmann Thrombasthenia
• Hereditary afibrinogenemia
• Acquired defects of aggregation
• Acquired vwd
• Acquired uremia
Qualitative abnormalities :changes in Plt FXn
( Thrombocytopathy)
• Disorder of Platelet Adhesion
• BSS
• VWD
• Acquired defects of platelet adhesion
• Myeloproliferative,
lymphoproliferative disorders,
dysproteinemias
• Antiplatelet antibodies
• Cardiopulmonary bypass surgery
• Chronic liver disease
• Drug-induced membrane modification
Qualitative abnormalities :changes
in Plt FXn ( Thrombocytopathy)
• Changes in Membrane Phospholipid Distribution
• Scott syndrome
• Stormorken syndrome
Qualitative abnormalities :changes in Plt FXn
( Thrombocytopathy)

• Disorders of Platelet Secretion (release reactions)

• Storage pool diseases
• Thromboxane pathway disorders
• Hereditary aspirin-like defects:
• Cyclooxygenase or thromboxane synthetase
deficiency
• Drug inhibition of the prostaglandin pathways
• Drug inhibition of platelet phosphodiesterase
activity
Clinical Manifestation of
Bleeding Disorders
1. Superficial bleeding
1. Petechiae
2. Epistaxis
3. Gingival bleeding
2. Deep Tissue Bleeding
1. hematomas
2. hemarthrosis
Glanzmann Thrombasthenia
• Originally - bleeding disorder associated with
abnormal in vitro clot retraction and normal
platelet count .
• Hemorrhagic Manifestation : petechiae , purpura,
menorrhagia, GIT bleeding and hematuria.
• Rare autosomal-recessive disorder of platelet
function .
• Deficiency or abnormalilty in GP IIb /IIIa
Glanzmann’s Thrombasthenia

• Bleeding is most common from mucosal surfaces

(easy bruisability, epistaxis, gingival bleeding,
prolonged bleeding for minor cuts and menorrhagia)

• Facial petechiae and subconjunctiva hemorrhages

seen in infants associated with crying

• Deep hematoma formations and recurrent

hemarthroses are not present
• Laboratory Feature:
• Normal : platelet count, platelet morphology
• Lack of platelet aggregation in response to all
platelet activating agent . ADP, collagen thrombin
and epinephrine.

• Treatment :
• Transfusion of platelet
• Recombinant factor VIIa
Disorder of Platelet Adhesion
• Bernard –Soulier syndrome ( BSS)

• An inherited disorder of the platelet GPIb/IX/V

complex characterized by thrombocytopenia, giant
platelets, and a failure of the platelets to bind GPIb
ligands (von Willebrand’s factor and thrombin)
• rare autosomal –recessive disorder
• bleeding time is prolonged clot retraction is normal
• Usually manifested in infancy or childhood
• Laboratory Features:
• BSS – normal responses to ADP,
Epinephrine,collagen and arachidonic acid
• Do not respond to : Ristocetin and Thrombin

• Treatment :
• No specific treatment
• Platelet transfusion –therapy of choice – ( alloabs)
 Glanzmann’s Bernard-Soulier
Thrombasthenia Syndrome
Platelet count Normal Decreased
Platelet morphology Normal Giant Platelets
Bleeding Time Prolonged Prolonged
Platelet aggregation
• ADP Abnormal Normal
•Thrombin Abnormal Abnormal
•Collagen Abnormal Normal
•Epineprhine Abnormal Normal
•Ristocetin Normal Abnormal

Clot Retraction Abnormal Normal

Platelet GP defect GPIIb/IIIa GPIb/IX
Inherited Giant Platelets Disorder
• BSS • May Hegglin anomaly
• Giant Platelets with Mediterranean
Velocardiofacial syndrome Macrothrombocy
• Giant platelets with • Fechtner Syndrome
abnormal surface • Sebastian syndrome
glycoproteins and mitral
valve insufficiency • Hereditary
• Familial macrothrombocytopenia
macrothrombocytopenia • Epstein Syndrome
with GP IV abnormality
• Gray Platelet Syndrome
• Montreal Platelet
Syndrome
Quebec Platelet Disorder
• Originally described as Factor V Quebec
• Early onset description of this autosomal-dominant
disorder include severe bleeding after trauma, mild
thrombocytopenia, decreased functional Platelet
Factor 5 and normal plasma Factor V.
• Diagnosis can be established by analysis of platelet
urokinase-type plasminogen activator or the
identification of degraded granule proteins by
immunoblot analysis
• Because the PF5 abnormality is prominent, this
defect may also be classified as defect in platelet
coagulant activity
Mediterranean
Macrothrombocytopenia
 Relatively common and mild form of
macrothrombocytopenia and has been described
in a group of healthy subjects from Italy and the
Balkan peninsula.
 An Aautosomal Dominant Thrombocytopenia
 Gene mutation to the short arm of chromosome 17
(GpIa)
 Genotype and phenotype are equivalent to that of
carrier of Bernard-Soulier syndrome
 Patients have mild bleeding diathesis, PBS shows
platelets that are larger than normal.
Hereditary Macrothrombocytopenia
Platelet Storage Pool Disease
• Dense Granules Deficiency
• Hermansky Pudlak Syndrome
• Chediak Higashi Synnrome
• Wiskott Adlrich syndrome
• TAR syndrome
• Alpha granule
• Gray platelet syndrome
Hermansky-Pudlak Syndrome

• An autosomal recessive disorder characterized

by a severe deficiency of dense granules

• Patients show albinism (oculocutaneous) and

may have hemorrhagic events
Chediak-Higashi Syndrome
• An autosomal recessive disorder, in which
patients show albinism and giant lysosomal
granules in neutrophils
• Storage pool defect on dense granules
• Patients show frequent infections because of
impaired phagocytic ability and death usually
occurs in childhood
• Patients manifest thrombocytopenia
• Partial oculocutaneous albinism
• Plt dense granule def and hemorrhges
Wiskott-Aldrich Syndrome

• An X-linked recessive disorder in which patients

show severe eczema, recurrent infections,
immune defects, thrombocytopenia and small
platelets
• Death from infection, hemorrhage or malignancy
is common before adulthood
• A defect in the surface glycoprotein sialophorin
(CD43, gp115, leukosialin) has also been
described in Wiskott-Aldrich syndrome
Gray Platelet
Syndrome
• It is associated with bleeding
tendencies and classical
abnormal platelet morphology
• Alpha Granules are absent or
greatly reduced
• Absence of alpha-granules,
one of the result is a continued
leakage of growth factors and
cytokines into the marrow,
causing myelofibrosis
• Acquired Defects of Platelet Function
Drug induced defects
Myeloproliferative Neoplasm
Multiple Myeloma
Waldenstrom Macroglobulinemia
Liver Disease
Uremia
Myeloproliferative Disorders

• Include polycythemia vera (PV), idiopathic

myelofibrosis, CML, and essential thrombcythemia
• Hemorrhagic manifestations include: epistaxis,
ecchymosis and mucocutaneous bleeding from GIT
and GUT
• Thrombosis includes DVT, pulmonary embolism,
stroke, MI, and thrombosis of the hepatic, portal,
splenic and mesenteric veins.
• Laboratory abnormalities include: abnormal release
and aggregation in response to epinephrine, collagen
and ADP
Myeloproliferative Disorders

• Bleeding time is prolonged in most cases

but does not correlate to bleeding
tendencies
• Other abnormalities include: acquired
storage pool defects, abnormal
prostaglandin and arachidonic acid
metabolism and platelet hyperactivity
Cardiopulmonary Bypass
• Abnormalities include decrease in platelet number and
function, factor deficiencies resulting from consumption
and hemodilution, increased fibrinolytic activity, DIC
and inadequate or excess neutralization of heparin or
protamine
• During the bypass, a prolonged bleeding time can be
seen in a mildly low platelet count (100 X 109/L)
• Platelet activation and platelet dysfunction account for
the bleeding complications
• Platelet concentrates are administered to stop bleeding
• FFP and cryoprecipitate should be given only to treat
bleeding associated with coagulation factor deficiency
Paraproteinemia
• Associated with multiple myeloma, Waldenström’s
macroglobulinemia, and other related malignant
paraprotein disorders
• Hemostatic abnormalities to be caused by interaction
of the paraprotein with platelets and coagulation
factors
• Hemorrhagic diathesis is characterized by a
prolonged bleeding time and platelet dysfunction
• Patients may present spontaneous epistaxis and
ecchymosis, or unexplained postoperative bleeding
in the face of a normal platelet count and coagulation
profile
Paraproteinemia
• Platelet abnormalities include decreased aggregation
in response to various aggregating agents, altered
shape change, abnormal release reactions, and a
prolonged bleeding time
• THERAPY: Plasmapheresis to reduce the circulating
paraprotein concentrations and chemotherapy to
inhibit paraprotein production
Liver Disease
• Associated with significant hemorrhagic diathesis as a result
of platelet dysfunction
• Mild to moderate thrombocytopenia is seen as a result of
splenic sequestration secondary to congestive splenomegaly
• Reduced platelet adhesion; abnormal platelet aggregation
to ADP, epinephrine & thrombin; and abnormal PF3
availability
• Transfusion with PC is helpful
• DDAVP may improve the qualitative defect
• Conjugated estrogens may decrease the over-all bleeding
tendency after an acute episode
Uremia

• Bleeding is a common complication

• Petechiae, purpura, epistaxis, ecchymosis and GIT
bleeding are common
• Abnormality in the interaction of vWF and platelet
GPIIb/IIIa complex; however, GPIb, GPIIb and GPIIIa
are quantitatively normal
• Other platelet abnormalities: abnormal prostaglandin
synthesis, decrease membrane procoagulant activity,
decreased platelet serotonin release, abnormal β-
thromboglobulin levels, elevated intracellular calcium and decreased TX
synthesis
Uremia

• Increased levels of uremic toxins such as

guanidosuccinic acid and phenols
• Mild thrombocytopenia (100 X 109/L), decreased
adhesion, abnormal aggregation and increased
bleeding time.
• EPO (r-HuEPO) effective in improving hemostasis
and decreasing bleeding tendencies
• Hemodialysis or peritoneal dialysis is the
treatment of choice to correct the hemostatic
defect.