Thrombocytopeni

a
dr Putra Hendra
SpPD
UNIBA

Lab Tests

Hemostasis

CBC-Plt
BT,(CT)
PT
PTT

BV Injury
Tissue
Factor

Neural

Blood Vessel
Constriction

Platelet
Aggregation

Coagulation
Cascade

Primary hemostatic plug

Reduced
Blood flow

Platelet
Activation

Fibrin
formation

Plt Study
Stable Hemostatic Plug

Morphology
Function
Antibody

Checkpoint Primary
Hemostasis

Its about vasculature

Its about platelets
Its about maintaining blood in
a fluid state within the blood
vessels and preventing
excessive blood loss after
vascular injury
Bottomline
Platelet Abnormalities
QUANTITAIVE OR QUALITATIVE result in
bleeding

Graphic accessed URL http://www.uv.es/~vicalegr/CLindex/CLvasculitis/vasleu11.jpg , 2005.

Bleeding

Surgical bleeding: less than 50,000

Spontaneous bleeding: less than

10,000 to 20,000

Severe life threatening bleeding:

less than 6000

Clinical Manifestations

Primary v.s. Secondary Disorders of

Hemostasis

Primary

Skin
petechiae
purpura
ecchymoses
Mucous membranes
nose bleeds
sclera
gums

Secondary

Tissues
Joints

http://heme-coag.uthscsa.edu/wwwbleed97/22apet.gif

Physical exam

Petechiae pinhead
sized, red, flat, discrete
lesions often occurring
in crops in dependent
areas
Purpura purplish
discoloration of the skin
due to the presence of
confluent petechiae.
Ecchymoses
nontender areas of
bleeding into the skin,
usually associated with
multiple colors, due to
the presence of
extravasated blood

Practical Importance of
Assessing Thrombocytopenia

1/3 of all Hematology Consults in a

General Hospital are for
thrombocytopenia
5 to 10% of all hospital patients are
thrombocytopenic in the ICU the
number increases to 35%
Thrombocytopenic patients in the
hospital suffer a twofold greater
mortality rate than those who are not

Platelet Kinetics

Normal circulating platelet count

150 to 450 K in Northern Europeans
90 to 300 K in people of Mediterranean descent

1/3 of platelets are sequestered in the

spleen
Half life of a platelet is 9 to 10 days
Platelet production is the function of the
multinucleated megakaryocyte
15 to 45 K platelets are produced daily to
maintain steady state

Figure 1. Clusters or chains of platelets are shed from the megakaryocyte and carried off
into the bloodstream

Maslak, P. ASH Image Bank 2005;2005:101324

Copyright 2005 American Society of Hematology. Copyright restrictions may apply.

Thrombopoietin (TPO)

TPO is the primary regulatory protein in the

production of platelets
TPO gene is on chromosome 3
TPO is expressed in the liver, kidneys, and
smooth muscle cells
Has a plasma half life of 30 hours
The receptor for TPO is c-MPL which is
present on the megakaryocytes and platelest
TPO rises with platelet fall and declines as
the megakaryocyte and platelet mass
increase

Thrombocytopenia
Definition

Thrombocytopeni
a is defined as a
platelet count less
than 150,000
2.5 percent of the
normal population
will have a
platelet count
lower than this

Thrombocytopenia
Causes

Impaired or Decreased
Production

Distribution/Dilution
Disorders

Megakaryocyte aplasia

Immune

BM Replacement

Ineffective poiesis

Increased
Destruction

Non-Immune

Decreased platelet
production

In almost all disorders caused by marrow

suppression or damage, white cell and
red cell production are also affected.

Viral infections- rubella, mumps, varicella,

parvovirus, hepatitis C, EBV
Direct megakaryocyte damage-HIV
Post chemotherapy or radiation therapy
Acquired bone marrow hypoplasia- Fanconi
anemia, acquired pure megakaryocytic
aplasia
Direct alcohol toxicity
B12 or folate deficiency

Increased Platelet
destruction

ITP and SLE- mechanism presumed to be

presence of autoimmune anti-platelet Abs
Alloimmune destruction- posttransfusion, posttransplantation
Hypersplenism
Disseminated intravascular coagulation
TTP- HUS
HELLP in pregnant women
Medications- heparin, quinine, valproic acid
Infections- EBV, CMV, sepsis
Physical destruction during cardiopulmonary
bypass, intravascular or intracardiac metastatic
lesions

Diagnosis

Repeat lab
Peripheral smear
Coagulation study
Fibrinogen, d-dimer
ITP- presumptive diagnosis if history, physical
examination, complete blood count, and
examination of the peripheral blood smear do
not suggest other etiologies.
Bone
marrow
biopsyunexplained
thrombocytopenia
severe
enough
to
constitute a risk for major bleeding

Types of Autoimmune
thrombocytopenia
Neonatal Thrombocytopenia
Isoimmune, Associated with Maternal ITP, Drug-Related
Drug Induced
Quinidine, Quinine, Sulfa, Gold Salts, Abx (Vanco etc),
Heparin
Lymphoma
Autoimmune disorders
Thyroiditis, SLE, Colitis, Sarcoidosis
Infections
HIV, Rubella, viral Hepatitis, CMV, Lyme disease
Postransfusion Purpura
ITP

Immune Mediated
Thrombocytopenia Purpura

ITP is defined as isolated thrombocytopenia with

no clinically apparent associated conditions or
other causes of thrombocytopenia
ITP is a high prevalence disease 16 to 27 per
million per year
Incidence increases with age
Female predominance under the age of 60 but
not over the age of 60
It can have an abrupt onset or insidious onset. It
is generally abrupt in onset with children

Pathogenesis of ITP

Increased platelet destruction

caused by antiplatelet antibodies
Lack of compensatory response by
megakaryocytes due to suppressive
effect of antiplatelet antibodies
Pathogenesis was proved by
Harrington when he infused himself
with plasma from a women with ITP

Pathophysiology
O

A
P

D
T
C

of ITP

A
P
O
D
P
T
C

Autoantibody
Production
Platelet
Opsonization
Platelet
Destruction
Platelet
Production
T-Cell
Mediated
Cytotoxicity

Evaluation of ITP

Features consistent with the diagnosis of ITP

Thrombocytopenia with normal or slightly large

platelets
Normal RBC morphology and number (may have
associated iron def or thallasemia etc.)
Normal white cell number and morphology
Splenomegaly rare

Features not consistent with the diagnosis of ITP

Giant platelets
RBC abnormalities ie schisotocytes
Leukocytosis or Leukopenia

Management of ITP

Most patients with ITP do not have

clinically significant bleeding
Risk of intracranial bleed 0.1 to 1% (This is
an overestimate)
Wet Purpura ie epistaxis, gingival bleeding
is a risk factor for major bleeding

In asymptomatic patients with platelets

counts greater then 20 K observation is
reasonable

Acute Pharmacologic
Management of ITP

Steroids
Prednisone 1mg/kg/day with taper over
2 to 3 months
Decadron 40 mg/day x 4 days
Solumedrol 1 gram/day x 2 days

Antibodies
IVIG 1 gram/day x 2 days
Anti-D 50 mcg/kg IV x1

Chronic Management of
ITP

Splenectomy

Chronic Anti-D therapy

Immunize with Pneumovax, Hib,

Meningococcal
Does not put the disease in remission

Rituximab
AMG 531, Eltrombopag c-MPL
agnonists
Observation

Management of ITP in
pregnancy

Gestational Thrombocytopenia

Platelet count >70K, occurs late in

gestation, not associated with fetal
thrombocytopenia, resolves after pregnancy

ITP in pregnancy
Treat if symptoms intermittent IVIG,
Prednisone, anti-D
Epidural anesthesia appears safe if platelet
count > 50K
Monitoring for neonatal thrombocytopenia

TTP Thrombotic
Thrombocytopenia Purpura

TTP is characterized my
microangiopathic hemolytic anemia and
profound intravascular platelet clumping
The disease was first reported in 1923 by
Dr. Eli Moschowitz at Beth Israel in NYC
16 year old girl who presented with anemia,
petechia ultimate coma and death
Terminal arterioles and capillaries were
occluded by hyaline thrombi mostly
composed of platelets

Clinical and Lab

Manifestations of TTP

Severe thrombocytopenia and hemolytic anemia

with one or several fragmented red cells in high
power oil >1% total number of RBC
Neurologic Manifestations, abdominal pain
Fever and Renal Abnormalities occur in the
minority of patients
Thrombocytopenia range from <30 K to 75 to
100 K
Elevated LDH
Initially coagulation studies are normal

Differential Diagnosis of
TTP

Hemolytic-uremic syndrome
DIC
Evans Syndrome
Malignant Hypertension
Malfunctioning prosthetic cardiac valves
Severe vasulitis
Pregnancy
Preeclampsia/eclampsia
HELLP

Treatment of TTP

Infusion of FFP 30 cc/kg/day until

ready for plasma exchange
Daily plasma exchange with either
FFP or cryopoor FFP (45 to 55
cc/kg/day)
Steroids (Prednisone 1 mg/kg/day)
Red Blood Cells if needed
Platelets only if absolutely necessary

Heparin Induced
Thrombocytopenia

Described in 1958 by Rodger Weismann

and Richard Tobin after extracting
platelet fibrin thrombi that formed after
1 to 2 week course of heparin
HIT is the presence of a multimolecular
complex between platelet factor 4, and
heparin
HIT is associated with thrombosis
despite profound thrombocytopenia

Clinical Features of HIT

Timing
Onset between days 5 and 10 after heparin
initiation
Rapid onset if previously exposed to heparin

Thrombocytopenia nadir between 15 K

to 150 K
>50% develop a new thrombosis both
venous and arterial
Absence of petechia

Treatment of HIT

Removal of all Heparin products

Begin direct thrombin inhibitor (DTI)
(Argatroban or Refludan)
Treat with DTI until platelet count
normalizes then may begin
anticoaguation with coumadin
Fondaparinux (Arixtra) is a reasonable
agent to use for DVT prophylaxis in
patient with history of HIT