THROMBOCYTOSIS,

THROMBOCYTOPENIA &
RELATED DISSODERS
MARSHELL TENDEAN, DPCP
DEPARTMENT OF INTERNAL MEDICINE
 THROMBOCYTOPENIA

1. Decreased bone marrow production;

2. Sequestration, usually in an enlarged spleen;
and/or
3. Increased platelet destruction
• Pseudothrombocytopenia is an in vitro artifact
resulting from platelet agglutination via antibodies
when the calcium content is decreased by blood
collection in ethylenediamine tetraacetic (EDTA).
 THROMOBCYTOSIS

(1) iron deficiency;

(2) inflammation, cancer, or infection (reactive
thrombocytosis);
(3) an underlying myeloproliferative process [essential
thrombocythemia or polycythemia vera) or, rarely,
the 5q- myelodysplastic process.
Harrison principle of Internal Medicine
th
DRUG RELATED THROMBOCYTOPENIA
• It is an autoimmune disorder characterized by
immunologic destruction of otherwise normal
platelets most commonly occurring in response to
an unknown stimulus. I
• TP may occur in isolation (primary) or in association
with other disorders (secondary).

Bromberg ME. N Engl J Med. 2006;355(16):1643-

1645.
 • Primary ITP :
“ Primary ITP was defined by the IWG as a platelet
count less than 100 􏰀 x109/L in the absence of other
causes or disorders that may be associated with
thrombocytopenia “
• The IWG also defines ITP :
• As newly diagnosed (diagnosis to 3 months),
• Persistent (3 to 12 months from diagnosis),
• Chronic (lasting for more than 12 months)

Rodeghiero F.Blood. 2009;113(11): 2386-

2393
 CAUSES OF SECONDARY ITP

• Antiphospholipid syndrome
• Autoimmune thrombocytopenia (eg, Evans
syndrome)
• Common variable immune deficiency
• Drug administration side effect
• Lymphoproliferative disorders
• Bone marrow transplantation side effect
• Vaccination side effect
• Systemic lupus erythematosus
*. Evans syndrome is associated with autoimmune
thrombocytopenia with coincident hemolytic anemia.
 ITP GUIDELINES AND
RECOMENDATIONS
• Necessary Evaluation
• History: Isolated bleeding symptoms consistent with
thrombocytopenia without constitutional symptoms (e.g.
significant weight loss, bone pain, night sweats).
• Physical examination: Bleeding symptoms in the absence of
hepatosplenomegaly, lymphadenopathy, or stigmata of
congenital conditions.
• Complete blood count: Isolated thrombocytopenia (platelet
count <100 x 10 /L). Anemia only if due to significant
9

bleeding—otherwise normal red cell indices, white blood cell

count and differential.
• Peripheral blood smear: Identified platelets should be normal
to large in size. Red and white blood cell morphology should
be normal

American Society of Hematology

2011
• Bone Marrow Evaluation
• Bone marrow examination is unnecessary in patients with
the typical features of ITP outlined above, irrespective of the
age of the patient.
• Bone marrow examination is felt to be unnecessary in
children with typical ITP prior to initiation of treatment with
corticosteroids, prior to splenectomy, or in patients who fail
intravenous immunoglobulin (IVIg) therapy.
• Additional Evaluations
• All adult patients with newly diagnosed ITP should undergo
testing for HIV and HCV.
• There is insufficient evidence to support theroutine use of
anti-platelet, antiphospholipid, and anti-nuclear antibodies,
thrombopoietin levels, or platelet parameters obtained on
automated analyzers in the evaluation of patients with
suspected ITP.
 MANAGEMENT :

• The goal of all treatment strategies for ITP is to

achieve a platelet count that is associated with
adequate hemostasis, rather than
a normal platelet count.
• The decision to treat should involve a discussion
with the patient and consideration of the severity of
bleeding, anticipated surgical procedures,
medication side effects, and health-related quality
of life.
 INITIAL MANAGEMENT OF ITP

1. Assessment of Disease Status:

• What bleeding is the patient experiencing?
• Determine the timing, location, and severity of bleeding
symptoms.
• Does this patiet have any additional risk factors for bleeding
such as use of antithrombotic agents or high-risk occupation?
• Is a surgical procedure anticipated?
• Is this patient likely to comply with recommended
treatments?
• Is the bleeding experienced by this patient interfering
with daily activities or causing significant anxiety?
 GENERAL CONSIDERATIONS FOR
INITIAL MANAGEMENT:
• The majority of patients with no bleeding or mild
bleeding (defined here as skin manifestations only,
such as petechiae and bruising) can be treated
with observation alone regardless of platelet count.
• Firstline treatment includes observation,
corticosteroids, IVIg, or anti-D immunoglobulin (anti-
D).
DEFINITIONS OF TIME TO AND DURATION
OF RESPONSE, AND THE TIME TO INITIAL
AND PEAK RESPONSE FOR DIFFERENT ITP
TREATMENTS*
• Adults:
• Consider treatment for patients with a platelet count < 30 x
109/L.
• Longer courses of corticosteroids are preferred over shorter
courses of corticosteroids or IVIg.
• IVIgmaybeusedinconjunctionwithcorticosteroidsifa more
rapid increase in platelet count is required.
• Either IVIg (1g/kg for one dose, repeated as necessary) or
anti-D (in appropriate patients) may be used as a first-line
treatment if corticosteroids are contraindicated
• Children:
• A single dose of IVIg (0.8-1.0g/kg) or a short course of
corticosteroids should be used as first-line treatment.
• IV Ig should be used instead of corticosteroids if a more
rapid increase in platelet count is required.
• There is no evidence to support using corticosteroids for
longer courses compared to very brief courses.
• Anti-D may be considered for first-line therapy in Rh+ non-
splenectomized children with recognition of the risks
outlined above.
SUBSEQUENT MANAGEMENT OF ITP

• 1. Assessment of Disease Status:

• What bleeding is the patient experiencing? Determine the
timing, location, and severity of bleeding symptoms.
• Does this patient have a changei n history o rphysical
examination that requires evaluation for another diagnosis
that could be causing thrombocytopenia?
• Does this patient have any contraindications to splenectomy?
• How is the diagnosis of ITP affecting the patient’s ability to
work, go to school, or participate in activities?
• Does the patient respond intermittently to current drug
therapy?
• Is the patient experiencing side effects from chronic
medication use?
• How is the patient coping psychologically with having a low
platelet count?
• General Considerations for Subsequent Management:
• Adults who have a platelet count > 30 x 10 /L and are
9

asymptomatic following splenectomy do not require further

therapy.
• In children, splenectomy or other interventions with potentially
serious complications should be delayed for at least 12 months,
unless warranted by severe disease unresponsive to other
measures or due to quality of life considerations.
• If previous treatment with corticosteroids, IVIg, or anti-D has
been successful, these options may be used as needed to
prevent bleeding.
• If previous treatment with corticosteroids, IVIg, or anti-D has
been unsuccessful, subsequent treatment may include
splenectomy, rituximab, thrombopoietin receptor agonists, or
more potent immunosuppression.
 SPECIAL CONSIDERATIONS FOR
SECONDARY ITP:
• Secondary ITP (HIV- associated):
• Treatment of the underlying HIV infection wit hantiviral
therapy should be considered prior to other treatment
options unless the patient has clinically significant bleeding.
• IVIg, corticosteroids, or anti-D may be used initially for
patients requiring further therapy.
• Splenectomy is considered preferable to otheragents in
symptomatic patients who have failed initial drug therapy.
• Secondary ITP (HCV- associated):
• Anti viral therapy should beconsidered in the absence of
contraindications (IVIg If considered).
• Secondary ITP (H. pylori- associated):
• Screening for H.pylori should be considered in adults for
whom eradication therapy would be undertaken if testing
were positive.
• Eradication therapy for H.pylori should be administered to
patients who are found to have infection
• MMR-related ITP:
• Children with a history of ITP who are not immunized should
receive their scheduled first MMR vaccine.
• ITP in Pregnancy:
• Pregnant patients requiring treatment should receive either
corticosteroids or IVIg.
 TTP VS HUS

• Thrombotic thrombocytopenic microangiopathies are a

group of disorders characterized by thrombocytopenia,
a microangiopathic hemolytic anemia evident by
fragmented RBCs and laboratory evidence of hemolysis,
and microvascular thrombosis.
• They include thrombotic thrombocytopenic purpura
(TTP) and hemolytic uremic syndrome (HUS), as well as
syndromes complicating bone marrow transplantation,
certain medications and infections, pregnancy and
vasculitis.
• The PT and aPTT are characteristically normal in TTP or
HUS
 THROMBOTIC THROMBOCYTOPENIC
PURPURA
• Thrombotic thrombocytopenic purpura (TTP) has a classic
pentad of thrombocytopenia, microangiopathic haemolytic
anaemia, neurological disturbance, fever and renal failure. The
defect is the absence of a vWF-cleaving protease (ADAMTS-
13) normally present in plasma.
• This results in abnormally large vWF polymers in the circulation,
which induce platelet microthrombi, resulting in end-organ
ischaemia.
• The common sporadic form is the result of cleaving protease-
directed autoantibodies.
• The rare autosomal recessive familial form of TTP is caused by
an inherited deficiency.
• Treatment is with plasma exchange which replaces the
enzyme and removes antibody and ultra-large vWF multimers.
• The patient is simultaneously started on steroids.
HAEMOLYTIC URAEMIC SYNDROME

• Haemolytic uraemic syndrome (HUS) presents with

thrombocy- topenia, renal failure and
microangiopathic haemolytic anaemia.
• Although clinically similar to TTP, the pathology is
different and is the result of endothelial damage
with subsequent platelet activation.
• It is often seen in children after infection with
verotoxin- producing strains of Escherichia coli.
• Treatment is supportive