THROMBOCYTOPENIA
Introduction
The normal platelet count is 150 – 400 / nl
Or 150-400 x 10 9 / L
Or sometimes quoted as 150,00-400,000 / microL (x 10 6 / L)
Thrombocytopenia is usually defined as a platelet count of < 150,000 / microL, (however
approximately 2% or the normal population have counts below this level).
Physiology
Normal individuals produce 35,000-50,000 platelets per microL of whole blood per day.
Platelets survive in the peripheral blood for an average of 8-10 days, after which they are
removed from the circulation by cells of the monocyte-macrophage system.
Normally approximately one third of the total platelet mass is found in the spleen, in
equilibrium with the circulating pool.
Causes
Reduced Platelet Production
1.
2.
Bone marrow failure:
●
Metastatic infiltration
●
Hematological malignancies, leukemias.
●
Aplastic anemias
●
Myelofibrosis
●
Radiation
●
Drug induced, chemotherapy in particular.
●
Toxins, including alcohol
●
Severe sepsis.
Nutritional
●
Folate deficiency
●
B12 deficiency
Increased Platelet Destruction
1.
2.
Intravascular platelet destruction:
●
Thrombotic thrombocytopenic purpura
●
Hemolytic uremic syndrome
●
Disseminated intravascular coagulation
Antibody mediated destruction:
●
ITP
●
The antiphospholipid antibody syndrome
●
SLE
●
Drug induced, in particular, heparin, quinine, quinidine and valproic acid
●
Transfusion reaction.
3.
HELLP syndrome in pregnancy / Severe Pre eclampsia
4.
HIV associated destruction of megacaryocytes.
5.
Physical destruction of platelets during cardiopulmonary bypass.
Dilutional Thrombocytopenia
Patients who have had massive blood loss and transfusional support with packed RBC will
have dilutional thrombocytopenia due to absence of viable platelets in packed RBC products.
Hypersplenism
Normally, about one-third of circulating platelets are sequestered in the spleen, where they
are in equilibrium with circulating platelets.
Splenic sequestration of platelets can be increased to 90 percent in cases of extreme
splenomegaly, although total platelet mass and overall platelet survival remain relatively
normal.
Thus, patients with cirrhosis, portal hypertension, and splenomegaly may have significant
degrees of “apparent” thrombocytopenia (with or without leukopenia and anemia), but rarely
have clinical bleeding, since their total platelet mass is usually normal.
Normal Pregnancy
Asymptomatic mild thrombocytopenia is seen near term in about 5 % of normal pregnancies.
Pseudothrombocytopenia
The platelet count can be falsely low in two clinical situations:
1.
If anticoagulation of the blood sample is inadequate, resulting platelet clumps can be
counted as leukocytes by automated cell counters. In these circumstances, the WBC
count is rarely increased by more than 10 percent and there is usually an associated
spurious thrombocytopenia
2.
Approximately 0.1 percent of normal subjects have EDTA-dependent agglutinins,
which can lead to platelet clumping and spurious thrombocytopenia and spurious
leukocytosis.
Clinical Features
Points of history to note:
1.
Any other medical conditions, especially autoimmune disease, malignancy
2.
Current medications.
3.
Toxin, chemical exposure, alcohol.
4.
Current or recent viral infection.
Points of examination to note:
1.
Petechiae and purpura have been arbitrarily defined by some. Petechiae are pinpoint
non-blanching spots. Purpura are larger non-blanching spots (>2mm), 2
2.
Petechiae will be seen most commonly in “dependent” parts of the skin, such as the
feet and ankles in ambulatory patients, or in the presacral region in bed-ridden
patients.
3.
Check for hepatosplenomegaly and lymphadenopathy.
4.
Fever, the possibility of serious underlying sepsis (such as meningococcal infection)
needs to be kept in mind as a differential diagnosis to simple “thrombocytopenia”
In general terms there are a number of clinical features will help differentiate a platelet defect
from a clotting factor deficiency as in the table below:
Clinical Feature
Platelet Defect
Clotting factor deficiency
Site of bleeding
Skin and mucus membranes
Deep in soft tissues, (joint
and muscle)
Bleeding after minor cuts
Yes
Not usually
Petechiae
Present
Absent
Ecchymoses
Small, superficial
Large, palpable.
Hemarthroses, muscle
hematomas
Rare
Common
Bleeding after surgery
Immediate , mild
Delayed, severe.
Surgical bleeding due solely to a reduction in platelet count does not generally occur until the
count is below 50,000 / microL
Clinical or spontaneous bleeding does not occur until the platelet count is less than 10-20,000
/ microL
Investigations
Investigation will depend on the index of clinical suspicion for any given condition.
The following will need to be considered:
1.
FBE
Important aspects here include
●
Hb, (hemolysis or part of a pancytopenia)
●
WCC, (sepsis or part of a pancytopenia, evidence of blast cells suggestive of a
leukaemia)
●
Examination of RBC morphology. This will be critical for making a
diagnosis of microangiopathic hemolyis for critical diagnoses such as
TTP-HUS
●
Platelet count, in the first instance it will often be useful to recheck the platelet
count, (request a “manual” count.)
●
Large platelets (megathrombocytes) on the peripheral smear without
significant bleeding suggests the presence of young, hemostatically active
platelets being produced in response to peripheral destruction.
2.
Coombs test for hemolysis.
3.
Coagulation studies
●
INR, APTT (DIC)
●
DIC screen (fibrinogen, D-dimers)
4.
U&Es, (TTP-HUS)
5.
Bone marrow aspiration and biopsy is indicated in most patients with unexplained
thrombocytopenia severe enough to constitute a risk for major bleeding. 1
6.
Folate/B12 levels.
Blood film findings that suggest reduced production of platelets include:
●
Small platelets
●
Blast cells
●
A “leukoerythroblastic” blood picture
●
Leukopenia and anemia
Blood film findings that suggest increased destruction of platelets include:
●
Microangiopathic blood film.
Management Issues
The most important issues in the management of thrombocytopenia will be:
1.
Is this part of a serious condition that requires urgent treatment, such as TTP-HUS,
DIC or meningococcal infection?
2.
Treatment of the underlying cause.
●
3.
This is the most important aspect of treatment of thrombocytopenia.
Is platelet transfusion required?
This will depend on the platelet level, the clinical status of the patient and the
condition that is causing the thrombocytopenia.
●
In some conditions such as TTP-HUS or immune mediated platelet
destruction, this will in fact be detrimental, and they are generally avoided due
to concerns that they may lead to new or worsening renal and neurological
symptoms due to further consumption and microvascular thrombi of the
infused platelets.
●
Platelet transfusions are appropriate in other conditions where there is
associated bleeding with significant clinical risk (See latest NH&MRC
guidelines on platelet transfusion).