Thrombocytopenia (Diagnostic approach)
OVERVIEW
1.
2.
Our approach to patient with unexplained thrombocytopenia involves confirmation of finding
by repeating CBC and reviewing peripheral blood smear, obtaining prior platelet counts if
available, and assessing other hematologic abnormalities. The pace of subsequent evaluation
and further testing depends on clinical presentation, which can range from asymptomatic to
acutely ill (table 7).
Initial question and pace of evaluation
A. When patient presents with unexpected thrombocytopenia.
i.
Is thrombocytopenia real?
ii.
Is thrombocytopenia new?
iii.
Are there other hematologic abnormalities?
B. Confirmation that thrombocytopenia is real (not laboratory error or in vitro artifact) is
done by repeating CBC and reviewing peripheral blood smear (or requesting review),
especially if PLT does not make sense within context of clinical picture.
C. A new reduction in PLT is more concerning than stable, mildly low count because it
suggests possibility of evolving condition. Prior PLT is helpful in this regard, if available,
and PLT should be monitored to determine trend going forward, with interval dependent
on severity of thrombocytopenia and other clinical findings.
D. Additional clues can also be identified from blood smear (giant platelets, which are read
by automated counter as RBC because of their size; or fragmented RBC, which are
3.
characteristic of thrombotic microangiopathy). Other hematologic abnormalities
(anemia, leukopenia, leukocytosis) generally suggest more serious diagnosis than
isolated thrombocytopenia.
E. Any patient with unexplained thrombocytopenia should be seen by hematologist to
determine cause and appropriate management; urgency depends on degree of
thrombocytopenia and other findings.
Asymptomatic, incidental finding, mild thrombocytopenia
A. Common diagnoses for asymptomatic outpatients with mild thrombocytopenia include
ITP, occult liver disease, HIV, and MDS. Congenital thrombocytopenic conditions,
sometimes misdiagnosed as ITP, may also occur.
B.
C.
In patient with incidentally discovered asymptomatic thrombocytopenia and probable
diagnosis of ITP, no further evaluation beyond routine Hx, PE, CBC, and review of
peripheral blood smear, and testing for HIV and HCV infection is necessary.
Referral to hematologist to confirm diagnosis is appropriate. Following that, routine
monitoring can be done by patient's primary care physician. Anti-platelet antibody
studies, imaging studies, and BM aspiration and biopsy are not necessary.
D.
4.
The natural history of asymptomatic, mild thrombocytopenia was studied prospectively
in 217 apparently healthy individuals referred to hematology center for incidentally
discovered PLT between 100,000 and 150,000/μL. At 6 months of observation, 23 (11%)
had normal platelet counts, 2 developed MDS (refractory anemia), and 1 developed SLE.
The remaining 191 individuals (88%) had persistent platelet counts < 150,000/μL during
this period without other signs of disease becoming evident; after 5 years, most (64%)
had spontaneous resolution or persistent mild thrombocytopenia without development
of associated condition, supporting diagnosis of ITP.
Thrombocytopenia with bleeding or other symptom
A. Patients who present with isolated thrombocytopenia and bleeding, manifested by
petechiae, purpura, and mucosal bleeding (epistaxis, menorrhagia), have different
diagnostic spectrum.
i.
Individuals with bleeding who lack signs of systemic illness or other abnormalities of
CBC are likely to have drug-induced thrombocytopenia or primary ITP. These
diagnoses are made based on appropriate history (drug exposure, bleeding,
absence of other specific symptoms) and lack of other findings on PE. No additional
laboratory testing is needed, with exception of HIV and HCV testing.
ii.
The role of testing for drug-dependent antibodies in potential drug-induced
thrombocytopenia is discussed separately.
iii.
Individuals with thrombocytopenia and other symptoms have broader range of
potential diagnoses. Specific diagnoses to consider depend on other clinical
5.
findings.
1. Fever – Possible infection, sepsis, DIC
2. Hepatosplenomegaly – Possible liver disease with hypersplenism, lymphoma
3. Neurologic finding – Possible TTP-HUS, vitamin B12 or copper deficiency
4. Lymphadenopathy – Possible infection, lymphoma, other malignancy
5. Thrombosis – Possible HIT, APS, TTP-HUS, PNH
iv.
These individuals should have additional laboratory evaluation directed at
diagnoses suggested by these other symptom.
Acutely ill/intensive care unit
A. Thrombocytopenia is common in acutely ill patients. As example, PROTECT, which
randomly assigned 3746 patients in ICU to treatment with UFH or LMWH for
thromboembolism prophylaxis, found thrombocytopenia in 26% of patients at time of
enrollment (before heparin administration). Most of thrombocytopenia that developed
following enrollment was mild (PLT 100,000 to 149,000/μL); incidences of mild,
moderate (50,000 to 99,000/μL), and severe (< 50,000/μL) thrombocytopenia were 15, 5,
and 2%.
B.
Predictors of developing thrombocytopenia in cohort of 145 patients in medical ICU
included DIC, CPR, and organ failure at admission. In PROTECT trial, which included
medical and surgical ICU patients, predictors of thrombocytopenia included higher
APACHE II, surgical diagnosis, liver dysfunction, receipt of inotropes or vasopressors in
preceding 3 days, RRT in preceding 3 days, and development of HIT.
C. The most common cause of new-onset thrombocytopenia in cohort of 329 medical and
surgical ICU patients was sepsis, accounting for 50% of cases. More than one cause of
thrombocytopenia was found in 26%. The frequency of specific causes of
thrombocytopenia included the following.
i.
Sepsis, all (48%)
ii.
Sepsis with documented bacteremia (28%)
iii.
iv.
v.
vi.
vii.
viii.
ix.
x.
xi.
xii.
D.
E.
F.
Liver disease/hypersplenism (18%)
Overt DIC (14%)
Unknown cause (14%)
Infection, other (11%)
Primary hematologic disorder (9%)
Medication, non-cytotoxic (9%)
Medication, cytotoxic (7%)
Massive transfusion (7%)
Other causes (7%)
Alcoholism (5%)
Based on this spectrum of findings, we have low threshold for performing coagulation
studies, LFT, and cultures of blood and body fluids in critically ill patients with
thrombocytopenia. BM evaluation is appropriate if thrombocytopenia is severe and/or
other cell lines are abnormal. For patients with moderate to severe thrombocytopenia, a
thorough review of medications that were started in 2 weeks prior to development of
thrombocytopenia should be undertaken, and, if drug-induced thrombocytopenia is
suspected, responsible medication(s) should be discontinued, with close monitoring of
platelet count recovery. Highly suspect medications (based on likelihood of causing
thrombocytopenia, timing and severity of platelet count drop) may be substituted with
alternative from different class, if available. HIT is uncommon cause of
thrombocytopenia in ICU. However, patients with clinical suspicion of HIT should
undergo HIT antibody testing.
Adverse outcomes generally correlate with severity of thrombocytopenia. The degree of
thrombocytopenia correlated with risk of bleeding in PROTECT trial (adjusted HR for mild,
moderate, and severe thrombocytopenia were 1.96, 3.52, and 3.54). Moderate and
severe thrombocytopenia also correlated with increased length of ICU stay and death.
Additional diagnostic considerations in acutely ill patients with pancytopenia (leukopenia,
anemia, and thrombocytopenia), such as hemophagocytic lymphohistiocytosis (HLH), are
presented separately.
6.
Emergency requiring immediate action
A. Certain presentations of thrombocytopenia are medical emergencies that require
immediate action.
i.
Bleeding in setting of severe thrombocytopenia (PLT < 50,000/μL)
ii.
Urgently needed invasive procedure with severe thrombocytopenia
iii.
Pregnancy with severe thrombocytopenia
iv.
Suspected HIT
v.
Suspected TTP-HUS
vi.
Suspected acute leukemia, aplastic anemia, or other BM failure syndrome
B. The consulting specialist (hematologist) can assist with patient evaluation, diagnosis and
management strategies, including platelet transfusions, other means of rapidly raising
platelet count (IVIG for ITP, plasma exchange for TTP-HUS), prevention of additional
complications (thrombosis), and treatment of underlying condition.
HISTORY
1. There is no substitute for thorough patient history for determining whether other conditions
are present that may explain thrombocytopenia. Certain conditions associated with
thrombocytopenia are obvious and can be immediately recognized by clinician, while others
may require specific questioning. In acutely ill patient who cannot provide history, this
information should be obtained from family members or other clinicians caring for patient.
A. Prior platelet counts, if available, because stable platelet count is less concerning than
new or decreasing count.
B.
C.
D.
E.
Family history of bleeding disorders and/or thrombocytopenia
History of bleeding (petechiae, ecchymoses, epistaxis, gingival bleeding, hematemesis,
melena, menorrhagia)
Medication exposures – It is important to include new prescriptions, medications that
are only taken intermittently, OTC medicines (aspirin, NSAID), herbal remedies, and
medicines prescribed for other family members or friends that patient may have taken
(table 3).
Ingestion of quinine-containing beverages should be addressed specifically, due to
strong association of quinine exposure with thrombocytopenia (table 4).For hospitalized
patients, one must review hospital chart, nursing notes, bedside flow sheets, and
anesthesia records. Relevant medicines may also be contained in materials used in
surgery (vancomycin mixed into joint replacement cement). The timing of onset of
clinical bleeding or first recognition of thrombocytopenia with use of medications should
be explored in depth since it may focus attention on the most likely agent(s), especially
in individuals receiving multiple medications.
F.
G.
H.
Special attention should be paid to administration of heparin in hospitalized or recently
discharged patients due to possibility of HIT, although this is rare. This includes UFH or
LMWH (enoxaparin, dalteparin, tinzaparin, nadroparin), and heparin flushes in vascular
access lines or exposure during surgery. In contrast, we are not aware of association of
thrombocytopenia with target-specific anticoagulants (direct thrombin inhibitors, factor
Xa inhibitors).
Infectious exposures, including recent infections (viral, bacterial, rickettsial) or live virus
vaccination; recent travel to area endemic for malaria, dengue virus, leptospirosis,
meningococcemia, rat-bite fever, rickettsial infections, hantavirus, and viral hemorrhagic
fevers (Ebola, Lassa fever); and risk factors for HIV infection.
Dietary practices that could cause nutrient deficiencies (veganism, vegetarianism, zinc
ingestion).
I. Other medical conditions, including hematologic disorders; rheumatologic diseases;
bariatric surgery or poor nutritional status; blood product transfusion or organ
transplantation.
PHYSICAL EXAMINATION
1. PE should focus on signs of bleeding, and presence of lymphadenopathy or
hepatosplenomegaly, which may be signs of underlying condition responsible for
thrombocytopenia. Signs of thrombosis may also suggest different spectrum of potential
causes of thrombocytopenia.
2. Skin and other sites of bleeding
A.
Bleeding into skin is one of the most common findings in thrombocytopenia. Of note,
thrombocytopenic bleeding differs from bleeding seen in individuals with coagulation
abnormalities (table 8). Patients with bleeding due to thrombocytopenia may have
petechiae, purpura, or frank mucosal bleeding.
i.
Petechiae are pinhead sized, red, flat, discrete lesions often occurring in crops in
dependent areas. Petechiae are caused by RBC extravasation from capillaries; they
are asymptomatic, nontender, non-palpable, and do not blanch under pressure.
They are most dense in dependent areas where the hydrostatic pressure on small
superficial vessels is greatest (feet and ankles in ambulatory patients; presacral area
in bedridden patients). Petechiae are not found on sole of foot, where vessels are
ii.
protected by strong subcutaneous tissue. Petechiae and other lesions should be
noted, especially in dependent parts of body.
Purpura refers to purplish discoloration of skin caused by confluent petechiae. Dry
purpura refers to purpura in skin; wet purpura refers to mucosal purpura. It is
generally thought that wet purpura is prognostic sign for potentially more serious
hemorrhage.
iii.
B.
C.
D.
3.
Ecchymoses (bruises) are non-tender areas of bleeding into skin, usually associated
with multiple colors due to presence of extravasated blood (red, purple) and
breakdown products of heme pigment (green, orange, yellow). Ecchymotic lesions
characteristically are small, multiple, and superficial. They may develop without
noticeable trauma and do not spread into deeper tissues.
Of note, petechiae and purpura differ from small telangiectasias, angiomas, and
vasculitic purpura.
It can be helpful to document extent of skin lesions (mark with pen) in order to identify
new lesions and/or expansion of existing lesions, which may signify persistent or
worsening thrombocytopenia, or raise additional concerns about increased bleeding risk.
Other sites of bleeding (occult blood in stool) require appropriate evaluation and
treatment, regardless of cause of thrombocytopenia.
Liver, spleen, lymph nodes
A. The liver and spleen should be palpated for tenderness and enlargement. Splenomegaly
can be sign of liver disease, lymphoma, or other hematologic condition; splenomegaly of
any etiology may cause mild thrombocytopenia.
B. Lymphadenopathy in patient with thrombocytopenia may suggest infection, lymphoma,
or other malignancy.
i.
Focal, tender LN enlargement is typical of localized bacterial infection.
ii.
Generalized lymphadenopathy may be associated with acute HIV infection, in which
it is typically nontender and involves axillary, cervical, and occipital nodes.
iii.
Lymphadenopathy may be associated with other infectious, malignant,
autoimmune, and inflammatory conditions.
LABORATORY TESTING
1. Review of CBC and peripheral blood smear are essential in patient with unexpected
2.
thrombocytopenia. Platelet clumping suggests possibility of pseudothrombocytopenia.
Repeat CBC
A. A platelet count that does not make sense within context of clinical findings should be
repeated before extensive evaluation is undertaken.
i.
For symptomatic patients (signs of bleeding) or those with severe
thrombocytopenia (< 50,000/μL), such retesting should be performed immediately.
ii.
For asymptomatic patients (non-bleeding, no associated comorbidities) with
moderate thrombocytopenia (50,000 to 100,000/μL), testing may be repeated in 1
to 2 weeks, provided patient is advised to report immediately any changes in
clinical status or bleeding during this interval.
iii.
For outpatients with isolated mild thrombocytopenia (100,000 to 150,000/μL),
testing may be repeated in one or more months, as small percent of these patients
will develop normal platelet count with observation only. An exception is patient
recently started on new medication, new clinical findings, or other abnormalities on
CBC, because mild thrombocytopenia may be sign of evolving disorder
(drug-induced or heparin-induced thrombocytopenia, TTP-HUS).
B. The default diagnosis in asymptomatic patient with isolated thrombocytopenia (no
bleeding or signs of other acute illness, normal values on remainder of CBC,
unremarkable peripheral blood smear) is immune thrombocytopenia (ITP), provided
other causes of thrombocytopenia have been eliminated (HIV, drug-induced
thrombocytopenia, MDS).
C. In contrast, diagnostic possibilities are more extensive for symptomatic patient and/or
patient with thrombocytopenia in setting of other hematologic abnormalities.
i.
Combined anemia and thrombocytopenia may occur if there has been
longstanding bleeding (gastrointestinal). Combined anemia and thrombocytopenia
also raises possibility of systemic disorders.
1. Sepsis with DIC
2. TTP-HUS
3. Autoimmune disorders (Felty's syndrome)
ii.
iii.
4. Nutrient deficiency (folate, vitamin B12, copper)
5. Infection
6. Bone marrow disorders (MDS, leukemia, BM infiltration by malignancy)
Combined leukocytosis and thrombocytopenia raise possibility of infection, chronic
inflammation, and malignancy.
Combined leukopenia, anemia, and thrombocytopenia (pancytopenia) is discussed
in detail separately.
3.
Peripheral blood smear
A. Review of peripheral blood smear is used to exclude pseudothrombocytopenia (falsely
B.
C.
low PLT due to platelet clumping) and to evaluate morphologic abnormalities of blood
cells that could be useful in determining cause of thrombocytopenia.
As example, giant platelets may suggest congenital platelet disorder (May-Hegglin
anomaly, Bernard Soulier syndrome [BSS]); these may be counted as red blood cells by
some automated counters.
Pseudothrombocytopenia
i.
The possibility of pseudothrombocytopenia (falsely low PLT) should be eliminated
before extensive evaluation is undertaken. Pseudothrombocytopenia can occur in
number of settings, all of which can be identified by review of peripheral blood
ii.
iii.
smear and/or repeating CBC using non-EDTA anticoagulant.
Incompletely mixed or inadequately anticoagulated samples may form clot that
traps platelets in collection tube and prevents them from being counted.
Exposure of some patient samples to EDTA anticoagulant in collection tube can
induce platelet clumps or platelet rosettes around WBC. These may be counted by
automated counters as leukocytes rather than platelets.
1. Approximately 0.1% of individuals have EDTA-dependent agglutinins that can
induce platelet clumping. This is thought to result from "naturally occurring"
platelet autoantibody directed against concealed epitope on platelet
membrane GP IIb/IIIa that becomes exposed by EDTA-induced dissociation of
2.
GP IIb/IIIa.
On occasion, platelets may rosette around WBCs (neutrophils, monocytes,
lymphoma cells). This phenomenon has also been called "platelet satellitism."
In one case, this resulted from presence of EDTA-dependent antibody with
dual reactivity against GP IIb/IIIa and neutrophil Fcγ receptor III.
iv.
If platelet clumping is observed, PLT is repeated using heparin or sodium citrate as
anticoagulant in collection tube. If citrate is used, PLT should be corrected for
dilution caused by amount of citrate solution; no such correction is needed for
heparin. Alternatively, fresh, non-anticoagulated blood can be pipetted directly into
platelet-counting diluent fluid.
D. RBC and WBC abnormality
i.
Abnormal RBC and WBC morphologies may suggest specific condition.
1. Schistocytes suggest microangiopathic process (DIC, TTP-HUS).
2.
Nucleated RBC, and Howell-Jolly bodies, may be seen post-splenectomy or
occasionally in patients with poor splenic function.
3.
Spherocytes suggest immune-mediated hemolytic anemia or hereditary
spherocytosis.
4.
Leukoerythroblastic findings, teardrop cells, nucleated RBC, or immature
granulocytes suggest infiltrative process in BM.
5.
Leukocytosis with predominance of bands (left shift) and/or toxic granulations
suggest infection.
6.
Myeloblast or dysplastic WBCs suggest leukemia or myelodysplasia.
7.
Hyper-segmented neutrophils (> 5 lobes) suggest megaloblastic process
(B12/folate/copper deficiency).
4.
5.
HIV and HCV testing
A. Thrombocytopenia has been identified as an important "indicator condition" for HIV
infection. Thus, adults with new thrombocytopenia should have HIV testing if not done
recently.
B. Thrombocytopenia may also be seen with HCV infection; testing is appropriate for adults
with thrombocytopenia if not done recently.
Other laboratory testing
A. Aside from testing mentioned above (CBC, blood smear, HIV and HCV), no additional
laboratory testing is absolutely required in patient with isolated thrombocytopenia.
However, additional testing may be warranted in patients with other findings.
B. Examples of findings that may trigger other laboratory testing include the following.
i.
Symptoms or findings of systemic autoimmune disorders (SLE, APS) may prompt
testing for ANA or APA. We do not test for these in patients with isolated
thrombocytopenia and no signs or symptoms suggestive of SLE or APS.
ii.
Findings of liver disease should prompt measurements of hepatic enzymes and
possibly tests of liver synthetic function (albumin, coagulation testing), depending
on severity of liver disease.
iii.
Thrombosis should prompt consideration of DIC, HIT, and APS. Depending on site of
thrombosis and other hematologic findings, PNH may also be consideration. Testing
for these conditions is discussed separately.
iv.
Microangiopathic changes on peripheral smear should prompt coagulation testing
(PT, aPTT, fibrinogen) and measurement of serum LDH and renal function to
evaluate for DIC and TTP-HUS; with subsequent evaluation based on results.
ADDITIONAL EVALUATION
1. Hematologist referral
A. Referral to hematologist is appropriate to confirm any new diagnosis of
thrombocytopenic condition or to determine cause of any unexplained
thrombocytopenia. The urgency of referral depends on degree of thrombocytopenia and
other abnormalities, and stability of findings.
B. In hospitalized patients, some conditions are medical emergencies that require
immediate action. Early hematologist involvement in diagnosis and management is
appropriate for the following.
i.
Suspected TTP-HUS.
ii.
Suspected HIT.
iii.
Suspected hematologic malignancy (acute leukemia), aplastic anemia, or other
bone marrow failure syndrome.
C. The consulting hematologist can also assist in diagnosis and management of patients
with severe thrombocytopenia (PLT < 50,000/μL) who have serious bleeding or require
2.
urgent invasive procedure, and in pregnant women with severe thrombocytopenia,
regardless of cause.
Bone marrow evaluation
A. Bone marrow evaluation (aspirate and biopsy) is not required in all patients with
thrombocytopenia. However, it may be helpful in some patients if cause of
thrombocytopenia is unclear, or if primary hematologic disorder is suspected. A possible
exception may be clinical picture consistent with nutrient deficiency in which bone
marrow would only be needed if deficiency could not be documented, or if hematologic
findings did not resolve upon nutrient repletion.
B. The following bone marrow findings may be helpful.
i.
ii.
Normal or increased numbers of megakaryocytes suggests that thrombocytopenia
is due, at least in part, to condition associated with platelet destruction
(drug-induced immune thrombocytopenia).
Decreased megakaryocyte numbers, along with overall decreased or absent
cellularity, is consistent with decreased BM production of platelets, as in aplastic
anemia.
iii.
iv.
v.
In rare cases, severe reduction or absence of megakaryocytes with no other
abnormalities (also called acquired amegakaryocytic thrombocytopenia or acquired
pure megakaryocytic aplasia) may occur. This finding is most often reported in
patients with SLE, and is typically due to autoantibody directed against the
thrombopoietin receptor.
Megaloblastic changes in RBC and granulocytic series suggest nutrient deficiency
(vitamin B12, folate, Cu), while dysplastic changes suggest myelodysplastic disorder.
Granulomata, increased reticulin or collagen fibrosis, or infiltration with malignant
cells establishes diagnosis of BM invasion, especially when leukoerythroblastic
blood picture is also present.
GENERAL MANAGEMENT PRINCIPLE
1. Management of specific thrombocytopenic disorders (once diagnosis is made) is discussed in
2.
3.
4.
5.
separate topic reviews. However, there are some general management principles that apply
to all patients with thrombocytopenia regardless of the cause, and for which questions may
arise before a diagnosis has been established.
Activity restriction
A. Patients who are otherwise healthy and have no manifestations of petechiae or purpura
may not require activity restrictions.
B. Individual considerations apply to participation in certain activities. As example,
individuals with moderate to severe thrombocytopenia (< 50,000/μL) should not
participate in extreme athletics such as boxing, rugby, and martial arts. However, no
restrictions are necessary for usual activities. Excessive mandated restrictions are more
likely to decrease the information the patient provides to the physician than to reduce
the patient’s activities.
Anti-platelet medications and over-the-counter remedies
A. Patients should be educated about which medications and non-prescription remedies
interfere with platelet function (aspirin, NSAID, ginkgo biloba). In general, these agents
are avoided unless there is specific indication for which equivalent alternatives are
lacking.
B. However, appropriate use of thromboprophylaxis or anticoagulants should not be
withheld from patient with mild to moderate thrombocytopenia (> 50,000/μL) if it is
indicated (postoperatively). For patients with more severe thrombocytopenia, decisions
are made on case-by-case basis regarding risks of bleeding and benefits of
anticoagulation.
Safe platelet count for invasive procedure
A. Most platelet count thresholds for invasive procedures are based on weak observational
evidence at best. In general, procedures with greater risk of bleeding are performed at
higher platelet counts. While there is some flexibility in individual circumstances,
anesthesiologists and surgeons performing these procedures will have the last word.
B. Optimal methods for raising platelet count in preparation for invasive procedure depend
on underlying condition (corticosteroids or IVIG for presumptive ITP; platelet transfusion
for MDS). These approaches are discussed in detail in separate topic reviews.
C. Individuals with impaired platelet function may require platelet transfusions despite
adequate platelet counts, depending on the procedure. Attention should also be paid to
correcting coagulation abnormalities if present.
Emergency management of bleeding
A. Urgent management of critical bleeding in setting of severe thrombocytopenia requires
immediate platelet transfusion, regardless of the underlying cause.
SUMMARY AND RECOMMENDATIONS
1. Thrombocytopenia (platelet count < 150,000/μL) may be associated with a variety of
2.
conditions, with associated risks that range from life-threatening to none. We are most
concerned about spontaneous bleeding with counts < 10,000/μL, and surgical bleeding with
counts < 50,000/μL. Rarely, thrombocytopenia is associated with a risk of thrombosis rather
than bleeding.
The potential causes of thrombocytopenia differ depending on the clinical setting in which it
occurs.
A. In asymptomatic outpatients with thrombocytopenia, common diagnoses include
immune thrombocytopenia (ITP), occult liver disease, HIV infection, and myelodysplastic
syndromes. Congenital thrombocytopenias (sometimes misdiagnosed as ITP) may also
B.
C.
D.
3.
4.
5.
occur.
In patients with bleeding who lack signs of systemic illness or other abnormalities of the
CBC, drug-induced thrombocytopenia or primary ITP are likely diagnoses.
In patients with other clinical findings, causes of thrombocytopenia include infection,
sepsis, disseminated intravascular coagulation (DIC), drug-induced thrombocytopenia,
heparin-induced thrombocytopenia (HIT), liver disease, lymphoma, other malignancies,
nutrient deficiencies (vitamin B12, folate, copper), thrombotic thrombocytopenic
purpura-hemolytic uremic syndromes (TTP-HUS), antiphospholipid syndrome (APS), and
paroxysmal nocturnal hemoglobinuria (PNH).
In acutely ill patients, common causes of new-onset thrombocytopenia include sepsis,
DIC, and drug-induced thrombocytopenia (table 1). Many patients in the intensive care
unit with thrombocytopenia have more than one cause.
E. Certain causes of thrombocytopenia are medical emergencies that require immediate
action (bleeding in the setting of severe thrombocytopenia; suspected HIT, TTP-HUS, or
bone marrow failure syndrome).
We confirm thrombocytopenia by repeating the CBC and reviewing the peripheral blood
smear; obtain prior platelet counts, if available, and assess other hematologic abnormalities.
The pace of the subsequent evaluation, further testing, and hematologist consultation
depends on the clinical presentation, which can range from asymptomatic to acutely ill.
The history should focus on prior platelet counts, family history, bleeding, medications, OTC
remedies, infectious exposures, dietary practices, and other medical conditions (hematologic
disorders, rheumatologic conditions, surgery, transfusion). The physical examination should
evaluate bleeding, lymphadenopathy, hepatosplenomegaly, thrombosis, and organ
involvement.
No additional laboratory testing besides the CBC and peripheral blood smear is absolutely
required in a patient with isolated thrombocytopenia. Adults with new thrombocytopenia
should have HIV and HCV testing if not done recently. Additional laboratory testing may be
warranted in patients with other finding.
6.
7.
8.
9.
Hematologist consultation is appropriate to confirm new diagnosis or if the cause of
thrombocytopenia is at all unclear. The urgency of referral depends on degree of
thrombocytopenia and other abnormalities, and stability of findings. In hospitalized patients,
early hematology involvement is appropriate for individuals with suspected TTP-HUS, HIT,
and some hematologic malignancies (acute leukemia).
BM evaluation is not required in all patients with thrombocytopenia; however, it may be
helpful in some patients if cause of thrombocytopenia is unclear, or if primary hematologic
disorder is suspected.
Management of patients with thrombocytopenia depends on the underlying diagnosis.
General principles that apply to all patients include avoidance of medications that interfere
with platelet function unless alternatives are unavailable; coordination with anesthesiologists
and surgeons before invasive procedures, and correction of coagulation abnormalities.
Activity restrictions are often not needed.
Thrombocytopenia in neonates and children, and thrombocytopenia during pregnancy are
discussed separately.