Emilio-Manuel Páez-Guillán, Joaquín Campos-Franco, Rosario Alende and Arturo Gonzalez-Quintela.
Department of Internal Medicine, Complejo Hospitalario Universitario, University of Santiago de Compostela, Spain.
Correspondence to:
Dr. Arturo González Quintela. Department of Internal Medicine, Hospital
Clínico Universitario, 15706 University of Santiago de Compostela,
Spain. Tel: +34 981 951265, Fax: +34 981 950501. E-mail:
arturo.gonzalez.quintela@usc.es
Published: March 1, 2023
Received: January 24, 2023
Accepted: February 27, 2023
Mediterr J Hematol Infect Dis 2023, 15(1): e2023023 DOI
10.4084/MJHID.2023.023
This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0),
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
|
Abstract
Background:
Thrombocytopenia during Epstein-Barr virus mononucleosis is well-known;
however, no recent series have investigated its frequency, associated
factors, and evolution. The present study aimed to investigate platelet
count characteristics in adult patients with infectious mononucleosis.
Methods: We reviewed the
clinical records of 400 patients admitted to the hospital with
infectious mononucleosis (52.0% male; median age, 19 years [range,
15-87 years]), focusing on blood platelet counts, thrombocytopenia
prevalence and outcomes.
Results: Thrombocytopenia
(platelet count ≤150 x109/L) was present in 119 (29.7%) patients.
Thirty-two (8.0%) patients showed platelet counts lower than 100
x109/L. Thrombocytopenia was severe (platelets <50 x109/L) in 6
(1.5%) patients. Thrombocytopenia was associated with a lower frequency
of typical mononucleosis symptoms such as sore throat and
lymphadenopathy, lower frequency of positive heterophil antibodies,
higher serum bilirubin concentration and prothrombin time, lower blood
leukocyte and lymphocyte count, lower concentration of serum
immunoglobulin G and immunoglobulin A concentrations, and larger spleen
size. Thrombocytopenia normalized quickly during follow-up. Only 2
cases required specific therapy. Platelet counts significantly
increased during follow-up, even in cases without baseline
thrombocytopenia. There were no significant hemorrhagic complications.
Conclusions: Transient
thrombocytopenia is common during infectious mononucleosis in adult
patients. Patients with thrombocytopenia have distinct clinical and
biological features; it is typically mild during infectious
mononucleosis. Cases of severe thrombocytopenia are rare and were not
associated with hemorrhagic complications in this series.
|
Introduction
Thrombocytopenia, often multifactorial, is common in many viral infections.[1,2]
An alteration in white blood cells is the most prominent feature in
primary Epstein-Barr virus (EBV) infection, giving the disease its name
(infectious mononucleosis). Additional hematological disturbances, like
thrombocytopenia, sometimes severe, have been less studied, although it
is almost always mentioned in descriptions of the disease.[3-6] To date, isolated cases of severe thrombocytopenia continue to be published,[7-10] but its exact frequency is not well known. A review spanning 30 years found 36 cases of severe (platelets <20 x109/L) thrombocytopenia during EBV-induced infectious mononucleosis.[7]
Classic studies on thrombocytopenia in EBV infection date back to the
1950s and 1960s. In 1956, Pader and Grossman reported 2 cases of severe
thrombocytopenia and purpura among 300 consecutive cases of infectious
mononucleosis.[11] In 1965, Carter observed some degree of thrombocytopenia in 50% of 57 cases;[12] in 1966, Cantow and Kostinas reported thrombocytopenia in 24% of 41 mononucleosis cases.[13]
These classic series continue to be the main reference in the most
recent case reports and small series of thrombocytopenia during
EBV-induced infectious mononucleosis.[7-10,14-17]
Since these old series were published, much has changed in the
diagnosis of EBV infection and even in the ease of measuring the blood
platelet count. The present study evaluated the current prevalence of
thrombocytopenia, its severity, associated factors, and evolution in a
larger series of adult patients with EBV-induced infectious
mononucleosis.
Method
Design and setting.
We reviewed the clinical records of adult patients (aged 15 years and
older) with infectious mononucleosis who were admitted to the
University Hospital of Santiago de Compostela (Spain) between 1995 and
2018, as reported elsewhere.[18,19] The hospital is
the reference center for an area including approximately 400,000
inhabitants. The main reasons for hospital admission were severe signs
of a systemic inflammatory response, difficulty with oral intake, and
complications.
Diagnosis of infectious mononucleosis.
A definitive diagnosis of infectious mononucleosis was considered when
a compatible clinical syndrome was accompanied by positive
immunoglobulin (Ig)M antibodies against the viral capsid antigen of EBV
and/or a positive heterophile antibody result, as revealed by either a
classic Paul-Bunnell test or a rapid commercial test.[6]
A total of 319 patients (of the 338 tested) had positive immunoglobulin
IgM antibodies against the viral capsid antigen, 338 (of the 380
tested) had a positive heterophile antibody result, and 257 patients
had both tests positive.
Study population and determinations.
A total of 401 patients met the diagnostic criteria. The platelet count
was unavailable for 1 case. The study, therefore, included 400 patients
(52.0% male; median age, 19 years [range, 15-87 years]). We reviewed
their clinical records, focusing on automated blood cell counts
(particularly platelet counts). Platelet counts >150 x109/L (and <450 x109/L)
were considered normal in the present study. Significant
thrombocytopenia was considered when the platelet count was below 100
x109/L, and severe thrombocytopenia was considered when the platelet count was below 50 x109/L.
Abnormally low platelet counts were routinely confirmed by blood smear
examination. Clinical characteristics, markers of liver damage (serum
alanine aminotransferase and bilirubin), prothrombin time, and serum
concentrations of immunoglobulins (IgG, IgA, and IgM) were also
registered. The first available laboratory determination, usually taken
on admission, was used for analyses. Spleen size was measured by
routine ultrasound when available. Follow-up of blood counts during
convalescence was available for 293 patients (median follow-up, 28
days; interquartile range [IQR] 20-42 days; [range 14-177 days]).
Statistical analyses.
We employed the Mann-Whitney test to compare the numerical data between
groups and the Wilcoxon test to compare paired samples of numerical
values. We employed the chi-squared test (with continuity correction
and trend analysis, when appropriate) to compare proportions and the
Jonckheere-Terpstra test for trend analysis of numerical variables
among ordinal categories. Lastly, we used Spearman’s rank test to
assess the correlations. All tests were two-tailed.
Ethical approval.
The study was reviewed and approved by the institutional Ethics
Committee (code 2017/578). The requirement for informed consent from
the study participants was waived, in agreement with Spanish
regulations for similar retrospective studies.
Results
Thrombocytopenia prevalence. Figure 1
is a histogram of the blood platelet counts for the patients with
infectious mononucleosis. The median platelet count on admission was
185 x109/L (range 15-441 x109/L; IQR 142-233 x109/L). Table 1 shows a comparison of the demographic, clinical, and biological characteristics of the patients with normal (>150 x109/L) platelet counts, those with platelet counts of 100-150 x109/L (n=87, 21.7%), and those with platelet counts <100 x109/L (n=32, 8.0%). Six (1.5%) patients had platelet counts <50 x109/L.
 |
Figure 1. Histogram of platelet counts in patients with infectious mononucleosis (n=400). |
 |
Table
1. Demographic, clinical, and biological characteristics of patients
with infectious mononucleosis, stratified by baseline blood platelet
count during hospital admission.
|
Clinical associations. Sex and age were not significantly associated with thrombocytopenia (Table 1).
Typical symptoms of infectious mononucleosis, such as sore throat and
lymphadenopathy, were less common in patients with low platelet counts (Table 1). However, spleen size tended to be larger in patients with low platelet counts (Table 1).
A total of 26 patients received corticosteroid therapy prior to
admission. The prevalence of low platelet counts tended to be lower
among those patients who received corticosteroids (typically indicated
by the general practitioner due to severe oropharyngeal symptoms that
made swallowing difficult) before admission (Table 1).
Hematologic associations. Total blood leukocyte counts and differential lymphocyte counts were lower in patients with low platelet counts (Table 1). The hemoglobin level was similar in the various platelet count strata (Table 1).
There were also no significant differences in hemoglobin levels among
platelet count categories when patients were stratified by sex (data
not shown). The prevalence of anemia was similar among platelet count
categories (Table 1). No cases of autoimmune hemolytic anemia were detected, although mild anemia was present in a sizeable proportion of cases (Table 1). The prothrombin time tended to be longer the lower the platelet count (Table 1).
Immunologic associations. Serum IgG and serum IgA concentrations were lower in the patients with low platelet counts (Table 1). Serum IgM concentrations were similar in the various platelet strata (Table 1). The prevalence of a positive heterophile antibody test tended to be lower as the level of platelet counts decreased (Table 1).
Outcome.
No bleeding complications related to thrombocytopenia were recorded. Of
the six patients with severe thrombocytopenia (platelets <50 x109/L), there were two patients with counts lower than 20 x109/L; both were treated with intravenous immunoglobulins (IVIG), with rapid initial recovery (Figure 2).
Thrombocytopenia relapsed in one of these two patients after a few
weeks, requiring a new course of IVIG and corticosteroid treatment for
several wplatelet counts between 20 x109/L and 50 x109/L, one died from developing a lymphoproliferative disorder associated with the EBV infection. The other 3 recovered eeks, after which the patient maintained normal platelet counts in the following years (Table 1). Of the remaining four patients with normal platelet counts in less than a month without needing treatment.
 |
- Figure
2. Time-course changes of blood platelet counts in the 2 patients from
the series with infectious mononucleosis and platelet counts lower than
20 x109/L. The upper panel (A) corresponds to a 16-year-old female presenting with fever and sore throat. The lowest platelet count was 14 x109/L. On admission, blood hemoglobin was 12.6 g/dL. White blood cell count was 14.0 x109/L
(17% neutrophils, 3% monocytes, 3% basophils, 69% lymphocytes, and 8%
large unstained cells [LUCs] in the automatic cytometry). Activated
lymphocytes were observed in the peripheral blood smear. Both
heterophil antibodies (rapid test) and IgM to EBV-viral capsid antigen
(VCA) were positive. She was treated with intravenous immunoglobulins
(IVIG, 0.6 g/kg) for three consecutive days, with rapid and stable
recovery. She did not develop hemorrhagic manifestations. The lower panel (B)
corresponds to a 17-year-old male presenting with fever, sore throat,
and peripheral lymphadenopathy. The lowest platelet count was 9 x109/L. On admission, blood hemoglobin was 14.2 g/dL. White blood cell count was 10.1 x109/L
(35% neutrophils, 7% monocytes, 2% basophils, 51% lymphocytes, and 5%
LUC in the automatic cytometry). Activated lymphocytes were observed in
the peripheral blood smear. Both heterophil antibodies (rapid test) and
IgM to EBV-VCA were positive. He was initially treated with IVIG (1
g/kg) for 2 consecutive days, with rapid initial recovery. However,
severe thrombocytopenia relapsed in the third week. He was treated
again with IVIG and corticosteroids (prednisone, initial dose 1 mg/kg).
Platelet counts quickly returned to normal. He did not develop
hemorrhagic manifestations. Prednisone was maintained for 10 weeks in
tapering doses. Platelet counts remained within normal limits during
the following months (panel B) and during the following 10 years
without specific therapy (data not shown).
|
Platelet
counts tended to increase in all baseline platelet strata, even in
those patients with normal platelet counts on admission. However, the
increased proportion was greater in the patients with lower platelet
levels at baseline (Table 2). The vast majority of patients (87 of 88, 98.8%) with platelet counts ≤150 x109/L on admission and available follow-up data increased their platelet counts in the immediate convalescent period (Table 2).
 |
- Table
2. Time-course changes of blood platelet count in patients with
infectious mononucleosis, stratified by their baseline count.
|
Among
the patients with available follow-up data, 96 received corticosteroids
during hospital admission (for reasons different from
thrombocytopenia), and 194 did not (data unavailable for 3 cases). The
calculated rate of platelet increase per day was not significantly
different between patients who received corticosteroids and those who
did not (median increase 1.4 x109/L per day [IQR 0.26-3.2 x109/L per day] versus median increase 2.0 x109/L per day [IQR 0.12-4.4 x109/L per day], respectively; P=0.171).
The three patients who died during hospitalization had low platelet counts (Table 1).
A 47-year-old male presenting with fever, lymphadenopathy, skin rash,
severe anemia, thrombocytopenia, and elevated markers of liver damage
died after multiorgan failure due to hemophagocytic syndrome during
EBV-related infectious mononucleosis on the 10th
day of hospital admission in the intensive care unit. In situ
hybridization revealed EBV-DNA in lymph nodes and bone marrow obtained
during the autopsy. No specific treatment was established for the
hematological process. A 33-year-old female presenting with fever,
hepatosplenomegaly, inguinal lymphadenopathy, pancytopenia, jaundice,
and elevated markers of liver damage was simultaneously diagnosed with
acute EBV infection and natural killer/T-cell lymphoproliferative
disorder. Epstein-Barr virus-DNA and EBV-encoded small RNA (EBER) were
demonstrated in lymph node biopsy. She died after multiorgan failure
due to Streptococcus mitis and Candida albicans-related sepsis on the 30th
day of hospital admission in the intensive care unit. Specific
treatment for the lymphoma could not be started. A 17-year-old male
patient with diabetes mellitus and a severe previous disability died
after multiorgan failure due to methicillin-resistant Staphylococcus aureus sepsis on the 40th day of hospital admission. As a whole, the hospital stays tended to be longer the lower the platelet count on admission (Table 1).
Discussion
Some degree of thrombocytopenia (platelet counts lower than 150 x109/L)
was present in nearly a third of patients with infectious mononucleosis
admitted to the hospital, confirming classic reports establishing this
frequency at between 25% and 50% in smaller series.[12,13]
Moreover, median platelet counts in patients with infectious
mononucleosis were very similar to that observed in a series of 47
college outpatients.[14] Severe thrombocytopenia (platelet counts lower than 50 x109/L)
was only observed in 1.5% of patients with EBV-induced infectious
mononucleosis admitted to the hospital, confirming classic reports.[11]
More importantly, even patients with normal platelet counts on
admission showed an increase in platelet counts during convalescence,
thus suggesting that relative thrombocytopenia is a common phenomenon
during infectious mononucleosis. It should be noted, however, that the
patients in this series were admitted to the hospital, thus selecting
the most severe cases.
Moreover, serum bilirubin, prothrombin time, and hospital stay were
higher in patients with lower platelet counts, suggesting that
thrombocytopenia might be associated with greater disease severity.
Along these lines, thrombocytopenia was present in the three patients
who died in this series, 2 of whom had EBV-related lymphoproliferative
disorders. Finally, it should be noted that all the patients were older
than 15 years. It is known that primary EBV infection can be more
severe in adulthood than in childhood,[3-6] although no association between age and thrombocytopenia was observed in the present series.
Low platelet counts were associated with some atypical features of
infectious mononucleosis, including a lower frequency of sore throat
and lymphadenopathy, lower blood leukocyte and lymphocyte counts, lower
serum IgG and IgA concentration, and lower frequency of positive
heterophil antibodies. These findings suggest that patients with
EBV-induced thrombocytopenia show a distinct clinical syndrome.
Thrombocytopenia normalized quickly during follow-up of infectious
mononucleosis without specific therapy in most cases. Even patients
with severe thrombocytopenia (platelet counts lower than 50 x109/L) recovered spontaneously, as described in the literature.[20] Only 2 cases with platelet count lower than 20 x109/L
were treated with IVIG, with rapid response, although one of these
patients suffered an early relapse that needed additional IVIG and
corticosteroid therapy, which was followed by total recovery, similar
to previous reports.[15] There were no significant hemorrhagic complications in the series.
The mechanism of thrombocytopenia in EBV-induced mononucleosis appears
to be peripheral and immune-mediated. In the bone marrow,
megakaryocytes are typically normal or increased.[7,10,16] Antiplatelet antibodies have been detected[7,16] and platelet-bound IgG[17]
in some cases of thrombocytopenia during infectious mononucleosis. In
the current series, however, thrombocytopenia was inversely correlated
with total serum IgG concentrations. Infection by EBV is restricted to
humans, so no experimental models exist. However, experimental
infections with the related murine gammaherpesvirus-68 produce a
mononucleosis-like illness in mice with reduced platelet count during
the early phase due to antibodies induced by the infection.[21]
The response of thrombocytopenia to corticosteroids and IVIG further
supports the notion of an immune basis for EBV-induced
thrombocytopenia. Moreover, thrombocytopenia tended to be less frequent
in patients receiving corticosteroids before admission. The use of
corticosteroids for symptom control in infectious mononucleosis is
controversial.[22,23] The most frequent indication
for corticosteroids was tonsillitis hindering swallowing, the same
reason why many patients received corticosteroid therapy during
hospital admission. This therapy, however, was not associated with a
more rapid increase in platelet counts between the acute and
convalescent periods. Furthermore, the fingerprint of EBV infection is
more frequent in patients with chronic immune thrombocytopenia than in
controls.[24,25] Yan et al. reported that the
positive rate of EBV-DNA in blood lymphocytes (as detected by
quantitative reverse transcription PCR) from patients with chronic
immune thrombocytopenia was higher than that observed in controls.[24]
Likewise, Wu et al. reported that the positive rate of EBV in the
spleen (as detected by immunohistochemistry) from patients
splenectomized for chronic immune thrombocytopenia was higher than that
observed in controls.[25] The history of previous infectious mononucleosis was not reported in these series.[24,25] Finally, splenic sequestration is another possible mechanism for thrombocytopenia during infectious mononucleosis;[7] spleen size was negatively correlated with platelet counts in our series. In addition, EBV can interact with platelets,[26] and impaired platelet function during the disease has been reported.[27]
The study has the strengths of sample size and availability of
follow-up (retrospective cohort design). As a weakness, the study is
observational and retrospective, with inherent drawbacks.[28]
All patients were adults (older than 15 years) and had been admitted to
the hospital. The findings can, therefore, only be applied to patients
with infectious mononucleosis of similar age and severity.
Conclusions
In
summary, thrombocytopenia is common in hospitalized patients with
severe infectious mononucleosis. Even many patients with normal
baseline platelet counts experience an increase during convalescence,
suggesting that relative thrombocytopenia can nearly be the rule in
EBV-induced infectious mononucleosis. Thrombocytopenia tends to be
negatively associated with typical findings of mononucleosis syndrome,
such as sore throat, lymphadenopathy, lymphocytosis, and heterophile
antibodies. Thrombocytopenia tends to be positively associated with
larger spleen size and surrogate markers of disease severity. Most
cases of thrombocytopenia are mild, and patients recover spontaneously
without needing treatment. Although thrombocytopenia during EBV-induced
infectious mononucleosis appears to be immune, more studies would be
needed to elucidate its pathogenic mechanisms more precisely.
References
- Raadsen M, Du Toit J, Langerak T, van Bussel B, van
Gorp E, Goeijenbier M. Thrombocytopenia in virus infections. J Clin Med
2021;10:877. https://doi.org/10.3390/jcm10040877 PMid:33672766 PMCid:PMC7924611
- Assinger A. Platelets and infection - an emerging role of platelets in viral infection. Front Immunol 2014;5:649. https://doi.org/10.3389/fimmu.2014.00649 PMid:25566260 PMCid:PMC4270245
- Cohen J. Epstein-Barr virus infection. N Engl J Med 2000;343:481-492. https://doi.org/10.1056/NEJM200008173430707 PMid:10944566
- Godshall SE, Kirchner JT. Infectious mononucleosis. Complexities of a common syndrome. Postgrad Med 2000;107:175-186. https://doi.org/10.1080/19419260.2000.12277439
- Straus
SE, Cohen JI, Tosato G, Meier J. NIH conference. Epstein-Barr virus
infections: biology, pathogenesis and management. Ann Intern Med
1993;118:45-58. https://doi.org/10.7326/0003-4819-118-1-199301010-00009 PMid:8380053
- Lennon P, Crotty M, Fenton JE. Infectious mononucleosis. BMJ 2015;350:h1825. https://doi.org/10.1136/bmj.h1825 PMid:25899165
- Pipp
ML, Means ND, Sixbey JW, Morris KL, Gue CL, Baddour LM. Acute
Epstein-Barr virus infection complicated by severe thrombocytopenia.
Clin Infect Dis 1997;25:1237-1239. https://doi.org/10.1086/516114 PMid:9402388
- Zhang
C, Kelly AM. Severe thrombocytopenia in a case of Epstein-Barr
virus-induced infectious mononucleosis. Cureus 2021;13:e17706. https://doi.org/10.7759/cureus.17706
- Likic
R, Kuzmanic D. Severe thrombocytopenia as a complication of acute
Epstein-Barr virus infection. Wien Klin Wochenschr 2004;116:47-50. https://doi.org/10.1007/BF03040424 PMid:15030124
- Walter
RB, Hong TC, Bachli EB. Life-threatening thrombocytopenia associated
with acute Epstein-Barr virus infection in an older adult. Ann Hematol
2002;81:672-675. https://doi.org/10.1007/s00277-002-0557-1 PMid:12454710
- Pader E, Grossman H. Thrombocytopenic purpura in infectious mononucleosis. N Y State J Med 1956;56:1905-1910.
- Carter RL. Platelet levels in infectious mononucleosis. Blood 1965;25:817-821. https://doi.org/10.1182/blood.V25.5.817.817 PMid:14282050
- Cantow EF, Kostinas JE. Studies on infectious mononucleosis. 3. Platelets. Am J Med Sci 1966;251:664-667. https://doi.org/10.1097/00000441-196606000-00005
- Macsween
KF, Higgins CD, McAulay KA, Williams H, Harrison N, Swerdlow AJ,
Crawford DH. Infectious mononucleosis in university students in the
United Kingdom: evaluation of the clinical features and consequences of
the disease. Clin Infect Dis 2010;50:699-706. https://doi.org/10.1086/650456 PMid:20121570
- Cyran
EM, Rowe JM, Bloom RE. Intravenous gammaglobulin treatment for immune
thrombocytopenia associated with infectious mononucleosis. Am J Hematol
1991;38:124-129. https://doi.org/10.1002/ajh.2830380210 PMid:1951302
- Steeper
TA, Horwitz CA, Moore SB, Henle W, Henle G, Ellis R, Flynn PJ. Severe
thrombocytopenia in Epstein-Barr virus-induced mononucleosis. West J
Med 1989;150:170-173.
- Kernoff
LM. Demonstration of increased platelet-bound IgG in infectious
mononucleosis complicated by severe thrombocytopenia. Scand J Infect
Dis 1980;12:67-69. https://doi.org/10.3109/inf.1980.12.issue-1.12 PMid:7367838
- Páez-Guillán
EM, Campos-Franco J, Alende R, Garitaonaindía Y, González-Quintela A.
Transient hypertriglyceridemia: a common finding during Epstein-Barr
virus-induced infectious mononucleosis. Lipids Health Dis 2021;20:177. https://doi.org/10.1186/s12944-021-01603-9 PMid:34895245 PMCid:PMC8667370
- Páez-Guillán
EM, Campos-Franco J, Alende R, Lázare H, Beceiro C, Gonzalez-Quintela
A. Jaundice in relation to immune activation during Epstein-Barr
virus-induced infectious mononucleosis. Am J Med Sci 2023 (in press). https://doi.org/10.1016/j.amjms.2022.12.004 PMid:36526005
- Wong SY, Bennett B. Natural history of severe thrombocytopenia in infectious mononucleosis. Postgrad Med J 1982;58:249-251. https://doi.org/10.1136/pgmj.58.678.249 PMid:7111109 PMCid:PMC2426381
- Freeman
ML, Burkum CE, Lanzer KG, Roberts AD, Pinkevych M, Itakura A, Kummer
LW, Szaba FM, Davenport MP, McCarty OJ, Woodland DL, Smiley ST,
Blackman MA. Gammaherpesvirus latency induces antibody-associated
thrombocytopenia in mice. J Autoimmun 2013;42:71-79. https://doi.org/10.1016/j.jaut.2012.11.005 PMid:23245703 PMCid:PMC3608809
- Thompson
SK, Doerr TD, Hengerer AS. Infectious mononucleosis and
corticosteroids: management practices and outcomes. Arch Otolaryngol
Head Neck Surg 2005;131:900-904. https://doi.org/10.1001/archotol.131.10.900 PMid:16230594
- Rezk
E, Nofal YH, Hamzeh A, Aboujaib MF, AlKheder MA, Al Hammad MF. Steroids
for symptom control in infectious mononucleosis. Cochrane Database Syst
Rev 2015;2015:CD004402. https://doi.org/10.1002/14651858.CD004402.pub3 PMid:26558642 PMCid:PMC7047551
- Yan
M, Zhang Y, Yang F, Ji L, Wang M, Wang W. Comparative study between
chronic immune thrombocytopenia patients and healthy population on
Epstein-Barr virus infection status by polymerase chain reaction.
Expert Rev Hematol 2020;13:781-786. https://doi.org/10.1080/17474086.2020.1772746 PMid:32498632
- Wu
Z, Zhou J, Wei X, Wang X, Li Y, Peng B, Niu T. The role of Epstein-Barr
virus (EBV) and cytomegalovirus (CMV) in immune thrombocytopenia.
Hematology 2013;18:295-299.
https://doi.org/10.1179/1607845413Y.0000000084 PMid:23540727
- Nunez
D, Charriaut-Marlangue C, Barel M, Benveniste J, Frade R. Activation of
human platelets through gp140, the C3d/EBV receptor (CR2). Eur J
Immunol 1987;17:515-520. https://doi.org/10.1002/eji.1830170413 PMid:2952514
- Clancy R, Jenkins E, Firkin B. Platelet defect of infectious mononucleosis. Br Med J 1971;11:646-648. https://doi.org/10.1136/bmj.4.5788.646 PMid:5134559 PMCid:PMC1799842
- Talari K, Goyal M. Retrospective studies - utility and caveats. J R Coll Physicians Edinb 2020;50:398-402. https://doi.org/10.4997/jrcpe.2020.409 PMid:33469615
[TOP]