Overcoming Cytomegalovirus Induced Immune Thrombocytopenia in Immunocompetent Adults – A Case of Antiviral Therapy Efficacy

Abstract

Patient: Male, 36-year-old

Final Diagnosis: Cytomegalovirus-induced thrombocytopenia

Symptoms: Anorexia • cough • fevers • eight loss • fatigue • flu-like symptoms • nausea

Clinical Procedure: —

Specialty: Hematology • Infectious Diseases • General and Internal Medicine

Objective:

Rare disease

Background:

Cytomegalovirus (CMV) infection is typically asymptomatic in immunocompetent individuals but can cause severe complications, such as immune thrombocytopenic purpura (ITP). This case report describes an uncommon instance of CMV-induced ITP in a 36-year-old immunocompetent man who was refractory to steroids and intravenous immunoglobulin (IVIG) and responded to antiviral therapy.

Case Report:

A previously healthy 36-year-old White man presented with flu-like symptoms, including subjective fevers, anorexia, nausea, cough, and a 6.8-kg weight loss over 2 weeks. Initial laboratory test results revealed severe thrombocytopenia (platelet count 4×10⁹/L) alongside elevated lymphocyte counts and mild splenomegaly. Additional serology confirmed a positive CMV IgM antibody. The patient was identified as having ITP and was treated with high-dose methylprednisolone and platelet transfusion, leading to initial platelet recovery. However, he returned within a week with severe epistaxis and a critical drop in platelet count to 0×10⁹/L. Subsequent testing confirmed CMV infection, with a viral load of 8790 copies/mL viral load. After unsuccessful IVIG treatment, antiviral therapy with valganciclovir was initiated, leading to a sustained increase in platelet count and eventual symptom resolution.

Conclusions:

CMV-induced ITP, although rare in immunocompetent individuals, should be considered in cases of refractory thrombocytopenia unresponsive to standard therapies. Prompt diagnosis and the initiation of targeted antiviral therapy are crucial for effective recovery, as they address the underlying viral etiology and can significantly improve patient outcomes. This case underscores the importance of including CMV in the differential diagnosis for persistent thrombocytopenia to ensure timely and appropriate treatment.

Introduction

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by the destruction of platelets through autoantibodies, resulting in thrombocytopenia and an increased risk of bleeding. ITP can be classified as primary, in which the cause is idiopathic or secondary and occurs in association with infections, drugs, or other autoimmune diseases [1,2]. The standard treatment for ITP typically includes corticosteroids and intravenous immunoglobulin (IVIG). However, secondary ITP, especially when caused by viral infections, can require additional and more targeted management approaches to address the underlying cause [2].

Cytomegalovirus (CMV) a ubiquitous member of the herpes-virus family that generally causes mild symptoms or remains asymptomatic in immunocompetent individuals. However, it can occasionally result in severe complications, such as ITP, particularly in immunocompromised hosts. The pathogenesis of CMV-induced thrombocytopenia is not fully understood but is believed to involve direct viral effects on megakaryocytes and immune-mediated platelet destruction [3,4]. While CMV-induced ITP in immunocompetent adults is rare, it has been documented, particularly in cases in which thrombocytopenia is resistant to standard ITP therapies [5,6].

The incidence of CMV-induced ITP, although infrequent, highlights the need for heightened clinical awareness, especially in cases in which thrombocytopenia does not respond to conventional treatments. Studies have shown that viral reactivation, even in the absence of immunosuppression, can lead to significant hematologic complications, underscoring the importance of considering viral etiologies in persistent or refractory ITP. Furthermore, intervention with antiviral therapies can significantly improve outcomes in these patients, making it crucial to include CMV in the differential diagnosis when managing complex cases of ITP. In this report, we present a case of CMV-induced thrombocytopenia in an immunocompetent adult, highlighting the importance of considering viral causes in cases of refractory ITP.

Case Report

A 36-year-old White man with no significant past medical history presented to the Emergency Department with flu-like symptoms, including subjective fevers, anorexia, nausea, cough, and a 6.8-kg weight loss over 2 weeks. He denied headaches, dizziness, weakness, vomiting, diarrhea, constipation, bone pain, abdominal pain, chest pain, shortness of breath, and myalgias. Two days prior, the patient noticed a possible tick bite. He reported no history of smoking, alcohol consumption, or drug use and had no known family history of autoimmune diseases. There were no sick contacts, recent travel, or new medications. On arrival, he had tachycardia, with a heart rate of 104 beats per min; otherwise, his vital signs were normal. There were no petechiae, bleeding, or ecchymosis noted on skin examination. Initial laboratory test results, including a complete blood count, comprehensive metabolic panel, coagulation studies, and hemolysis labs, were collected (platelet count was 4×10⁹/L) and are shown in Table 1. Further work-up was initiated to determine the cause of thrombocytopenia. Abdominal ultrasound showed mild splenomegaly, with the spleen measuring 15 cm in length (Figure 1). An antinuclear antibody screen was positive at 1: 320, but reflex testing was negative. CMV IgM antibody was positive, while other serologies were all negative (Table 2).

Table 1.

Comprehensive blood count, metabolic panel, and additional laboratory parameters.

Description	Result	Reference range	Units
Complete blood count
WBC count	14.43	4.10–12.20	103/uL
RBC count	3.66	4.40–5.50	106/uL
Hemoglobin	11.2	12.2–16.7	g/dL
Hematocrit	32	38.2–49.2	%
MCV	81.9	77.8–97.4	fL
MCH	27.3	25.9–32.7	Pg
MCHC	33.1	31.5–35.4	g/dL
RDW	14.2	12.3–15.9	%
Platelet count	4	153–369	103/uL
Immature granulocytes	3.9 H	0.0–0.3	%
Nucleated RBCs	0.2		%
Absolute neutrophil count	4.37	1.50–7.50	103/uL
Absolute lymphocyte count	8.25	1.10–3.40	103/uL
Absolute monocyte count	1.02	0.30–1.10	103/uL
Absolute eosinophil count	0.39	0.00–0.50	103/uL
Absolute basophil count	0.02	0.00–0.30	103/uL
Band neutrophil	0	0–5	%
Atypical lymphocytes	4.5	0–6	%
Tear drop cells	Occasional
Platelet morphology	Normal
Diff type	Manual
Complete metabolic panel
Sodium	131	(133–145)	mmol/L
Potassium	3.4	(3.5–5.0)	mmol/L
Chloride	98	(96–108)	mmol/L
CO2	23	(22–29)	mmol/L
BUN	8	(6–20)	mg/dL
Creatinine	1.4	(0.7–1.2)	mg/dL
Glucose	103	(70–100)	mg/dL
Calcium	8.4	(8.6–10.0)	mg/dL
Anion gap	10	(7–17)
Calc osmolality	261		mosm/kg
BUN/CREAT	6	(5–28)
GFR African American	>60	(>60)	GFR unit
GFR non-African American	>60	(>60)	GFR unit
Bilirubin, total	0.8	(<1.0)	mg/dL
Total protein	6.6	(6.4–8.3)	g/dL
Albumin	3.4	(3.5–5.2)	g/dL
Alk phos	52	(39–117)	U/L
ALT	49	(<42)	U/L
AST	49	(<39)	U/L
Chemistries, other
D-dimer	1.51	0.49	ug/mL
Fibrinogen level, blood	477	209–478	mg/dL
Protime	15.5	12.5–15.5	s
International normalized ratio	1.2
Partial thromboplastin time	36	27–39	s
Thrombin time	15.4	13.8–19.6	s
Adamts13 activity assay	96	≥70
Dat, broad spectrum Coombs serum	Negative	Negative
Cold antibody titer	1: 08
C-reactive protein	4.8	<0.5	mg/dL
Sed. rate, erythrocytes ESR	12	0–15	mm/h

Figure 1.

Abdominal ultrasound showing splenomegaly. This sagittal grayscale ultrasound image of the spleen demonstrates significant splenomegaly. The spleen measures 15.53 cm in length (longitudinal axis, labeled as measurement 1) and 5.87 cm in width (anteroposterior axis, labeled as measurement 2), exceeding the normal size range. The black arrow highlights the enlarged spleen, consistent with splenomegaly.

Table 2.

Microbiology serology.

Description	Result	Reference range	Units
CMV IgG	Negative	Negative
CMV IgM	Positive	Negative
CMV DNA Qn by PCR	8790	Undetected	IU/mL
EBV VCA IgM Ab	Negative	Negative
EBV VCA IgG Ab	Negative	Negative
Parvovirus B19 Ab, IgG	Negative	Negative
Parvovirus B19 Ab, IgM	Negative	Negative
Ehrlichia Chaffeensis (HME) Ab, IgG	<1: 64	<1: 64
Anaplasma phagocytophilum Ab, IgG, S	<1: 64	<1: 64
Babesia microti IgG Ab, S	<1: 64	<1: 64
Lyme disease serology, S	Negative	Negative
HIV 1 and 2 antigen and antibody screen	Non-reactive	Non-reactive
Hepatitis screen	Non-reactive	Non-reactive

The patient was admitted with a diagnosis of ITP. Hematology and infectious disease consultations were obtained. The patient received high-dose intravenous methylprednisolone (1 g per day), along with a platelet transfusion. His platelet counts initially increased to 43×10⁹/L on day 1. By day 2, his platelet count continued to improve, and he was discharged with a prednisone taper. At the time of discharge, his platelet count was 92×10⁹/L. However, 7 days after discharge, he returned to the Emergency Department with sudden onset severe epistaxis and a platelet count of 0×10⁹/L. Further workup was conducted, including a bone marrow biopsy and CMV viral load testing. The CD8 count was 56, CD4 count was 22, and the CD4/CD8 ratio was 0.4, consistent with CMV infection. The bone marrow biopsy showed hypercellular marrow with trilineage hematopoiesis and no increase in blast cells, monotypic B cells, or abnormal T-cell populations. CMV polymerase chain reaction (PCR) testing revealed a viral load of 8790 copies/mL. At this point, a diagnosis of CMV-induced ITP was made. The patient was given IVIG, without significant improvement in platelet count. Given the refractory nature of the thrombocytopenia, the patient was started on valganciclovir (900 mg twice daily). His platelet count began to improve after starting valganciclovir. The platelet count continued to increase, and he was discharged on valganciclovir, with close outpatient follow-up with infectious disease and hematology specialists. Upon discharge, his platelet count was recorded as 92×10⁹/L. Over the following 2 weeks, his platelet count increased to 150×10⁹/L, and his viral load decreased to 413 copies/mL. His symptoms resolved completely, and follow-up laboratory work after 4 months showed sustained recovery of platelet count and an undetectable viral load (Figure 2).

Figure 2.

Cytomegalovirus viral overload by polymerase chain reaction.

Discussion

Infection-associated ITP can occur with many different pathogens. Commonly implicated infectious agents include Epstein Barr virus, CMV, parvovirus, varicella-zoster virus, COVID-19, hepatitis C virus, HIV, Rickettsia, and Helicobacter pylori. Conditions frequently associated with secondary causes of ITP include chronic lymphocytic leukemia, systemic lupus erythematosus, antiphospholipid syndrome, common variable immune deficiency, autoimmune lymphoproliferative syndrome, selective immunoglobulin A deficiency, and measles, mumps, and rubella vaccination [1,2]. This case illustrates a rare but significant complication of CMV infection in an immunocompetent individual, presenting as ITP. While CMV infections are generally asymptomatic in healthy individuals, this case demonstrates the potential for severe complications, such as thrombocytopenia, even in those without predisposing immunosuppressive conditions.

The mechanisms through which CMV induces thrombocytopenia remain incompletely understood. Several hypotheses have been proposed, including direct viral infection of megakaryocytes leading to impaired platelet production and immune-mediated destruction of platelets via molecular mimicry. CMV may also trigger the production of anti-platelet antibodies, exacerbating thrombocytopenia [3,4]. In this patient, the combination of refractory thrombocytopenia and a confirmed CMV infection supports the hypothesis of immune-mediated and direct viral effects on platelet levels. This highlights the importance of considering viral etiologies like CMV when standard ITP therapies fail [5–7].

Current treatment of ITP attempts to either increase the level of thrombopoietin (thrombopoietin receptor agonists) or decrease the immune response (corticotherapy, CD20-targeted monoclonal antibodies, immunoglobulins, immunosuppression, and splenectomy), or both. Steroid treatment remains the cornerstone of first-line therapy. IVIGs can be added to the treatment of patients with a contraindication to steroids or those whose platelet counts decrease with steroid tapering [1,2]. Conventional treatments for ITP, including corticosteroids and IVIG, were ineffective in this patient, highlighting the limitations of these therapies in cases with an underlying viral etiology. The initiation of antiviral therapy with valganciclovir resulted in a significant and rapid recovery both in terms of platelet count and the patient’s overall condition. This outcome emphasizes the pivotal role that antiviral therapy can play in CMV-induced ITP, particularly when first-line treatments fail [8,9].

This case underscores the clinical challenge of managing secondary ITP caused by CMV. If ITP associated with CMV is suspected, a PCR test for CMV should be conducted. Upon confirmation of CMV-related ITP, antiviral therapy can be considered. Some experts recommend tapering immunosuppressive agents, including corticosteroids, as quickly as possible. Intensive immunosuppression could worsen ITP by exacerbating the underlying CMV infection. If platelet-specific treatment is required while awaiting a response to antiviral therapy, IVIG can effectively minimize additional immunosuppression [9].

Although valganciclovir is recommended as first-line treatment for immunocompromised adults with severe CMV disease, its use has not been evaluated for treatment in immunocompetent adults because of significant adverse effects, namely myelosuppression [10]. The dramatic improvement observed after the initiation of valganciclovir aligns with findings from other case reports, suggesting that antiviral therapy is critical in managing CMV-related thrombocytopenia. One literature review showed the response rate to first-line steroid-containing regimens was only 31%, whereas patients who were treated with an antiviral agent had a response rate of 82%. Moreover, patients who received thrombopoietin receptor agonists had a response rate of 75% [11]. Antiviral therapy with valganciclovir 900 mg twice daily should be continued at least until the CMV viral load is undetectable for 1 or 2 consecutive weeks and symptoms are resolved. The dosage should subsequently be reduced to once per day. The decision to discontinue antiviral therapy depends on the patient’s clinical condition and platelet levels. If valganciclovir-induced myelosuppression occurs, switching to foscarnet is recommended [6]. By reducing the viral load, antiviral agents like valganciclovir address the root cause of the thrombocytopenia, leading to clinical recovery. This case contributes to the expanding evidence supporting the early consideration of viral testing and antiviral therapy in the management of refractory ITP.

CMV is a common virus that infects people of all ages. The bulk of CMV-related disease in immunocompetent hosts is related to primary infection. Differentiating between endogenous reactivation and exogenous reinfection is difficult in clinical practice. Reactivation of CMV can occur at any time during the life of the human host, although the risk is higher in the setting of systemic immunosuppression [12]. A review of the literature [5,7] suggests that primary CMV infection is more frequently linked to ITP. This report underscores the significance of early CMV testing in patients with persistent or refractory thrombocytopenia, even in immunocompetent individuals. Given that viral infections like CMV can significantly alter the course of ITP, prompt recognition and initiation of antiviral therapy may prevent unnecessary exposure to prolonged corticosteroid or IVIG therapy and reduce the risk of complications.

The development of CMV-induced thrombocytopenia in this previously healthy patient suggests that viral causes should be included in the differential diagnosis for severe thrombocytopenia, regardless of immune status. The rarity of this condition in immunocompetent individuals underscores the need for greater awareness and vigilance among clinicians. Although this case provides valuable insight into the management of CMV-induced ITP, it is important to acknowledge its limitations. As a single case report, the findings may not be broadly generalizable. Further research is needed to clarify the exact mechanisms of CMV-induced thrombocytopenia and to establish more definitive treatment protocols. Larger studies evaluating the efficacy of antiviral therapy in CMV-induced ITP would help determine whether early antiviral intervention should become a standard approach in managing viral-induced thrombocytopenia.

Conclusions

This case illustrates a rare and severe occurrence of CMV-induced thrombocytopenia in an immunocompetent adult, highlighting the critical need for early identification and management. When CMV-related ITP is suspected, a PCR test for CMV should be performed. Antiviral therapy should be strongly considered upon confirming the diagnosis of ITP secondary to CMV. In such cases, antiviral treatment can be more beneficial and effective than conventional ITP therapies and should be regarded as a primary treatment option. Data on the efficacy of steroids in CMV-associated ITP remains limited, with some experts advising against their use, particularly in immunocompromised patients. The failure of standard therapies and the successful outcomes achieved with antiviral treatment underscore the importance of considering viral causes in refractory ITP cases. Early diagnosis and prompt initiation of antiviral therapy can lead to rapid platelet recovery and prevent complications. Clinicians should maintain a high index of suspicion for CMV in cases of persistent thrombocytopenia, even in immunocompetent patients, and incorporate antiviral therapy as a key component of the treatment strategy.

Abbreviations:

CMV

cytomegalovirus;

ITP

immune thrombocytopenic purpura;

IVIG

intravenous immunoglobulin