Thrombocytopenia in Virus Infections: A Brief Review

Introduction

Patients presenting with viral infections are advised to undergo blood count estimation. Clinically, mild thrombocytopenia with lymphopenia (low lymphocyte count) creates a suspicion of a viral infection. However, they are not significant criteria and do not distinguish between bacterial, viral, and parasitic infections. This article discusses briefly about thrombocytopenia caused a viral infection.

What Is Thrombocytopenia in Viral Infections?

Thrombocytopenia, a low platelet count (below 150x109/L), is common in individuals with viral infections. Platelets are vital for blood clotting. Their deficiency causes bleeding and bruising. It is considered an indicator of viral infection severity. Thrombocytopenia has been noticed in several viral infections. For example, there is a high risk of developing thromboembolic complications during or after an influenza virus infection.

What Are the Symptoms of Thrombocytopenia in Viral Diseases?

The clinical manifestations of thrombocytopenia in viral disease are:

• Petechiae and Ecchymosis: Small red or purple spots or bruises develop on the skin due to bleeding beneath the skin.

• Mucosal Bleeding: Individuals with thrombocytopenia have mucosal bleeding, causing gum, nose, and gastrointestinal bleeds. Severe cases of bleeding can be dangerous.

• Menstrual Irregularities: Women with thrombocytopenia have irregular menstruation.

• Internal Bleeding: Thrombocytopenia causes internal bleeding, which is not clinically apparent. It manifests as black stools, hematuria, and abdominal pain.

• Enhanced Bleeding Risk: Individuals with thrombocytopenia risk increased bleeding during medical procedures. Adequate monitoring is essential before starting surgical procedures in such patients.

How Does Thrombocytopenia Develop in Viral Infections?

1. Aggregation: Platelet agglutination and adhesion are often common in patients with viral infections. Standard hematology analyzers fail to identify platelet aggregates and report a low count. Chronic viral infection such as hepatitis B, C, and HIV (human immunodeficiency virus) is suspected in isolated thrombocytopenia.

2. Impaired Hematopoiesis: Some viruses directly infect hematopoietic stem cells in bone marrow, causing defective hematopoiesis and thrombocytopenia. HIV and cytomegalovirus cause thrombocytopenia by invading bone marrow. The platelet production is further affected by lower transpoietin production in the liver.

3. Sequestration and Intravascular Destruction: Platelet destruction occurs with direct interaction with the virus. A viral infection causes a systemic inflammatory response, resulting in platelet activation and clearance. Additionally, platelet bind to neutrophils and form platelet-neutrophil aggregates, leading to phagocytosis of platelets.

4. Immune-Mediated Platelet Destruction: The body’s immune system produces an exaggerated response to viral infection, causing platelet destruction. This phenomenon is seen in dengue fever and Epstein-Barr virus infection.

5. Platelet Consumption: Some viral infections consume most platelets during blood clotting. It is common in severe viral infections such as disseminated intravascular infection (DIC).

What Are the Viral Disorders Causing Thrombocytopenia?

Viral infections presenting with thrombocytopenia are:

1. Dengue Virus: The severe dengue virus is associated with thrombocytopenia. Platelets become activated by circulating dengue virus particles and immune factors. Activated platelets become degranulated and attach to the vessel fall forms thrombi. Therefore, the platelets get removed from circulation, causing thrombocytopenia.

2. Chikungunya Virus: Thrombocytopenia has occasionally been reported in patients with chikungunya virus.

3. Crimean Congo Hemorrhagic Fever: It is a tick-borne virus associated with pronounced thrombocytopenia. Such patients have lower platelet counts and increased platelet distribution. A lower platelet lymphocyte ratio predicts adverse outcomes for thrombocytopenia patients.

4. Japanese Encephalitis Patients: Flavivirus causes infection in the central nervous system, resulting in mortality. In non-encephalitic cases of viral infection, encephalitis is common during the acute phase.

5. Severe Fever With Thrombocytopenia Syndrome: It is an emerging infectious disease causing profound thrombocytopenia. A lack of arginine and its metabolite (nitric oxide) disinhibits platelet activation, causing platelet aggregation, destruction, and thrombocytopenia.

6. Tick-Borne Encephalitis Virus: It is a tick-borne virus that also causes thrombocytopenia. However, the developing thrombocytopenia is mild and not associated with bleeding.

7. Viral Hemorrhagic Fever: It is a group of highly pathogenic viruses. Mild thrombocytopenia in viral hemorrhagic fever does not cause significant bleeding or need for platelet transfusion. Few studies indicate platelet play a crucial role in controlling viral fever.

8. West Nile Virus: Severe thrombocytopenia or hemorrhage has not been reported in West Nile virus. The virus can be transmitted through platelet transfusion, raising the possibility that the virus resides in platelets.

9. Yellow Fever Virus: The characteristic of disseminated yellow fever is a hepatic failure with resulting thrombocytopenia.

10. Zika Virus: Patients infected with Zika virus have reported thrombocytopenia. However, a small group of patients reported platelet levels below 150x109/L. Fulminant cases of Zika virus present with severe thrombocytopenia, bleeding, liver failure, and coagulation disorders.

11. Hepatitis B and C: Chronic cases of hepatitis B and C present with hepatic cirrhosis, portal hypertension, liver failure, and hepatocellular carcinoma. Thrombocytopenia helps predict the extent of adverse outcomes in hepatitis B and C. Additionally, there is increased platelet activation and consumption due to chronic inflammation from the viral process.

12. HIV: Thrombocytopenia is common in HIV infections. Individuals with unexplained thrombocytopenia are often tested for HIV infection. Decreases in platelet count in HIV patients are associated with dementia and gray matter disease.

13. Hantavirus: It causes hemorrhagic fever and renal syndrome. The condition is associated with severity-dependent thrombocytopenia. Platelet consumption is known to have a significant role in thrombocytopenia pathogenesis.

14. Enterovirus: Thrombocytopenia has been reported in neonatal cases of Coxsackievirus.

15. Rotavirus: Viral gastroenteritis is a major cause of child mortality in the developing world. The infection is limited to the gastrointestinal epithelium and rarely includes other organs or causes severe inflammation. Thrombocytopenia is a dominant feature of viral gastroenteritis.

How Is Thrombocytopenia Managed in Patients With Viral Infections?

Underlying viral infection must effectively be managed in individuals with thrombocytopenia. Antiviral medications are given to control the viral replication. However, not all infections can be treated with antivirals, and supportive care becomes vital.

Thrombocytopenia caused by immune-mediated destruction is treated with immunosuppressive drugs. Corticosteroids and other immunosuppressive agents help alter the immune response and prevent platelet destruction. Severe cases of thrombocytopenia require platelet transfusion to increase platelet count and decrease bleeding rapidly. Individuals with thrombocytopenia must be closely monitored for platelet levels and clinical symptoms. It is better to avoid medications that may aggravate thrombocytopenia symptoms. Patients are advised to avoid activities that increase injury or bleeding risk.

Conclusion

Thrombocytopenia is a common complication of several viral infections. There are several mechanisms by which thrombocytopenia develops in viral infections. Diagnosing and managing virus-induced thrombocytopenia requires a proper understanding of the mechanism.