Thrombocytopenia in HIV patients coinfected with tuberculosis

Abstract

Thrombocytopenia is one of the most common hematological manifestations seen in HIV patients with approximately 40% of the patients developing thrombocytopenia during their course of illness. Opportunistic infection like tuberculosis is a rare but curative cause of thrombocytopenia in these patients. Clinically, it is a challenge to determine the exact cause and decide the treatment of thrombocytopenia in these patients as both infections can lead to significant thrombocytopenia by varied mechanisms. The treatment options are limited by drug antitubercular treatment highly active antiretroviral therapy (ATT and HAART)-induced thrombocytopenia. A 25-year-old male patient presented with low grade, intermittent fever with left-sided pleuritic chest pain for 2 months along with dry cough, weight loss, malaise, and lethargy. Hematological examination showed anemia, leukopenia, and thrombocytopenia. The patient was found to be HIV reactive. Chest X-ray revealed nonhomogenous opacity with cavitation in the left upper and middle zone suggestive of tuberculosis. He received multiple units of blood and platelets and was started on isoniazid, rifampicin, pyrazinamide, and ethambutol. HAART was initiated 2 weeks after starting ATT. Patient's hematological parameters improved and he was discharged on ATT and HAART with recovery of the platelet counts. Thrombocytopenia is a complication associated with both HIV and tuberculosis and hence determining the cause and deciding the appropriate treatment is challenging. Decision about whom and when to treat has to be taken cautiously considering all possible contributors and treatment has to be individualized.

Introduction

Thrombocytopenia is one of the most common hematological manifestations seen in HIV patients (anemia being the most common[1]) sometimes presenting as the first sign. Approximately 40% of the patients may develop thrombocytopenia during their course of illness with the incidence increasing with worsening of CD4 counts.[2] It is associated with deterioration in CD4 counts, increased morbidity and mortality, and sometimes progression to full-blown AIDS despite adequate treatment.[3]

Opportunistic infections in these patients are also an important cause of thrombocytopenia, tuberculosis being the most common among them. Tuberculosis is a rare but curative cause of thrombocytopenia.

Clinically, it is difficult to determine the exact cause of thrombocytopenia in patients presenting with HIV coinfected with tuberculosis as both the infections can lead to significant thrombocytopenia by varied mechanisms. This dual infection makes deciding the appropriate treatment a challenge. The treatment options also are limited as some of the drugs used for the treatment of HIV and TB may cause bone marrow suppression resulting in thrombocytopenia. Here, we present a case of a patient diagnosed as pulmonary tuberculosis and HIV who presented with thrombocytopenia.

Case Report

A 25-year-old male patient presented with fever with left-sided chest pain for 2 months. Fever was intermittent, low grade with evening rise of temperature. Chest pain was dull aching and pleuritic in nature. The patient had dry cough on and off along with complaints of weight loss, malaise, and lethargy. The patient was treated for these complaints outside by antibiotics and symptomatic treatment, but his symptoms persisted.

On examination, the patient was moderately built, nourished, conscious, oriented, hemodynamically stable, and maintaining 97% SpO₂ on room air. Chest examination revealed coarse crackles in the left infrascapular area. His cardiovascular and neurological examination was unremarkable. His complete blood count [Table 1] showed anemia, leukopenia, and thrombocytopenia with blood picture showing dimorphic, macrocytic anemia. The liver and kidney functions were within normal limits. On further investigation, the patient was found to be HIV reactive. Chest X-ray revealed nonhomogeneous opacity with cavitation in the left upper and middle zone [Figure 1] suggestive of tuberculosis. Sputum examination could not be done as patient was not expectorating. The patient was not on any drugs that could lead to thrombocytopenia. The patient was transfused blood and multiple units of platelets and were started on isoniazid, rifampicin, pyrazinamide, and ethambutol. Highly active antiretroviral therapy (HAART) was initiated 2 weeks after starting antitubercular treatment (ATT). Patient's hematological parameters slowly improved after blood product transfusions and starting appropriate chemotherapy. With recovery of the platelet counts, the patient was discharged on ATT and HAART and was asked to follow-up in the outpatient department.

Table 1.

Hematological and biochemical profile

Figure 1.

Chest X-ray on presentation showing infiltrates with cavitation in the left upper and middle zone

Discussion

The causes of thrombocytopenia in patients with HIV and TB are multifactorial, and a meticulous, logical approach, including consideration of all the possible contributors, has to be considered. Thrombocytopenia in HIV patients can be either primary to HIV infection or secondary to various opportunistic infections such as TB, malignancy, drugs, hypersplenism, or other comorbid conditions. In primary thrombocytopenia, the etiologies may differ in different stages of infection. The most common reasons being.[3]

• Peripheral destruction of platelets due to cross-reactivity of HIV antibodies

• Apoptosis of megakaryocytes due to direct HIV infection

• Abnormal and dysfunctional platelet production.

Autoimmune destruction predominates early in infection while defective thrombopoiesis is seen in the later stages.[4]

Tuberculosis presenting with thrombocytopenia is a rare phenomenon and may sometimes present as idiopathic thrombocytopenic purpura. Causes of thrombocytopenia secondary to tuberculosis are as follows.[5]

• Immune-mediated platelet destruction

• Tuberculosis-induced hemophagocytosis

• Defective platelet production due to bone marrow infiltration

• Hypersplenism, intravascular coagulation[6]

• ATT-induced thrombocytopenia.

Although most commonly seen in pulmonary tuberculosis, this complication is also observed with lymph node, abdominal, or disseminated tuberculosis. Although thrombocytopenia may occur at any time during HIV infection, the incidence and presentation generally correlates with the degree of immunosuppression. Most of the patients have mild thrombocytopenia, with platelet counts >100,000 but 6%–24% will have more severe thrombocytopenia defined as platelet count <30,000 with or without evidence of clinical bleeding.[7] Most of the patients do not have evidence of bleeding, but ecchymoses, petechiae, gingival bleeding, and epistaxis are the most common clinical features. Rarely, severe gastrointestinal bleeding and central nervous system hemorrhage have been reported.

Determining the exact cause in these patients is challenging and impedes the effective management due to the multifactorial etiology. Instituting treatment becomes even more difficult due to drug-induced thrombocytopenia. Both ATT and HAART can lead to decreased platelet counts and platelet dysfunction. Our patient was not on any medication previous to the presentation that could cause thrombocytopenia. Since the patient had a reduction in other hematological parameters too (anemia, leukopenia), direct infiltration of bone marrow by HIV, or mycobacterium tuberculosis seems to be the reason for the presentation. Improvement after starting chemotherapy further strengthens the above fact.

Treatment is generally started when there are <30 000 platelets or <50 000 if the patient is on warfarin or a hemophiliac.[8] Institution of correct treatment in these patients depends on determining the exact cause. Spontaneous remission is seen in approximately 18% of patients.[2] Most patients recover over a period when appropriate ATT or HAART is started. Other treatment modalities such as corticosteroids, intravenous IgG, splenectomy, anti-D therapy, dapsone, interferon, and vincristine are used in nonresponsive patients. ATT-induced thrombocytopenia[9] in itself is a common adverse reaction, and careful monitoring is warranted when such patients are started on ATT.

Conclusion

Thrombocytopenia is a complication associated with both HIV and tuberculosis and hence determining the cause and deciding the appropriate treatment is challenging. Decision about whom and when to treat has to be taken cautiously, and treatment has to be individualized. One must keep in mind that thrombocytopenia correlates with a poorer prognosis, especially in HIV patients. In the absence of significant bleeding complications, patients may be maintained even with low platelet counts. While several reports on HIV-related thrombocytopenia and tuberculosis-associated thrombocytopenia have been documented in the world and Indian literature, there are very few reports citing this abnormality in HIV patients with TB.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.