Abstract
Summary
Though HIV infection is considered as a hypercoagulable state, but occurrence of acute pulmonary embolism (PE) is rare and usually seen in the advanced stage of the disease. PE as a presentation in a case where there is no previous history of having HIV infection is very rare; a Medline search revealed only one case reported previously. We describe two cases who presented with acute PE and were treated; they were subsequently diagnosed as having HIV infection.
INTRODUCTION
Infection with the human immunodeficiency virus (HIV) is now a major health problem worldwide and a chronic disease. 1 In recent literature, the relationship between HIV infection and cardiovascular disease has been addressed. 1 Studies have shown an increased risk of arterial and venous vascular diseases in HIV patients. 2 HIV infection has been recognized as a prothrombotic condition, proven by a large number of studies, with a reported venous thromboembolism (VTE) frequency among HIV patients ranging from 0.19% to 7.63%/year, whereas frequency of pulmonary embolism (PE) is about 0.26%. 3 HIV infection is associated with a 2–10-fold increased risk of venous thrombosis in comparison with a general population of the same age. 2 Some risk factors have stronger associations with VTE, such as low CD4 in the presence of clinical AIDS, protein S deficiency and protein C deficiency or malignancy. 2 Asymptomatic patients presenting with acute PE as a first presentation of HIV is extremely rare, with only a single case reported. 4 We present two cases who were admitted for acute PE and later found to be HIV positive.
CASE REPORT
Case 1
A 44-years-old man was admitted to our hospital for acute onset dyspnoea of five days duration. He also gave a history of significant weight loss in the last three months and had history of exposure. On examination, his oxygen saturation was 90% in room air and he had tachycardia (heart rate 120/min), tachypnoea (respiratory rate 28/min) and normal blood pressure (BP) of 110/76 mmHg. Cardiac and other system examinations did not reveal any other abnormality. Haematological parameters and coagulation profile were within normal limits (Hb 11.3 g/dL; total leukocyte count (TLC) 5800/mm3; platelet count – 254000/mm3). Chest X-ray (CXR) was normal and electrocardiogram (ECG) showed sinus tachycardia with S1Q3T3 pattern and T wave inversion in the mid-chest leads. D-dimer was positive at 1.26 mg/L (normal value – <0.6 mg/L) and cardiac troponin T assay was within normal limits. Echocardiography at admission showed dilation right atrium (RA) and right ventricle (RV) with pulmonary artery systolic pressure (PASP) of 64 mmHg. As he had acute onset dyspnoea, positive d-dimer test and electrocardiogram and echocardiographic evidences suggestive of acute PE, he was treated with an injection of streptokinase (STK) 2.5 lakh unit bolus and followed by 1 lakh unit/hour infusion. Routine serological investigation, which is performed on all admitted patients as a protocol in our hospital, showed a HIV-positive result. Computed tomography pulmonary angiogram (CTPA) after 24 hours of STK was within normal limits. Doppler venography was also within normal limits. After 24 hours, PASP had come down to only 24 mmHg and both tachycardia and tachypnoea had settled. STK was stopped after 24 hours without any complications. He was put on oral anticoagulants and referred to the HIV centre for antiretroviral therapy (ART). This patient belonged to World Health Organization (WHO) clinical stage II of HIV infection due to the presence of moderate unexplained weight loss with CD4 count was of 375/mm3.
Case 2
A 48-year-old man with diabetes mellitus and old pulmonary tuberculosis was admitted to our hospital due to having dyspnoea on exertion for 10 days along with chest pain. On examination, his oxygen saturation in room air was 92% and he had tachycardia (heart rate 124/min), tachypnoea (respiratory rate 24/min) and hypotension (BP 90/70). On cardiac system examination he had engorged neck veins. Other systems were normal. He had normal CXR and ECG showed sinus tachycardia, S1Q3T3 with features of right ventricular hypertrophy and right axis deviation. Routine haematological parameters and coagulation profile were within normal limits (Hb 15.2 g/dL; TLC 8760/mm3; platelet count 452000/mm3). Both d-dimer (2.69 mg/L) and cardiac troponin T were positive. Echocardiography at admission showed both RA and RV dilation with features of RV dysfunction and PASP of 72 mmHg. In this case CTPA was done at admission which showed thrombi in both right and left pulmonary arteries (Figure 1). Doppler venography was normal. He was also given an injection of STK for 48 hours with no complications. In this case the patient was also diagnosed as having HIV infection. The PASP had come down to 42 and 30 mmHg at 24 hours and seven days, respectively. The patient was discharged and referred to the HIV centre after starting oral anticoagulants. He was in WHO clinical stage I (asymptomatic) of HIV infection with a CD4 count of 521 cell/mm3.
Computed tomography pulmonary angiogram showed thrombi in both pulmonary arteries suggestive of acute pulmonary embolism .
So in both these cases, acute PE was the first presentation of HIV infection and HIV infection was diagnosed incidentally on routine investigation. Both patients undiagnosed before admission to our hospital.
DISCUSSION
Patients with HIV infection have an increased risk of thrombosis, with an incidence as high as 8% compared with non-HIV-infected individuals. 5 Some studies reveal up to a 43% increase in risk of developing a PE and 10% increase in DVT in an HIV-infected individual over the nine-year study period after adjusting for age. 6 The causes of thrombosis in patients with HIV infection include opportunistic infection (mainly that due to cytomegalovirus), related malignancies and receipt of medications (e.g. protease inhibitors, abacavir and megestrol acetate), and injection drug use. 5 The increased risk of DVT in HIV-infected patients could be related to increased levels of procoagulant factors with acquired haematological disorders (protein S and protein C deficiency, protein C resistance with factor V Leiden mutation, lupus anticoagulant positivity and aCL) and HIV infection itself. 6 Additionally, there is a significant correlation between thrombotic disease and a CD4+ cell count of <200 cells/mm3. 7 Endothelial cells could play an important role in the activation of the coagulation cascade during HIV infection. 5 Another triggering factor of the coagulation cascade in HIV patients could be stimulation of micro particles. 6 The increased risk of DVT during HIV infection could also be related to the impaired functioning of several important anticoagulant proteins. 5 In HIV-infected patients with thrombosis, lowered levels of antithrombin (AT) were reported. AT is the most important physiological inhibitor of activated coagulation factors (IIa, IXa, Xa, Xia and XIIa). 7 Except for one case, 4 all other reported cases were in those with advanced HIV infection where VTE is common. In our cases HIV was diagnosed incidentally after admission for acute PE and both the cases had normal coagulation profiles.
In the search for suspected pulmonary emboli, basic imaging investigations may support clinical suspicion and exclude alternative diagnoses. Chest radiographic appearances may be relatively non-specific and often confusing. CTPA is the imaging modality of first choice. 4 One of our patients had CTPA features of PE but in the other case CTPA was normal, though it was done 24 hours after receiving STK. The first case had significant weight loss but the other case did not have any features of HIV infection. Treatment of PE in cases with HIV is the same as for other patients. As both patients had features of RV dysfunction, they were treated with injections of STK. 8 We treated both with injections of STK and both patients showed improvement with this treatment. Oral anticoagulants were also started. Some ART has interactions with oral anticoagulants. 7 In our cases ART was not started and they were referred to HIV centre.
Though PE is usually seen in advanced HIV infection, in any patient presenting with acute PE even without any symptoms of HIV or acquired immunodeficiency syndrome, HIV infection should be ruled out. Treatment with fibrinolytic agents like STK should be given if there is RV dysfunction or hypotension, which is the same as for patients without HIV infection. If patients need ART then frequent monitoring is needed while they are on oral anticoagulants.
Footnotes
Acknowledgements