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Case Reports

HIV Infection and Thromboembolism

H Basavanagowdappa*, M Suresh Babu**, Subrahmanyam Karuturi***

*Prof. of Medicine and Principal, **Associate Prof. of Medicine, ***Postgraduate in Medicine, JSS Medical College, Mysore
Received: 29.09.2009; Revised: 31.12.2009; Accepted: 31.12.2009


Abstract

An increased incidence of venous thromboembolic disorder has been described in the setting of underlying HIV infection. Various abnormalities leading to hypercoagulable state have been reported in HIV patients with thrombotic disease. We hereby report a HIV patient with venous thromboembolism who had normal CD4 count with decreased protein C and protein S and increased serum homocysteine levels.

Introduction

Several cases of venous thrombosis with an increased incidence of venous thromboembolic disease have been described in the setting of underlying HIV infection. This incidence was lower for individuals with asymptomatic HIV infection (1.3 per 1000 person years) than for person with clinical AIDS (6.2 per 1000 person years).1 Various abnormalities leading to hypercoagulable state have been reported in HIV patients who have thrombotic disease.2 We hereby report a case of HIV with venous thromboembolism who had a normal CD4 cell count with hypercoagulable state secondary to protein C, protein S deficiency with hyperhomocysteinemia.

Case Report

A male patient aged 27 years who was a lorry driver by occupation presented to us with chief complaints of progressive breathlessness, swelling of lower limbs and distension of abdomen of 15 days duration. There was no history of PND or orthopnea or fever. Patient was not a known diabetic, hypertensive or rheumatic heart disease. There was no history of tuberculosis or HIV infection. There was no history of intake of drugs for any significant illness. Patient had a high risk sexual behavior.

On general physical examination, patient was dyspneic, central cyanosis was present with bilateral pitting pedal oedema with left more than right. There was no local rise of temperature or tenderness. There was tachycardia with tachypnea. Blood pressure was normal. On cardiovascular system examination, JVP was elevated with prominent v waves. There was left parasternal heave with apical impulse in left 5th intercostal space 1 cm lateral to mid clavicular line. There was loud P2 with grade 3/6 ejection systolic murmur which increased on inspiration in tricuspid area. RVS3 was present. Respiratory examination showed central trachea. There was decreased movements, stony dull note on percussion with decreased breath sounds over right infrascapular and infraaxillary regions suggestive of right sided pleural effusion. Per abdominal examination revealed tender hepatomegaly. Central nervous system examination was within normal limits.

Investigations revealed – Hemoglobin – 13.2gm%, TC – 6,700 cells/cumm, DC – N – 50%, L- 47%, E-02%, ESR – 40 mm/hr, Platelet count – 2.34 lakh/cumm. Blood Sugar, Blood Urea, Serum Creatinine, Serum Electrolytes were within normal limits. ECG showed RBBB pattern (Fig. 1). Sputum for AFB was negative. Chest X-ray showed features of right sided pleural effusion (Fig. 2). Pleural fluid analysis revealed features of exudate. Transthoracic 2D Echo revealed grossly dilated RA, RV, moderate to severe TR, dilated MPA, thrombus in left pulmonary artery (Fig. 3), intracardiac clot in right ventricle (Fig. 4), mild PR, mild pericardial effusion with normal left ventricular systolic function. Ultrasound abdomen showed right sided pleural effusion with minimal ascites, congested and enlarged liver. Paraaortic area was normal. Venous Doppler of left lower limb showed a large thrombus measuring 3.9 cm in the left common femoral vein (Fig. 4). External iliac veins appeared normal. There was no evidence of thrombus in right lower limb. Anti cardiolipin antibodies were negative. Serum homocysteine was 20.03 micro mol/L (Normal

range – 5.9 -16.0). Protein C antigen – 48 % (Normal 72-160%). Protein S antigen– 45 % (Normal 60-150%). CD4 count was 454 cells/mcl (Normal 326-763).

A final diagnosis of HIV infection with deep vein thrombosis and intracardiac thrombus in right ventricle with Pulmonary Thromboembolism with Severe Pulmonary Hypertension and Right Ventricular Failure associated with Tubercular Pleural Effusion was made. He was treated with anticoagulants and antitubercular drugs. Patient had symptomatic improvement during follow up.

Discussion

HIV infection has been recognized as a prothrombotic

condition with the first isolated case reports of association between venous thromboembolism (VTE) and HIV infection starting to appear in the late 1980's. This association has now been conclusively proven by a large number of studies, the first significant study by Hassel et al3 in 1994 reporting an incidence of deep vein thrombosis (DVT) of 18% in a group of 60 HIV positive patients. A systematic review published in 2005 found an incidence ranging from 0.19% to 18%.4 This incidence is well in excess of what one would expect in a non infected population, where the average risk of developing DVT is reported to be approximately 5/10,000. In a Multistate Adult and Adolescent spectrum of HIV Disease Surveillance Project sponsored by CDC, the incidence of thrombosis among 49,935 HIV infected individuals was 2.6 per 1000 person years. The incidence was lower for asymptomatic HIV infection (1.3 per 1000 person years) than for persons with clinical AIDS (6.2 per 1000 person years).

The mechanism for the occurrence of thrombosis in HIV infection appears to be multifactorial and complex. Venous abnormalities predisposing to a hypercoagulable state have been detected in HIV patients who had thrombotic diseases. Such abnormalities consistent with a hypercoagulable state include presence of anitphospholipid antibodies, lupus anticoagulant, increased levels of von Willebrand factor and d-dimer, deficiencies of protein C5, protein S, antithrombin and heparin cofactor II. Also the coexistence of other medical conditions associated with HIV infection such as malignancy, inflammatory or autoimmune disorder, use of megasterol acetate and indinavir may also predispose HIV infected patients to thrombosis. The concurrent active illness found to be associated with the risk of thrombotic disease in AIDS patients can be classified as 1) Infections including Mycobacterium avium intracellulare, cytomegalovirus retinitis, Pneumocystis carinii pneumonia, herpes simplex virus, mycobacterium tuberculosis and toxoplasmosis 2) Neoplasms including Kaposi's sarcoma and lymphoma 3) Autoimmune disorders including autoimmune hemolytic anemia secondary to HIV infection. HIV infection is known to result in increased levels of proinflammatory cytokines such as tumor necrosis factor TNF-alpha, IL-1 and IL-6 which can contribute to the development of a procoagulant state by increased levels of factor VIII and decreased levels of protein S. These cytokines have been shown to down regulate the expression of numerous proteins necessary for fibrinolysis. These abnormalities correlate with the severity of HIV associated immunosuppression as measured by CD4 cell counts6 and with the presence of concurrent infectious or neoplastic diseases. The significant features found in this HIV patient with venous thromboembolism were a normal CD4 count with deficiencies in protein C, protein S and hyperhomocysteinemia with presence of tuberculosis.

To conclude, although the incidence of venous thromboembolic events is clearly not as common as other hematologic disorders, an increase in such events is expected in the setting of HIV infection and clinicians should be alert and aware of this possibility.
Acknowledgment

We acknowledge the help of staff and management of JSS Medical College and Hospital during the preparation of this article.

References

  1. Sullivan PS, Dworkin MS, Jones JL, et al: Epidemiology of thrombosis in HIV-infected individuals. AIDS 2000;14:321. 
  2. Becker DM, Saunders TJ, Wispelwey B, Schain DC: Case report: Venous thromboembolism in AIDS. Am J Med Sci 1992;303:395.
  3. Hassell KL, Kressin DC, Neumann A, et al. Correlation of antiphospholipid antibodies and protein S deficiency with thrombosis in HIV-infected men. Blood Coagul Fibrinolysis 1994;5:455-462.
  4. Klein SK, Slim EJ, de Kruif MD, et al. Is chronic HIV infection associated with venous thrombotic disease? A systemic review. Neth J Med 2005;63:129-136.
  5. Erbe M, Rickerts V, Bauersachs RM, et al: Acquired protein C and protein S deficiency in HIV-infected patients. Clin Appl Thromb Hemost 2003;9:325. 
  6. Saif MW, Bona R, Greenberg B. AIDS and thrombosis: Retrospective study of 131 HIV-infected patients. AIDS Patient Care STDS 2001;15:311–320.
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