CASE REPORT Haemorrhagic transformation of cerebral infarction in an AIDS patient – thrombophaelia screen essential! K Yoganathan MBBS FRCP* and A Benton FRCP FRCPath† *Department of Genitourinary Medicine; †Department of Haematology, ABM University NHS Trust, Singleton Hospital, Sketty, Swansea SA2 8QA, UK Summary: Patients with advanced HIV disease with low CD4 count are more prone to thrombo-embolism and various predisposing factors have been identified. These include the presence of anticardiolipin antibodies and the lupus anticoagulant, deficiencies of proteins C and S, heparin co-factor II and antithrombin. Increased levels of Von Willebrand factor and d-dimers have also been linked with thrombo-embolism, as has the presence of concurrent infections and malignancies. We report a case of an AIDS patient who presented with acute hemiparesis. He was severely immunosuppressed. Computed tomography of the head confirmed cerebral infarction with haemorrhagic transformation. He had no known risk factors apart from being severely immunocompromised and had high anticardiolipin antibodies and low free protein S. Keywords: HIV, AIDS, cerebral infarction, haemorrhagic transformation, thrombophaelia screen INTRODUCTION Patients with advanced HIV disease with low CD4 count are more prone to thrombo-embolism and various predisposing factors have been identified. These include the presence of anticardiolipin antibodies and the lupus anticoagulant, deficiencies of proteins C and S, heparin co-factor II and antithrombin.1 Increased levels of Von Willebrand factor and d-dimers have also been linked with thrombo-embolism, as has the presence of concurrent infections and malignancies.2 We report a case of an AIDS patient who presented with acute hemiparesis. He was severely immunosuppressed. Computed tomography (CT) of the head confirmed cerebral infarction with haemorrhagic transformation. He had no known risk factors apart from being severely immunocompromised and had high anticardiolipin antibodies and low free protein S. CASE REPORT A 31-year-old homosexual Caucasian man was diagnosed HIV infection in 1995. In 1996, he was treated with zidovudine and didanosine (DDI). In 1997, triple therapy with stavudine, lamivudine and ritonavir was commenced. In 1999, he developed oesophageal candidiasis. At this time his HIV RNA level (VL) was 845,000 copies/mL. Following genotype testing, therapy was changed to stavudine, DDI, amprenavir and nelfinavir. In February 2000, he developed painful peripheral neuropathy and stavudine was replaced with lamivudine. In July 2000, he developed severe giant molluscum contagiosum of the face. His VL level was 1.7 million copies/mL and CD4 count was 10 cells/mm3. Salvage therapy was introduced with stavudine, DDI, hydroxyurea, efavirenz and lopinavir/ritonavir. By October 2000, his VL had fallen to 160,054 copies/mL and the CD4 count was 24. In December 2000, his VL rebounded to 844,000 copies/mL, efavirenz was stopped, and tenofovir introduced. Correspondence to: Dr K Yoganathan Email: kathir.yoganathan@swansea-tr.wales.nhs.uk In 2001 he was admitted with acute right hemiparesis. He had no headache, visual disturbances or speech impediment. Examination revealed that he was in sinus rhythm and there was no evidence of murmurs or carotid bruit. His blood pressure was normal. CT head confirmed small infarction in the left insular region (Figure 1). He was commenced on clopidogrel but he collapsed at home four days later. Examination now revealed dense right hemiplegia. A repeat CT head showed a large haemorrhage in the left tempero parietal region with no mass effect (Figure 2). Echocardiogram and electrocardiogram were normal. Clopidogrel was stopped. Two weeks later, low-dose aspirin was commenced. An magnetic resonance imaging scan with contrast did not reveal any aneurysms (Figure 3). A thrombophaelia screen showed that total protein S was 55.0% (55.0–125.0), free protein S was low at 14.0% (65.0–155.0), activated partial thromboplastin time – 34.4 (22– 32), KCT test ratio 0.55 (0–1.2), DR VV test ratio 1.08 (0.9–1.1); immunoglobulin G (IgG) cardiolipin antibodies 10.4 GPL (G[Ig]PhosphoLipid) u/mL (0–10), IgM cardiolipin antibodies were raised at 14.7 MPL (m[IgM]PhosphoLipid) u/mL (0–7.0). Full blood count was normal with platelets of 277. Four months later, repeat thrombophaelia screen was normal. In 2003 he developed cytomegalovirus retinitis and died in 2005. DISCUSSION Increased incidence of thrombo-embolism such as deep vein thrombosis, pulmonary embolism, superior sagittal sinus thrombosis3 and bilateral central vein occlusions4 have been reported in HIV-positive patients especially in those with advanced stage disease and low CD4 counts. Risk factors for thrombo-embolism include surgery, pregnancy, trauma, stasis, concurrent infections and malignancies. Our patient had no known risk factors. Investigations showed that he had persistently low CD4. IgM cardiolipin antibodies were raised and free protein S was low. The presence of anticardiolipin antibodies is associated with arterial and venous thrombosis whereas protein S deficiency is mostly linked with venous thrombosis. Our patient had high DOI: 10.1258/ijsa.2009.008440. International Journal of STD & AIDS 2009; 20: 801 –802 Downloaded from std.sagepub.com at University of Manitoba Libraries on June 21, 2015 802 International Journal of STD & AIDS Volume 20 November 2009 ................................................................................................................................................ Figure 1 CT head (arrow) shows infarction in the insular region anticardiolipin antibodies, hence arterial thrombosis leading to cerebral infarction. Protein S deficiency has been reported up to 65% of HIV-positive patients, where it correlates well with the degree of immunodeficiency and associates with increased risk of thrombosis.5,6 Both autoantibodies to ionic phospholipids bound to phospholipids binding protein and increase prevalence of lupus anticoagulants have been described in HIV-positive patients.7 Transient ischaemic attacks, mild thrombotic stroke, avascular necrosis of bones and skin necrosis have been reported with anticardiolipin antibodies in HIV-positive patients.8 Induction of anticardiolipn antibodies have been linked to syphilis, Pneumocystis jirovecii and hepatitis C infection in HIV-positive patients. Our patient did not have any of these infections. Figure 3 A contrast magnetic resonance imaging scan shows normal cerebral arteries, particularly in the middle cerebral artery Risk factors for haemorrhagic transformation of ischaemic stroke in non-HIV patients include hypertension, concomitant use of two or more antiplatelet or antithrombotic therapies, major early infarct signs on pretreatment CT including cerebral oedema and mass effect and severe neurological defect.9 None of these were present in our patient for haemorrhagic transformation. Our patient initially presented with mild thrombotic stroke and subsequently developed haemorrhagic stroke. The administration of anti-platelet agent, clopedogrel, may have played a role and this was stopped after the evidence of cerebral haemorrhage. Most importantly, physicians should be aware of this complication of thrombo-embolism in patients with an advanced HIV disease and low CD4 counts although it is uncommon. This is particularly important when there are no known predisposing factors associated with thrombosis and a thrombophaelia screen is recommended. ACKNOWLEDGEMENT The authors would like to thank Dr A Blackwell for her assistance with the manuscript. REFERENCES Figure 2 Shows a large intra-cerebral haemorrhage in the left tempero parietal with no evidence of midline shift 1 Saif WM, Greenberg B. HIV and thrombosis: a review. AIDS Patient Care STD 2001;15:15 –23 2 Thaler P, Lechner K. AT 111 defiency and thromboembolism. Clin Haematol 1981;10:369– 90 3 Doberson MJ, Kleinschmidt-DeMasters BK. Superior sagittal sinus thrombosis in a patient with acquired immunodeficiency syndrome. Arch Pathol Lab Med 1994;118:844– 6 4 Friedman SM, Margo CE. Bilateral central retinal vein occlusions in a patient with acquired immunodeficiency syndrome. Arch Ophthalmol 1995;113:1184–8 5 Bissuel F, Berruyer M, Causse X, et al. 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