Disseminated intravascular coagulation as a manifestation of abacavir hypersensitivity reaction

Abacavir is a nucleoside analogue reverse transcriptase inhibitor that can easily be incorporated into multidrug regimens currently used in the management of HIV disease. An advantage of abacavir is its convenient dosing (one 300 mg tablet twice a day) with no food or water restriction or requirements. The most serious adverse event is a hypersensitivity reaction that occurs in 3% of patients receiving abacavir [^1,2]. The reaction is characterized by fever, skin rash, fatigue, and gastrointestinal symptoms, and can occasionally be life threatening [³]. The reaction occurs within the first 6 weeks of taking the drug, with the peak being around 10 days.

We describe a patient in whom disseminated intravascular coagulation (DIC) developed within 6 days after starting abacavir for the treatment of HIV infection. This 36-year-old man had been an intravenous drug user in 1987. He was found to be seropositive for HIV and hepatitis C virus (HCV; serotype 1) in October 2000. He was then hospitalized for a Pneumocystis carinii pneumonia. Apart from trimethoprim-sulfamethoxazole treatment with an antiretroviral treatment (ART) with zidovudine, lamivudine, ritonavir (400 mg twice a day) and indinavir (400 mg twice a day) was instituted. On 19 April 2001, ART was stopped because of liver test abnormalities. The laboratory values are shown in Table 1. He had anti-hepatitis B core IgG antibodies but was negative for hepatitis B surface antigen and hepatitis A virus IgM. Ultrasonography of the abdomen was normal. A biopsy specimen of the liver showed a moderate hepatic inflammation and a moderate fibrosis without cirrhosis. The metavir activity score was A1F2.

Table 1

After ART was stopped, liver tests improved, suggesting that protease inhibitors played a greater role than HCV infection in the occurrence of hepatitis. On 6 June 2001, treatment with abacavir, zidovudine and lamivudine (Trizivir) was instituted. On 14 June, the patient was hospitalized because of fever, chills, headaches, myalgia and a sudden hypotension with a blood pressure of 80/50 mmHg. Hypotension did not last for more than 1 h. The physical examination revealed enlarged cervical lymph nodes and oral candidiasis. The main biological disturbances were DIC, acute renal failure and liver test abnormalities (Table 1). Blood and urine cultures remained negative, there was no evidence of opportunistic infection, or haemolytic syndrome. He had IgG antibodies for Epstein-Barr virus, mumps virus, parvovirus B19. Mycoplasma pneumoniae- polymerase chain reaction on pharyngeal swab was negative. Cytomegalovirus pp65 and Cryptococcus neoformans antigenaemia were negative. The lymphocytic CD4 cell count was 37 cells/mm³ (7%). The chest X-ray was normal. The antiretroviral regimen was stopped on 14 June and the patient was treated with antithrombin III and fluconazole for candidiasis. The patient's clinical condition improved and he was discharged on 26 June.

Our patient was very insistent on trying the same treatment again because of its convenience. Because DIC had never been described as a manifestation of abacavir hypersensitivity reaction, the treatment was reinstituted at hospital on 10 July. Two hours after the first dose, the patient presented with fever, chills, vomiting, diarrhoea, skin rash, enlarged cervical lymph nodes and severe hypotension (lowest values 50/30 mmHg). Laboratory abnormalities were still a DIC, renal failure and abnormal liver tests (Table 1). During the following 72 h, the patient was treated with antithrombin III and vasoactive drugs. He was stabilized with difficulty, but recovered without sequelae. He was discharged on 16 July and remained well at clinical follow-up at 6 months.

The causal role of abacavir is obvious because zidovudine and lamivudine had been taken for the past 6 months without clinical manifestations, and abacavir was the only new drug. It seems that hypotension did not explain DIC because the first episode wa was of very short duration. There was no sepsis or any other clinical manifestations that could explain DIC. The mechanisms of abacavir hypersensitivity reaction are still unknown, and the impact of abacavir upon the haemostasis system has not been described. To our knowledge, abacavir hypersensitivity presenting with DIC has never been reported. This case report strongly suggests that abacavir hypersensitivity reaction by itself may trigger the development of DIC. Physicians should be aware of such haemostatic disorders, and we suggest that haemostatic parameters should be monitored in patients with suspected abacavir hypersensitivity reaction.

Sylvie Dargère

Renaud Verdon

Karine Bouhier

Claude Bazin