Human immunodeficiency virus associated thrombotic thrombocytopenic purpura – favourable outcome with plasma exchange and prompt initiation of highly active antiretroviral therapy

Abstract

Summary Thrombotic thrombocytopenic purpura (TTP) is an acute prothrombotic disorder. Human immunodeficiency virus (HIV) is an identified precipitant. This study reviewed 30 episodes of HIV‐associated TTP in 24 patients from the South‐East England Apheresis units, over the last 10 years. All patients were heterosexual Black Africans. First presentation of TTP revealed a new diagnosis of HIV in eight patients. TTP relapse occurred on six occasions (in four patients) as a result of non‐adherence to highly active antiretroviral therapy (HAART). Prompt initiation/re‐initiation of HAART in parallel with plasma exchange (PEX) ± steroid led to prompt remission. Adjunct immunomodulatory agents (e.g. Rituximab) were required in 10% of cases. Once‐daily HAART regimens are recommended, being compatible with PEX requirement, maximizing drug exposure between PEX. High viral loads (>500 000 copies/ml) require more PEX to remission. ADAMTS13 activity was reduced (<5%) as detected by collagen‐binding assay and anti‐ADAMTS13 immunoglobulin G antibodies were raised in 80%. Continued HAART‐adherence ensured a durable TTP remission with associated viral control resulting in no evidence of relapse. PEX and HAART are associated with replenishment of ADAMTS13 and viral suppression. More PEX is required in cases with higher viral loads. Continued HAART maintains remission. In a small proportion of cases, further immunomodulatory therapy may be required.

Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura

“…Indeed, HIV status often does not alter the usually favorable prognosis of TMA with severe ADAMTS13 deficiency. Such patients should benefit from the usual measures in TTP management (e.g., intensive and possibly prolonged plasma therapy with TPE, along with antiretroviral treatment) [66,68,69]. In contrast, patients with TMA in the setting of a more advanced HIV infection with AIDS-related complications usually display a poor response to plasma therapy [66,67], which places the use of prolonged TPE sessions in such patients under question.…”

Is complement a culprit in infection-induced forms of haemolytic uraemic syndrome?

“…Other aetiologies which have been postulated include development of anti-ADAMTS13 IgG antibodies (seen in Thrombotic Thrombocytopenic Purpura) (Hart et al 2011). Remission of TMA has been achieved with prompt initiation of HAART in addition to PEX (Hart et al 2011). A role for complement has not yet been proposed in HIV-associated HUS.…”

“…TMA may result from a direct interaction between HIV virions and the renal EC (Huang et al 2001). Other aetiologies which have been postulated include development of anti-ADAMTS13 IgG antibodies (seen in Thrombotic Thrombocytopenic Purpura) (Hart et al 2011). Remission of TMA has been achieved with prompt initiation of HAART in addition to PEX (Hart et al 2011).…”

Haematological complications of HIV Infection

“…HAART should be simultaneously (re-)initiated. 9 This protocol is feasible in cost-limited settings and has become the standard of care for HIVassociated TTP in SA. FFP can be commenced at a local hospital, but all TTP patients should be referred to a tertiary centre for definitive management.…”

“…HIV-associated TTP typically occurs in young African females not on HAART and with high viral loads. 9 In First World settings, the standard of care for HIV-associated TTP is plasma exchange in conjunction with steroids and HAART; however, plasmapharesis is not widely available in resource-poor settings. Our department showed that HIV-associated TTP is highly responsive to plasma infusion therapy; 10 daily fresh-frozen plasma (FFP) infusions at 30 ml/kg/day in conjunction with prednisone 1 mg/kg/day resulted in excellent response rates (95%).…”