Abstract

Background Thrombotic Thrombocytopenic Purpura (TTP) is now being seen with increasing frequency in association with HIV infection. Successful treatment depends on early institution of plasma infusion or plasmapheresis and it is often necessary to make the diagnosis in the presence of a microangiopathic haemolytic anaemia (MIAHA) and thrombocytopenia alone before the full diagnostic pentad of features has emerged. This requires exclusion of other possible causes for the clinical picture including Disseminated Intravascular Coagulopathy (DIC). The absence of abnormalities on a coagulation (DIC) screen is therefore often quoted as an important diagnostic criterion. However, although other coagulation parameters appear normal, we have frequently observed extremely high D-Dimer levels in patients with HIV related TTP. This study was done to analyze the results of coagulation screening in patients with HIV related TTP and to compare these with the findings in HIV negative patients with TTP. Materials and Methods The HIV status and results of DIC screens done on consecutive patients diagnosed with TTP at the Johannesburg Hospital between August 2002 and January 2005 were reviewed. Patients were identified from records of haematology consults received during this period. The diagnosis of TTP required at least the presence of MIAHA and thrombocytopaenia in the absence of other possible causes. Laboratory data was retrieved from the hospital computer system. HIV status was confirmed on ELISA testing

Results Fifteen patients with HIV related TTP and 3 patients with Idiopathic TTP were identified. Two patients with pregnancy related TTP who suffered spontaneous abortions prior to assessment were excluded as alterations in coagulation parameters in these patients were not solely dependent on the TTP process. The median haemoglobin and platelet levels at diagnosis were 5.4g/dl and 11x10^9/l respectively for the patients with HIV related TTP and 8.0g/dl and 19X10^9/l respectively for the patients with idiopathic TTP. Median INR, PTT and Antithrombin levels were normal and not significantly different between the 2 groups (INR 1.14 vs1.12, PTT 29.9 vs31.5 secs, Antithrombin 103 vs12 IU). However the median D-Dimer level was significantly higher in the HIV related TTP group (3.66 mg/l, range 0.95–6.95 vs.0.28mg/l, range 0.22–0.3. p=0.0024)

Discussion This study confirms our clinical impression that extremely high D-Dimer levels, in the absence of any other abnormalities in coagulation parameters, appear to be a consistent feature of HIV related TTP. In our experience this finding is often helpful in suggesting the diagnosis. The D-Dimer levels appear to be significantly higher than those in patients with idiopathic TTP although the small numbers of HIV negative patients in this study limits the reliability of the comparison and few reported case series give sufficiently detailed data to confirm this finding. It is possible that the very high D-Dimer levels noted in HIV positive patients reflect differences in the pathogenesis of TTP in HIV infection. Endothelial damage with loss of its antithrombotic properties may result in both localized coagulation activation (as evidenced by raised D-Dimer levels) and release of stored Von Willebrand Factor. The consequent relative deficiency of Von Willebrand Cleaving Protease could then result in accumulation of high molecular weight multimers and platelet activation with clinical outcomes similar to that seen in “classical” TTP where an absolute deficiency in the protease (either congenital or acquired due to the presence of antibodies) is implicated.

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