Thrombotic microangiopathy as first manifestation of acute human immunodeficiency virus infection: a case report and review of the literature

This case demonstrates the wide variation of clinical manifestations found in patients
with early HIV infection. The most frequent hematological findings in this condition
are changes to peripheral blood cells, although coagulation disorders may also occur.
Furthermore, the coexistence of immunological-mediated thrombocytopenia with TTP has
been reported in chronic HIV infection 5].

Thrombotic manifestations such as serious thrombosis, TTP, and TMA usually occur in
late stages of chronic HIV infection or in patients with poor adherence to ART 6]. The classic form of TTP is caused by an acquired or hereditary malfunction/deficit
of ADAMTS13, which fails to cleave the ultra-large multimers of the von-Willebrand
factor (v-WF) and produces classic thrombotic microangiopathic anemia and multiorgan
failure 7]. On the other hand, TMA associated with drugs, neoplasia, or infections has the same
features as classic TTP but other mechanisms lead to thrombosis without ADAMTS13 inhibition.
In HIV infection, multiple alterations have been described that can induce either
immune TTP triggered by dysfunctional ADAMTS13 or TMA generated by diverse conditions
such as alterations to complement proteins, endothelial injury secondary to cytokines
induced by the virus, or endothelial cell damage directly mediated by viral particles
8]. Because of these multiple pathological pathways, treatment of patients with either
TTP or TMA associated to HIV should be directed to rapidly control the viral load,
reduce the virus-induced immunosuppression, and replace the defective ADAMTS13 and
coagulation proteins by TPE.

Miller et al. showed that 12 % of patients diagnosed with TTP had concomitant HIV infection, and
they were more often found to be at advanced stages of the disease with profound immunosuppression.
In this situation, there was a clear therapeutic benefit of adding ART in addition
to TPE 9]. However, in the largest cohort of patients, the Oklahoma Thrombotic Thrombocytopenic
Purpura – Hemolytic Uremic Syndrome (TTP-HUS) register, only 1.84 % of 326 patients
with TTP had HIV infection and the authors concluded that HIV infection, similar to
other inflammatory conditions, could trigger acute episodes of TTP in susceptible
patients. Moreover, HIV-induced oncological and infectious disorders could mimic the
clinical features of TTP and must be included in the differential diagnosis 10].

Our patient’s case is remarkable in some aspects. The first and perhaps most interesting
is that his acute HIV infection debuted with severe TMA, which to the best of our
knowledge has not been previously reported. Negative anti-HIV antibodies with a very
high HIV viral load defines acute HIV infection and is characteristically associated
with extremely high viremia. Our patient emphasized that sexual risk behaviors were
recent events (1 month), and that bleeding and constitutional symptoms appeared almost
immediately upon presumed HIV exposure.

In this case, TMA was quickly controlled with TPE and prompt ART initiation. Although
TPE could have had some role in our patient’s recovery, information is not available
to support use in TMA. In this particular case, the use of TPE was an extreme action
given the severity of the patient’s symptoms. In clinical hematology practice it is
well recognized that TPE is mainly beneficial in cases where TTP coexists with an
immune inhibitor of ADAMTS13, and not in non-immune TMA forms. However, there are
several recent reports showing that TPE and other immunological therapies such as
rituximab and eculizumab may be useful in cases not necessarily associated with autoimmunity.
This effect could be associated to reposition of other coagulation regulatory proteins
or modulation of this effect could be associatedwith reposition of other coagulation
regulatory proteins or B lymphocytes modulation 11].