most frequently observed.1Many reports are
available on the pathogenesis, prognostic
meaning and treatment of ITP.
Thrombotic thrombocytopenic purpura
(TTP) is another hematologic disorder
observed in the context of HIV infection. This
syndrome, described by Moschowitz in 1924, is
far more unusual than ITP and is characterized
by microangiopathic hemolytic anemia, throm-
bocytopenia, renal dysfunction, fluctuating
neurologic abnormalities and fever.
HIV-associated TTP was first described in
1987.2The authors also referred to a previously
reported case of hemolytic uremic syndrome (a
thrombotic microangiopathy closely related to
TTP) in an HIV-positive man.3Since then, 27
cases (25 from the USA, 2 from Canada) have
We describe, for the first time in Europe, a
case of HIV-associated TTP. In this case the
hematologic disorder represents the first clini-
cal manifestation of the HIV infection.
mong HIV-associated hematologic man-
ifestations, immune thrombocytopenia
(ITP) was the first recognized and the
A healthy 40-year-old man suddenly com-
plained of paresthesia in the right hemiface and
right upper limb, slight diplopia and visual
agnosia. On January 25, 1993 the patient was
admitted to our department: he appeared con-
fused, amnesic, with expressive and nominal
aphasia, paresthesia had regressed. The patient
was febrile (38°). A brain CAT scan proved to
be normal; initial laboratory findings showed
anemia (Hb 5.8 g/dL; Hct 16.7 L/L) and throm-
bocytopenia (Plt 24?109/L). Fluctuating neuro-
logic abnormalities were observed in the fol-
lowing hours: faltering speech and deficit of the
left facial nerve, reappearance of paresthesia in
the perioral area and left limbs, occasional state
of confusion, heaviness in the head, continued
numbness in the left limbs and, finally, tem-
Physical examination revealed subicterus,
lymphadenopathy in the left laterocervical area
and splenomegaly. An electroencephalogram
showed slight diffuse reduction in activity with
a prevalence of widespread irritative abnormal-
ities in the right temporal region. Examination
Correspondence: Dr. Virgilio Cruccu, via E. Vaina 12, 20122 Milan, Italy. Tel: international +39.2.50316023.
Received December 14, 1993; accepted April 8, 1994.
HIV-RELATED THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)
AS FIRST CLINICAL MANIFESTATION OF INFECTION
Virgilio Cruccu, Elena Parisio, Donata Pedretti, Antonio Villa, Franco Confalonieri
III° Medical Department, Fatebenefratelli-Oftalmico Hospital, Milan, Italy
Haematologica 1994; 79:277-279
A case of thrombotic thrombocytopenic purpura (TTP) in a 40-year-old bisexual man unaware
of being HIV positive is reported. The hematologic syndrome represented the first clinical mani-
festation of this viral infection. The clinical picture, characterized by severe hemolytic microan-
giopathic anemia, thrombocytopenia, fluctuating neurologic abnormalities and fever, quickly
improved after plasma exchange and corticosteroid therapy. Two blood tests showed severe
depletion of the CD4+ lymphocyte count and HIV antigenemia was positive. This case represents
a clinical epiphenomenon of HIV infection in an advanced phase. According to recent CDC crite-
ria the patient should be considered in AIDS. Antiretroviral treatment was started and after nine
months of follow-up there has been no relapse.
Key words: thrombotic thrombocytopenic purpura, HIV, AIDS
©Ferrata Storti Foundation
of the fundus oculi revealed a plane papilla with
indistinct margins, normal vessels and an unin-
Laboratory analyses on January 26 confirmed
severe anemia and thrombocytopenia, with
numerous schistocytes in peripheral smears
(30%), elevated levels of lactic dehydrogenase
(LDH 1875 U/mL) and bilirubin (prevalently
indirect: 1.78 mg/dL), an erytrocyte sedimenta-
tion rate of 120 mm/hr, reduced haptoglobin
(<38.3 mg/dL), absence of antiplatelet antibod-
ies, negative direct/indirect Coombs’, normal
level of circulating immunocomplexes, micro-
The association of microangiopathic hemolyt-
ic anemia, thrombocytopenia, neurologic fea-
tures and fever suggested a diagnosis of TTP.
We started treating the patient with fresh
plasma and a steroid (prednisone 50 mg daily)
and acetyl-salycilic acid (500 mg daily): the first
plasmapheresis procedure was programmed for
Since the patient reported having engaged in
at risk sexual behavior (homosexual activities),
on January 29 we obtained his consent to test
for HIV antibodies. The results showed the
patient was positive for both HIV antibodies
and HIV antigenemia. Skin tests for delayed
hypersensitivity (Multitest Merieux) demon-
strated severe hypoergy. Two consecutive tests
showed severe depletion of CD4+lymphocytes:
11% total lymphocytes; absolute counts of
0.101 and 0.108?109/L, respectively, and a
CD4+/CD8+ratio of 0.11. Serum ?2-microglob-
ulin was 3.6 (normal values <3) mg/L.
After the first plasmapheresis treatment
platelets rose to 42?109/L, after the second to
70?109/L and after the third to 183?109/L.
Hemoglobin and hematocrit improved, and
schistocytes gradually disappeared from
peripheral smears. Clinically, fever resolved and
the neurologic picture improved. The steroid
On February 22 the patient was discharged
on oral prednisone (37.5 mg daily) and acetyl-
salicylic acid (500 mg daily), and enrolled for
follow-up in the Day Hospital.
In the following months (March-October)
hematocrit and platelets values held steady; nei-
ther neurologic abnormalities nor fever reap-
peared, and the steroid was tapered to zero on
May 25, when the antiaggregant was discontin-
Check-ups in April and June confirmed deple-
tion of CD4+lymphocytes (respectively, 0.151
and 0.100?109/L). Antiretroviral treatment with
zidovudine (250 mg twice day) and primary
prophylaxis against Pneumocystis carini pneu-
monia was begun with trimethoprim/sulpha-
methoxazole (160/800 mg daily).
A continuous spectrum of diseases and a
wide variety of clinical features are associated
with HIV infection. A broad range of hemato-
logic disorders has also been reported: impaired
hematopoiesis, cytopenia, coagulation abnor-
malities. The pathogenesis of these disorders is
certainly multifactorial. For instance, cytopenia
may result from a direct suppressive effect of
HIV, from an opportunistic infection or tumor
infiltration in the marrow. The etiology of
thrombocytopenia in HIV patients may be due
to direct infection of megakaryocytes by the
virus, immune-mediated destruction, impaired
hematopoiesis, toxic effects from medications
and microangiopathic anemia syndromes.
While the pathogenesis of ITP is usually consid-
ered to be autoimmune, that of TTP remains an
Our report confirms that TTP can be associ-
ated with HIV infection and may constitute its
first clinical manifestation. In at least seven of
27 previously described cases, TTP has led to
detection of HIV seropositivity;2-5in some of
these TTP represented the only manifestation of
HIV infection for a long time. In three patients
TTP was preceded by ITP.4-6In at least two oth-
ers8TTP was responsible for the death of the
patients: the first was the result of a massive
glossal hemorrhage, while in the second it pro-
voked a cardiac arrest before plasmapheresis
could be performed.
The positive antigenemia, hypoergy to tests
for delayed cutaneous hypersensitivity, severe
and confirmed depletion of CD4+lymphocytes
showed that the infection in our subject was in
V. Cruccu et al.
©Ferrata Storti Foundation
an advanced phase. According to recent CDC
criteria this patient should be considered in
AIDS. Previously described cases belonged to
stages II, III and IV (ARC, AIDS) (CDC criteria
of August, 1987).
The treatment indicated for this pathology
– plasmapheresis, fresh plasma, steroids and
antiaggregants – is the same as that used in non
HIV-associated cases. Our patient responded
well, achieving total remission. Twelve months
later, we can say that there has been no relapse.
Among the 27 cases described in the litera-
ture, a relapse was reported in two: fourteen9
and twenty months,5respectively, after the first
episode of TTP. The follow-up in the above
mentioned cases is too inhomogeneous to allow
an evaluation of the prognostic meaning of
TTP in the natural history of HIV infection.
Our opinion is that, like ITP, TTP does not
influence the clinical evolution of HIV infec-
The present case and the increasing number
of reports on TTP lead us to suggest that HIV
serodiagnosis should be performed every time a
TTP is observed.
1. Landonio G, Nosari A, Spinelli F, Vigorelli R, Caggese L,
Schlacht I. HIV-related thrombocytopenia: four different
clinical subsets. Haematologica 1992; 77:398-401.
2. Jokela, J, Flynn, T, Henry, K. Thrombotic thrombocytopenic
purpura in a human immunodeficiency virus (HIV)-
seropositive homosexual man. Am J Hematol 1987; 25:341-3.
3. Boccia RV, Gelmann EP, Baker CC, Marti G, Longo DL. A
hemolytic-uremic syndrome with the acquired immunodefi-
ciency syndrome. Ann Intern Med 1984; 101:716-7.
4. Routy JP, Beaulieu R, Monte M, Saint-Louis J, Sauvageau G,
Toma E. Immunologic thrombocytopenia followed by
thrombotic thrombocytopenic purpura in two HIV-1
patients. Am J Hematol 1991; 38:327-8.
5. Thompson CE, Damon LE, Ries CA, Linker CC. Thrombotic
microangiopathies in the I980s: clinical features, response to
treatment, and the impact of the human immunodeficiency
virus epidemic. Blood 1992; 80:1890-5.
6. Manner CE, Gathe J jr, Novak I, Sawyer G, Holder P, Stool E.
Thrombotic thrombocytopenic purpura (TTP) in a man
with AIDS and prior idiopathic thrombocytopenic purpura
(ITP). Abstract presented at the IX International Conference
on AIDS, Berlin, 1993: 451.
7. Rarick MU, Espina B, Mocharnuk R, Trilling Y, Levine AM.
Thrombotic thrombocytopenic purpura in patients with
human immunodeficiency virus infection: a report of three
cases and review of literature. Am J Hematol 1992; 40:103-9.
8. Leaf AN, Laubenstein LJ, Raphael B, Hochster H, Baez L,
Karpatkin S. Thrombotic thrombocytopenic purpura associ-
ated with human immunodeficiency virus tipe 1 (HIV1) infec-
tion. Ann Intern Med 1988; 109:194-7.
9. Platanias LC, Paiusco D, Bernstein S, Murali MR. Thrombot-
ic thrombocytopenic purpura as the first clinical manifesta-
tion of human immunodeficiency virus infection. Am J Med
©Ferrata Storti Foundation