© JAPI • VOL. 53   MAY 2005 www.japi.org 489
Case Report
Thrombotic Thrombocytopenic Purpura Associated
with Human Immunodeficiency Virus Infection
C Geethesh+, S Mukherjee*, A Chakroborty #, R Ray**, Arghya Majumdar ***,
SK Todi****, S Mukherjee++
Abstract
Thrombotic thrombocytopenic purpura (TTP) belongs to the group of diseases called Thrombotic
microangiopathies (TMA). While several triggering conditions are known, often none is apparent in the
individual case.
We report a patient presenting with TTP that was associated with a Human Immunodeficiency Virus (HIV)
infection, with its consequent diagnostic, therapeutic and prognostic implications. Further, our case had
individual clinical features that were of interest within the TTP-HIV subgroup. ©
CASE REPORT
A 39-year-old male engineer, a smoker, presented with
paraesthesia of the left side of body and slurring of
speech.
Two weeks prior to this, the patient had developed
gradual onset of numbness and tingling of the right
lower limb progressing to the right half of body including
face. He also had slurred speech, swallowing difficulty
and occipital headache. He did not complain of dimness
or blurring of vision, convulsions or vomiting.
Neurological consultation then had revealed an extensor
right plantar reflex, finger-nose incoordination and a
positive Romberg’s sign. Cranial nerves were normal.
This episode had resolved spontaneously over a week.
The patient had been suffering from irregular fever with
cough and perceptible weight loss for some months prior
to the present episode.
On initial examination in the hospital, the patient
was found to be alert and oriented. Neurological
examination was unremarkable barring bilateral
horizontal nystagmus. Computed tomography (CT) of
the brain on admission showed no abnormality. Five
days after admission, the patient had a dizzy spell in
the ward followed by a confusional state. Repeat CT
and Magnetic Resonance Imaging (MRI) scans of the
brain were normal.
Baseline investigations revealed marked anaemia (Hb
6 gm/dl), with hypochromia, anisocytosis and
schistocytes visible on the peripheral blood smear. His
reticulocyte count was 5%, serum haptoglobin level was
decreased (5.83 mg/dl) while lactate dehydrogenase
level was significantly elevated (912 U/L). He had
unconjugated hyperbilirubinemia. Coombs tests were
+Registrar, Critical Care; *Consultant Neurologist; **Consultant
Physician; ***Consultant Nephrologist; ****HOD Critical Care;
++Consultant Physician; AMRI Hospitals, Kolkata. #Specialist
in Infectious Diseases, Calcutta Medical Research Institute,
Kolkata.
Received : 12.10.2004; Accepted : 5.1.2005
INTRODUCTION
Thombotic Thrombocytopenic Purpura belongs to the
and is characterized by the classic pentad of fever,
anaemia, neurological symptoms, thrombocytopenia,
oliguria (renal impairment) and microangiopathy
(mnemonic : fantom). Triggers of TMA include infection,
drugs, collagen vascular disease, cancer and pregnancy
among  others.
TMA has also been reported to be rarely associated
with Human Immunodeficiency Virus infection. A
diagnosis of HIV in the presence of TMA and vice versa,
therefore, needs to be considered in the appropriate
clinical setting. Furthe, prognosis of TMA in HIV
infection depends on the clinical stage of the latter. In
those asymptomatic for HIV infection, it responds as
well to adequate therapy as in HIV negative patients. In
those with the Acquired Immune Deficiency Syndrome
(AIDS), the outcome is often poor.
We report a patient presenting with Thrombotic
Thrombocytopenic Purpura who was subsequently
detected to be suffering from AIDS, which is an
uncommon clinical presentation of the latter disease.
Further, our case had individual clinical features that
were of interest in the TTP-HIV subgroup.
490 www.japi.org © JAPI   VOL. 53   MAY 2005
negative. Haemoglobin electrophoresis was normal.
There was no evidence of iron, vitamin B12 or folate
deficiency. This fitted with a diagnosis of
microangiopathic haemolytic anaemia (MAHA). He also
had thrombocytopenia. Prothrombin time (PT), Activated
partial thromboplastin time (APTT) and fibrin
degradation products (FDP) were all normal excluding
a diagnosis of DIC. Serological investigations showed
absence of Anti Nuclear Factor and antibody to double
stranded DNA. Screening for Human Immunodeficiency
Virus (HIV) by Enzyme Linked ImmunoSorbent assay
was positive further confirmed by a positive Immunoblot
test for anti HIV 1 antibody. Flow cytometry showed the
absolute CD4 lymphocyte count to be 124/ mm3 (normal:
290 - 2600/mm3) satisfying the criteria for Acquired
Immune Deficiency Syndrome. Microbiological
investigations were noncontributory.
This guided us to a diagnosis of Thrombotic Micro
Angiopathy (TMA), most likely thrombotic
thrombocytopenic purpura (TTP) associated with HIV
infection. Renal function was however normal.
He was treated with 10 units of fresh frozen plasma
infusions daily and transfused with packed red cells.
Logistic constraints rendered plasmapheresis infeasible.
Highly Active Anti Retroviral Therapy (HAART) as well
as prophylaxis against Pneumocystis carinii infection
was instituted. The patient initially improved, enabling
oral feeding and transfer from intensive care to the
general ward. After a week, however, his condition
precipitously declined over a span of four days,
terminated by a fatal cardiac arrest.
DISCUSSION
The causes of cytopenias in HIV Infection or AIDS are
listed in Table 1:1
Thrombotic thrombocytopenic purpura is part of the
spectrum of thrombotic microangiopathies (TMA) and
is characterized by the classic pentad of
microangiopathic hemolytic anemia (MAHA),
thrombocytopenia, neurological disorders, noninfectious
fever, and renal impairment.2 Plasma infusion or
plasmapheresis is the recommended treatment modality
in TTP, plasmapheresis now showing better outcomes.
In idiopathic TMA, plasmapheresis with or without
prednisolone decreases the mortality rate from almost
100% to 10%.3 It is therefore suggested that the presence
of MAHA and thrombocytopenia alone without another
clinically apparent cause may prompt one to initiate
plasma exchange.2  The triggers of TMA include
infections, drugs, collagen vascular disease, cancer and
pregnancy among others; often, however, no triggering
condition is apparent. TMA is a possible complication
of HIV-1 infection.4
In 1984, Boccia et al first observed a thrombotic
microangiopathy, Haemolytic Uraemic Syndrome (HUS),
in a man with AIDS being treated with chemotherapy
for Kaposi’s Sarcoma.2 Gervasoni et al reported a
cumulative incidence of 1.4% among patients with AIDS
in the pre HAART era but could not identify a single
case of TMA in their patients with AIDS since the start of
the HAART era.4 de Man et al observed that TTP usually
seems to occur in patients with a CD4 lymphocyte count
of less than 250 cells/ mm3 and that plasma exchange is
the preferred treatment modality, resulting nevertheless
in a mortality of 22%.5 Possible triggers of TMA in HIV
infection include cytomegalovirus, malignancies and
anti neoplastic agents. HIV itself has been implicated
following the detection of viral p24 antigen in
endothelial cells.4
With regard to prognosis, patients with no previous
HIV –related symptoms have been reported to respond
as well to adequate therapy as HIV negative patients.
On the contrary, the outcome in patients with AIDS is
often poor, despite administration of treatment and is
related to the severity of the underlying disease. In their
series, Gervasoni et al reported 100% mortality for TTP
and 71 % mortality for HUS in patients with advanced
HIV infection4 echoing our patient’s fate.
There were several features of interest in this particular
case of TTP associated with HIV. Renal insufficiency to
some degree is universal and even necessitates dialysis
from the outset in 20% of such cases.6 Renal function
was normal throughout in this patient. Severe
hypertension is present in 50%.6 Our patient was
normotensive.
To conclude, Thrombotic microangiopathies may be
an uncommon presenting feature of HIV infection.
Table 1 : Causes of cytopenia in HIV infection and AIDS
Anemia Thrombocytopenia Leukopenia
Anemia of chronic HIV-associated Lymphopenia
disease immune destruction (characteristic)
Parvovirus B19 HIV-associated Neutropenia due
infection decreased to HIV- related
production decreased
production
Adverse drug Adverse drug Adverse drug
reaction reaction reaction
Thrombotic Thrombotic Antineutrophil
thrombocytopenia thrombocytopenic antibodies
purpura purpura
Hypersplenism Hypersplenism Hypersplenism
Marrow infiltration Marrow infiltration Marrow infiltration
with tumor or with tumor or with tumor or
opportunistic opportunistic opportunistic
infection infection infection
Megaloblastic
anemia
Autoimmune
hemolytic anemia
Iron-deficiency or
blood loss anemia
Preexisting or
coexisting condition
© JAPI   VOL. 53   MAY 2005 www.japi.org 491
Serological testing for HIV infection may have to be
considered in patients presenting with TMA, especially
if the patients have associated risk factors and suggestive
clinical history. Similarly, a diagnosis of TTP needs to be
considered in patients with HIV infection who present
with severe anemia and thrombocytopenia.
REFERENCES
1. Coyle TE. Management of the HIV infected patient, part II:
Hematologic complications of Human Immunodeficiency
Virus infection and the Acquired Immuno Deficiency
Syndrome. Med Clin North Am 1997;81:449-70
2. Nabhan C, Kwaan HC. Current concepts in the diagnosis
and management of thrombotic thrombocytopenic purpura.
Hematol Oncol Clin North Am 2003;17:177-99
3. Rock GA, Shumak KH, Buskard NA, et al. Comparison of
plasma exchange with plasma infusion in the treatment of
thrombotic thrombocytopenic purpura. Canadian Apheresis
Study Group N Engl J Med 1991;325:393-7.
4. Gervasoni C, Ridolfo AL, Vaccarezza Mauro,  et al.
Thrombotic Microangiopathy in patients with Acquired
Immunodeficiency Syndrome before and during the era of
introduction of Highly Active Antiretroviral therapy. Clin
Infect Dis 2002; 35:1534-40.
5. de Man AM, Smulders YM, Roozendaal KJ, Frissen PH. HIV
related thrombotic thrombocytopenic purpura: report of 2
cases and a review of the literature. Neth J Med 1997;51:103-
9.
6. Droz D, Nochy D, Noel LH,  et al. Thrombotic
Microangiopathies: Renal and Extrarenal lesions. In Grunfeld
JP, Bach JF, Kreis H (eds): Advances in Nephrology, volume
30. St Louis, Mosby, 2000, pp246-247.
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