GMHC Treatment Issues 1996 Jan 1; 10(1): 6
Immune thrombocytopenic purpura (ITP) is a relatively
frequent condition in people with HIV infection. Although
most common early in disease, it can occur at any stage of
disease. "Thrombocytopenia" refers to an abnormally low
platelet count, platelets being the blood cell fragments
involved in the clotting process. Low platelet counts are
associated with easy bruising and spontaneous bleeding, which
can be life threatening especially if the platelet count
drops below 20,000 per cubic millimeter of blood.
Treatment of ITP has been limited in the past by short
duration of response, high cost and sometimes serious side
effects of the available therapies. But a therapy approved
last March by the Food and Drug Administration promises to
improve the management of ITP. This new treatment (brand
name: WinRho) utilizes the therapy that protects against the
classic illness that occurs in Rh-positive babies born to Rh-
ITP and HIV Infection
Platelets coated with antibodies are cleared from the body,
mostly by macrophages residing in the spleen and liver. This
phenomenon is seen as the major factor behind ITP during HIV
infection, although the source of the antibodies bound to the
platelets is open to interpretation. In an individual with
HIV, platelets may have particular surface antigens that
become the targets of antiplatelet antibodies that make them
targets for destruction. Platelets also sponge up
antibody/antigen complexes as well as any free antibody
floating in the blood, and both of these are present to a
high degree during HIV infection.
Other factors in thrombocytopenia during HIV infection
include reduced bone marrow production probably due to direct
HIV infection of the megakaryocyte, the precursor stem cell
of the platelet. These cells have CD4 receptors that allow
HIV to adhere to the cells and alter their function. Other
factors that may contribute to decreased platelet production
include the low levels of interleukin-3 and interleukin-6,
which serve as growth factors for megakaryocytes.
Treatment modalities for HIV-related thrombocytopenia include
AZT, corticosteroids, immuno-globulin therapy and splenectomy
(surgical removal of the spleen).
AZT has been considered the most effective therapy, with 30
to 90 percent of patients responding within twelve weeks of
initiating the drug.1 ddI has also been tried but is much
less effective. The newer antiretroviral agents have not been
formally studied for this purpose, although theoretically
they should provide a similar effect as AZT, by interfering
with HIV infection of the megakaryocyte.
Corticosteroids can elevate platelet count in 40 to 80
percent of patients yet result in long-term remission in only
ten to twenty percent of patients. They are associated with
intolerable side effects in many people, including further
immune suppression, reactivation of opportunistic infections
such as candidiasis, herpes simplex and tuberculosis and
increases in blood glucose, blood pressure and peripheral
Splenectomy offers the most durable response but has some
surgical risks and may increase the risk of infections with
such encapsulated bacteria as pneumococcus, haemophilus
influenzae, which are often effectively removed by the
spleen. Patients who are to under splenectomy should be
vaccinated against these two bacteria prior to surgery.
Other similar treatment modalities which have been partially
successful include low dose splenic irradiation. Small
studies have shown a 70 percent acute response rate and a
durable response rate of 40 percent.2 This procedure requires
total doses of radiation of approximately 900 to 1,000
centigrays (centijoules per kilogram of body weight)
administered over one month, which allows for some degree of
splenic function to be preserved.
Finally, immunoglobulin (transfused antibody, also known as
Ig or gammaglobulin) therapy is the quickest therapeutic
approach and is used in cases of very severe thrombocytopenia
and prior to surgery to rapidly lower the risk of bleeding.
Immunoglobulins saturate the receptors on the platelet-
trapping macrophages in the spleen, thus sparing the
platelets from destruction.
The duration of response is only about one to three weeks and
sustained remissions from a single course of treatment occur
in less than ten percent of patients. The cost of
immunoglobulin therapy is about $1,500 to $2,000 per
treatment, which makes long-term therapy prohibitive.
WinRho, also called anti-D antibody therapy, consists of
concentrated antibodies that bind to the Rh antigen on red
blood cells. WinRho, like broader immuno-globulin therapy, is
thought to act by overloading the reticuloendothelial system
by increasing the number of antibody-coated cells to
eliminate. WinRho will lead to some reduction in the number
of red blood cells, but not enough to cause significant
anemia. The treatment will not work in patients who are Rh-
negative or who have had their spleen removed.
In one study by Bussell and others,3 43 Rh-positive patients
with ITP were treated with WinRho at a dose of 10 mg/kg of
body weight followed by daily doses of 20 mg/kg until either
their platelet count increased to a minimum of 20 to 30,000
per mm3 or hemoglobin levels decreased greater than 2 gm/dl
of blood, indicating the onset of anemia. The mean platelet
increase was 95,000 per mm3, with children having better
responses than adults.
In the largest study to date, 267 patients treated at New
York Hospital/Cornell University between 1987 and 1994, had
mean platelet increases of 76,000 cells. Study participants
with HIV had a poorer response (a mean increase of 49,000
platelets per mm3) than HIV-negative ones.4 Again, younger
patients (less than eighteen years of age) had a better
response than older ones. Changing the dose of WinRho did not
alter the response rate or the decrease in hemoglobin levels,
which were on average 0.8 gm/dl. The HIV-positive patients
had a lower decrease in hemoglobin than the HIV-negative
patients. Concomitant use of AZT affected neither the
platelet response nor the rate of red blood cell clearance.
CD4 cell counts were not adversely affected by the WinRho
treatment, nor was there any other evidence of acceleration
of HIV disease progression.
1 Stricker RB. Hematology-Oncology Clinics of North
America. Apr 1991; 5(2):249-65.
2 Calverley DC, Jones GW, Kelton JG. Annals of
Internal Medicine. Jun 5, 1992; 116(12 pt1):977-81.
3 Bussel JB et al. Blood. May 1, 1991; 77(5):1884-93.
4 Scaradavou A et al. American Society of Hematology
Thirty- Seventh Annual meeting, December 1-5, 1995;