translation agency

Gay Men's Health Crisis
A More Practical Therapy for Low Platelets
Gabriel Torres, M.D.
January 1, 1996
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- negative mothers.

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 Options 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 edema.1 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 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; (abstract).