Article

Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect.

Department of Pediatrics, New York Hospital, New York, NY.
Blood (Impact Factor: 9.78). 06/1991; 77(9):1884-93.
Source: PubMed

ABSTRACT The efficacy, toxicity, and mechanism of effect of intravenous Anti-D (Winrho) were studied in 43 Rh+ patients with immune thrombocytopenia purpura (ITP) who had not undergone splenectomy and in three already splenectomized patients. The mean platelet increase for the 43 nonsplenectomized patients was 95,000/microL (median 43,000/microL). Children had greater acute platelet responses than did adults. Human immunodeficiency virus status and duration of thrombocytopenia did not affect response. Maintenance treatment was given to patients as needed: the average interval between infusions was 24 days. The three splenectomized patients had no platelet response whatsoever. Toxicity was minimal; infusions were completed in less than 5 minutes. The generally accepted mechanism of effect of Anti-D has been Fc receptor blockade by substitution of antibody-coated red blood cells for antibody-coated platelets. Evidence is presented suggesting that the effect of IV Anti-D is not limited to Fc receptor blockade, including: (1) no correlation of parameters of hemolysis with platelet increase; (2) a 48- to 72-hour delay before platelet increase; (3) a tendency of the change in monocyte Fc receptor I expression to correlate with platelet increase; and (4) increased in vitro production of antibodies to sheep red blood cells following IV Anti-D infusion.

0 Bookmarks
 · 
34 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background In patients with immune thrombocytopenia (ITP) who are Rhesus (Rh) D positive and who have not undergone splenectomy, the platelet count can be supported by anti-D Ig therapy. The response rate to plasma-derived intravenous anti-D at a dose of 50–75 μg/kg is 70–80% with an increase in platelet count after 24–72 h and duration for more than 21 days in 50% of responders. Rozrolimupab is a mixture of 25 fully human IgG1 recombinant monoclonal anti-D antibodies produced in CHO cells using a single-batch manufacturing strategy from a polyclonal cell bank. Materials & Methods The primary objective of the phase I/II study was to evaluate safety of a single dose in adult RhD-positive non-splenectomized patients with ITP. The secondary objectives were evaluations of the efficacy and appropriate dose for pivotal study. Patients were dosed with a single rozrolimupab dose ranging from 75 to 300 μg/kg, infused intravenously over 15–20 min. ResultsRozrolimupab was well tolerated with no unexpected toxicities. The most frequent adverse events were headache, pyrexia, chills and fatigue. Serious adverse events were observed in nine patients, mainly in cohorts treated with doses of 200 μg/kg and 250 μg/kg, but only considered related to rozrolimupab in four patients: decrease in Hb (one patient), extravascular haemolysis (one patient) and transient increase of D-dimers (two patients). Hb decreased by ≥3.0 g/dl in six patients, but decrease by ≥5 g/dl was not observed. Seven patients required blood transfusions. Across all cohorts, 21 of 61 patients (34%) met the response criterion on day 7. The best response was noted in the 300 μg/kg dose cohort with response observed in eight of 13 patients (62%). Median time to response was 2 days and median duration of response was 14 days. DiscussionThe advantage of rozrolimupab over polyclonal anti-D immunoglobulin is unlimited supply, high and reproducible specificity and activity, and an improved safety profile. Conclusion In conclusion, our data suggest that rozrolimupab is safe, well tolerated and has efficacy similar to plasma-derived anti-D immunoglobulin in the treatment of primary ITP.
    ISBT Science Series 06/2013; 8(1).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmune thrombocytopenic purpura (AITP) is a common nonmalignant disease that can be complicated by life-threatening haemorrhage. The thrombocytopenia is due to antiplatelet antibodies that opsonise the platelet membrane, leading to platelet destruction by phagocytes, principally in the spleen. Acute and chronic forms are observed; spontaneous remission only occurs in the former. Treatment with high doses (2 g/kg) of intravenous immunoglobulin (IVIg) originating from the plasma of blood donors is frequently given at disease onset in severe thrombocytopenia, as it regularly induces rapid platelet recovery. The best responses are obtained when IVIg is administered over 2 days and when ‘intact’ (chemically unmodified) immunoglobulin concentrates are used. However, the effect is usually transient, severe adverse effects may occur and the cost is high, leading many physicians to reduce the dosage of IVIg and to limit its use to patients with life-threatening complications and contraindications to corticosteroids. Finally, even if repeated administration of IVIg can sometimes induce prolonged remissions, there is no proof that the treatment can cure a significant number of patients with chronic AITP. Anti-D (Rhesus) human immunoglobulin concentrates can also transiently increase the platelet count in patients with AITP. However, the platelet response is slower than with IVIg and use should be limited to selected patients in whom a transient, possibly delayed, increase in the platelet count is required, or where splenectomy is contraindicated.
    BioDrugs 02/1997; 7(2). · 2.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 5-year-old boy presents with platelet count of 2 × 10(9)/L and clinical and laboratory evidence of immune thrombocytopenia. He has epistaxis and oral mucosal bleeding. Complete blood count reveals isolated thrombocytopenia without any decline in hemoglobin and he is Rh(+). You are asked if anti-D immunoglobulin is an appropriate initial therapy for this child given the 2010 Food and Drug Administration "black-box" warning.
    Hematology 12/2013; 2013:283-5. · 1.49 Impact Factor

Full-text (2 Sources)

Download
20 Downloads
Available from
Jun 4, 2014