Key Points• The baseline characteristics of multirefractory ITP differed from "typical" ITP, outcome was severe, and was associated with high morbidity and mortality.• Combining immunosuppressant therapy with a thrombopoietinreceptor agonist may be a relevant option for these patients.Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31-17.86; P 5 .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P 5 .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n 5 2; sepsis n 5 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease. (Blood. 2016;128(12):1625-1630
SummaryIn women with pre-existing immune thrombocytopenic purpura (ITP), the effect of pregnancy on the course of the disease is poorly known. We performed a dual-centre retrospective cohort study of 118 pregnancies in 82 women with primary ITP. In early pregnancy, the platelet count was <100 9 10 9 /l in 35Á6% of pregnancies. During pregnancy the median platelet count nadir was 66 9 10 9 /l (25th-75th percentile: 42-117), with platelet count <30 9 10 9 /l for 26 pregnancies (22%). In 49% of pregnancies, a significant decrease of the platelet count required treatment at least transiently in preparation for delivery. At the time of delivery, the median platelet count was 110 9 10 9 /l (77-155). Compared to before pregnancy, at 3 months post-partum, only 11% of pregnancies [95% confidence interval (95% CI): 6Á8-20Á2] showed disease worsening. Previous splenectomy was the only factor significantly associated with ITP worsening after pregnancy (53Á9% vs. 10Á3%, P < 0Á001). For 8Á3% of the pregnancies (95% CI: 3Á8-15Á1), neonatal thrombocytopenia required treatment, especially in case of previous maternal splenectomy (adjusted odds ratio 16Á7, 95% CI: 2Á61-106). The overall risk of exacerbation of ITP and severe thrombocytopenia during pregnancy is acceptable.
Background
Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti‐PP1Pk or anti‐P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti‐P and a history of recurrent miscarriages.
Case Report
This P2k (GLOB:‐1; P1PK:‐1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non‐reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti‐P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti‐P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required.
Discussion and Review of the Literature
The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1k (GLOB:‐1; P1PK:1,3), P2k (GLOB:‐1; P1PK:‐1,3), or Tj(a‐)/p (GLOB:‐1; P1PK:‐1,‐3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported.
Conclusion
Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti‐PP1Pk or anti‐P fetomaternal incompatibilities.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.