Clinical Study Of Recombinant Human Thrombopoietin In Management Of Primary Immune Thrombocytopenia In Pregnancy

BackgroundPrimary immune thrombocytopenia also called idiopathic thrombocytopenic purpura (ITP) is common hemorrhagic disease. It is an acquired immune mediated disorder characterized by isolated thrombocytopenia. The main pathogenesis is excessive platelet destruction and decreased platelet production mediated by humoral and cellular immunity. ITP is estimated to occur in 1 in 1000 to 1 in 10 000 pregnant women including a history of ITP before pregnancy and newly diagnosed during pregnancy. Primary treatment options for ITP in pregnancy are similar to those for other adult ITP patients. But choices are limited if the patients have no response to first-line therapy(IVIG or corticosteroids).Optimum management of ITP in pregnancy requires collaboration among the obstetrician experienced in the management of ITP, the hematologist and the neonatologist.Thrombopoietin is the main cytokine regulating platelet production and produce biological effect by combining with the specific receptor (c-Mpl) on the surface of megakaryocyte. Namely, it can regulate the maturation of megakaryocyte and promote platelet production. Studies show that serum TPO level in patients with ITP is similar to normal or increase slightly. So TPO is relatively deficiency. A series of domestic research has confirmed the efficacy and safety of recombinant human thrombopoietin (rhTPO) in management of chronic ITP. But There is no related report on rhTPO in management of pregnant women with ITP before.ObjectiveEvaluate the efficacy and safety of rhTPO in management of ITP in pregnancy.MethodsWe reported 24 pregnant women with ITP from 8 centers who had been treated with corticosteroid and/or IVIG but had no response. All the patients received rhTPO at the dose of 300U/kg, s.c. daily in 14 consecutive days. Dose would be tapered to 300U/kg every other day when platelet count rose to above 50×109/L in less than 14 days and treatment was terminated when platelet count was above 100×109/L. Withdrawal would be performed if the platelet count was still below 30×109/L after 14 days. Efficacy and safety of rhTPO was evaluated subsequently. Maintenance therapy continued for some patients responding to rhTPO. Initial dose of rhTPO was 300U/kg every other day. According to the response to rhTPO, patients would continue to receive therapy or withdraw the study. Investigators performed individualized therapy depending on the platelet count. The target of platelet count was 30～100×109/L. If two consecutive blood routine examination all showed that platelet count was below 30×109/L during maintenance therapy, administration of rhTPO would be stopped. Observe the general condition of neonate and platelet count of patients during pregnancy.ResultsThe median platelet count of 24 patients was 9.5×109/L(1-28×109/L) before treatment.23 cases completed the treatment of initial stage (14 days). Complete response was achieved in 10 cases, response in 7 cases and no response in 6 cases. The overall response rate was 73.9% and CR rate was 43.5%.The median time to response was 6 days. A history of ITP before pregnancy and the efficacy of rhTPO had no obvious correlation(p>0.05). At last,6 cases underwent maintenance therapy. 5 cases sustained in response with platelet count over 50 ×109/L until delivery. The platelet count of 1 case dropped to 21 x 109/L during maintenance therapy. After adjusting the therapy, her platelet count can keep within remission range until delivery. No adverse effects were observed during the administration of rhTPO. At last,20 cases delivered infants and 3 cases underwent induction of labor while 1 case was lost to follow-up. All the neonates had normal growth and development. Severe thrombocytopenia (<50 X 109/1) occurred in one neonate with platelet count 20 X 109/L and there was no bleeding.After administration of IVIG, the platelet count rose to normal. One of the neonates had abdominal distension, but there was no evidence to prove that it was related to rhTPO.ConclusionrhTPO is an effective, fast-onset and ideal alternative treatment for ITP in pregnancy. It has no side effects on mother and fetus. Maintenance treatment is also effective. It is a safe option for pregnant women with ITP to maintain peripheral platelet count at safe level and reduce bleeding risk during pregnancy.