Rituximab for Prevention of Recurrent Pregnancy Related Thrombotic Thrombocytopenic Purpura in High Risk Patients with Previous Episodes of Thrombotic Thrombocytopenic Purpura during Pregnancy

Introduction

We describe the use of rituximab for the successful prophylaxis and delivery of a multiparous female with a history of pregnancy related thrombotic thrombocytopenic purpura (TTP) now presenting with a high risk of relapse during subsequent pregnancy.

Case Presentation

A 33 year-old African American female with a history of post-partum TTP diagnosed two years prior was referred to the hematology clinic for suspected recurrence of her TTP at 22 weeks gestation.

Two years ago the patient had presented with symptoms of severe headache and hypertension which began 1 week after the delivery of her 3rd child. She was referred to the emergency department where she was found to have microangiopathic hemolytic anemia with a hemoglobin of 7.6g/dL, platelets of 10k/uL and abundant schistocytes on peripheral smear. Her blood chemistry revealed renal failure with an elevated creatinine of 2.7mg/dL, LDH of 2001 IU/L. She was found to have a moderately low ADAMTS13 level of 16% (normal >66%) and an inhibitor was detected (1.0 BEU). Her ANA, HIV, hepatitis and lupus serologies were all negative. Her C3 level was 105 (normal 70-225mg/dL) and C4 was 20 mg/dL (normal 14-55 mg/dL). She was promptly initiated on plasma exchange in addition to magnesium supplementation and strict blood pressure control. She underwent 11 days of daily plasma exchange and steroids with improvement of her platelets and resolution of schistocytes on peripheral smear. Despite this, she again had rise in her parameters and rituximab was added to the regimen which she responded to with continued normalization of her hematologic parameters and clinical resolution of symptoms.

Approximately 2 years later, the patient presented again at 22 weeks gestation of her fourth pregnancy for suspected recurrence of her TTP. Blood chemistry revealed a low ADAMTS13 (<3%), anemia (Hb 10.8g/dL) and moderate thrombocytopenia (platelets 156k/uL). Her liver and renal functions were unaffected and she had no evidence of bruising or bleeding on physical exam. Serial repeat testing showed persistently low ADAMTS13 level (<3%) and worsening thrombocytopenia (platelets decreased to 113k/uL) without development of other clinical manifestation of TTP.

Prophylactic plasma exchange was offered to the patient however the patient declined due to its associated risks. She was initiated on weekly rituximab (375mg/m2) with decadron (6mg weekly) from 27th to 30th weeks of pregnancy. After 4 infusions, her platelets improved to 190k/uL along with an increase in ADAMTS13 level to 62%. A healthy male child weighing 3.2 kilograms was delivered by C-section at 36 weeks without complications. Post-partum, the patient's CBC remained stable with platelets above 100k/dL along with her LDH, haptoglobin and renal function and was subsequently discharged with no further documentation of relapse in her TTP.

Discussion

TTP is a severe, and often life threatening condition characterized clinically by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, neurologic changes and fever.

Pregnancy is a known trigger for onset of TTP and has been well described in literature, usually presenting in the third trimester or post-partum period with a constellation of symptoms that may mimic other thrombotic microangiopathies (Martin JN Jr, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol.2008; 199(2):98-104). Recurrent TTP complicating subsequent TTP is uncommon (George. JN, et al.Blood, 2014; 123 (11):1674-1680). Patients with a history of pregnancy related TTP continue to be at high risk of relapse with subsequent pregnancies and their management often presents as a challenge to both hematologist as well as obstetricians .

While plasma exchange and immunosuppression is a cornerstone of successful treatment of confirmed pregnancy related TTP, literature regarding optimal prophylaxis to prevent the onset of subsequent TTP in women with a history of pregnancy related TTP is lacking. Rituximab for the prevention of TTP relapse during pregnancy may be a viable option.