Successful pregnancy for woman with PNH, blood clotting disorder
Patient treated with Soliris, anti-clotting therapy
A pregnant woman with paroxysmal nocturnal hemoglobinuria (PNH) and an inherited blood clotting disorder had a successful and uneventful pregnancy after receiving tailored treatment with Soliris (eculizumab) and anti-clotting therapy.
“With the combined expertise of hematologists and obstetricians, comprehensive care can be provided to pregnant women with PNH, minimizing the risks and optimizing the management of this complex condition throughout the pregnancy,” wrote researchers in “Targeted management of coexistent severe thrombophilias—A case report of a successful pregnancy despite paroxysmal nocturnal hemoglobinuria and hereditary protein C deficiency,” a case report published in eJHaem.
PNH is a rare disease marked by an immune-mediated attack against blood cells that results in their destruction. Patients often have low red blood cell levels, or anemia, and many develop blood clots that can result in life-threatening conditions.
The disease is caused by acquired mutations in blood stem cells, which cause some blood cells to be without a molecular identification badge that tells the immune system they are a healthy part of the body. As a result, the cells are attacked by the complement system, a part of the immune system.
The mainstay treatment for PNH includes medications such as Soliris that block the complement system’s activation to help prevent complement-mediated blood cell destruction. Managing PNH during pregnancy remains complicated and the literature is scarce, however.
Managed treatment of PNH, blood clotting disorder
Here, researchers at the University of Lausanne in Switzerland write about a 44-year-old woman with PNH and hereditary protein C deficiency who was treated with Soliris and anti-clotting medications during pregnancy.
The woman had a stroke in 2001 at age 21 and clinical exams showed she had hereditary thrombophilia, an inherited condition marked by an increased risk of blood clots. In her case, this was caused by a deficiency in protein C, a natural anti-clotting protein.
PNH wasn’t considered a possible culprit at that time, but the researchers noted the woman already had signs consistent with a PNH diagnosis. She received preventive treatment with anticoagulants, which was only stopped at age 38 when she received a PNH diagnosis and started Soliris.
The woman’s clinical history included two miscarriages during the first trimester and two pregnancy terminations. One pregnancy occurred within two years of her PNH diagnosis and the woman was placed on prophylactic treatment with heparin, an anticoagulant, while she continued Soliris.
During that pregnancy, a routine examination at 24.3 weeks of gestation, or about six months, showed fetal death. No abnormalities were detected, but the placenta was below the expected weight for gestational age and had numerous infarctions, meaning areas that lacked blood supply, which causes cells to die.
After several years of unsuccessful attempts, the woman became pregnant again in 2021 at age 44 with a donated egg. She started an anticoagulation regimen with heparin and aspirin. Dosing with Soliris was intensified from 900 mg to 1,200 mg every two weeks.
The woman was closely monitored and lab work showed no signs of red blood cell destruction, called hemolysis. Her complement levels also were under control, indicating Soliris was effective.
Her pregnancy developed normally up to 36 weeks of gestation, but labor was induced at that time because no increased weight had been seen after 34 weeks and due to the woman’s age and history of miscarriages. The baby was born healthy at 2,660 g (about 5.864 pounds) from a normal vaginal delivery, with an uneventful follow-up.
The woman had stopped the aspirin two weeks before the delivery was induced. Heparin was also switched 24 hours before induction to another formulation to minimize the risk of clots after birth and was reintroduced after labor for another six weeks. Soliris was tapered to 900 mg and kept during breastfeeding before being switched to Ultomiris (ravulizumab), another complement-inhibitor approved for PNH.
No complications were reported during postpartum and breastfeeding. An analysis of the placenta revealed villitis of unknown cause, an inflammatory placental injury. No signs of blood disruption or clots were observed, however.
“To the best of our knowledge, this is the first case report of a positive pregnancy outcome despite PNH in conjunction with hereditary thrombophilia,” the researchers wrote. “With appropriate management of each component, the pregnancy proceeded without any thrombotic complications nor breakthrough hemolysis, and outcome was favorable for both mother and child.”
About the Author
