Introduction:
Pregnancy, a time of profound physiological changes, poses distinct challenges for individuals with Paroxysmal Nocturnal Hemoglobinuria. This rare hematopoietic stem cell disorder, marked by a deficiency of Glycosylphosphatidylinositol (GPI)-anchored proteins, requires careful consideration during pregnancy due to increased risks of thrombosis and hemorrhage. This article delves into the challenges and management of PNH during pregnancy.
What Is Paroxysmal Nocturnal Hemoglobinuria?
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare disorder caused by a genetic mutation in the PIGA gene, leading to a lack of certain proteins in blood cells. PNH is characterized by intravascular hemolysis, bone marrow failure, and thrombosis. It can be mistaken for other blood disorders like aplastic anemia and myelodysplastic diseases. Common signs include unusual blood test results, anemia, and clotting issues. To confirm PNH, flow cytometry is used to identify the absence or deficiency of specific proteins in blood cells, known as PNH clones. This test is crucial for a definitive diagnosis.
Whom Does PNH Impact?
Approximately six out of every one million individuals receive a diagnosis of PNH annually. This condition is observed in both men and women within the age range of 30 to 40. There is a slightly higher incidence of PNH in women compared to men. Frequently, individuals with bone marrow disorders such as aplastic anemia or myelodysplastic syndrome are prone to developing paroxysmal nocturnal hemoglobinuria.
What Are the Signs of PNH?
Though named for a specific symptom, individuals with paroxysmal nocturnal hemoglobinuria usually consult medical professionals due to significant and enduring fatigue or tiredness impacting their daily activities. Additional symptoms encompass:
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Shortness of breath (dyspnea).
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Kidney issues.
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Challenges in swallowing (dysphagia).
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Esophageal spasms.
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Abdominal pain.
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Back pain.
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Erectile dysfunction.
How Is PNH Diagnosed?
Healthcare providers utilize a range of tests to identify potential signs of Paroxysmal Nocturnal Hemoglobinuria (PNH). Following these initial tests, they may employ flow cytometry to examine the composition of blood cells. The tests include a Complete Blood Count with Differential (CBC w/diff) to detect blood disorders like anemia and thrombocytopenia, a Basic Metabolic Panel (BMP) to assess signs of chronic kidney disease and renal dysfunction, and a Urinalysis to reveal indicators such as hemoglobinuria (blood in urine) and hemosiderosis (excessive iron deposits). Additionally, a Reticulocyte Count measures immature red blood cells, providing insight into bone marrow health, while a Haptoglobin Test assesses protein levels responsible for clearing debris from damaged red blood cells. Elevated levels of Lactate Dehydrogenase (LDH), an enzyme in red blood cells, may indicate increased red blood cell destruction. Lastly, a Liver Function Test measures bilirubin levels, offering insights into potential red blood cell breakdown. These tests collectively contribute to a comprehensive evaluation of PNH.
What Is the Treatment of PNH?
The present approach to treating PNH involves using eculizumab, a monoclonal antibody that inhibits the final stage of complement activation. This leads to decreased hemolysis and, for many individuals, an enhancement in their overall quality of life. Pregnant women with PNH face an elevated risk of both blood clotting and bleeding, often presenting a challenge in treatment decisions. The safety and effectiveness of eculizumab during pregnancy and breastfeeding have not been thoroughly investigated. Due to its potential for causing birth defects, contraception is advised.
What Are the Challenges in Pregnancy Associated With PNH?
Pregnant individuals with PNH encounter a dual challenge, managing the intricacies of pregnancy while navigating the inherent risks linked to PNH. There is a heightened risk of thrombosis and bleeding during pregnancy for PNH patients. The delicate balance required for optimal maternal and fetal outcomes necessitates a thorough understanding of these challenges.
Eculizumab falls under pregnancy class C, and studies on animals revealed a rare occurrence of retinal dysplasia and umbilical herniation. Information on its safety during pregnancy is limited, with a study involving pregnant patients on eculizumab showing a 4 percent rate of fetal deaths. Eight percent had miscarriages during the first trimester. Eculizumab was found in 7 of 20 cord blood samples, while breast milk samples tested negative. In a series involving two pregnant patients treated shortly before delivery, eculizumab had no impact on complement activity in the newborns. Adjustments to the dose and frequency may be necessary if hemolytic parameters worsen during pregnancy.
How Is Pregnancy With PNH Managed?
People with PNH have a higher risk of blood clots and death during pregnancy, but there are no established guidelines for preventing Deep Vein Thrombosis (DVT) in this situation. However, experts generally recommend preventive measures for pregnant PNH patients with a clone size exceeding 50 percent. Around 10 percent of patients may experience bleeding issues, mostly after childbirth. Some studies show that using heparin, a blood thinner, can be safe and effective during pregnancy to prevent clots. Low platelet counts and potential differences in clotting risks between PNH patients from different regions complicate the decision. Despite these challenges, limited evidence supports the safety and effectiveness of preventive measures in pregnant women with PNH due to the increased clotting risk from ongoing hemolysis and the natural clotting tendency during pregnancy. Many patients in studies have used low molecular weight heparin (LMWH) at various doses (REF). Both unfractionated heparin (UFH) and LMWH have been considered safe and effective for prevention in high-risk patients. Considering our patient's very low platelet count (ranging between 20 and 30,000 during pregnancy), we chose to give UFH 5000 subcutaneously twice daily, aiming to balance the risk of bleeding with the need for preventive measures.
Conclusion:
Paroxysmal Nocturnal Hemoglobinuria (PNH) is an uncommon blood disorder characterized by the immune system's targeted assault on red blood cells and platelets, leading to damage. If not addressed, PNH can result in hemolytic anemia, chronic kidney disease, or thrombosis (formation of blood clots). Healthcare professionals manage PNH by administering medications designed to prevent damage to blood cells. Expectant women with Paroxysmal Nocturnal Hemoglobinuria face an elevated risk of both thrombosis and hemorrhage, attributable to the combined impact of pregnancy and their underlying PNH condition. The introduction of eculizumab has significantly reduced maternal mortality and post-partum thrombosis, marking a positive impact. However, studies highlight persisting challenges, including higher fetal and neonatal mortality rates and an increased prevalence of preterm deliveries in PNH pregnancies.
