Can fondaparinux (a synthetic pentasaccharide anticoagulant) be used for heparin-induced thrombocytopenia (HIT) in pregnancy?

Management of Heparin-Induced Thrombocytopenia in Pregnancy

Fondaparinux should be used for heparin-induced thrombocytopenia (HIT) in pregnancy only when danaparoid is not available, as danaparoid is the preferred agent due to its lack of placental transfer.

First-Line Treatment for HIT in Pregnancy

• Danaparoid is the recommended first-line treatment for pregnant patients with acute or subacute HIT due to its established safety profile and lack of placental transfer 1
• In a retrospective case series of 30 pregnant women with acute HIT who received danaparoid, there was no evidence of anti-Xa activity in the umbilical cord blood of the six infants who were checked after delivery 1
• Despite the low quality of evidence supporting danaparoid use in pregnancy, the number of patients exposed to this agent and its proven lack of placental transfer make it the current best choice 1

Fondaparinux as an Alternative Option

• Fondaparinux should be considered only if danaparoid is not available (Grade 2C recommendation) 1
• Fondaparinux crosses the placenta in small amounts, with anti-Xa activity detected in umbilical cord blood at approximately one-tenth the concentration in maternal plasma 1, 2
• The American Society of Hematology (ASH) guidelines specifically state that fondaparinux is an option for HIT treatment where danaparoid is not available (including in the United States) 1
• Experience with fondaparinux in pregnancy remains very limited, especially during the first trimester 1

Safety Considerations with Fondaparinux

• The FDA label for fondaparinux notes that it crosses the placenta, with cord plasma concentrations approximately 1/10th of maternal levels 2
• Recent evidence suggests that while fondaparinux can cross the placental barrier, real-world data have not established a direct association between fondaparinux and teratogenicity or adverse fetal outcomes 3
• Fondaparinux may increase the risk of bleeding events during pregnancy and postpartum, requiring careful monitoring 3
• Caution is advised when administering fondaparinux to patients with renal insufficiency, as it is eliminated by the kidneys 1

Case Reports Supporting Fondaparinux Use

• There are successful case reports of fondaparinux use in pregnant women with HIT, including a 24-year-old woman at 34 weeks gestation with acute pulmonary embolism who developed HIT after initial treatment with UFH and LMWH 4
• Another case report describes a 41-year-old female with confirmed HIT in the first trimester who was successfully treated with therapeutic fondaparinux for 3 months followed by prophylactic dosing until delivery 5

Dosing Considerations

• For treatment of venous thromboembolism (VTE), fondaparinux is dosed based on weight: 5 mg for patients <50 kg, 7.5 mg for patients 50-100 kg, and 10 mg for patients >100 kg 1
• In patients with moderate renal insufficiency (CrCl 30-50 mL/min), the dose of fondaparinux should be reduced by 50% 1
• Monitoring is not routinely recommended but can be performed using fondaparinux-specific anti-Xa assays if necessary 1

Important Caveats and Pitfalls

• Unlike heparins, fondaparinux has no specific antidote; recombinant factor VIIa may be effective in cases of uncontrollable bleeding 1
• Labor and delivery planning is critical for women on fondaparinux due to the risk of epidural or spinal hematomas with neuraxial anesthesia 2
• Consider switching to a shorter-acting anticoagulant as delivery approaches to minimize bleeding risks 2
• Careful monitoring for evidence of bleeding or unexpected changes in coagulation parameters is essential throughout pregnancy 2