Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency

Abstract

ObjectiveThe aims of the study reported here were to provide data from six pregnant subjects who were enrolled in a clinical trial of antithrombin (AT) concentrate, discuss other published case series and case reports, and provide general guidance for the use of AT concentrate for inherited AT deficiency in pregnancy.MethodsIn the late 1980s, 31 AT-deficient subjects were enrolled in a prospective treatment trial of the plasma-derived AT concentrate Thrombate III®. Herein, newly available treatment data about the six pregnant subjects in the trial is tabulated and summarized.ResultsAll six experienced venous thromboembolism (VTE) during pregnancy, were dosed according to a weight-based protocol, and were treated concomitantly with anticoagulation. Loading doses of AT concentrate of 54–62 units/kg were followed by maintenance doses of 50%–100% of the loading dose for 3–10 days. At the time of labor, loading doses of 46–50 units/kg were followed by maintenance doses of 50%–75% of the loading dose for 5–7 days. None of the six experienced recurrent thrombosis while receiving treatment with AT concentrate.ConclusionCurrently we suggest that women with AT deficiency who are pregnant or postpartum and have a personal history of VTE or current VTE receive AT concentrates.

Management of Venous Thromboembolism in Patients with Hereditary Antithrombin Deficiency and Pregnancy: Case Report and Review of the Literature

“…Four other patients developed severe adverse events several weeks after the discontinuation of AT concentrate (e.g., intra-abdominal bleeding, anterior rectus muscle hematoma, sepsis, and pyrexia) all of whom resolved with appropriate management. An additional 20 cases were described in other studies [35, 36, 38, 47–49, 51, 53–56]. Although most of these cases started AT concentrate 24 hours before the time of expected delivery, they did not have a consistent initiation or discontinuation timeline.…”

“…However, based on limited, small studies of AT deficient patients undergoing surgery or giving birth, AT concentrate was shown to lower rates of VTE when anticoagulation was held during the perioperative and peripartum periods [41, 49, 61]. Other cases reported in the literature suggest that pregnant women with hereditary AT deficiency who receive therapeutic AT concentrate during pregnancy might have low rates of recurrent thrombosis and bleeding [38]. In this review, across the 23 pregnant patients (a total of 24 pregnancies), 14 (58%) pregnancies had term deliveries with favorable outcomes for the mother and newborn.…”

“…Six (25%) pregnancies resulted in pregnancy loss despite AT concentrate. Two pregnancies resulted in miscarriage, and four underwent therapeutic/induced abortion [34, 38, 55]. In one study, a pregnant woman was found to have an iliofemoral DVT at gestational week 28, and, despite receiving therapeutic dose anticoagulation, AT concentrate 2000 IU daily for three days, and an IVC filter, developed PE [39].…”

“…Although most of these cases started AT concentrate 24 hours before the time of expected delivery, they did not have a consistent initiation or discontinuation timeline. Three cases who developed VTE during pregnancy were managed with therapeutic anticoagulation and were later started on AT concentrate as prophylaxis around delivery and continued for six days postpartum [38, 48]. The dose of AT used in these studies ranged from 30 to 93 IU kg −1 daily and was often titrated to a targeted AT activity of 80–120%.…”

Peripartum Haemorrhage: Haemostatic Aspects of the New German PPH Guideline

“…The decreased antithrombin activity after PPH (some women presented with an absolute activity below 0.5 kIU/l) must be considered when administering coagulation factors, especially prothrombin complex concentrate [66], to parturients [67]. Substitution with antithrombin might aim at ≥80% [68] or ≥0,8 kIU/l [69]. However, antithrombin substitution is controversially discussed and not equally accepted in different countries.…”