Disseminated Intravascular Coagulation in Pregnancy: Insights from an International Collaborative Registry

Postpartum hemorrhage (PPH) remains a leading cause of maternal mortality in both low- and high-income countries, responsible for 27% of global maternal mortality (approximately 70,000 deaths annually) (1). With adequate resources and evidence-based care, nearly all deaths from PPH can be prevented (2). PPH resulting in mortality is almost always preceded by onset of coagulopathy. Consequently, onset of disseminated intravascular coagulation (DIC) — defined as a widespread hypercoagulable state leading to micro- and macrovascular clotting and followed by consumption of clotting factors and bleeding — is a dreaded finding regardless of one’s role on the care team (3). DIC is an uncommon outcome of pregnancy and delivery, with an incidence estimated to range from approximately 0.03% to 0.4% (4). For decades, clinical guidance on obstetric DIC has been derived from single-center series, national audits, and expert consensus rather than multinational data (5). In this issue of JTH, Erez and colleagues, on behalf of the International Society on Thrombosis and Haemostasis Scientific and Standardization Committees (SSCs) on Women’s Health Issues in Thrombosis and Hemostasis and on Disseminated Intravascular Coagulation, report outcomes from the first international registry of DIC in pregnancy (6). Across 13 countries and 148 cases collected between 2018 and 2024 (104 with individual-level clinical data), the registry offers a unique perspective on this rare but life-threatening complication.

Two pathways to one morbid outcome

Through a detailed description of a diverse range of PPH etiologies, Erez and colleagues highlight the importance of two common phenotypes of obstetric DIC. Although both phenotypes have been previously described,(7) the registry’s contribution is to pool cases of this uncommon condition into a multinational cohort with individual-level data, testing whether patterns seen in isolated single-center reports hold across diverse settings. Antepartum DIC is primarily a disease of placental abruption and its related placental pathologies (e.g., preeclampsia spectrum disorder including Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome). Antepartum DIC, particularly in the setting of placental abruption, can be insidious owing to concealed blood loss. Mechanistically, placental abruption triggers massive tissue factor release through trophoblast disruption, driving a coagulopathy that exceeds in severity what blood loss alone would predict (8). The combination of suspected placental abruption with intrauterine fetal demise (IUFD) is a particularly ominous scenario and should prompt urgent assessment of coagulation, blood count, and organ perfusion, and proactive arrangement of blood products for both fibrinogen replacement and volume repletion. Recent mechanistic work suggests that placental abruption-associated coagulopathy may involve dysregulated plasmin generation and systemic fibrinogenolysis, which may rapidly impair fibrinogen function, and supports clinical observations that favor early tranexamic acid administration and higher-than-expected fibrinogen replacement dosing (9).

For patients with intrapartum or postpartum DIC, the dominant risk factors are obstetric in nature. In the registry, refractory uterine atony was the leading cause of postpartum DIC (53.1% of postpartum cases), most often preceded by labored cesarean delivery. Similarly, abnormally implanted placenta (accreta, previa, or both) accounted for one-third of postpartum DIC and is climbing in step with the global cesarean rate (10). DIC prevention and mitigation in this context requires a multifactorial approach. Prevention of primary cesarean delivery would reduce risk for future abnormal placentation. When cesarean delivery is required in the setting of significant hemorrhage risk (e.g., labored cesarean delivery or abnormal placentation), delivery in a center that can provide rapid assessment of coagulation function, repletion of coagulation factors with a low threshold to test and treat empirically, and access to blood banking and intensive care is essential. For cases of suspected placenta accreta spectrum disorder, delivery in a center with multidisciplinary expertise in the management of this condition has additional potential to reduce morbidity and mortality (11).

Regardless of etiology, the toll of obstetric DIC documented in this registry is substantial. Maternal mortality reached 2.8%, renal failure occurred in 9.6%, and thrombotic and respiratory complications each occurred in 2.8% of cases, with smaller proportions experiencing liver or multi-organ failure. One-third of patients required transfusion of more than four units of packed red cells, and a similar proportion received more than four units of fresh frozen plasma. Procedural management was frequent, with 25% of patients requiring hysterectomy, and 21% of patients requiring a laparotomy after vaginal delivery or a second laparotomy after cesarean delivery to obtain hemostasis.

The pregnancy-adjusted DIC score

The registry also offers the first multinational external validation of the pregnancy-specific DIC risk score (12). Derived from the ISTH DIC Score, the pregnancy-adjusted score was created by eliminating the fibrin split products component because D-dimer levels rise physiologically in pregnancy and deriving pregnancy-specific cutoffs and regression-based weights for the remaining three components: platelet count, fibrinogen, and prothrombin time difference. In this registry, the pregnancy-specific score performed similarly in the included high- and low-income centers, suggesting that the score generalizes to a range of obstetric care settings. Notably, only half of cases met DIC score criteria at admission, but nearly 90% eventually did during the peripartum period. This finding suggests that the score may be best applied for serial monitoring of at-risk patients, rather than as a one-time test to exclude the possibility of evolving peripartum DIC. Its high eventual sensitivity also makes the score potentially valuable as a research instrument for identification of obstetric DIC cases. Whether the pregnancy-specific score becomes the definitive diagnostic standard for DIC in pregnancy will require prospective validation in larger, more geographically diverse cohorts; of note, in this study all included patients had clinical suspicion for DIC and thus the score’s performance in the overall obstetric population remains unknown. The score may thus be best understood as a tool for risk-stratifying patients who have DIC risk factors or a concerning clinical presentation, rather than as a broadly employed screening test. For now, the score (like laboratory testing in general) should complement, but not constrain, clinical judgment. In the setting of high clinical concern for DIC, initiating empiric treatment is appropriate even if initial laboratory testing is not diagnostic.

Limitations and registries

The Obstetric DIC Registry is a product of long-standing collaboration between the SSCs that has improved our understanding of DIC in pregnancy. However, despite being an international registry, the 94 observations with the most complete clinical and laboratory data were derived from four centers, with the three highest-volume centers contributing 93 of the 94 cases. Additionally, there was limited geographic diversity of the highest-volume centers, with two of the three located in Israel and the remaining center located in Chile. The limited geographic diversity also underscores a broader challenge for rare hematologic and obstetric disease registries: participation may be driven less by disease incidence than by local infrastructure, regulatory feasibility, and research engagement. As a result, registry findings may disproportionately reflect the practices and patient populations of highly engaged centers, rather than the full spectrum of global obstetric care. Despite the involvement and endorsement of the members of two active SSCs, these limitations in geographic representation highlight the challenges of a research paradigm centered on voluntary contribution of cases. In most countries, submission of cases even without individual patient identifiers requires Institutional Review Board approval, execution of a Data Transfer Agreement, and/or patient consent. These are necessary safeguards for the ethical conduct of research; in the context of a voluntary, largely unfunded registry, however, they raise practical barriers to research participation. DIC is rare, and for most potential sites, the per-case “overhead” of these processes would be substantial, which likely contributed to the concentration of contributions among a small number of centers rather than broader global participation. Furthermore, without funding for dedicated research personnel, chart abstraction and data submission can be onerous even for motivated collaborators (oftentimes, themselves busy clinicians).

As with many hematologic complications of pregnancy, the relative infrequency of DIC events makes single-center studies impractical and requires a collaborative approach to generate sufficient sample sizes for analysis. Future studies might leverage federated data platforms to address the administrative challenges of data sharing approval and common data models to facilitate collaborative research without the burden of manual chart review, acknowledging that such approaches will privilege centers using electronic medical records (13). Investigators adopting these approaches will have challenges of their own to overcome, including ensuring data harmonization and interoperability, ensuring consistency among testing performed with different assays and reported with different units and reference ranges, and ensuring sustainable governance across international institutions. One promising example of a collaborative study currently underway is the Obstetric Bleeding UK Study, which is using routinely collected National Health Service data to study PPH care bundles across 40 maternity wards (14). This initiative, which has enrolled over 250,000 participants since 2024, aims to produce a linked dataset of obstetric bleeding outcomes as well as further mechanistic understanding of obstetric coagulopathy through laboratory investigation.

When prospective studies are impractical, international registry collaboration becomes the most realistic path to generating evidence that can inform care. Erez and colleagues should be commended for giving the community an international view of this lethal obstetric complication.