Thrombosis in women presents unique clinical challenges due to sex-specific risk factors, hormonal influences, and reproductive considerations. While the core principles of venous thromboembolism (VTE) management apply broadly, tailoring care to the female patient can improve outcomes and reduce complications.
Nicole Randall, MD, adult hematologist at Innovative Hematology, home of the Indiana Hemophilia & Thrombosis Center in Indianapolis, points to differing opinions in testing for thrombophilia (a condition with a tendency to clot) before starting, continuing, or stopping anticoagulation. The most common conditions considered part of thrombophilia testing include:
- Factor V Leiden
- Prothrombin Gene Mutation
- Antithrombin Deficiency
- Protein S Deficiency
- Protein C Deficiency
- Antiphospholipid Antibody Syndrome (Anticardiolipin IgG/IgM antibodies, anti-beta-2 glycoprotein IgG/IgM antibodies, and lupus anticoagulant testing)
“Published guidelines only advise testing depending on the unique circumstances of a case before making a determination about anticoagulation management,” Dr. Randall says. “There are cases when a practitioner might be most comfortable with the assurance of definitive test results, but there are times when specific factors alone can inform go-forward anticoagulation plans.”
Recognize Sex-Specific Risk Factors
According to the American Society of Hematology (ASH), thrombophilia affects approximately 10% of the population, but routine testing is not recommended unless specific clinical criteria are met—such as VTE at unusual sites, a strong family history, or recurrent pregnancy loss.
The reasons not to test vary (insurance coverage is one), and Dr. Randall says ordering thrombophilia testing can be complicated.
“Physicians are encouraged to refer their patients to hematology if they are concerned thrombophilia testing is needed. We need to be sure important labs aren’t missing from the panel,” she says. “Hematology can also help interpret labs.”
The ASH 2023 Guidelines for Management of Venous Thromboembolism include 23 recommendations about thrombophilia testing and anticoagulation management. As women face distinct thrombotic risks across their lifespan, Dr. Randall comments on the below controversial recommendations and encourages physicians to consider case-by-case testing:
- Unprovoked VTE: ASH advises no thrombophilia testing. Indefinite anticoagulation is
- Surgery-provoked VTE: ASH advises no thrombophilia testing. Anticoagulation can be stopped after 3 to 6 months.
- Non-surgical major transient risk factors (hospitalization or trauma): ASH advises thrombophilia testing may be considered to guide anticoagulation duration.
- Pregnancy-provoked or VTE on estrogen oral contraceptive pill (OCP): ASH guidelines state thrombophilia testing may be considered to guide anticoagulation duration, although Dr. Randall notes that this recommendation can be controversial. She points to the below graphic noting that women with either of these types of VTE events have about a 6% risk of 5-year
“But with positive thrombophilia testing, that might increase a patient’s 5-year risk to 15%,” Dr. Randall says. “Hence why longer-term anticoagulation could be considered.”
Tailor Anticoagulation to Reproductive Status
For pregnant patients, Dr. Randall says Innovative Hematology focuses attention on the stage of pregnancy and adjusts anticoagulation accordingly.
“For women with a history of estrogen-provoked VTE (estrogen contraceptive pill or pregnancy), we treat with a daily anticoagulant as soon as we get the call with a positive pregnancy test,” she said. “We adjust their treatment throughout their pregnancy—starting, stopping, and even changing products
—and each decision is based on clinical symptoms, the week of pregnancy, whether they’re in labor, and the type of planned delivery.”
She says the same case-by-case attention is given to women who develop deep vein thrombosis or pulmonary embolism during their pregnancy. Post-partum anticoagulant use typically continues in these patients, she says, which helps prevent recurrence of VTE.
“If they have a first degree relative with VTE before the age of 50, they should be strongly considered for VTE prophylaxis with pregnancy,” she says. “In these cases, family history outweighs any positive thrombophilia testing.” 2
For that same reason, Dr. Randall also notes that hormonal therapies should be thoughtfully managed. Providers should determine a woman’s personal and family history of thrombosis or known thrombophilia before considering estrogen-containing contraceptives or hormone therapies. The ASH guidelines strongly discourage routine thrombophilia testing before prescribing hormonal contraception unless there is a clear clinical indication.
Safer options for these high-risk populations are progestin-only and non-hormonal alternatives. These can help mitigate bleeding symptoms without increasing thrombotic risk in those already on anticoagulation.
Special considerations in autoimmune and cancer-associated thrombosis
Autoimmune conditions like systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) disproportionately affect women and carry elevated thrombotic risk. Screening for APS is essential in young women with unprovoked VTE or recurrent pregnancy loss.
In cancer-associated thrombosis, bleeding risk must be weighed carefully, especially in gynecologic malignancies. The ASH guidelines suggest pharmacologic thromboprophylaxis in ambulatory cancer patients with additional risk factors.
Emphasize shared decision-making
Women’s health decisions often intersect with reproductive goals, lifestyle factors, and bleeding concerns. ASH notes that engaging patients in shared decision-making fosters adherence and satisfaction and advises using decision aids to discuss the risks and benefits of long-term anticoagulation, especially in cases of unprovoked VTE or borderline recurrence risk.
Educating patients on signs of recurrence and bleeding and ensuring follow-up plans are in place is also key.
Managing thrombosis in women requires a nuanced, individualized approach. By recognizing sex-specific risks, tailoring anticoagulation, and prioritizing patient-centered care, clinicians can optimize outcomes and support women through complex health decisions.
Outstanding Care at Indiana’s Comprehensive Treatment Center
As home to the state’s only federally designated comprehensive hemophilia treatment center, Innovative Hematology partners with external medical professionals to guide patients and their families through life events by leveraging advanced training in bleeding disorders.
The team at Innovative Hematology is recognized among the nation’s leaders in research and clinical practices, uniting nationally and internationally known practitioners from a wide variety of specialties. Within a state-of-the-art facility, the team utilizes a care model that acknowledges the whole person, including how bleeding and blood disorders can impact areas outside the healthcare setting—such as work, school, and personal life.
Another defining element of Innovative Hematology and the Indiana Hemophilia & Thrombosis Center (IHTC) is their highly individualized approach to treatment. Center physicians and other experts look at a patient’s specific disease subtype, lifestyle, bleeding and treatment history, and risk factors to develop a personalized plan. The center’s compassionate staff then provides one-on-one guidance to help each patient manage their condition with confidence and minimize the impact on their daily activities.
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References
- Van Gorder, (2023, December 5). Guideline: Management of anticoagulation in the anticoagulation clinics (ACC). Anticoagulation Forum. Retrieved from https://acforum.org/web/resource_files/1739988420-34123.pdf
- Bates, S. M., Middeldorp, S., Rodger, M., James, A. H., & Greer, I. (2016, January). Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. Journal of Thrombosis and Thrombolysis, 41(1), 92–128. https://doi.org/10.1007/s11239-015-1309-0
