How to manage bleeding risk in a pregnant patient with factor XI deficiency?

Jean Marie Connors, MD
Assistant Professor, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

This month, Jean Marie Connors, MD, discusses how to manage the bleeding risk in a pregnant patient with factor XI deficiency.

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I have a pregnant 38-year-old female patient who was noted to have factor XI (FXI) deficiency when an assay was ordered because of her Jewish heritage. She has never had any heavy menstrual complaints, had genitourinary (GU) surgery for repair of reflux at 8 years of age with no bleeding, and had her wisdom teeth removed with no excess bleeding. No one in her family has bleeding problems or is known to have FXI deficiency. FXI runs 39-55 percent so far. I was thinking of observation and reserving fresh frozen plasma (FFP) for bleeding. Thoughts?


Jean Marie Connors, MD
Assistant Professor
Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts

Pre-conception or prenatal genetic screening is available to identify carriers of inherited disorders such as cystic fibrosis, Tay-Sachs disease, and sickle cell anemia. Many commercial genetic screening panels vary the gene panel based on the ethnicity and background of the patient and include genes based on the prevalence of the disorder in that population. FXI deficiency is common in the Ashkenazi Jewish population; therefore, pregnancy-related genetic screening panels often include evaluation for FXI mutations in this group. The clinical utility of finding an FXI mutation by this type of genetic screening, however, is not known and is likely to be irrelevant in the absence of a personal or family history of bleeding.

This patient has a partial deficiency of FXI, with activity levels of 39-55 percent; the lower limit of normal is 70 percent in most labs. She is likely heterozygous for a known FXI mutation. Severe deficiency is defined as activity less than 15 percent and is usually the result of homozygous or compound heterozygous mutations. In tertiary referral practices, patients with levels of <1% are often encountered. Although the risk of bleeding is not always tied to FXI activity, those with severe deficiency have the highest risk of bleeding. Unlike other coagulation factor levels, such as fibrinogen and von Willebrand factor, FXI levels do not change during pregnancy. In this patient, the lack of menorrhagia and lack of bleeding with surgery in areas of high fibrinolytic activity (GU surgery and wisdom teeth extraction) as well as a negative family history of bleeding make it unlikely that she has clinically significant FXI deficiency.

The plan to observe during labor and delivery is the best approach in this patient. If excessive bleeding develops, FFP is the only source of FXI available in the United States. The amount usually given is 10-20 mL/kg. For patients with severe deficiency and levels of <1%, with the goal of achieving an FXI level of 30 percent, it can take 1.5 liters of plasma or more. In this patient, who is starting with a higher baseline FXI level, less plasma may be required, but the FXI level needed to achieve is not defined. Two to four bags of FFP should be sufficient, and administration should be based on severity of bleeding and response. Antifibrinolytic agents such as aminocaproic acid or tranexamic acid should be used to augment hemostasis if bleeding develops. The use of neuraxial anesthesia is acceptable in this patient.

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An 82-year-old female with chronic myeloid leukemia presented 8 years ago in chronic phase, without any particular high-risk factors. She went into major molecular response (MMR) on imatinib and remains in this state. Her complete blood count has been normal except for mild anemia. However, over the last 2 months, her white blood cell count dropped from normal to 1,400/μL,with an absolute neutrophil count (ANC) of 300/μL. Hemoglobin dropped from 10.9 g/dL to 8.9 g/dL and platelets dropped from normal to 98,000/μL. She remains in MMR by polymerase chain reaction. She has no symptoms except mild fatigue, and her spleen is not palpable. She is on no new medications. She has been on ezetimibe, lisinopril/hydrochlorothiazide, and metoprolol for years. Metoprolol dose was increased 6 months ago. I held the imatinib and will probably consider dose reduction after the ANC goes back up. However, is there anything else I should worry about? It seems odd that her counts went down after so many years.

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