Factor VII Deficiency: A Diagnostic Dilemma

Background/Introduction:

Factor VII deficiency is a rare bleeding disorder, estimated to affect 1 in 300,000 to 500,000 individuals in the general population. The disease is associated with autosomal recessive inheritance or could be acquired. Clinical manifestations range from asymptomatic to severe, life-threatening bleeds. There is poor correlation between the level of factor VII and the severity of symptoms, thus making diagnosis and management a challenge. Here we present a case of incidental finding of elevated international normalized ratio (INR) and found to have factor VII deficiency.

Description of Case:

Patient is a 74 year-old male with a history of CREST, pulmonary fibrosis, Raynaud's Disease, COPD, referred by his cardiologist for recurrent, unresolved pericardial effusion. Compared to his previous echocardiogram, the pericardial effusion is now circumferential and enlarged, leading to an immediate need for pericardiocentesis. Due to the urgency of the patient’s condition and lack of bleeding history, we proceeded with the procedure without obtaining INR. CT scan taken during the course of hospitalization revealed a cavitary lesion of the lung, which prompted planning of a CT biopsy with Interventional Radiology. At this time, INR was 1.8 (Ref 0.8-1.1) with normal PTT and there was no reported anticoagulants use. Due to increased INR, ultrasound of the liver was done and showed no features of fibrosis. Vitamin K was preemptively administered without improvement of INR. Mixing study resulted in correction for PT and the ensuing factor assay revealed a deficiency of factor VII. FFP was administered prior to other procedures.

Discussion/Conclusion:

Factor VII deficiency is an extremely heterogeneous disorder with regard to clinical presentation, sites, and severity of bleeding. Symptoms exist on a continuum of severity, ranging from epistaxis, gum bleeds, easy bruisability, and menorrhagia to hemarthrosis, gastrointestinal and intracranial bleeds (3). Despite being a prime protein in the coagulation system, patients mostly present with mucocutaneous bleeding, which sometimes can be confused with platelet-related bleeding and hence require thorough evaluation (2). Most patients with Factor VII deficiency are diagnosed incidentally with abnormal PT, which can then be confirmed by one-stage PT-based assay for factor VII level. However, PT and factor VII levels do not correlate with the severity of bleeding symptoms and future risk of bleeding (3). In addition, previous studies have shown a marked phenotype-genotype disparity among patients (4). This could be attributed to various genetic polymorphisms of the gene or environmental factors, such as pregnancy, increasing age, obesity, underlying disorders, and vitamin K deficiency. The lack of correlation also poses a challenge for management strategies. Treatment cannot depend on the level of Factor VII alone, but also on severity of disease, risk of certain medications or procedures, and patient’s age and comorbidities. Several modalities have been used as treatment, such as recombinant activated factor VII (rFVIIa), plasma-derived factor VII, fresh frozen plasma, and IV prothrombin complex concentrates (5).