I [Geo] received this post on Monday, December 18:
Hi George, I have a few questions that I was hoping you could help me with. I’m a patient with factor 7 deficiency and have a background in nursing. I was diagnosed at 49% but have had issues with fluctuations in percentages between standalone labs and HTCs. For most HTCs I average between 55-65% but at reference labs I’ve been 80-96%. I have had genetic testing done and turned up homozygous for the Arg413Gln mutation as well as heterozygous for both the -323 insertion and c.805+7 A>G (splice site variant) in addition to being a carrier for the F2 mutation. I have a history of bleeding with trauma, and have had issues with getting treatment centers on board to treat me. Most recently I’ve had my F7 activity assay come back at 64% [ref: 50-129%] but my PT time was at 14.1sec [10.6-13.3] and INR was 1.2. Subsequently mixing studies were performed where my PT was 13.9 and corrected immediately to 12.3 seconds [using PNP with a control of 11.7s]. I’m under the assumption that PNP has 100% F7 activity, and that PT does not prolong until clotting factors are below 50%. This leads me to believe that the splice site mutation may impact the binding of the F7 to the TF, which could give a normal assay level but incorrect protein shape, thus a qualitative F7 deficiency. This would be backed up by the math that the PT mixing study provides as in theory it should be a ~72% correction or RI of 4.3, leading to disqualification of inhibitors. This would make me think that I’m actually at about 32-45% rather than 64%.
I was wondering if you could explain the following things:
1) Am I correct in my assumption of math figures and tests?
2) Why do my F7 levels vary wildly between laboratories?
3) Is there any testing that would be able to get a more accurate factor 7 activity level for qualitative defects?
I reached out to Dr. Emmanuel Favaloro.
Here is Dr. Favaloro’s response:
I then requested additional information from the patient and received this response:
Hi George, Thank you so much for looking into this. I’m aware that the Arg413Gln mutation decreases the amount of F7 available and is commonly found with the -323 insertion, I’d be more interested in seeing how the splice site variant is affecting things. A doctor sequenced my F7 gene for me. In a presentation, she talks about how splice site variants impact the proteins and the importance of developing newer assays. All other coagulation testing has come back normal. Platelet function and aggregation studies have also been normal. I’m still awaiting the ATHN-10 sequencing results, though it should be about April when I receive them.
I would be glad to give you some insight into my trauma-related symptoms. My predominant symptom has always been nosebleeds that last anywhere from 5 to 45 minutes and repeat over several days but have not had any cauterization. In 2011 I was diagnosed at 49% with an INR of 1.35 and twice was given NovoSeven pre-operatively for spinal decompression (discectomy) surgery without any complications. In 2015 I had a third spinal decompression surgery that turned into a spinal fusion, at the time I was 70% and had an INR of 1.3 again, and bled into the surgical drains for 5 days. With the fusion surgery I had a drop in hemoglobin from 14 to 10g/dL and hematocrit (42% to 30%) and orthostatic hypotension as a result. I was not given any hemostatics or blood products after the spinal fusion out of fear relating to the F2 mutation and risk of clotting. I’ve had two different incidents with bleeding related to teeth removal, in 2006 (prediagnosis, 12 years old at the time) I had two baby teeth removed which I bleed for about 6 hours. In 2018 I had wisdom teeth removal that resulted in off and on bleeding over 3 days with antifibrinolytics (Amicar). I’ve had muscle hematomas related to collisions in sports that HTC ERs have refused to do any diagnostics on outside of X-rays. I’ve also had episodes of hemorrhagic ovarian cysts with the most recent one estimated to have about 55ml of blood by ultrasound.
From George, I’d like to get additional comments from our participants. Here’s the citation: