The investigations show adequate VWF levels and therefore exclude VWD. It is shocking that this patient was not managed immediately in an urgent/emergency fashion for severe anemia with intravenous iron and rapid assessment by obgyn (5 days is too much). Furthermore, this patient may have bled enough to be in DIC and consumptive coagulopathy and developed VTE as a consequence. The link between elevation in factor 8 and VTE is weak as it does not accurately predict recurrence or first thrombosis.
There has been some population level data to suggest it may predict recurrence but that evidence hasn’t been reproduced to my knowledge. Being an acute phase reactant, factor 8 levels are useless in diagnosis and follow up in my opinion and do not change management. One caveat, is that recently an Italian family with recurrent VTEs were described with a duplication of the factor 8 gene and extremely elevated levels - but this is exceedingly rare.
Thanks for the comment! I hadn't thought of the connection of bleeding to DIC to VTE. The timeline seems a bit too long (3 months from Hgb 6 to VTE) but we don't have any labs during that whole time period so not exactly clear.
Doesn't sound like there's good data to support the factor 8 / VTE connection, even IF it was found to be elevated when the patient was not under physiologic stress.
Pathologist with a decent amount of coag lab experience. First off, yay, a relevant case! I agree that the chronically elevated Factor 8-increased thrombosis risk is weak. We typically sign these out with somewhat wishy-washy language that in certain clinical contexts it may be associated with increased thrombosis risk. Even that language would only be added after confirmation of chronically elevated F8 (which we don't have evidence of here) and typically with levels that are way higher than what were seen here (e.g. 400+).
To me, what is most shocking is that so little was done in response to Hgb of 6.0 i/s/o vaginal bleeding but I will admit that what is the standard of care there is outside my scope.
Thanks for the comment! Pathologists don't have a ton of med mal cases, glad I finally got one relevant to you! Can you comment on the units for factor 8 tests? I've seen some listed as percentages and some as IU/dL.
Feb 8, 2023·edited Feb 8, 2023Liked by Med Mal Reviewer
They are interchangeable. Fibrinogen is usually reported in mg/dL so I guess that’s where IU/dL comes from rather than IU/mL or IU/L, but 100%=100IU/dL.
Feb 7, 2023·edited Feb 8, 2023Liked by Med Mal Reviewer
I'm a hematologist and I share the opinion on weak and undisclosed connection between elevated VIII and thrombosis risk. I also have a feeling that knowing the test results would not change approach of a gyncologist as there would be no evidence based argument to witheld therapies to control bleeding in such serious prolonged major bleeding episode. It is evident that serious bleeding diathesis was present despite elevated factor VIII levels which is also somewhat contradictory with the view that she had inherited pro-thrombotic condition (however possible). I treated a young female patient with VTE that developed proximal leg thrombosis due to untreated mioma of uterus due to compressive effect of the tumor. We do not know what was the cause of such serious vaginal bleeding in the described case.
Agree, seems bizarre to argue that she had an inherited pro-thrombotic condition while she was being treated for bleeding. I supposed those two things are always mutually exclusive but just raises a red flag from the very beginning that the plaintiff never even tried to address.
I'm wondering what the CBC's Hgb/Hct showed, I've seen the POC Hgb be wildly off. Either way yes, the pediatrician would either have to get a stat CBC or send the patient to the ED to determine the need for transfusion. Agree with everyone's sentiment about needing to understand why the patient was bleeding so much. Would need to see the patient's other risk factors for DVT as well.
Glad to see a hematologist comment. Thanks! I came to comment re: transfusion that depending on her symptoms and her young age, she probably would have been a candidate for iron infusion instead of blood transfusion despite her Hgb of 6. Given today’s EMRs, it’s unfortunate that the Ob/Gyns did not have access to her results, although, honestly, what would they have done with them? Was there ever an U/S ordered? We still don’t really know why she was bleeding so heavily. Polyp(s), fibroid(s), bizarre AVM, thyroid issues, PCOS, cancer, etc etc.
How fast do you usually see hemoglobin improve after iron transfusion? In the ED setting its not really ever something we consider, usually just go for transfusion if they have severe bleeding and Hgb < 7.
I’m an EM doc and not anything I would consider as first line either. However, having talked to hematologists about some of the anemic pts we see, having an infusion center next door, etc, just thought that this might be an option. I free though we typically would consider transfusing but it would be a risks/benefits discussion with the pt re: transfusion with quick improvement of anemia symptoms vs iron infusion with 1-2 week increase of Hgb. All in all, this is such a bizarre case and overall not enough of a work up re: labs or imaging as to why she was bleeding so much.
I see a fair amount of women with bleeding disorders. Generally speaking I prefer iron infusions to avoid transfusion associated risks mainly reactions and future allo-immunization risk. If you have access to newer formulations such as derisomaltose on your formulary you could give 1 gram and that’s all they will need. The patients will start to feel crappy for a day or two while the marrow uptakes the iron but slowly over 4-5 days they will start producing reticulocytes and the Hb will start to rise. Expect normal Hb levels in 4-6 weeks (if adequately replaced and not losing iron). Obviously, this needs close out patient follow up to ensure the bleeding is not worse so I understand why in some circumstances transfusions are preferred.
Hematologist here, thanks for this case.
The investigations show adequate VWF levels and therefore exclude VWD. It is shocking that this patient was not managed immediately in an urgent/emergency fashion for severe anemia with intravenous iron and rapid assessment by obgyn (5 days is too much). Furthermore, this patient may have bled enough to be in DIC and consumptive coagulopathy and developed VTE as a consequence. The link between elevation in factor 8 and VTE is weak as it does not accurately predict recurrence or first thrombosis.
There has been some population level data to suggest it may predict recurrence but that evidence hasn’t been reproduced to my knowledge. Being an acute phase reactant, factor 8 levels are useless in diagnosis and follow up in my opinion and do not change management. One caveat, is that recently an Italian family with recurrent VTEs were described with a duplication of the factor 8 gene and extremely elevated levels - but this is exceedingly rare.
Thanks for the comment! I hadn't thought of the connection of bleeding to DIC to VTE. The timeline seems a bit too long (3 months from Hgb 6 to VTE) but we don't have any labs during that whole time period so not exactly clear.
Doesn't sound like there's good data to support the factor 8 / VTE connection, even IF it was found to be elevated when the patient was not under physiologic stress.
Sorry I missed that the timeline was 3 months, that does make it unlikely - I agree with you.
Pathologist with a decent amount of coag lab experience. First off, yay, a relevant case! I agree that the chronically elevated Factor 8-increased thrombosis risk is weak. We typically sign these out with somewhat wishy-washy language that in certain clinical contexts it may be associated with increased thrombosis risk. Even that language would only be added after confirmation of chronically elevated F8 (which we don't have evidence of here) and typically with levels that are way higher than what were seen here (e.g. 400+).
To me, what is most shocking is that so little was done in response to Hgb of 6.0 i/s/o vaginal bleeding but I will admit that what is the standard of care there is outside my scope.
Thanks for the comment! Pathologists don't have a ton of med mal cases, glad I finally got one relevant to you! Can you comment on the units for factor 8 tests? I've seen some listed as percentages and some as IU/dL.
They are interchangeable. Fibrinogen is usually reported in mg/dL so I guess that’s where IU/dL comes from rather than IU/mL or IU/L, but 100%=100IU/dL.
I'm a hematologist and I share the opinion on weak and undisclosed connection between elevated VIII and thrombosis risk. I also have a feeling that knowing the test results would not change approach of a gyncologist as there would be no evidence based argument to witheld therapies to control bleeding in such serious prolonged major bleeding episode. It is evident that serious bleeding diathesis was present despite elevated factor VIII levels which is also somewhat contradictory with the view that she had inherited pro-thrombotic condition (however possible). I treated a young female patient with VTE that developed proximal leg thrombosis due to untreated mioma of uterus due to compressive effect of the tumor. We do not know what was the cause of such serious vaginal bleeding in the described case.
Agree, seems bizarre to argue that she had an inherited pro-thrombotic condition while she was being treated for bleeding. I supposed those two things are always mutually exclusive but just raises a red flag from the very beginning that the plaintiff never even tried to address.
I'm wondering what the CBC's Hgb/Hct showed, I've seen the POC Hgb be wildly off. Either way yes, the pediatrician would either have to get a stat CBC or send the patient to the ED to determine the need for transfusion. Agree with everyone's sentiment about needing to understand why the patient was bleeding so much. Would need to see the patient's other risk factors for DVT as well.
Glad to see a hematologist comment. Thanks! I came to comment re: transfusion that depending on her symptoms and her young age, she probably would have been a candidate for iron infusion instead of blood transfusion despite her Hgb of 6. Given today’s EMRs, it’s unfortunate that the Ob/Gyns did not have access to her results, although, honestly, what would they have done with them? Was there ever an U/S ordered? We still don’t really know why she was bleeding so heavily. Polyp(s), fibroid(s), bizarre AVM, thyroid issues, PCOS, cancer, etc etc.
How fast do you usually see hemoglobin improve after iron transfusion? In the ED setting its not really ever something we consider, usually just go for transfusion if they have severe bleeding and Hgb < 7.
I’m an EM doc and not anything I would consider as first line either. However, having talked to hematologists about some of the anemic pts we see, having an infusion center next door, etc, just thought that this might be an option. I free though we typically would consider transfusing but it would be a risks/benefits discussion with the pt re: transfusion with quick improvement of anemia symptoms vs iron infusion with 1-2 week increase of Hgb. All in all, this is such a bizarre case and overall not enough of a work up re: labs or imaging as to why she was bleeding so much.
I see a fair amount of women with bleeding disorders. Generally speaking I prefer iron infusions to avoid transfusion associated risks mainly reactions and future allo-immunization risk. If you have access to newer formulations such as derisomaltose on your formulary you could give 1 gram and that’s all they will need. The patients will start to feel crappy for a day or two while the marrow uptakes the iron but slowly over 4-5 days they will start producing reticulocytes and the Hb will start to rise. Expect normal Hb levels in 4-6 weeks (if adequately replaced and not losing iron). Obviously, this needs close out patient follow up to ensure the bleeding is not worse so I understand why in some circumstances transfusions are preferred.