Factor VIII and XIII Deficiency?

Factor VIII and XIII Deficiency?
George Fritsma
Dec 28, 2010 4:04am

I had a recent communication through the American Society for Clinical Laboratory Science Consumer Forum in which a patient with severe chronic bleeding symptoms had been diagnosed as having both a factor VIII and a factor XIII deficiency. Given prevalence data, I compute the odds of this combination as 1 in 10 billion, and have found no published cases, though I found two cases of combined von Willebrand disease and factor XIII deficiency. I suggested the factor XIII deficiency conclusion could be false, based on a false positive urea solubility assay. It struck me that factor VIII deficiency would generate a weak clot that would dissolve in the urea solution, giving the false impression of a factor XIII deficiency, but I can’t find anything in writing to support my conclusion. I recommended the patient’s physician ensure the lab was using one of the updatedchromogenic factor XIII assays. Do you have any experience with a combined VIII and XIII deficiency? Also, would you please comment on the urea solubility test?

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I had a recent communication through the American Society for Clinical Laboratory Science Consumer Forum in which a patient with severe chronic bleeding symptoms had been diagnosed as having both a factor VIII and a factor XIII deficiency. Given prevalence data, I compute the odds of this combination as 1 in 10 billion, and have found no published cases, though I found two cases of combined von Willebrand disease and factor XIII deficiency. I suggested the factor XIII deficiency conclusion could be false, based on a false positive urea solubility assay. It struck me that factor VIII deficiency would generate a weak clot that would dissolve in the urea solution, giving the false impression of a factor XIII deficiency, but I can’t find anything in writing to support my conclusion. I recommended the patient’s physician ensure the lab was using one of the updatedchromogenic factor XIII assays. Do you have any experience with a combined VIII and XIII deficiency? Also, would you please comment on the urea solubility test?

By Lab Tech Herb Crown
Jan 5, 2011 2:20pm
Hello George and friends. To respond to this question, I would say that one of the most common clerical errors we see in our reference laboratory is the free exchange or should I say interchange in orders written for factor VIII and factor XIII. Hardly a day goes by where we have not had to ask for clarification of a factor XIII order and usually we find it should have been written for factor VIII. In addition, there are a number of preanalytic variables that can result in a low factor VIII being reported. As well, you are correct, this would be very very rare (but possible), but before a person is labeled for life with this kind of diagnosis, repeat testing is imperative.
I have never asked the question, “What would the factor XIII urea clot look like in a factor VIII deficient plasma?” So, I took Precision BioLogic factor VIII deficient plasma and performed a urea clot solubility test on it. It tested out as “normal”. That is a “n” of one. I did not test any other factor deficient plasmas for this experiment.

George, you had previously posted an excellent paper on factor XIII deficiency by Jennings and Kitchen:
http://www.fritsmafactor.com/upload/J%20Thromb%20Haemost%202003%201%202603-8.pdf

As I read this paper, the issue that became very clear to me is that assaying for factor XIII is problematic for both methods. I believe it is more problematic for the quantitative method, “for the untreated factor XIII-deficient sample, a mean XIII of 7.6 u/dL was obtained with results ranging from 2 to 55 u/dL.” (Jennings and Kitchen) The conclusion of the authors is, “the use of solubility screens employing thrombin alone to clot plasma and acetic acid for lysis allows for greater sensitivity to moderate factor XIII deficiency.”

Factor XIII does not get a lot of attention in the US. Clearly more work needs to be done in this area to standardize the test methods and diagnosis of our patients. It is almost an orphan disease. I would suspect (my opinion only, unencumbered by facts) if we spent the time, money and effort, we would find a “multi-level” strategy such as we have in hemophilia A and B.

As for this patient, repeat testing is required, paying particular attention to specimen acquisition and processing.

Regards,
Herb Crown
St. Louis University Hospital Coagulation Reference Laboratory
By Ejaz
Sep 30, 2019 3:52pm
Dear George and friends I have read the whole thread, I have 2 years son which has been diagnosed with both factor VIII and XIII deficiency by Agha Khan labs in Pakistan, I am totally a lay man in medical things, I just want to know how can I make sure that my son suffer from both disorders, particular after George said this could happen 1 in million people, please guide me with details.
By George Fritsma
Oct 4, 2019 8:14am
To Ejaz, the prevalence of factor VIII deficiency is 1–2 per 10,000 boys. The prevalence of factor XIII deficiency is 1 in several million (Seminars in Thrombosis and Hemostasis, 2016). We can predict on a statistical basis that the possible prevalence of both occurring in one individual is vanishingly small. I suggest you ask your doctor to reorder the factor XIII assay for confirmation, given that the condition is rare and tests for factor XIII deficiency may be slightly less reliable than factor VIII assays.

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