Elevated Factor VIII in Liver Disease

I had lots of coagulation blood work drawn after being diagnosed with a DVT (deep vein thrombosis). One of those tests happened to be a Factor VIII test which ended up being elevated. The test was actually ordered on accident and the doctor could not explain anything about the test. I started research Factor VIII and decided most doctors really don’t know much about this coagulation factor.

Interestingly I discovered some articles that explain Factor VIII is actually increased in liver disease when most all the other clotting proteins and factors are reduced due to impaired liver function. This sounds like a contradiction but scientists have discovered that the cirrhotic liver in unable to produce adequate amounts of a protein called low density lipoprotein receptor-related protein (LRP). One of the functions of LRP is to control the amount of Factor VIII in the blood stream by metabolizing excess amounts of Factor VIII. Another contributing factor to the increase of Factor VIII in liver disease is the increased production of von Willebrand factor (vWF) in cirrhosis. Just as LRP helps regulate the levels of Factor VIII by destroying the extra Factor VIII, vWF helps preserve Factor VIII. Therefore extra vWF and low levels of LRP would lead to higher levels of Factor VIII.


Factor VIII expression in liver disease

There is yet one more reason for increased levels of Factor VIII in liver disease. The liver is composed of tons of special cells found only in the liver called sinusoidal endothelial cells. They are very permeable and allow the liver to directly interact with the blood and perform its life essential functions. In autoimmune hepatitis (AIH) and other autoimmune liver conditions, antibodies attack these sinusoidal endothelial cells and turn them into normal capillary endothelial cells found throughout the body, which are not permeable. These special sinusoidal endothelial cells have some other important properties. One of which is they do not make Factor VIII, which normal capillary endothelial cells do. Therefore Factor VIII increases when lots of sinusoidal endothelial cells are replaced with Factor VIII producing normal endothelial cells.

Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis

Doctors Who Apologize

As illustrated in my last couple posts, autoimmune patients can be treated pretty poorly by medical professionals. The next couple articles show how a sincere apology from a doctor can actually heal both the doctor and the patient. As a patient who has been unfairly judged, I would like to think those doctors who have hurt me in the past realized what they did was wrong but just couldn’t bring themselves to apologize. Whether it was because of fear of admitting wrong and being sued or just plain pride, I’ll never know.


The Healing Power Of Apologies

“For moral reasons, physicians should be held to the same standards as others; that is apologies should be offered for “offenses,” not for predictable and expected mistakes.”


A Doctor's Apology Can Heal

"For me, the biggest piece of this conversation was her offering me forgiveness, you know … And it still sends a chill down my spine. Forgiveness goes both ways. It helps both sides."

“Nine years ago, no one ever blamed my mother's doctor for her death from a disease that ravaged her nonsmoker's lungs. But the memory of his apology and his earnest attempt to learn from what had happened still comforts me. There are times when "sorry" is the only thing to say. And sometimes, a doctor's apology helps everyone to heal.”


A Doctor's Apology, An Intensely Moving Experience

“The idea of a doctor apologizing to a patient was unheard of as few as 5 years ago. I first came upon the concept shortly after my misdiagnosis was resolved, through a piece run by CBS news. I promptly printed it off and mailed it to the doctors involved in my misdiagnosis. Then in 2007, CBS aired still another piece that talks about the physician's relief once the apology is made.”


Saying sorry is good for your health

“Physicians in particular may find it hard to apologize. Dr. Leape says this has to do with the culture of medicine. ‘First, our training leaves us with emotional baggage,” he says. “Physicians are selected for and socialized to expect perfect performance. A serious failure, such as an error that results in a major injury or death, can be so devastating to a doctor’s self-image that it may be overwhelming.’”

“In addition, he says, ‘Most physicians receive no training or support in offering apologies. They don’t know how to do it; they may feel ashamed and worry about being sued. So, it’s not a big surprise that apologies don’t always happen or are offered in the wrong way.’”

Doctors Feel Threatened By Invisible Illnesses

While this article deals with Fibromyalgia, it will ring true with anyone who is suffering from an autoimmune disease. Almost everyone with an autoimmune disease has had at least one rude encounter with a doctor, friend, or loved one questioning their pain.

Some Doctors, Friends, Relatives Dismiss Sickness

"I know in my case I just had the idea if you got sick you went to a doctor and they treated you," Matallana said. "I never, ever imagined someone would question my pain and my inability to function. That was to me almost as bad as enduring the physical symptoms.”

“The transformation of dynamic people into suffering wrecks, without any apparent cause, prompts confusion and questioning. Fibromyalgia patients say even friends, relatives and spouses find it hard to accept the reality of what has been called an invisible illness.”

“Dr. Patrick Wood, an assistant professor of medicine at Louisiana State University, decided to specialize in fibromyalgia … I don't think it makes me popular with my colleagues, but we're trained to be little gods and anything that challenges our god-like capacity we dismiss," Wood said. "(A doctor) could say, 'There's nothing to objectively demonstrate you're really sick. How do I know you're sick?' You have to trust the patient's report, which we're often not willing to do when it comes to pain."

“Some doctors dismiss patients with vague complaints of pain as hypochondriacs or malingerers, lazy people looking for an excuse not to work. It doesn't help matters that he and other doctors regularly encounter true malingerers, about whom they must make judgments to determine government disability payments.”

"Every doctor is faced with being a useful idiot, being a tool for somebody who wants to get out of work," said Lubin, who trained at Yale and Harvard. "I'd rather you fooled me once and then I could say, 'Shame on you,' rather than try to prevent my ego from ever being bruised by assuming everyone whoever asked me for a pill for their pain is a drug-seeker. We can't lose our humanity just because we're afraid of being hoodwinked."

ANCA Antibodies Found in Autoimmune Hepatitis

My positive CANCA test puzzled all the doctors so I started researching ANCA antibodies in light of my other symptoms and test results. I had just recently been diagnosed with Autoimmune Hepatitis (AIH) which is an autoimmune disease where the immune system attacks the liver. I found a couple articles written by German scientists who discovered that AIH patients can be positive for CANCA as well as PANCA. Even more interesting they discovered that the target antigen responsible for creating the CANCA test result was smooth muscle. Anti Smooth Muscle Antibody (ASMA) is the commonly known antibody associated with AIH. I also tested positive for ASMA so the positive CANCA could probably be explained by ASMA.

Actin is a target antigen of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune hepatitis type-1.

Characterization of target antigens from anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis type-I.

Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis.

High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis.

What Do ANCA Antibodies Look Like?

When I tested positive for C-ANCA more than once by different labs, I definitely wanted to know what they looked like.

University of Birmingham

Testing positive for CANCA still did not reveal a diagnosis. In my search to learn more about ANCA antibodies I ran across a very interesting article. The article gives images of ANCA antibodies, but the neat thing is it gives a description of all the antibodies the patient tested positive and negative for. The images do look different depending on the combination of positive antibodies.

A review of immunofluorescent patterns associated with antineutrophil cytoplasmic antibodies (ANCA) and their differentiation from other antibodies

ANCA Antibody Specialty Lab - University of Iowa

Doctors tested my blood for ANCA antibodies (Anti-Neutrophil Cytoplasmic Antibodies) when I was showing symptoms of vasculitis (inflammation of the blood vessels). ANCA antibodies are usually positive in vasculitis and make 2 patterns if positive, C-ANCA or P-ANCA. P-ANCA antibodies have been found in other rheumatic diseases such as Lupus, but C-ANCA is highly specific for Wegener’s, a rare form of vasculitis. When my blood came back positive for C-ANCA and it was clear I did not have Wegener’s, doctors didn’t know what to make of this. The University of Iowa has researchers who specialize in the ANCA antibodies and is where unusual ANCA results are retested.

Dr. Targoff

University of Iowa Lab Description

University of Iowa Lab Requisition Form

Why Your Doctor Behaves The Way He Does When He Doesn’t Know What Is Wrong

Doctors and patients often don’t understand one another especially when a definite diagnosis seems impossible. Doctors and patients are frustrated by the same problem and end up at odds with one another instead of partners searching for the same solution. This is a very insightful website from a doctor about how doctors think and how you can influence your doctor to best help you. I wish I had read this article years earlier.

When Doctors Don't Know What's Wrong