HCV-Infected Individuals at Increased Risk for Immune Thrombocytopenia Purpura and Autoimmune Hemolytic Anemia

Does anyone have either or both of these disorders? Is there always something new and unsettling or is it just me?

HCV-Infected Individuals at Increased Risk for Immune Thrombocytopenia Purpura and Autoimmune Hemolytic Anemia
           Eurona Earl Tilley

February 26, 2009 — The incidence of 2 severe autoimmune cytopenias — immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA) — has been shown to be elevated among individuals infected with hepatitis C virus (HCV). Research published in the February 23 issue of the Archives of Internal Medicine reveals that HCV-infected patients in the Veterans Affairs (VA) health system were at increased risk of developing ITP. However, those who underwent treatment were also at increased risk for AIHA.

"Prior studies suggesting that HCV might be an etiologic risk factor for the development of autoimmune cytopenias have been based on small series of patients from single institutions," write Elizabeth W. Chiao, MD, MPH, from the Department of Medicine, Baylor College of Medicine, Houston, and the Houston Center for Quality of Care and Utilization Studies, Health Service Research and Development Service, Michael E. DeBakey Veterans Affairs Medical Center, Texas, and colleagues. "To our knowledge, no large study has been conducted. Given that US military veterans have a high prevalence of HCV infection (5%), this population provides a unique opportunity to observe HCV-related phenomena."

To determine the effect of HCV infection on the incidence rates of ITP and AIHA, researchers analyzed the inpatient and outpatient records as well as pharmacy data from HCV-infected (n = 120,691) and matched uninfected (n = 454,905) veterans. The diagnosis of ITP and AIHA was identified via hospitalization codes. Those with a prior diagnosis of lymphoproliferative disease, HIV, or cirrhosis were excluded from the analysis.

"In this large national cohort study including over half a million US veterans, we observed HCV-infected persons to be at increased risk of ITP and AIHA," explain the authors. A Cox proportional hazards regression model revealed that the hazard ratios (HRs) for ITP and AIHA were 1.8 (95% confidence interval [CI], 1.4 – 2.3) and 2.8 (95% CI, 1.8 – 4.2), respectively.

"Because both ITP and AIHA have been previously associated with interferon alfa use, we were also interested in assessing pharmacy data to account for the effects of HCV treatment," write Dr. Chiao and colleagues. While the incidence of ITP was elevated among both treated and untreated HCV-infected individuals, the incidence of AIHA was only elevated among those who had received treatment (HR, 11.6; 95% CI, 7.0 – 19.3).

These findings were further illustrated by examining the Kaplan-Meier curves of the cumulative incidence of each of the outcomes. The cumulative incidence of ITP was significantly greater among HCV-infected individuals vs matched control individuals (P < .001) and remained significant following censorship at the time of treatment (log rank test; P = .002). However, the cumulative incidence of AIHA was significantly greater among HCV-infected individuals vs matched control individuals (P < .001), but this difference was no longer significant following censorship at the time of treatment (log rank test; P = .84).

The main advantage of this study is that it is the first involving a large cohort to evaluate the effect of HCV infection on autoimmune cytopenias. However, there were several potential limitations. These included that the diagnoses of ITP and AIHA were not confirmed through a review of the medical records; that the calculation of the cumulative incidence of ITP and AIHA did not take into consideration other competing risks, which could have resulted in biased estimates; that the study involved a relatively short follow-up, which resulted in fewer ITP and AIHA events, thereby limiting the power to detect differences; that the incidence rates of ITP and AIHA in this study were higher than the incidence rates previously reported for the general population; that the HCV genotype or the rates of sustained virologic response after treatment were not confirmed via laboratory data; that there was a limited ability to account for bias introduced by other factors, which resulted in patients being excluded from treatment based on their physician's decision; and last, that the study population was made up almost entirely (96.5%) of men.

Several biological mechanisms have been suggested to explain the relationship between HCV infection and the development of ITP. The current findings illustrate that chronic HCV infection may cause ITP via a platelet-specific mechanism in addition to the occurrence of generalized autoimmunity. Thus, the researchers suggest that the term "HCV-associated thrombocytopenias" may be appropriate for future studies. Furthermore, interferon alfa has previously been associated with ITP and AIHA. The results of this study reinforce the theory that immunomodulatory effects of interferon alfa many cause an increased risk for autoimmune cytopenia.

"Future research is needed to clarify the underlying mechanisms and implications of our findings," conclude the authors.

This study was supported by the Intramural Program of the National Cancer Institute, National Institutes of Health, and the Houston VA Health Services Research and Development Center of Excellence. The authors have disclosed no relevant financial relationships.

Arch Intern Med. 2009;169:357–363.

See:   http://www.medscape.com/viewarticle/588787?src=mp&spon=3&uac=39980BG

Mike

[jdwithhcv]

There is ALWAYS something new to alarm us!

[justme53]

What concerns me is the "damned if you do and damned if you don't" ramifications of HCV and tx. Both seem to have growing lists of risks involved......

[portann]

What I liked was how it fully disclosed the potential limitations of the study and there were quite a few.

What I didn't understand was this:

"A Cox proportional hazards regression model revealed that the hazard ratios (HRs) for ITP and AIHA were 1.8 (95% confidence interval [CI], 1.4 – 2.3) and 2.8 (95% CI, 1.8 – 4.2), respectively."

What does hazard ratio mean? Does it mean that the risk for developing ITP and AIHA is 1.8 to 2.8?  Does this mean one person in eight or two people in eight or is it 1.8% or 2.8%. Two in eight is shockingly high but as a percentage, it's low, unless you're among the under 3%.

[mikesimon]

It looks the same way to me Pam.
I have wondered for a while whether I might have a touch of hemolytic anemia. I am borderline anemic - Hb is 12.6 with low normal at 13.2 and RBC is 3.94 with low normal at  4.2.
Since I see labs very frequently I know this is typical for me. I have asked about it on occasion but since I am not fatigued and my RBC is not really noteworthy at all I have not had any intense studies. Also with liver transplant recipients there is often  signs of minor bone marrow suppression. That is what I've thought was at play with me. But, after reading this I am not so sure. The good thing is my values are stable and I feel no signs or symptoms at all. I also see transient increases in my serum bilirubin - nothing serious but noticeable. Now I wonder if the bilirubin increase is due to a transient spike in hemolytic anemia where unconjugated or indirect bilirubin rises due to premature destruction of red blood cells.
Oh boy, this will be fun to run by my doctors. Maybe I'll pass. After all I do feel good.
Mike

[CoWriter]

This is really going to help Vets.  Many of them can't treat because their platelets are too low.  But they don't usually get diagnosed with ITP.

A diagnosis of ITP would allow them to use Promacta (eltrombopag)....which is the only indication it can be prescribed for.  So now we have to make sure they get diagnosed.

This is really good news.  Thanks for the article Mike.

Co

[mikesimon]

I sure didn't see that side of it. I didn't have a clue.
Thanks for the info.
Mike

[GreatBird]

I've always been borderline anemic, but then so was my mother and she didn't have HCV. I have wondered if that borderline anemia is one of the reasons that my HCV progressed so slowly--i.e., the lack of iron since iron seems to "feed" the virus.

[mikesimon]

I don't know about that. The first thing that occurs to me is whether your anemia is due to iron deficiency. Since iron deficiency is the most common cause of anemia I'd think that you and your Mother would have been tested and diet changes would have been recommended and/or iron supplementation would have been prescribed.
Aside from that I doubt that low iron stores would slow the progression of HCV. I don't know for certain but it seems unlikely.
Mike

[ejoli]

My first symptom of HCV was low platelets( in 2003) .I was misdianosed by hemotologist as having ITP. I was treated with high dose predisone for 6 months. I weaned myself off those and just monitered my platelets. In 2006 I changed Drs. and they tested me for hep c and low and behold... I have cirrhosis.  I think that they pretty much have decided that I don't have ITP Just HCV...  ITP is dianosed by exclusion.  They tested everything else (including bone marrow) and decided it was ITP. They just never tested me for HCV.... I think that if I had txed in 2003 before the steroids I would have been alot better off.              -Libby

[mikesimon]

I agree with you. I also think that your treatment or lack thereof might possibly give rise to a malpractice claim. I would suspect that your liver enzymes were elevated at the time but perhaps they weren't. In any event the steroids certainly didn't help in your battle against the HCV.
Mike

[ejoli]

Yes, as it turned out my liver enzymes were mildly elevated. I talked to a bunch of lawyers in '06 when I was dianosed and they all declined. It would be too hard to prove acual damages they say.  I'm sure the fact that the Dr. is a big time oncologist/hemotologist had alot to do with it too. Oh, well ...wouldn't make any difference at this point. I txed once and relapsed. I'm just hoping to get in a trial. I have been evaluted for a tp and am way down on the list. (meld is 10, I think)  I still have low platelets (80 to 100) I'm just glad I didn't let him remove my spleen like he wanted to. :)

[mikesimon]

I'm sorry that this happened to you. I could tell you some horror stories about my care but I won't.
I wish you the very best.
Mike

[alagirl]

Its thought that I have autoimmune hemolytic anemia.  However, my anemia pre-dated both my hep c infection and its treatment.  Mine is thought to be caused by antiphospholipid disorder/syndrome.

[alagirl]

My anemia is not stable like yours though.  If I don't take procrit it just keeps tanking.  For years it hovered around 8 or 9, sometimes even hitting 10 when I was lucky.  Then a few years ago it just stopped being stable even at that low number, so I am permanently on epogen.  Which works pretty well actually, allowing me to be symptom free.