Aa
Cryoglobulinemia and HCV, lengthy and wordy, sorry!
I was diagnosed with cryoglobulinemia a few months ago from a blood test that showed cryoglobulins in my blood. Usually cryoglobulinemia is caused by an underlying disease one of which is HCV. Some research suggests that a substantial amount of people with HCV have cryoglobulins in their blood. Usually people who have cryo associated with HCV, also have rheumatoid arthritis factor in their blood and the most common symptom is vasculitis. I have read that this type of RA level mimics rheumatoid arthritis not associated with HCV, and as always causes joint pain and inflammation.
Usually with cryo if you can eliminate the underlying disease then you eliminate the cryo. Interferon will often destroy cryo, but if you eliminate hcv while on tx and the cryo comes back afterwards, it is usually because another underlying disease is causing the cryo. Other diseases associated with cryo are multiple myeloma, waldenstrom's macroglobulinemia, rheumatoid arthritis, non-hodgkins lymphoma and many others that are not as serious. I was tested for these blood cancers after I had a blood test that revealed a monoclonal protien that points to those type of cancers, this was the same blood test that confirmed that I had cryo oroiginally.
The blood test for cryo has to be handled in a very specific manner regarding temperature of test tubes, type of test tubes and has to be centrifuged promptly and watched for many days at different temperatures. The first test I had was not kept a proper temperatures and was sent to an outside lab for evaluation which caused a false positive IGM monoclonal protein. I spent two months being checked for multiple myeloma before I was told I definately didn't have it.
I still had the cryoglobulins in my blood after being retested. At the time of the original test, I told the nurse for my very prominent hcv doctor that I was concerned that the test tubes not being warmed and being kept at room temp in the lab, they acted as if I didn't know what I was talking about. This was done at a hospital. I later had it redone at Stanford medical center who did it properly. Only certain hospitals are equipped to handle this test properly.
The first specialist tested me for cryo, RH factor and RA level and all were positive. They also biopsied and confirmed my vasculitis (red pooled up blood sports all over my legs which were not raised). The vasculitis has been mostly inactive for the last year, but was very active for a year and a half before that.
A diagnosis of cryo includes the cryoglobulin level in your blood, warning signs of it being serious can be vasculitis, because that blood can also pool in your kidneys, heart and brain (or anywhere) and kill you. Often it doesn't harm the patient if at a low level.
Sorry if I didn't write this very clearly, I just started tx and I am having a bit of trouble thinking and writing.
Usually with cryo if you can eliminate the underlying disease then you eliminate the cryo. Interferon will often destroy cryo, but if you eliminate hcv while on tx and the cryo comes back afterwards, it is usually because another underlying disease is causing the cryo. Other diseases associated with cryo are multiple myeloma, waldenstrom's macroglobulinemia, rheumatoid arthritis, non-hodgkins lymphoma and many others that are not as serious. I was tested for these blood cancers after I had a blood test that revealed a monoclonal protien that points to those type of cancers, this was the same blood test that confirmed that I had cryo oroiginally.
The blood test for cryo has to be handled in a very specific manner regarding temperature of test tubes, type of test tubes and has to be centrifuged promptly and watched for many days at different temperatures. The first test I had was not kept a proper temperatures and was sent to an outside lab for evaluation which caused a false positive IGM monoclonal protein. I spent two months being checked for multiple myeloma before I was told I definately didn't have it.
I still had the cryoglobulins in my blood after being retested. At the time of the original test, I told the nurse for my very prominent hcv doctor that I was concerned that the test tubes not being warmed and being kept at room temp in the lab, they acted as if I didn't know what I was talking about. This was done at a hospital. I later had it redone at Stanford medical center who did it properly. Only certain hospitals are equipped to handle this test properly.
The first specialist tested me for cryo, RH factor and RA level and all were positive. They also biopsied and confirmed my vasculitis (red pooled up blood sports all over my legs which were not raised). The vasculitis has been mostly inactive for the last year, but was very active for a year and a half before that.
A diagnosis of cryo includes the cryoglobulin level in your blood, warning signs of it being serious can be vasculitis, because that blood can also pool in your kidneys, heart and brain (or anywhere) and kill you. Often it doesn't harm the patient if at a low level.
Sorry if I didn't write this very clearly, I just started tx and I am having a bit of trouble thinking and writing.
Now I get it, I didn't realize this was an old thread and I finally figured it out.lol It all makes sense now. Yeah, I don't have the bumps but my feet and my legs swell, even my hands. I finally was able to get my PCP to give me a referral to a Heptologist saw him the first week of August and hopefully I will get to the bottom of my swelling. Glad to hear you're doing well, I appreciate you getting back to me. ~ kind regards
This is great to hear Dave
Same here, it took ages for someone to realise what the issue is. For the last 3 years I was mentioning to every doctor I met. Only now, a few months back, after HCV diagnose my hepatologist finally identified it. If only more doctors will be more clued up about it..
Same here, it took ages for someone to realise what the issue is. For the last 3 years I was mentioning to every doctor I met. Only now, a few months back, after HCV diagnose my hepatologist finally identified it. If only more doctors will be more clued up about it..
"I am wondering about how you came to taking the blood test as not everyone gets sent for it?"
I had vasculitis, red spots all over me from waste down coming and going over a couple of years. My PCP couldn't figure it out but my hepatologist thought I needed to be tested and also had a dermatologist do a biopsy of the vasculitis to confirm it. I was positive for both.
Good luck and I hope you don't have it. My cryo resolved and never returned after I started tx. I have been SVR for about 1.5 years now and was tested for cryo post tx at a hospital that does the testing correctly (Standford medical center in California)
Take care,
Dave
I had vasculitis, red spots all over me from waste down coming and going over a couple of years. My PCP couldn't figure it out but my hepatologist thought I needed to be tested and also had a dermatologist do a biopsy of the vasculitis to confirm it. I was positive for both.
Good luck and I hope you don't have it. My cryo resolved and never returned after I started tx. I have been SVR for about 1.5 years now and was tested for cryo post tx at a hospital that does the testing correctly (Standford medical center in California)
Take care,
Dave
I have the HCV genotype 1b with Cryo type II and of course there is a raised RA factor (27). And I also have Non Hodgkins Marginal Zone Lymphoma.
I have been told not to worry about the RA and the Cryo. We have established that the cancer is caused by the HCV with Cryo being the proof and the link. All my research point that by treating the HCV all the other ones will just go in remission/heal/dissaper.
I am waiting for Telaprevir hopefuly to be aproved , it is difficult as the ones in charge are asking for proof. SOC for lymphoma is chemo so I am am having a real fight to show that I am right. I am shattered after ech specialist visit and I feel so hopeless. But Standard chemo is something I will never do. (yeah I know even Interferon is chemo)
Frustrating!!!!
I have been told not to worry about the RA and the Cryo. We have established that the cancer is caused by the HCV with Cryo being the proof and the link. All my research point that by treating the HCV all the other ones will just go in remission/heal/dissaper.
I am waiting for Telaprevir hopefuly to be aproved , it is difficult as the ones in charge are asking for proof. SOC for lymphoma is chemo so I am am having a real fight to show that I am right. I am shattered after ech specialist visit and I feel so hopeless. But Standard chemo is something I will never do. (yeah I know even Interferon is chemo)
Frustrating!!!!
I hope I don't have cryoglobulins but today I faced the music and went to have my blood drawn for this test, 9 tubes. Bumping this thread back up to expose cryoglobulinemia and everything that goes with it. Anyone else have it?
Hey I thought about you when I was reading these slides. I remember in your other post how you outlined the LabCorp Protocol for detecting Cryo:
http://www.medhelp.org/user_photos/show/288860?personal_page_id=1282072
http://www.medhelp.org/user_photos/show/288860?personal_page_id=1282072
I have actually been a little concerned about Cryo myself recently. Or more accurately: Reynaud's.
This is a really cool slide presentation that mentions all three types of Cryo. It trims the fat off a journal article and just has the salient details on each slide.
I think you have to be logged into Google to read it however (it is a huge PDF file).
The first 8 slides are patient studies so you have to arrow down.
http://tinyurl.com/bnfxldm
Ha just as an aside I have always heard people on here say that in most HCV-related cases that treating the virus is essentially treating the Cryo and now I understand why:
http://www.medhelp.org/user_photos/show/288857?personal_page_id=1282072
Cryo Lab Findings:
http://www.medhelp.org/user_photos/show/288858?personal_page_id=1282072
This is a really cool slide presentation that mentions all three types of Cryo. It trims the fat off a journal article and just has the salient details on each slide.
I think you have to be logged into Google to read it however (it is a huge PDF file).
The first 8 slides are patient studies so you have to arrow down.
http://tinyurl.com/bnfxldm
Ha just as an aside I have always heard people on here say that in most HCV-related cases that treating the virus is essentially treating the Cryo and now I understand why:
http://www.medhelp.org/user_photos/show/288857?personal_page_id=1282072
Cryo Lab Findings:
http://www.medhelp.org/user_photos/show/288858?personal_page_id=1282072
I appreciate the information as I am supposed to take a test very soon specifically for cryoglobulin and I am wondering about how you came to taking the blood test as not everyone gets sent for it? I recently got a new doctor and this guy is really good he's actually a Heptologist which makes me feel alot better than the Gastro I was seeing as he seemed to hate working with heppers. Anyways, I am being sent to get the blood test b/c my feet, legs and hands swell. How about you, do you have a problem with swelling?. I will most likely get the test done this week. Hope you're doing well.
Test ID: CRGSP83659
Cryoglobulin and Cryofibrinogen Panel, Serum and Plasma
Useful For
Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases
Evaluating patients with macroglobulinemia or myeloma in whom symptoms occur with cold exposure
Profile Information
Test ID Reporting Name Available Separately Always Performed
CRY_S Cryoglobulin, S Yes Yes
CRY_P Cryofibrinogen, P No Yes
Reflex Tests
Test ID Secondary ID Reporting Name Available Separately Always Performed
IMFXC 28265 Immunofixation Cryoglobulin No No
Testing Algorithm
If cryoglobulin has a result other than negative, then immunofixation will be performed at an additional charge. Positive cryoglobulins of > or =0.1 mL of precipitate will be typed once.
Method Name
CRY_S/80988, CRY_P/80550: Quantitation and Qualitative Typing Precipitation at 1 Degree C
Includes cryofibrinogen.
IMFXC/28265: Immunofixation
Reporting Name
Cryo Panel, S and P
Aliases
Cryocrit (suggest cryoglobulin-better test)
Cryofibrinogen
Cryoglobulin Mixed Determination
Cryoglobulin, Plasma and Serum
Cryoprotein
Specimen Type
Plasma EDTA
Serum
Specimen Required
Plasma and serum are required.
Cryofibrinogen
Collection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Tube must remain at 37 degrees C.
2. Centrifuge at 37 degrees C. (Do not use a refrigerated centrifuge. If absolutely necessary, ambient temperature is acceptable.) It is very important that the specimen remain at 37 degrees C until after separation of plasma from red cells.
3. Place plasma into an appropriately labeled plastic vial.
Cryoglobulin
Collection Container/Tube: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 5 mL
Collection Instructions:
1. Tube must remain at 37 degrees C.
2. Allow blood to clot at 37 degrees C.
3. Centrifuge at 37 degrees C. (Do not use a refrigerated centrifuge. If absolutely necessary, ambient temperature is acceptable.) It is very important that the specimen remain at 37 degrees C until after separation of serum from red cells.
4. Place serum into an appropriately labeled plastic vial.
Additional Information: Analysis cannot be performed with <3 mL of serum. Smaller volumes are insufficient to detect clinically important trace (mixed) cryoglobulins. Less than 3 mL will require draw of a new specimen.
Specimen Minimum Volume
Serum: 3 mL/Plasma: 0.5 mL
Reject Due To
Hemolysis
Mild OK; Gross OK
Lipemia
Mild OK; Gross OK
Icterus
Mild OK; Gross OK
Other
Serum gel tube or plasma gel tube
Specimen Stability Information
Specimen Type Temperature Time
Plasma EDTA Refrigerated (preferred)
Frozen
Serum Refrigerated (preferred)
Frozen
Clinical Information
Cryoglobulins are immunoglobulins that precipitate when cooled and dissolve when heated. Because these proteins precipitate when cooled, patients may experience symptoms when exposed to the cold. Cryoglobulins may be associated with a variety of diseases including plasma cell disorders, autoimmune diseases, and infections. Cryoglobulins may also cause erroneous results with some automated hematology instruments.
Cryoglobulins are classified as:
-Type I (monoclonal)
-Type II (mixed--2 or more immunoglobulins of which 1 is monoclonal)
-Type III (polyclonal--in which no monoclonal protein is found)
Type I cryoglobulinemia is associated with monoclonal gammopathy of undetermined significance, macroglobulinemia, or multiple myeloma.
Type II cryoglobulinemia is associated with autoimmune disorders such as vasculitis, glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It may be seen in infections such as hepatitis, infectious mononucleosis, cytomegalovirus, and toxoplasmosis. Type II cryoglobulinemia may also be essential, ie, occurring in the absence of underlying disease.
Type III cryoglobulinemia usually demonstrates trace levels of cryoprecipitate, may take up to 7 days to appear, and is associated with the same disease spectrum as Type II cryoglobulinemia.
A cryoprecipitate that is seen in plasma but not in serum is caused by cryofibrinogen. Cryofibrinogens are extremely rare and can be associated with vasculitis. Due to the rarity of clinically significant cryofibrinogenemia, testing for cryoglobulins is usually sufficient for investigation of cryoproteins.
Reference Values
CRYOGLOBULIN
Negative (positives reported as percent)
If positive after 1 or 7 days, immunotyping of the cryoprecipitate is performed at an additional charge.
CRYOFIBRINOGEN
Negative
Quantitation and immunotyping will not be performed on positive cryofibrinogen.
Interpretation
An interpretive report will be provided.
Cautions
Failure to follow specimen handling instructions may cause false-negative results.
Not useful for general screening of a population without a clinical suspicion of cryoglobulinemia.
Clinical Reference
Kyle RA, Lust JA: Immunoglobulins and laboratory recognition of monoclonal proteins. Section III. Myeloma and related disorders. In Neoplastic Diseases of the Blood. 3rd edition. Edited by PH Wiernik, GP Canellos, JP Dutcher, RA Kyle. New York, Churchill Livingstone, 1996, pp 453-475
Method Description
The normal proteins of plasma and serum do not precipitate in the cold. An aliquot of plasma and of serum are incubated for 24 hours at 1 degree C. If a precipitate develops in the serum, the specimen is centrifuged and the percent precipitate is reported. Negative specimens are kept at 1 degree C for 7 days and rechecked. All positive cryoglobulins are analyzed by immunofixation to determine if the precipitate is a monoclonal protein, polyclonal protein, or a mixed cryoglobulin. Precipitates that occur in plasma and not serum are reported as positive for cryofibrinogen. Cryofibrinogen-positive specimens are not quantitated or immunotyped. Slowly forming fibrin clots (as may occur in hemophilia) are distinguished from cryoprecipitates by their inability to redissolve on warming.(Lerner AB, Watson CJ: Studies of cryoglobulins. I. Unusual purpura associated with the presence of a high concentration of cryoglobulin [cold precipitatable serum globulin]. Am J Med Sci 1947;214:410-415)
Day(s) and Time(s) Test Performed
Monday through Friday; 4 p.m.
Analytic Time
2 days
Maximum Laboratory Time
10 days
Specimen Retention Time
Neg, 7 days/Pos, until reported
Performing Laboratory Location
Rochester
NY State Approved
Yes
CPT Code Information
82585-Cryofibrinogen
82595-Cryoglobulin
86334-Immunofixation (if appropriate)
http://www.mayomedicallaboratories.com/test-catalog/print/83659
Cryoglobulin and Cryofibrinogen Panel, Serum and Plasma
Useful For
Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases
Evaluating patients with macroglobulinemia or myeloma in whom symptoms occur with cold exposure
Profile Information
Test ID Reporting Name Available Separately Always Performed
CRY_S Cryoglobulin, S Yes Yes
CRY_P Cryofibrinogen, P No Yes
Reflex Tests
Test ID Secondary ID Reporting Name Available Separately Always Performed
IMFXC 28265 Immunofixation Cryoglobulin No No
Testing Algorithm
If cryoglobulin has a result other than negative, then immunofixation will be performed at an additional charge. Positive cryoglobulins of > or =0.1 mL of precipitate will be typed once.
Method Name
CRY_S/80988, CRY_P/80550: Quantitation and Qualitative Typing Precipitation at 1 Degree C
Includes cryofibrinogen.
IMFXC/28265: Immunofixation
Reporting Name
Cryo Panel, S and P
Aliases
Cryocrit (suggest cryoglobulin-better test)
Cryofibrinogen
Cryoglobulin Mixed Determination
Cryoglobulin, Plasma and Serum
Cryoprotein
Specimen Type
Plasma EDTA
Serum
Specimen Required
Plasma and serum are required.
Cryofibrinogen
Collection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Tube must remain at 37 degrees C.
2. Centrifuge at 37 degrees C. (Do not use a refrigerated centrifuge. If absolutely necessary, ambient temperature is acceptable.) It is very important that the specimen remain at 37 degrees C until after separation of plasma from red cells.
3. Place plasma into an appropriately labeled plastic vial.
Cryoglobulin
Collection Container/Tube: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 5 mL
Collection Instructions:
1. Tube must remain at 37 degrees C.
2. Allow blood to clot at 37 degrees C.
3. Centrifuge at 37 degrees C. (Do not use a refrigerated centrifuge. If absolutely necessary, ambient temperature is acceptable.) It is very important that the specimen remain at 37 degrees C until after separation of serum from red cells.
4. Place serum into an appropriately labeled plastic vial.
Additional Information: Analysis cannot be performed with <3 mL of serum. Smaller volumes are insufficient to detect clinically important trace (mixed) cryoglobulins. Less than 3 mL will require draw of a new specimen.
Specimen Minimum Volume
Serum: 3 mL/Plasma: 0.5 mL
Reject Due To
Hemolysis
Mild OK; Gross OK
Lipemia
Mild OK; Gross OK
Icterus
Mild OK; Gross OK
Other
Serum gel tube or plasma gel tube
Specimen Stability Information
Specimen Type Temperature Time
Plasma EDTA Refrigerated (preferred)
Frozen
Serum Refrigerated (preferred)
Frozen
Clinical Information
Cryoglobulins are immunoglobulins that precipitate when cooled and dissolve when heated. Because these proteins precipitate when cooled, patients may experience symptoms when exposed to the cold. Cryoglobulins may be associated with a variety of diseases including plasma cell disorders, autoimmune diseases, and infections. Cryoglobulins may also cause erroneous results with some automated hematology instruments.
Cryoglobulins are classified as:
-Type I (monoclonal)
-Type II (mixed--2 or more immunoglobulins of which 1 is monoclonal)
-Type III (polyclonal--in which no monoclonal protein is found)
Type I cryoglobulinemia is associated with monoclonal gammopathy of undetermined significance, macroglobulinemia, or multiple myeloma.
Type II cryoglobulinemia is associated with autoimmune disorders such as vasculitis, glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It may be seen in infections such as hepatitis, infectious mononucleosis, cytomegalovirus, and toxoplasmosis. Type II cryoglobulinemia may also be essential, ie, occurring in the absence of underlying disease.
Type III cryoglobulinemia usually demonstrates trace levels of cryoprecipitate, may take up to 7 days to appear, and is associated with the same disease spectrum as Type II cryoglobulinemia.
A cryoprecipitate that is seen in plasma but not in serum is caused by cryofibrinogen. Cryofibrinogens are extremely rare and can be associated with vasculitis. Due to the rarity of clinically significant cryofibrinogenemia, testing for cryoglobulins is usually sufficient for investigation of cryoproteins.
Reference Values
CRYOGLOBULIN
Negative (positives reported as percent)
If positive after 1 or 7 days, immunotyping of the cryoprecipitate is performed at an additional charge.
CRYOFIBRINOGEN
Negative
Quantitation and immunotyping will not be performed on positive cryofibrinogen.
Interpretation
An interpretive report will be provided.
Cautions
Failure to follow specimen handling instructions may cause false-negative results.
Not useful for general screening of a population without a clinical suspicion of cryoglobulinemia.
Clinical Reference
Kyle RA, Lust JA: Immunoglobulins and laboratory recognition of monoclonal proteins. Section III. Myeloma and related disorders. In Neoplastic Diseases of the Blood. 3rd edition. Edited by PH Wiernik, GP Canellos, JP Dutcher, RA Kyle. New York, Churchill Livingstone, 1996, pp 453-475
Method Description
The normal proteins of plasma and serum do not precipitate in the cold. An aliquot of plasma and of serum are incubated for 24 hours at 1 degree C. If a precipitate develops in the serum, the specimen is centrifuged and the percent precipitate is reported. Negative specimens are kept at 1 degree C for 7 days and rechecked. All positive cryoglobulins are analyzed by immunofixation to determine if the precipitate is a monoclonal protein, polyclonal protein, or a mixed cryoglobulin. Precipitates that occur in plasma and not serum are reported as positive for cryofibrinogen. Cryofibrinogen-positive specimens are not quantitated or immunotyped. Slowly forming fibrin clots (as may occur in hemophilia) are distinguished from cryoprecipitates by their inability to redissolve on warming.(Lerner AB, Watson CJ: Studies of cryoglobulins. I. Unusual purpura associated with the presence of a high concentration of cryoglobulin [cold precipitatable serum globulin]. Am J Med Sci 1947;214:410-415)
Day(s) and Time(s) Test Performed
Monday through Friday; 4 p.m.
Analytic Time
2 days
Maximum Laboratory Time
10 days
Specimen Retention Time
Neg, 7 days/Pos, until reported
Performing Laboratory Location
Rochester
NY State Approved
Yes
CPT Code Information
82585-Cryofibrinogen
82595-Cryoglobulin
86334-Immunofixation (if appropriate)
http://www.mayomedicallaboratories.com/test-catalog/print/83659
I know, I know, I have posted on many of these threads but I need to know, is there any cryo test out there that will produce the correct decision on if you are positive with cryo or not. Yes, I cleared 3A virus 10 years ago but I have alot of the symptoms now and the doctors say I am alright.
Problem is the Cryo going into MPGN and ruining your kidneys because of the antibodies clumping up. Hate to bring this up on this thread. Is there a thread for "old timers who cleared" Thanks
Problem is the Cryo going into MPGN and ruining your kidneys because of the antibodies clumping up. Hate to bring this up on this thread. Is there a thread for "old timers who cleared" Thanks
My genotype is 1a, 30 years with disease, f2.5,g2-3
I just began the boceprivir study 9 days ago, first time treating. It took several tries before my hemoglobin was acceptable. I had given up on getting in the trial, but they re-screened me because they were having trouble find subjects with low enough hemoglobin.
The problem with the test being done incorrectly is that you can get a false negative and not know you have cryo, If you test positive, the amount of cryoglobulins in your blood may be incorrect.
-Dave
I just began the boceprivir study 9 days ago, first time treating. It took several tries before my hemoglobin was acceptable. I had given up on getting in the trial, but they re-screened me because they were having trouble find subjects with low enough hemoglobin.
The problem with the test being done incorrectly is that you can get a false negative and not know you have cryo, If you test positive, the amount of cryoglobulins in your blood may be incorrect.
-Dave
We had a member here a while ago who also said that the test for cryoglobulinemia was not performed correctly and, as a result, had to be retested.
What is your genotype, by the way?
Are you currently treating and/or have you treated previously?
Mike
What is your genotype, by the way?
Are you currently treating and/or have you treated previously?
Mike
Cryo is the most common non liver manifestation of chronic long term hcv. Many people don't know the have it, and most docs don't test for it.
Thank you most all of us old timers understand what cryo is but probably the brand new people don't have a clue as fortunately it's not really all that common amongst the general population of heppers as you would think.
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