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 Post subject: Chronic Anaemia
PostPosted: 04 Jun 2016 20:09 
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Joined: 20 Jul 2013 17:30
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Dear Colleagues
Greetings n good wishes
Just to refresh ur memories , I had a Benign NeuroFibroma removed from my Spinal Cord at level T 8/9 in March 2012, with resultant complications. Had numerous consultations in South Africa and Abroad. The final conclusion is that I have
1 Residual myelopathy from Spinal cord tumour and surgery to remove it.
2 Partial Cauda Equine syndrome from Lumbar Spinal Stenosis from L2 to L4 and Spondylolithesis of L4 / L5 grade II
The problems from the above are marked Paraesthesia n Low Backache
Recently a new problem has cropped up.
Just to recap'
1 Hypertension at age 61yrs in 2001. on Diltiazem n Hydrochlothiazide
2 Chronic Lymphocytic Leukemia CLL at age 62yrs .....in Remission
3 Atrial Fibrillation at age 67yrs in 2006.....on Warfarin as per INR readings and Lanoxin 0.25mg

My present problem is a gradual drop in my Haemoglobin ( Hb )
In July 2014 my Hb was 13.1 and Platelets 184
In July 2015 Hb 11.4 Platelets 170
In Dec 2015 Hb 10.9 Platelets 136
In Feb 2016 Hb 10.1 Platelets 133
In March 2016 Hb 9.8 Platelets 143

On the 13 March 2016 had 1 Unit of Packed Cells and Colonoscopy and Endoscopy - showed a Normal Upper Endoscopy : Colonoscopy showed a Caecal Polyp n Early Diverticular Disease. Then had a a Capsule Endoscopy a week later which showed Antral Erosions and the small bowel mucosal pattern looked normal with no cause for Iron Deficiency was identified
Had a CT scan of Abdomen n Pelvis showed a mild Hepato-splenomegaly with subcentimeter upper abdominal and
para-aortic adenopathy

My Hb went up to 10.2 on the 30 May 2016 ( following the 1 unit of packed cells )
Now on the 30 May 2016 my Hb has dropped to 9.1 and Platelets 123.

Saw a Cardiologist cum Electrophysiologist on 2 June 2016. he suggested I stop the Lanoxin and change from Warfarin to Pradaxa 110mg twice daily
The problem is no one knows the cause of my slow drop in Hb n Platelets. Can some one brain storm my case and see what could be the likely cause
Would really appreciate some feedback
With many thanks and kind regards
Yours Chil Dr DN Charles
e-mail chilcharles@gmail.com


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 Post subject: Re: Chronic Anaemia
PostPosted: 05 Jun 2016 03:43 
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Dear Chil, we will need a systematic approach this.
We need to define the exact type of Anaemia.


1.Anaemia of chronic disease (ACD) may be secondary to:

Chronic infection.
Inflammation - including connective tissue disorders.
Neoplasia.
Anaemia is also commonly associated with chronic kidney disease.


Pathogenesis
The anaemia of chronic disease is still not fully understood. Different causes contribute to anaemia in chronic diseases, including diversion of iron, reduced erythropoiesis and reduced response to erythropoietin.

Interleukin-6 appears to be the central mediator of anaemia of chronic disease in a range of inflammatory diseases, including end-stage renal disease and rheumatoid arthritis.

ACD is associated with hyposideraemia (low serum iron) and altered iron transport. Cytokines are implicated by reducing erythropoiesis and increasing iron sequestration in the reticuloendothelial system.
Interleukin-6 induces the expression of hepcidin, which suppresses the expression of the iron transporter, ferroportin-1, so inhibiting the absorption of iron from the duodenum and the release of iron from the reticuloendothelial system.

Hepcidin is a peptide hormone produced by the liver and is a key regulator of iron homeostasis.
Hepcidin binds to the iron export protein ferroportin, causing ferroportin to be phosphorylated and degraded in lysosomes.
Hepcidin inhibits iron release from the reticulo-endothelial system. Increased expression of hepcidin also leads to decreased iron absorption and iron-deficient anaemia.
The regulation of iron absorption across the epithelium of the proximal small intestine is essential for maintaining body iron concentrations.

The Anaemia of Chronic Renal Disease is somewhat different . Will address it later.

Presentation
The presentation may be quite subtle in a patient already suffering with chronic disease. The presentation may include the new onset or increased tiredness, pallor, breathlessness and tachycardia.

Investigations
ACD typically occurs despite adequate reticuloendothelial iron stores.

Reduced serum iron, transferrin and total iron-binding capacity.
Exclusion of a mixed cause for anaemia - B12 and folate levels.

Measuring serum ferritin is essential in investigating unexplained anaemia:

Serum ferritin concentration is directly related to reticuloendothelial iron stores, and normally 1 μg/L serum ferritin roughly corresponds to about 8 mg of storage iron.

Normal or raised ferritin is typical in ACD.This is because of the increased storage and retention of iron within the reticuloendothelial system. There are also increased ferritin levels due to immune activation accompanying the chronic disease.

In the presence of inflammation, ferritin concentrations may remain normal even when reticuloendothelial iron stores are absent.

High erythrocyte sedimentation rate (ESR), and CRP.

Red cells often normochromic, normocytic, but may be hypo chromic, microcytic (as frequently seen in rheumatoid arthritis and Crohn's disease).

Bone marrow examination for iron is the definitive test for deficiency - very uncomfortable and expensive.( Not to rush into this , but may have a place once a better profile of the Anaemia is ascertained.)
Estimation of soluble transferrin receptor (if available):

Measurement of soluble transferrin receptor provides a marker of bone marrow iron stores and improves the diagnosis of iron-deficiency anaemia, therefore helping to differentiate between iron-deficiency anaemia and ACD.
The test is much more expensive than ferritin measurement.

Bone marrow examination for the sole purpose of assessing iron stores is rarely justifiable.

Chill , remind me- Have we ruled out Occult GI bleeds?

Kindly discuss the above tests with your Physician , to consider.

Paradoxa seems a logical move .

Best wishes,

Mohan.


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 Post subject: IRON DEFICIENCY ANAEMIA
PostPosted: 05 Jun 2016 03:56 
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Dear Chil, To bring us updated:

Epidemiology
In the developed world, 2-5% of adult men and postmenopausal women have IDA.
Iron deficiency and IDA are common in young children.

Iron deficiency is the most common cause of anaemia in pregnancy worldwide; severe anaemia can have very serious consequences for mothers and babies.

Premenopausal women have a higher incidence of IDA because of heavy menstrual blood losses and pregnancy.

Aetiology
Causes of iron deficiency may be classified as those due to:


Excessive blood loss
Blood loss from the gastrointestinal (GI) tract is the most common cause of IDA in adult men and postmenopausal women.

Blood loss due to menorrhagia is the most common cause of iron deficiency in pre-menopausal women.

In tropical countries, infestation of the gut may cause IDA, especially with hookworm and schistosomiasis.

Common causes of blood loss include:

Non-steroidal anti-inflammatory drug (NSAID) use.
Colonic carcinoma.
Gastric carcinoma.
Gastric or duodenal ulceration.
Angiodysplasia.
Heavy menstruation.

Other causes include:

Other GI tract malignancies.
Bleeding oesophageal varices.
Inflammatory bowel disease.
Haemorrhoids.
Oesophagitis and gastro-oesophageal reflux disease.
Postpartum haemorrhage.
Recurrent epistaxis.
Malignancy of the renal tract.
After major surgery or major trauma, if replacement has been inadequate.
After blood donation.

Dietary inadequacy
Dietary iron deficiency is fairly uncommon.
Meat tends to be more rich than vegetables in iron and so vegetarians are at greater risk. However, green vegetables are a good source of iron and a proper vegetarian diet should not lead to deficiency.
Growing children and elderly people with iron-poor diets may become deficient.

Failure of iron absorption
Not only does the diet have to contain adequate amounts of iron but the iron has to be in a form that can be absorbed.
Iron can be absorbed in the ferrous state much more readily than in the ferric state.

Factors affecting iron absorption:
Some drugs can bind to iron and prevent absorption. Tetracyclines and quinolones chelate with iron so that neither the antibiotic nor the iron is absorbed.
Antacids and proton pump inhibitors may also impair absorption by raising gastric pH.
Phytate (found in wholegrain cereals, nuts, seeds and legumes), polyphenols (found in tea and coffee) and calcium (in dairy products) impair iron absorption.
Iron absorption can be increased in a diet rich in fish, red meat and white meat.
Vitamin C may enhance iron absorption. Patients can be encouraged to drink a glass of orange juice with their iron tablets.

Malabsorption conditions such as coeliac disease (usually accompanied by folate deficiency).
It may occur after partial or total gastrectomy, more commonly with increased number of postoperative years.
Helicobacter pylori colonisation appears to impair iron uptake and increase iron loss.

G Mohan


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PostPosted: 05 Jun 2016 04:12 
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Joined: 24 Mar 2013 02:28
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Dear Chil,

Let us also pick up CLL :
This is a malignant monoclonal expansion of B lymphocytes with accumulation of abnormal lymphocytes in the blood, bone marrow, spleen, lymph nodes and liver. Morphologically these lymphocytes have a normal appearance but are immature and nonreactive, resulting in immunological compromise.
Chronic lymphocytic leukaemia (CLL) represents about a quarter of all leukaemias seen in clinical practice and is largely a disease of older people.

The diagnosis of CLL is established by the following:[

The presence in the peripheral blood of ≥5,000 monoclonal B lymphocytes/mcL for the duration of at least three months. The clonality of the circulating B lymphocytes needs to be confirmed by flow cytometry.
The leukaemia cells found in the blood smear are characteristically small, mature lymphocytes with a narrow border of cytoplasm and a dense nucleus lacking discernible nucleoli and having partially aggregated chromatin.

Epidemiology
CLL is the most common leukaemia in the Western world with an incidence of 4.2/100,000/year.
The incidence increases to >30/100,000/year at an age of >80 years. The median age at diagnosis is 72 years. About 10% of CLL patients are reported to be younger than 55 years.

Risk factors
Some individuals with CLL may have a genetic predisposition, although a familial history is rare.

Presentation
Symptoms
Presentation is variable with insidious onset. 90% are now asymptomatic at presentation, with CLL diagnosed incidentally following routine blood tests. Symptoms may include:

Susceptibility to infection (pneumonia, herpes simplex, and herpes zoster).
Symmetrically enlarged lymph nodes.
Abdominal discomfort from an enlarged spleen.
Bleeding or petechiae in skin or mucous membranes - from thrombocytopenia.
Tiredness and fatigue from anaemia.

Signs
Local or generalised lymphadenopathy.
Splenomegaly (30-40%).
Hepatomegaly (20%).

Petechiae.
Pallor.
Skin infiltration (rare).
Tonsillar enlargement.
Involvement of the lacrimal and salivary glands (Mikulicz's syndrome) is rare.

Differential diagnosis
Other forms of leukaemia.
Lymphoma.
Myelodysplasia and myeloproliferative diseases.

Investigations
Blood

FBC shows a minimum clonal B cell lymphocytosis (>5 x 109 lymphocytes/L, may be ≥300 x 109 lymphocytes/L).[4]
Normocytic, normochromic anaemia is present in advanced disease with marrow infiltration or hypersplenism.

Peripheral blood smear confirms lymphocytosis often with smudge cells (artefacts from damage to lymphocytes during preparation of the slide).

Direct anti globulin test (DAT) - also known as the direct Coombs' test - in all anaemic patients and prior to starting treatment (to identify autoimmune-related haemolytic anemias).

Bone marrow aspirate shows lymphocytic replacement of normal marrow elements.
It is not necessary in all cases but may help to establish the diagnosis and assess other complications such as anaemia and thrombocytopenia, eg thrombocytopenia of peripheral destruction (splenic) versus marrow infiltration.
Lymph node biopsy is required, if lymph nodes enlarge rapidly, to assess the possibility of transformation to a high-grade lymphoma. This transformation with fever, weight loss and pain is called Richter's syndrome.

Immunophenotyping - peripheral blood flow cytometry is the most valuable test to confirm CLL and shows circulating clonal B lymphocytes expressing particular antigens (CD5, CD19, CD20 and CD23).
Measurement of immunoglobulin levels if there are repeated infections.
Cytogenetics are not usually performed but trisomy 12 or 14q+ or translocation 11:14 are the most usual findings.

Patients should be tested for deletion of (tumour protein) TP53 gene before treatment. This is a tumour supressor gene and deletion of it is associated with a lower response rate (to treatment), short progression-free survival and overall survival.
The status of relevant infections (hepatitis B and C, cytomegalovirus and HIV) should be evaluated prior to chemo-immunotherapy, alemtuzumab or allogeneic stem cell transplantation (alloSCT) in order to avoid virus reactivation.

Imaging
Note: staging in CLL is done based on blood and clinical examination, rather than imaging.

Liver and spleen scan may confirm enlargement.
CT scan of the chest, abdomen or pelvis may show obstructive uropathy or airway obstruction from lymph node compression on organs or internal structures.

Staging
The Binet system is used in Europe but in the USA the Rai-Sawitsky staging predominates. The International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) has recommended integrating the two.

Stage A: haemoglobin (Hb) at least 10 g/dL, platelets at least 100 x 109/L, and less than three lymph node areas involved.
Stage B: Hb and platelet levels as in stage A and three or more lymph node areas involved.
Stage C: Hb <10 g/dL, platelets <100 x 109/L, or both.
Hb level, blood lymphocyte count, lymphocyte doubling time and bone marrow infiltration pattern are useful to identify subsets of patients in the early stage with different progression and survival rates, with the 'smouldering' form of the disease being identified fairly accurately.

Medicine being the Art , where theory needs to be applied to the relevance of each Individual case.

Let us keep talking, and Investigating Logically.

G Mohan.


Last edited by gmohan on 11 Jun 2016 04:23, edited 2 times in total.

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 Post subject: Re: Chronic Anaemia
PostPosted: 06 Jun 2016 03:57 
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Dear Chil,

Mohan has written in great detail about the causes for anaemia. I would like to add something simple to check for causes ie tests.

Anaemia is due to either poor production of RBCs or to increased destruction or loss of red cells from the body. So the tests that should give you a cause for the anaemia should include the following :

1. Complete blood count checking for the type of anaemia and also the WBCs and Platelets. Add ESR and CRP.

2. Stool for occult blood.

3. Serum iron, transferrin and ferritin level.

4. Folate and Vitamin B12 levels

5. Liver function tests to check Bilirubin level

6. Reticulocyte count

7. Kidney function test as erythropoietin deficiency can lead to anemia.

8. Bone marrow biopsy as the last test if necessary.


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 Post subject: Re: Chronic Anaemia
PostPosted: 09 Jun 2016 03:30 
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Dear Mohan and Badri,
Thank you so much for such an in-depth explanation and answer to my problems.
I have been fully investigated by my colleagues in Durban and had all the tests as you had mentioned ,Mohan. The last test that I am scheduled to have on the 23rd June is a bone marrow biopsy.
On the cards are the following.
My Elder brother had the similar problems at the age of 80yrs. He had CLL as well as AF and was on Warfarin. He was fully investigated and they couldn't find any obvious cause. He had to have Packed Cell transfusion every 3 to 4 months to relieve his systems of anaemia. He died at age of 83yrs ffg a subdural haemorrhage. ( negligence of the hospital )
The probable causes they are looking at:
1 Hereditary
2 Chronic Lymphocyctic Leukemia. CT scan of Abdomen n Pelvis showed mild Hepatosplenomegaly in March.
3 Being on Warfarin . My Heamatologist not keen on the 2nd generation Anti-coagulants eq Pradaxa or Xarelto
4 Awaiting the bone marrow biopsy report .( Will keep u informed. )
Thanks again
With kind regards
Chil


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 Post subject: Re: Chronic Anaemia
PostPosted: 09 Jun 2016 12:37 
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Hi Charles,

My regards to your wife and your family members

Mohan has given an exhaustive account of anaemia which is your current problem.

You have stated that you have undergone most of the relevant investigations suggested by Mohan. You are awaiting bone marrow report. Hope and wish it will be also negative.
A few practical points from the point of view of a practising physician I want to some observations here. Mohan has made a passing mention of H pylori. I think you must give an extra attention to this aspect.
H pylori infection is known to influence your ability to digest food. H pylori can create an autoimmune response against the parietal cells of the stomach. These cells are responsible for the production of stomach acid (hydrochloric acid).
If the H pylori bacteria cause damage to the parietal cells, stomach acid levels can decrease significantly. When acid levels in the stomach are low, food may not be broken-down properly. In particular, you’ll have a hard time breaking down proteins and releasing minerals such as iron so that they can be absorbed into your body via the intestine.
Dear Charles, in spite of the important role it played in the causation of anemia, it usually does not get the attention it deserves. H pylori may be able to cause anaemia (and its symptoms – fatigue, weakness, and malaise) without causing any digestive symptoms whatsoever. Without digestive symptoms patients and doctors don’t focus their attention to this problem.This is one of the reasons why H pylori infection is so insidiously dangerous
I have seen in some of my patients quite good results after treating H pylori. Without treating this highly treatable malady, tons of iron load and liters of blood transfusions are not going to benefit anyone. The conventional investigations for H pylori are not very helpful. False negative results due to so many causes are common. So when negative, doctors don’t look that way. What I suggest to you is forget about investigations. Since you have exhausted all forms of treatment for anemia I advise you to start treatment on an empirical basis. Take a course of clarithromycin, metronidazole and omeprazole for 2 weeks. Some doctors use amoxicillin in the place of metronidazole in this combination. Let us see what happens.
Another point I want to make a mention is about malaria. Unlike other infections and infestations, this one directly attacks red blood cells and causing lysis and leakage of iron from the cells. You don’t look for typical signs and symptoms of malaria. Malaria presents in odd forms. You would have investigated for malaria. I don’t know. Here also don’t go after investigations. They may not always be helpful. I have seen many times when treated on suspicious ground, they had given immense relief to the patients even when investigations failed us. I think malaria is very common in your place. Here also I suggest a course of antimalarial therapy on empirical grounds depending upon the sensitivity of the drugs in your area. These short course therapies for H pylori and malaria are not going to do much harm. Since your suffering is such that sometimes this sort of seemingly unscientific methods may give you relief. I always say ‘Doctors are scientists but they cannot afford to be scientific’. Suppose do you wait for a throat swab test before you start treating diphtheria when you see a typical patch in the throat of a child. With your scientific outlook, you are going to wait for the patient to go into a severe carditis which may be even fatal, as we all know.

UA Mohammed


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