Heparin Induced Thrombocytopenia

Heparin Induced Thrombocytopenia

Although I will think that thrombocytopenia is not such a common case in MRCP, it is certainly a very common scenario in clinical practice.

The best way to think about high/low level in clinical medicine is the remember logically how a subtance/ product is being produced and destroyed in the normal physiology.

Therefore, low thrombocytopenia can be due to 2 main causes- reduced production from the bone marrow or increased destruction in the periphery.

I will talk about HIT ( Heparin Induced Thrombocytopenia) today in this post.
If you ask who is prone to get HIT, then I think is the group of patients who is being exposed to heparin almost everday. Yes, you are right, these patients are End stage renal failure patients who are on regular haemodialysis.

There are 2 types of HIT- early and late stage HIT. Type 1 HIT refers to condition of thrombocytopenia developing 1-2 days after heparin usage. It is a non immune condition due to direct effect of heparin on platelet. It is usually self-limiting and the platelet count usually normalizes after continued heaprin usage.

For type 2 HIT, it is an immune condition that happens later, usually 4-10 days after usage and it is life-threatening. The only option you have is to stop heparin usage.

Iron Deficiency Anemia

Iron Deficiency Anemia


In my last post, I talk about iron metabolism in MRCP, as you all know, iron is an important ingredient in heme synthesis. Therefore iron deficiency leads to anemia ( hypochromic,microcystic anemia) which is a type of anemia manifested by small red cells ( low MCV- mean corpuscular volume) and pale red blood cells ( low MCHC- mean cospuscular hemoglobin concentration).

Iron deficiency is diagnosed by diagnostic tests as a low serum ferritin, a low serum iron level, an elevated serum transferin and a high total iron binding capacity (TIBC).

So what causes iron deficiency anemia- yes, it is mainly due to chronic blood loss and the main cause worldwide is worms infestations! (hookworms, whipworms, roundworms). However, another reason for chronic blood loss is GIT bleeding, therefore, for anyone older than 50 years, always think of the possibility of GIT malignancy!

One thing to take note, Thalassemia minor also has the similar lab results as iron deficiency and you must always consider Thalassemia as your differential diagnosis in iron deficiency anemia!

Iron Metabolism for MRCP

Iron Metabolism For MRCP

Iron metabolism is always an interesting topic to discuss in MRCP. It is a very important topic to know in depth as well if you are preparing for MRCP Part 1 and 2.

To make this topic as easy as possible to answer, it is best illustrated as the picture below,

There are a few important fact to remember for MRCP,

1) Majority of iron in our body is contained in heme, which is the oxygen carrying molecules.

2)Some iron is bound as ferritin in cells of liver or hepatocytes. Therefore, high ferritin should also represent higher iron store, however, remember that ferrin is an acute phase protein. It is raised in acute/chronic inflammation.

3)Iron is also stored as a pigment called hemosiderin in an apparently pathologic process.

How about for iron absorption?

You can remember this process by the following picture,

A few important facts to remember,

1) Iron absorption occurs predominantly in the duodenum and upper jejunum.

2) Iron is best absorped in the form of heme and then Fe2+, therefore agents such as Vitamin C than can reduce Fe3+ to Fe2+ increases iron absorption.

3) Hepcidin role in iron metabolism is out of topic for MRCP but it is getting momentum in Nephrology field in explaining the reason behind functional iron deficiency.

Pancytopenia for MRCP

Pancytopenia for MRCP

Recently I saw a patient with pancytopenia in my ward. A 24-year old ESRF gentleman on CAPD for the past 4 years ( with primary disease of SLE) came to us with fever and joint pain. Full blood count showed a Hb of 4.5, TWC of 1.2 and Plt count of 45.




As we all know, bone marrow produces red cell, white cell and platelet. Pancytopenia just means a condition with reduction of all these three cell types.

It is always interesting to find the underlying cause for pancytopenia and I always try to remember the causes as the following order,

1) Inability for production/Infiltration of bone marrow

- Certainly one of the commonest cause is leukaemia, however, you have to always bear in mind the possibility of aplastic anemia. In older patients, always consider the possibility of bone marrow infiltration by tumour due to secondaries. Severe folic and Vitamin B12 also can cause pancytopenia but frankly speaking, I have never encountered one in my life!

2) Consumption

- although the production in the bone marrow is normal, all these cells can be broken down ( consumed) in the periphery. This can happen either in the spleen ( due to hypersplenism) or in circulation because of autoimmune respond ( due to underlying autoiimune disease)

3) Drugs

- certain drugs or even some infections can cause bone marrow suppression leading to pancytopenia. Popular drugs include choramphenicol, azathioprine ( especially used with allupurinol). Various infections can lead to pancytopenia but always remember about Parvovirus b 19.

Back to our patient, he actually has azathioprine induced pancytopenia. However, pancytopenia due to SLE should be entertained as well!



The worrying thing about pancytopenia is of course managing the neutropenic sepsis if it occurs. My patient actually developed neutropenic sepsis and he was treated with broad spectrum antibiotics. His cell counts improved after azathioprine was stopped.

Multiple Myeloma in MRCP

Multiple Myeloma in MRCP

Multiple myeloma is always an interesting disease to diagnose because patients might just present to you with acute kidney injury! My university lecturer told me once, when an elderly patient comes to see you with kidney failure with no previous medical history, you must always look for multiple myeloma or drug induced ( especially NSAID!)

Another interesting fact about Multiple myeloma is Urine Bence Jones protein. I still remember during medical school time, lecturer always asked us about how to differentiate Urine Bence Jones protein from proteinuria at bed side, I hope you all know the way!

Urine Bence Jones is named after Henry Bence Jones, a famous British physician and chemist. In 1848, he was cited as the driving force for the investigation of an unusual chemical analysis discovered in the urine of a patient with myeloma in a paper titled "On the microscopical character of mollities ossium" (mollities ossium was the name for myeloma, which at the time was thought of as a bone disease based on the osteolytic bone metastases which resulted).

As for you, remember that Multiple myeloma patients always present with hypercalcemia, osteolytic bone lesions ( bone pain) and classical bone marrow findings ( proliferation of plasma cell in bone marrow). Patients might present with polyuria because hypercalcemia is one of the causes for nephrogenic diabetes insipidus!

Chronic Myeloid Leukemia in MRCP

Chronic Myeloid Leukemia in MRCP

Chronic Myeloid Leukemia (CML) is always a popular differential diagnosis in your MRCP PACES examination if you encounter massive hepatosplenomegaly during your abdominal short case.

CML is one of the 4 disorders ( besides polycythamia rubra vera, essential thmrobocythemia and myelofibrosis) termed as myeloproliferative disorders.

The term myeloproliferative disorders describes a group of conditions characterized by clonal proliferation of one or more haemopoietic components in the bone marrow and in many cases, the liver and spleen.

OK, patients usually present the following ways,

1) abdominal pain and distention because of massive hepatoslpenomegaly
2) bleeding tendency due to platelet dysfunction
3) features of anaemia
4) gout or renal impairment due to hyperuricaemia ( because of excessive purine breakdown)
5) some rare symptoms such as priapism ( this is the only cause of priapism I can remember during my medical school time because there was no Viagra yet at that time!!)

I think if you see a case of CML during your MRCP PACES, you must know how to come to a diagnosis of CML, basically, you can do the following,

1) You always find very high total white cell count when you do full blood count. I remember when I was a house-officer, I encountered a patient who were well and had a TWC of 150,000!!
2) Neutrophil alkaline phosphatase ( NAP) score is low!! ( Remember this well because it is a popular question in MRCP. Also remember diseases that have low NAP score!)
3) Chromosomal study- Remember that you usually find Philadelphia Chromosome which is a translocation of chromosome 9 and 22. ( This is the hottest exam question in MRCP and also your final MBBS!!)
4) Bone marrow is hypercellular with granulopoitic predominance.

5) Peripheral blood film may show various stages of granuloiesis including promyelocytes, myleocytes, metamyelocytes and band and segmented neutrophils

When I was a house officer, I remember that my consultant used a lot of hydroxyurea to treat CML. However, currently imatinib ( Gleevec) which is a tyrosine kinase inhibitor has become the first line treatment for CML.

Peripheral Blood Film in MRCP(3)

Peripheral Blood Film in MRCP (3)

OK,sorry for the long inactivity and quietness of this blog.

Today, we are going to learn a few more important blood films that are frequently asked in MRCP.

4) Megaloblastic anaemia

During your MRCP examination, they will always show a film with hypersegmented neutrophils. Remember that a normal neutrophil usually has 3-4 segments instead of 8 lobes as shown above!

5) Rouleaux Formation

I was always asked by my lecturer during my second year medical school the question about the abnormality you can detect in blood film for a patient with multiple myeloma. You notice that the RBC's here have stacked together in long chains. Learn more about Multiple myeloma because it is popular in your MRCP.

6) Filariasis

You can detect this only in thick blood film. Although it is almost extinct in UK, you can find this is tropics and subtropics. I always remember it as one of the causes of unilateral leg swelling during my medical school.

Unilateral leg swelling

Peripheral Blood Film in MRCP(2)

Peripheral Blood film in MRCP(2)

I told you a few basic terms used in haematology in my previous post. Today, I will talk about a few common and popular blood films that are commonly asked in MRCP Part 1 and 2.

1) Sickle Cell disease

( Blood film of sickle cell, polychromasia and target cell)

By far, I think this the most popular blood film in MRCP. Remember that patients with sickle cell may present with bone pain ( due to bone necrosis), osteomyelitis, leg ulcers or even iron overload. Remember that it is one of the important causes of chronic haemolysis anaemia, therefore, you might find pallor with jaundice in patients with Sickle Cell Disease. However, remember that you may not find splenomegaly ( although you anticipate splenomegaly in patients with chronic haemolysis) because there is a possibility of splenic infarct!!

( Patient presents with painful bony infarction)

2) Thalassemia

This disease needs no further explanation. I have seen so many Thalassemic patients during my paediatric posting when I was a medical student.

Look at the following blood film,

( Blood film showing hypochromic, microcyctic red cells)

You may be given a photo of patient with classical thalassemic facies and you are expected to know about types of Thalassemia, chromosome involved and complications!

3) Malaria

OK, if you are living in UK or Ireland, you may not seen a case of malaria in your whole life. However, malaria is endemic in tropical countries including Malaysia and Thailand. You may still remember that there are various species of Plasmodium such as P.falciparum, P.vivax and P.ovale. Anyway, remember that in your MRCP, they always show you the ring form!

Blood Film in MRCP(1)

Peripheral Blood Film in MRCP(1)

Certainly before your MRCP Part 1 and 2, you need to know a very important topic in haematology, you are right, many candidates have the tendency to go to the examination without knowing anything about blood film.

You must know a few popular blood films in MRCP, before we proceed to revise a few important blood films, I think you must remember these useful terms here,

1) AniSocytosis- Variation in Size.
2) Poikilocytes- Variation in shaPe
3)

Basophilic stippling of RBCs is seen in lead poisoining, thalassemia and other dyserythropoetic anaemias

( Image over the left with arrow)

4) Blasts- Nucleated precursors cells
5) Howell Jolly bodies- Nuclear remnants seen in in RBCs especially in post splenectomy
6) Leukaemoid reaction- A marked reactive leucocytosis
7) Left shift- Immature white cells seen in circulating blood
8) Right shift- Hypersegmented polymorphs ( Image below)

9) Rouleaux formation- Red cells stack on each other
10) Target cells RBCs with central staining, a ring of pallor and an outer rim