Week 2 - E - Pancytopenia - Reduced production - Inherited (fanconi's), Acquired (primary and secondary), Increased destruction - Hypersplenism Flashcards
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This man shows that he his anaemic, thrombocytopenic and neutropenic - he has a pancytopenia
Define pancytopenia?
This is a deficiency of all the blood cell lineages - red blood cells, white blood cells and platelets The deficiency in WBCs usually refers to neutrophils and not lymphocytes
Pancytopenia is NOT a diagnosis (it reflects a diagnosis) Pancytopenia does NOT always mean bone marrow failure In the steady state, what is the difference between cell production and cell destrcution?
In the steady state - the rate of cell production = the rate of cell destruction and therefore homeostasis is kept
In the steady state, cell loss is balanced by cell production For example: - State the lifespan of platelets, red cells and neutrophils? Also state how many are produced and lost per second?
Red cells * Lifespan is ~120 days * 2.5million are produced and lost per second Neutrophils * Life span is 7-8hours * 1.2 million are produced and lost per second Platelets * Life span is 7-10 days * 1 million are produced per second
Which blood cell is usually the first to decrease in a pancytopenia? Why may this be?
Platelets are usually the first blood lineage to decrease in pancytopenia This may be because in terms of marrow stress,the small cells are fighting to leave the marrow whereas the big megakaryocytes are large and therefore may be unable to - as megakaryocytes contain many platelet for budding, this can cause a vast decrease
Redcued production is caused by bone marrow failure This can be separated into inherited syndromes that cause failure or acquired failure Inherited causes of bone marrow failure are very uncommon Can you name an inherited condition causing failure?
An inherited condition that can cause bone marrow failure leading to reduced production of cells is Fanconi’s anaemia
What causes Fanconi’s anaemia to arise?
Fanconi’s anaemia arises due to an impaired response to DNA damage It is specifically the inability to correct inter-strand cross links
As said fanconis anaemia arises due to the impaired ability to repair damaged DNA - specifically inter-strand cross links What is the inheritcance of anconi’s syndrome? What age does it usually present?
Fanconis anaemia - arises due to gene mutations causing the inability to repair inter-strand cross links that have damaged the DNA The inheritance of the condition is autosomal recessive and usually presents around age 7 of childhood development
What haematological abnormalities can result from fanconis anaemia?
There is usually bone marrow failure due to aplastic anaemia There is also a greatly increased risk of acute myeloid leukaemia
Fanconis anaemia also can cause multiple abnormalities in the child, what are these?
SHort stature Hypogenitalia Microcephaly Cafe-au lait spots The child may also have absent or small thumbs Can also affect multiple systems, endocrine, cardio, renal, GI, already talked about haem
Fanconi anaemia It can cause aplastic anaemia in the bones, WHat is usually the order of the anaemia in these children?
Causes a macrocytic anaemia followed by thombocytopenia followed by neutropenia
What does fanconi syndrome greatly increase the risk of? (haematological disorder)
Greatly increases the risk of acute myeloid leukaemia (and breast cancer)
Now we have talked about the inherited cause of decreased production (pancytopenia) due to bone marrow failure, will now talk about acquired - primary and secondary - causes leading to pancytopenia In acquired primary bone marrow failure, there is an intrinsic bone marrow failure with no obvious cause usually due to a stem cell defect What are the three main types of acquired primary bone marrow failure?
Idiopathic aplastic anaemia Myelodysplastic syndrome Acute leukaemia
What happens in idiopathic aplastic anaemia?
There is an autoimmune attack against the haemopoietic stem cells leading to pancytopenia
What is the pathogenesis of the aplastoc anaemia?
There is an autoimmune reaction where auto-reactive T cells produce TNFa and IFNy which then attack the HSC causing reduced reduction of the lineages causing pancytopenia
Bone marrow biopsy is required for diagnosis What does the patients bone marrow biopsy show here? Name an inherited cause of reduced production of cells in the bone marrow
Patients marrow here shows the absence of any haematopoietic activity as only trabeculae (the bone) is seen on the biopsy - no red or yellow marrow is visible Fanconi’s anaemia is an inherited condition resulting in aplastic anaemia which causes pancytopenia
3 causes of acquired primary bone marrow failure Aplastic anaemia MYELODYSPLASTIC SYNDROMES Acute leukaemia What is myelodysplastic syndrome?
Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells. Like the other two causes of primary bone marrow failure, there is no obvious cause and it is thought to be due to a haemopoietic stem cell defect
What is seen in the marrow biopsy in myelodysplastic syndromes? What are types of cells that may be seen on biopsy?
There is increased cells - hyercellularity as there is increased proliferation but as erythropoiesis is ineffective, there is also increased apoptosis The cells on the film/aspirate/biopsy are also dysplastic Ringed sideroblasts are often seen in the marrow with this condition
What are ringed sideroblasts? What are the crystals of granules that collect to form needle like shapes in the marrow that may be seen with myelodysplastic syndromes? What are they a poor prognostic sign of?
Ringed sideoblasts are erythroblasts with iron loaded mitochondria presenting as a ring Also seen in sideroblastic anaemia The granules of crystals that can collect are known as Auer rods and are a poor prognosctic sign as it highlights acute myeloid leukaemia
3 causes of acquired primary bone marrow failure * Aplastic anaemia * Myelodysplastic syndromes * ACUTE LEUKAEMIA How can acute leukaemia cause pancytopenia?
In acute leukaemia there is the abnormal proliferation of cells (Blasts) from leukaemic stem cells which cause the failure of these cells to differentiate into more mature forms Pancytopenia in AML arises from The failure of cells to differentiate / mature and The abnormal cells preventing normal HSC development
Acquired Secondary bone marrow failure can be for a number of reasons Eg drugs, deficiencies, infiltration disorders and viral diseases What drugs can cause secondary failure? What do they cause? What deficiencies can cause pancytopenia?
Chloramphenicol, chemotherapy and alcohol can all lead to pancytopenia as they cause aplasia B12/folate affect all lineages and therefore deficiencies in these can lead to bone marrow failure as the nuclea division of all the lineages is impaired and therefore undergo apoptosis
Do B12 / folate deficiencies result in a hypo or hyperceullar state? What is increased destruction causing pancytopenia due to?
B12/folate deficiencies result in a hyperceullar state Increased destruction causes pancytopenia due to hypersplenism
What are the primary lymphoid organs? What are the secondary lymphoid organs?
Primary lymphoid organs - bone marrow and tonsils Secondary lymphoid organs - lymph nodes, spleen, tonsils (Waldeyer’s ring) and lymphoid tissue found along the alimentary canal
In hypersplenism there is an increased splenic pool -ie more blood is flowing through the spleen than is meant to What is the main cause of hypersplenism? Hypersplenism is basically when the spleen is overactive What does the hypersplenism cause?
Hypersplenism is caused by splenomegaly When the spleen enlarges there is incresed flow of blood through the spleen (Splenic pool) and therefore the spleen destroyed more blood cells than the bone can compensate for resulting in pancytopenia
