Meeran Haem Flashcards
Name the causes of microcytic anaemia
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning (basiphilic stippling)
Sideroblastic anaemia
What is aplastic anaemia and how does it present on a blood count?
Aplastic anaemia is caused by bone marrow failure resulting in pancytopenia and hypocellular bone marrow. 80% is idiopathic, 10% is primary (dyskeratosis congenita and fanconi anaemia) and 10% is secondary (viruses, SLE, drugs, radiation). It is caused by CD8+/ HLA-DR+ T cell destruction of bone marrow resulting in fatty changes.
Blood results will show reduced Hb, reticulocytes, neutrophils, platelets and bone marrow cellularity with raised MCV - the macrocytosis is due to the release of fetal haemoglobin in order to comepnsate for reduced red cell production
What would iron studies in iron deficiency anaemia show?
Low serum ferritin and Fe
Raised TIBC and transferrin
What is anaemia of chronic disease and how does it present in laboratory studies?
It occurs in chronic infection and inflammation e.g. TB, rheumatoid arthritis, IBD and malignancy.
It is mediated by IL-6 produced by macrophages which induces hepcidin production in the liver. Hepcidin works by retaining iron in macrophages (reduced delivery to RBCs for erythropoiesis) and reduces export from enterocytes (reduced plasma iron levels).
Lab findings would show microcytic hypochromic anaemia, rouleaux formation (increased plasma proteins), raised ferritin (acute phase protein) and reduced serum iron and TIBC
What differentiates megalobastic anaemia from non-megaloblastic macrocytic anaemia?
There are hypersegmented neutrophils in megaloblastic anaemia
What type of anaemia does blood loss cause?
Normocytic anaemia - due to reduced number of circulating RBCs
What type of anaemia does chronic alcohol consumption cause?
Non-megaloblastic macrocytic anaemia.
A poor diet in these patients cause further lead to folate and B12 deficiency which exacerbates this anaemia
What type of anaemia does chronic renal failure cause?
Normocytic normochromic anaemia - due to reduced production of RBCs due to diminished secretion of erythropoietin by damaged kidney cells
What type of anaemia does lead poisoning cause?
Microcytic anaemia due to dysfunctional haem synthesis.
We see basophilic stippling which reflects RNA found in RBCs due to defective erythropoiesis
What is autoimmune haemolytic anaemia (AIHA)?
It is the destruction of RBCs in the spleen after being bound by autoantibodies. Direct antiglobulin test (DAT) is positive and spherocytes are present on blood film
AIHA is classified as warm or cold
Warm - IgG, binds to RBCs at 37ºC. Caused by lymphoproliferative disorders, drugs (e.g. penicillin) and autoimmune diseases (e.g. SLE)
Cold - IgM, binds to RBCs <4ºC. Caused usually after an infection by mycoplasma and EBV
What is Glucose-6-phosphate dehydrogenase (G6PD) important for?
It is an essential enzyme in the RBC pentose phosphate pathway - it maintains NADPH levels whin supply glutathione to neutralise free radicals that may have otherwise caused oxidative damage.
What are G6PDD patients at risk of?
Oxidative crises which can be precipitated by certain drugs (primaquine, sulphonamide, aspirin, trimethoprin and nitrofurantoin), fava beans and henna.
These attacks result in haemolytic anaemia with jaundice and a blood film will show bite cells and Heinz bodies
What are causes of microangiopathic haemolytic anaemia (MAHA)?
It is caused by the mechanical destruction of RBCs. Causes include:
* Thrombotic thrombocytopenic purpura (TTP)
* Haemolytic uraemic syndrom (HUS)
* Disseminated intravascular coagulation (DIC)
* Systemic lupus erythematous (SLE)
What is the pathophysiology of sickle cell anaemia?
It is autosomal recessive condition where there is a point mutation in the beta-globulin chain of haemoglobin (chromosome 11) - substitutes glutamic acid at position 6 for valine
What are hereditary spherocytosis and hereditary eliptocytosis?
These are autosomal dominant disorders that result in RBC membrane defects and extravascular haemolysis
What is paroxysmal nocturnal haemoglobinuria (PNH)?
Rare stem cell disorder which results in intravascular haemolysis, haemoglobinuria (especially at night) and thrombophilia. Ham’s test is positive.
What are howell-jolly bodies?
They are nuclear DNA remnants found in circulating erythrocytes.
Usuually healthy erythrocytes expel these DNA fragments and those with Howell-Jolly bodies are removed by the spleen.
Common causes of Howell–Jolly bodies include splenectomy secondary to trauma and autosplenectomy resulting from sickle cell disease.
What are tear-drop cells?
These are also known as dacrocytes, caused by myelofibrosis - the bone marrow undergoing fibrosis, usually following a myeloproliferative disorder such as polycythaemia rubra vera or essential thrombocytosis.
Bone marrow production of blood cells decreases resulting in a pancytopenia. The body compensates with extra-medullary haemopoiesis causing hepatosplenomegaly.
Blood film will demonstrate leuko-erythroblasts, tear-drop cells and circulating megakaryocytes. Bone marrow aspirate is described as a ‘dry and bloody’ tap.
What are cabot rings?
They are looped structures found within erythrocytes which can be caused by megasloblastic anaemia.
What is rouleaux formation?
Commonly seen in multiple myeloma, it is the stacks of erythrocytes that form in high plasma protein states
What are target cells?
Erythrocytes with a central area of staining, a ring of pallor and an outer ring of staining.
They are formed in thalassaemia, asplenia and liver disease.
What are pappenheimer bodies?
Granules of iron found within erythrocytes.
Causes include lead poisoning, sideroblastic anaemia and haemolytic anaemia.
What type of hypersensitivity reaction is immune thrombocytopenic purpura (ITP)? Acute and Chronic
Acute ITP is a type 2 hypersensitivity reaction where IgG binds to viral-coated platelets. This precedes a viral illness approximately 2 weeks prior, and is self-limiting.
Chronic ITP is gradual in onset with no hx of previous viral infection. It is also a type 2 hypersensitivity reaction with IgG targeting GLP-2b/3a
What can cause disseminated intravascular coagulation (DIC)?
Gram-ve sepsis
Malignancy
Trauma
Placental abruption
Amniotic fluid embolism
What is the pathophysiology of disseminated intravascular coagulation (DIC)?
Tissue factor is released which triggers the activation of the clotting cascade, leading to platelet activation (thrombosis in microcirculation) and fibrin deposition (haemolysis). The consumption of platelets and clotting factors predisposes to bleeding. Plasmin is also generated in DIC which causes fibrinolysis, perpetuating the bleeding risk.
The clinical manifestations of DIC are therefore linked to microthombus production (renal failure and neurological signs) and reduced platelets, clotting factors and increased fibrinolysis (bruising, gastrointestinal bleeding and shock).
What is hereditary haemorrhagic telangiectasia?
It is also known as Osler-Weber-Rendu syndrome and is an autosomal dominant condition characterized by telangiectasia formation on the skin and mucous membranes leading to nose and gastrointestinal bleeds.
What is prothrombin G20210A mutation?
It is an inherited thrombophilia caused by the substitution of guanine with adenine at the 202010 position of the prothrombin gene. This amplified prothrombin production, increasing the risk of clotting and causing a predisposition to DVTs and PEs.
*Physiologically, prothrombin promotes clotting after a blood vessel has been damaged.
What is Factor V Leiden?
It is an autosomal dominant inherited thrombophilia.
Normally protein C inhibits factor V. However in Factor V Leiden, a mutation to the F5 gene swaps arginine for glutamine, resulting in an impairment of degradation of factor V by protein C.
Hence these patients are at risk of DVTs and miscarriages
What are the common presentations of antiphospholipid syndrome?
Stroke (arterial thrombosis)
DVTs (venous thrombosis)
Miscarriages
What is Buerger’s disease?
Also known as thromboangitis obliterans. It is a vasculitis of small/medium arteries and veins of the hands and feet. It is strongly related to smoking.
First presentation is claudication however as the disease progresses it leads to gangrene and amputation in severe cases.
Angiogram will show a corckscrew appearance of the arteries
What is protein S deficiency?
It is associated with impaired degradation of factors Va and VIIIa. This leads to persistence of factors Va and VIIIa in the ciruclation so increased susceptability to venous thrombosis.
Three types:
* Type I (quantitative defect) - decreased levels of total protein S
* Types II (qualitative defect) - normal total levels, decreased function
* Type III (qualitative defect) - normal total levels, decreased free protein S, decreased function
*Protein S is a vitamin K dependent anticoagulant so warfarin treatment and liver disease will increase venous thrombosis in rarer cases.
What is antithrombin deficiency?
Inherited cause of venous thrombosis.
Under physiological conditions antithrombin inhibits clotting factors thrombin and factor 10a.
