Mrcpch Guide Heme

MRCPCH GUIDE Heme Acute lymphoid leukaemia Acute lymphoid leukaemia may present following a viral infection with non-specific symptoms mainly arising from: • bone-marrow failure – anaemia, thrombocytopenia • tissue and organ infiltration – splenomegaly, lymphadenopathy, gum hypertrophy, bone pain • metabolic effect – fever, lethargy Patients may have a normal blood picture but 99% with acute presentation have circulating blasts with or without thrombocytopenia. Two-thirds are neutropenic and 90% are anaemic. Bone marrow is needed for specific diagnosis. The following are poor prognostic factors in ALL:       

age < 1 year and > 10 years male sex high white cell count t(4:11) t(9:22) - dismal prognosis CNS disease at presentation hypodiploidy

A hypochromic microcytic blood picture is seen in iron deficiency, the sideroblastic anaemias, lead poisoning (perhaps due to a concomitant iron deficiency), thalassaemia traits (alpha or beta) and occasionally the anaemia of chronic disease.

Factor 8 Antigen Factor VIII is produced mainly in the liver. Hence hepatic transplantation cures haemophilia. In the circulation it is bound loosely to von Willebrand antigen. It is von Willebrand antigen that is produced by megakaryocytes and by endothelial cells and that mediates to platelet interaction with the endothelial surface (via platelet glycoprotein 1B). The principal cause of bleeding in von Willebrand’s disease is deficiency of von Willebrand protein or poor function of this von Willebrand protein (Types 1 and 2 respectively). There is low circulating factor VIII in von Willebrand’s disease and this is helpful in diagnosis (it causes long APTT and a low Factor VIII level). Only Type 3 von Willebrand’s disease is there anything like the type of bleeding that you see in Haemophilia A, with joint bleeds and muscle bleeds. Factor VIII is a co-factor. It is activated by Thrombin and mediates the conversion of X to XA. Its half life in circulation is some 12 hours (in contrast to Factor IX that has a half life of 24 hours). When given therapeutically therefore, it needs to be given twice daily in contrast to Factor IX, which can be given daily.

Von Willebrand’s disease is a deficiency or dysfunction of von Willebrand protein. This is a large protein that is usually multimeric. It mediates the binding of platelets to the subendothelial surface. It binds on platelets via platelet antigen 1B. It also serves to protect Factor VIII in the circulation. In type I there is a quantitative deficiency of von Willebrand’s protein. Its multimeric pattern in the circulation is normal. There will be a reduction in von Willebrand antigen and function (as measured by the ristocetin co-factor activity, in platelet function tests). In Type II von Willebrand’s disease the von Willebrand’s protein is present although its function is reduced. Therefore, the antigen level is higher than the ristocetin co-factor activity level. In Type 2B there is also thrombocytopenia. In Type 3 there is a very severe quantitative deficiency. This is autosomal recessive. This presents as Haemophilia A does but also with the mucosal and skin bleeding typical of von Willebrand’s disease. Treatment: In Type I there may be no need for any treatment or DDAVP may be used as this increases production of von Willebrand antigen. In type 2 a concentrate may be required of von Willebrand protein (this is plasma derived and is not a recombinant product). Fresh frozen plasma will require very little von Willebrand protein and litres will be required for a correction of bleeding diathesis. In Type 3 again concentrates are required.

The  globin gene cluster is located on chromosome 16 and the  globin gene cluster is located on chromosome 11. The  genes are duplicated on each chromosome 16 and therefore we inherit two  genes from each parent. The  genes are not duplicated and we inherit one from each parent.

peripheral blood morphology of hyposplenism There are Howell-Jolly bodies, there is thrombocytosis and there is polychromasia (increased reticulocytes and macrocytosis). There will also be target cells. Howell-Jolly and Heinz bodies, nucleated RBCs, siderocytes and acanthocytes are frequently encountered.

Sickle cell disease is the combination of two diseases. First of all it is a haemolytic anaemia and therefore has all the features of a haemolytic anaemia – increased reticulocyte count, jaundice, predisposition to gallstones, predisposition to Parvo-virus induced aplastic crisis and increased spleen size in infants. The other component of sickle cell disease is that it is a vaso-occlusive illness and therefore presents with crises. The symptoms of the crises depend on where the vaso-occlusion is taking place. The commonest would be a painful crisis where there is bone marrow infarction. There are also CNS symptoms such as stroke from CNS vaso-occlusion, there is hepatic and splenic sequestration crises caused by hepatic and splenic vaso-occlusion within the chest. Priaprism is another example of a vaso-occlusive crisis. Sickle cell trait is entirely asymptomatic. They are thought to get less falciparum malaria and this is why the defect has evolved in evolutionary terms.

Henoch–Schönlein purpura (HSP) is a systemic vasculitis of unknown aetiology involving the skin, joints and some viscera. (Schönlein associated the purpura and arthritis, and Henoch the purpura and gastrointestinal involvement.) The syndrome may also include urticaria and, not infrequently, focal proliferative glomerulonephritis. The characteristic onset is a symptomless purpuric eruption confined largely to the extensor surfaces of the lower limbs, including the buttocks. The trunk may also be affected and, occasionally in the very young, the face. The eruption begins as a raised urticarial rash rapidly becoming purpuric without losing its urticarial character. Such a rash is virtually diagnostic of HSP. The lesions tend to fade through the typical brown–yellow discoloration of haemorrhage in the skin. Joint involvement is not always present and is usually transient but without the obvious migratory or ‘flitting’ character of the arthritis of acute rheumatic fever. Joint involvement may be confined to tenderness and pain on movement or associated with distinct swelling and intra-articular exudate. Gastrointestinal involvement is often common and distressing. Haemorrhage into the gut wall produces intermittent or persistent colicky pain, occasionally vomiting, and less commonly melaena. Where there is no frank blood in the stools, occult blood is usually present. Renal involvement is more common than generally recognised and may occur in 25–50% of patients. It is usually asymptomatic, in contradistinction to the acute glomerulonephritis of streptococcal origin. The patient presents without oedema, hypertension or oliguria and the haematuria is often microscopic. There is no specific therapy but symptomatic treatment may be of great benefit.

Anemia of chronic disease: Serum transferrin (and TIBC) low to normal, serum iron low, saturation low or normal. Transferrin decreases with many inflammatory diseases. With chronic disease there is a block in movement to and utilisation of iron by marrow. This leads to low serum iron and decreased erythropoiesis. Examples include acute and chronic infections, malignancy and renal failure. Ferritin levels are also useful for iron deficiency. Low iron level may not indicate iron deficiency in acute infection with leukocytosis. Low iron levels may be misleading in chronic infection, inflammation and malignancy; high ferritin levels occur in many such states.

Haemoglobin F (2 alpha globin chains + 2 delta chains) is an ‘early’ haemoglobin manufactured from 8 weeks of foetal life and present in normal individuals until approximately 6 months after birth. HbF is usually only present at very low levels (38°C, drenching night sweats, an unexplained weight loss of >10%, pruritis, alcohol-induced pain (1–10%) and a lymphocyte count