Anaemia and Transfusions Caroline Young Anaemia iron deficiency* RBC microcytic due to defect in haem [Fe def/sideroblastic

c anaemia] or globin [thalassaemias] Low Fe due to: Intake e.g. vegans/elderly Demands e.g. childhood/pregnancy/breast-feeding Blood loss e.g. GI malignancy, Uro/gynae malignancy, Menstruation Absorption SI/ stomach presenting features Signs/symptoms of Anaemia Signs/ symptoms of Bleeding Fe def associated with koilonychias, glossitis, angular stomatitis appropriate investigations Full blood count, blood film: hypochromic, microcytic, Poikilocytosis [variable shape], Anisocytosis [variable size]. Iron binding capacity increased, Ferritin decreased [nb is an acute phase protein] Ix of potential sources of bleeding differential diagnosis Thalassaemias Sideroblastic anaemia [abnormality of haem synthesis] Chronic disease normocytic or microcytic principles of management Blood transfusion Iron replacement Treat cause complications and outcome Strain on organs e.g. heart failure, myocardial ischaemia Complications of cause prevention of disease Diet meat, spinach Screening e.g. Bowel Ca Macrocytic anaemia megaloblastic [B12 def, folate def] intake: [B12 vegans , folate foliage elderly, anorexia, alcoholics] absorption: stomach, SI demands: pregnancy, lactation, malignancy, inflammation metabolism e.g. trimethoprim

non-megaloblastic [ETOH, hypothyroid, haemolysis, myelodysplasia, pregnancy] presenting features Symptoms/signs associated with anaemia Symptoms/signs associated with cause e.g. angular stomatitis, glossitis, subacute combined degeneration of the spinal cord, dementia, optic atrophy, diarrhoea, steatorrhoea appropriate investigations FBC, Blood film: macrocytosis, hypersegmented neutrophils Raised bilirubin [ineffective erythropoeisis] B12 and folate blood levels Schilling test, ab versus parietal cells or IF, TTG principles of management Replace b12 first otherwise exacerbate subacute combined degeneration of spinal cord, IM B12 injections, po folic acid blood transfusion Treat cause complications and outcome As above. Pernicious anaemia associated with other autoimmune disease plus increased risk of gastric Ca. prevention of disease Folic acid if on methotrexate Folic acid in pregnancy Acute non-haemolytic reactions during transfusion* acute haemolytic reaction anaphylaxis non-haemolytic febrile reaction TRALI [donor plasma contains ab that recognise host leucocytes] Bacterial contamination [esp platelets] Fluid overload presenting features Febrile, SOB, increased RR, decreased BP, increased HR, skin rash, sense of impending doom, agitation, chest/abdo pain, airway obstruction appropriate investigations Stop transfusion ABC management Call lab Send FBC, U and E, clotting, blood cultures, urine [intravascular haemolysis], send back the bag of blood CXR principles of management ABC then depending on the cause:

Tx of anaphylaxis Tx of sepsis 02 Paracetamol Clorphenamine Furosemide complications and outcome Death DIC, MOF prevention of disease blood sample labelling wristband and safety checks monitoring throughout stopping transfusion if any doubt Haemolytic anaemias destruction of red blood cells, intravascular or extravascular [i.e. spleen] aetiology Hereditary: membrane defects e.g. spherocytosis, elliptocytosis metabolic defects e.g. pyruvate kinase def, G6PD def [Heinz bodies, x linked, ox stress e.g. drugs, fava beans] Hb defects e.g. sickle cell, thalassaemias Traumatic: march, prosthetic heart valves, microangiopathic e.g. DIC, malaria Immune: mismatched blood transfusions, haemolytic disease of newborn [Rh-ve mother, Rh +ve baby, exposed to babys rbc at birth, makes anti Rh ab, these cross placenta if subsequently pregnant with Rh+ ve baby], warm antibodies [SLE, lymphoma] cold antibodies [mycoplasma, EBV, lymphoma], drugs Paroxysmal Nocturnal Haemoglobinuria [destruction by complement] presenting features Anaemia, jaundice, hepatosplenomegaly. appropriate investigations FBC anaemia, raised MCV. Blood film reticulocytosis [polychromasia], leucoerythroblastic picture Increased unconjugated bilirubin Decreased haptoglobin Haemoglobinuria, haemosiderinuria [if intravascular haemolysis] coombs test

osmotic fragility test hb electrophoresis principles of management Treat cause, blood transfusions, splenectomy complications and outcome Anaemia plus complications associated with some of the diseases prevention of disease Genetic counselling Lymphomas lymphoma malignancy of lymphoid cells, different types depending on different cell type and degree of cell differentiation Involvement of lymph nodes, but can also involve bone marrow and blood Hodgkins lymphoma Reed-Sternberg cells, pain after ETOH Non Hodgkins lymphoma presenting features Mass, lymphadenopathy, hepatosplenomegaly B symptoms: fever, night sweats, wt loss Bone marrow failure appropriate investigations FBC, blood film, LN biopsy, bone marrow biopsy, CT scan, PET scan Staging: Ann Arbor 1 [single LN region], 2 [disease 1 side of diaphragm], 3 [disease both sides of diaphragm], 4 [extranodal disease] differential diagnosis TB, malignancy LN infection local, infection systemic, inflammation, malignancy principles of management chemotx or radiotx Myeloma plasma cell malignancy pathology lytic bone lesions [pain, pathological fractures] paraprotein i.e. monoclonal immunoglobulin plus excess light chains [immunoparesis, renal failure, hyperviscosity, amyloidosis] presenting features pathological fractures/bone pain/hypercalcaemia [stones, bones, moans, groans] recurrent infections renal failure hyperviscosity [headaches, visual disturbances] amyloidosis [macroglossia, carpal tunnel] appropriate investigations FBC: normochromic normocytic anaemia

Raised CRP/ESR Serum electrophoresis M band [paraprotein], urine electrophoresis may show bence jones proteins Bone marrow aspirate/trephine: raised plasma cells x-rays lytic lesions Ca increased ALP NORMAL principles of management Chemotherapy Tx infection Tx high Ca Analgesia/radiotherapy for bones Tx kidney disease complications and outcome Kidney failure Infection Amyloidosis Bone fractures and pain Disseminated intravascular coagulation Causes: sepsis, obstetric, malignancy, trauma, burns Widespread activation of clotting cascade [clotting], consumption of clotting factors [bleeding] fibrin webs [haemolytic anaemia] Bleeding/purpuric rash/ petechiae / epistaxis MOF [oliguric, shocked, confused, ARDS] Thrombosis Ix: raised APTT and d-dimer, low fibrinogen, platelets , Hb [schistocytes] Treat the cause ASAP , may need to transfuse blood components Sickle cell disease Autosomal recessive mutation in B-globin gene Hb SS Increased prevalence in countries with malaria [heterozygous condition thought to be protective vs malaria] HbS sickles in conditions of low ph/low o2/ infection/dehydration 1] RBC are fragile and destroyed by RES. Anaemia. Shortened life of RBC hence aplastic crisis if parvovirus infection halts RBC production. 2] RBC stick in blood vessels: Bones: pain, necrosis Lungs: infarct, SOB Spleen: auto-splenectomy Brain: stroke Eyes

Skin: leg ulcers Ix: FBC, blood film, Hb electrophoresis Tx: O2, IVF, Abx, Analgesia, Blood transfusions, Hydroxyurea [increases HbF], avoid stressful conditions, prophylaxis re auto-splenectomy, genetic counselling Thalassaemia Mediterranean countries, Middle East Autosomal recessive Decreased globin hence microcytic, hypochromic Decreased alpha globin: Mutation 4 alpha genes Hb Barts and Hydrops Fetalis Mutation 3 alpha genes symptomatic Mutation 1 or 2 alpha genes milder Decreased beta globin: Major: symptomatic at 3-6 months when fetal Hb decreases. Failure to thrive, anaemia, jaundice. Intermedia: mild defect in beta chain synthesis Trait: heterozygous carrier Ineffective erythropoeisis, haemolysis, anaemia, extramedullary haematopoiesis [bossing of skull, hair on end x-ray appearance, hepatosplenomegaly] Electrophoresis Tx: Blood transfusion plus iron chelation, BM transplant, splenectomy Haemophilia A deficiency factor V111 B deficiency factor 1X C deficiency factor X1 X linked recessive Bleed into joints [joint deformities], haematuria [Fe def anaemia], excess bleeding after trauma/surgery Tx: factor transfusions [used to be risk of HIV/Hepatitis and can develop ab to factors], lifestyle advice, no IM injections Thrombophilia Factor v leiden not degraded by APC Prothrombin mutation Protein c def [protein c inactivates factor v] Protein s def [protein s inactivates factor v111] Antithrombin def Antiphospholipid syndrome venous, arterial, miscarriages Family history, young age, recurrent, unusual site

Shouldnt be on OCP, may need life-long anticoagulation Thrombocytopenia BM failure Splenic sequestration ITP immune thrombocytopenic purpura TTP thrombotic thrombocytopenic purpura [1 fever, 2 fluctuating CNS signs, 3 haemolytic anaemia, 4 thrombocytopenia, 5 renal failure] acquired e.g. dx, pregnancy, hiv, sle/inherited. Defective VWF-cleaving protein - large VWF multimers. HUS [ecoli 0157, shigella, dx, familial]. Triad haemolytic anaemia, ARF, thrombocytopenia. Abdo colic, watery diarrhoea, malaise, fatigue, fever, CNS signs. Caused by endothelial injury. Tx plasma exchange, FFP, steroids, splenectomy Pancytopenia Bone marrow failure leukaemia/myeloma/myelofibrosis, drugs, idiopathic, viruses, inherited Anaemia Thrombocytopenia Leukopenia Often hypocellular bone marrow Low reticulocytes Neutropenia Chemotherapy, sepsis. Viral, bm failure, ab, feltys syndrome Low threshold for abx Bone marrow replacement Destroy host BM Transplant allogeneic stem cells Repopulate BM Stem cells repopulate Allows high intensity chemotx to be used Graft versus leukaemia Graft versus host Infections Relapse Acute leukaemia

ALL lymphoblasts Peak age 3-7 [70% cure], second peak in elderly [30% cure] BM failure Infiltrates bones, LN, meninges, liver, spleen FBC, blood film, bone marrow aspirate/trephine, x-rays, cytogenetics Tx: chemotx, stem cell transplantation, supportive AML - myeloblasts BM failure Infiltrates bones, LN, meninges, liver, spleen Some types associated with DIC FBC, blood film [may have Auer rods], bone marrow aspirate/trephine, x-rays, cytogenetics Tx: chemotx, stem cell transplantation, supportive Chronic myeloid leukaemia Malignancy of granulocyte precursors 95% 9;22 ph ch systemic symptoms bone marrow failure hyperviscosity splenomegaly gout FBC raised wcc, B/E/N, low Hb Blood film immature granulocytes BM aspirate Cytogenetics Tx chemotherapy Can transform Chronic lymphocytic leukaemia Malignancy of mature lymphocytes [failure to apoptose] Excess lymphocytes in bone marrow, blood, liver, spleen, lymph nodes Asymptomatic/ Systemic symptoms/ BM failure/ Anaemia [anaemia due to BM failure/hypersplenism/ autoimmune haemolysis] FBC/ Blood film [smudge/smear cells]/ BM aspirate/CT Early: watch and wait Later: chemotherapy plus treat complications Can transform