Haematology and Transfusions

Dr Caroline Young

Aims and Objectives

Whistle-stop tour of the syllabus. Hope to demonstrate that a lot of haematology can be worked out from first principles. There's a lot of overlap.
Will highlight one key learning point per topic either something that you really, really need to know..... or something esoteric that the examiners love.

Syllabus

Anaemias: microcytic [iron deficiency, thalassemia,]

macrocytic, haemolytic [sickle cell]

Malignancies: myeloma, lymphoma, leukaemia Clotting Disorders: haemophilia. thrombophilia,

thrombocytopenia, DIC

Failure: pancytopenia, neutropenia Replacement: transfusion reactions, bone marrow

replacement

Anaemias

Microcytic Anaemia
Defect in: haem [Fe def/sideroblastic anaemia] or

globin [thalassaemias]

Iron Deficiency Anaemia

Problem of : Intake eg vegans/elderly Absorption eg SI/ stomach Demand eg childhood/pregnancy/breast-feeding Loss eg GI malignancy, uro/gynae malignancy, menstruation

Presenting features
Signs/symptoms of Anaemia Signs/ symptoms of Cause

Signs of Fe def: koilonychia, glossitis, angular stomatitis

On investigation
Hypochromic, Microcytic Poikilocytosis [variable shape], Anisocytosis [variable size] Iron binding capacity increased, Ferritin decreased Ix causes

Treatment
Anaemia: blood transfusion Iron deficiency: replacement Cause

Thalassaemias
Autosomal recessive condition

Decreased globin synthesis

Decreased alpha globin: Mutation 4 alpha genes Hb Barts and Hydrops Fetalis Mutation 3 alpha genes symptomatic Mutation 1 or 2 alpha genes milder I

Decreased beta globin: Major: symptomatic at 3-6 months when fetal Hb decreases
Intermedia: mild defect in beta chain synthesis

Trait: heterozygous carrier

Presenting features
Ineffective erythropoeisis and haemolysis
Extramedullary haematopoiesis

[bossing of skull, hair on end x-ray appearance,hepatosplenomegaly]

Investigation and Treatment

Investigation: Electrophoresis Treatment: Blood transfusion plus iron chelation, splenectomy

Macrocytic Anaemias

Macrocytic Anaemias

Megaloblastic Non-megaloblastic

Non megaloblastic
ETOH
Hypothyroid

Haemolysis
Myelodysplasia Pregnancy

Megaloblastic
B12 or folate deficiency
Problem of:

intake: B12 vegans Folate foliage elderly, anorexia, alcoholism absorption: stomach, SI

demand: pregnancy, lactation, malignancy, inflammation

metabolism eg trimethoprim

Presenting features
Symptoms/signs associated with Anaemia Symptoms/signs associated with Cause

Symptoms/signs associated with B12 deficiency eg angular stomatitis, glossitis, subacute combined degeneration of the spinal cord, dementia, optic atrophy

On investigation

macrocytosis, hypersegmented neutrophils raised bilirubin

low B12 and folate blood levels Investigate the cause: schilling test, ab versus parietal cells or IF, TTG

Treatment
Anaemia: blood transfusion B12, folate deficiency: replacement. Replace B12 first if deficient in both. Cause

Haemolytic Anaemias

Haemolytic Anaemias
Hereditary:

membrane defects eg spehrocytosis, elliptocytosis metabolic defects eg pyruvate kinase def, G6PD def [fava beans] Hb defects eg sickle cell, thalassaemias

Traumatic:

march prosthetic heart valves

microangipathic eg DIC
malaria

Immune:

mismatched blood transfusions haemolytic disease of newborn warm antibodies [SLE, lymphoma] cold antibodies [mycoplasma, EBV, lymphoma]

drugs
paroxysmal nocturnal haemoglobinuria [complement]

On investigation
Anaemia, jaundice, hepatosplenomegaly Raised MCV, reticulocytosis [polychromasia] Increased unconjugated bilirubin

Decreased haptoglobin, haemoglobinuria, haemosiderinuria [if intravascular haemolysis]

Coombs test
Osmotic fragility test Hb electrophoresis

Treatment
Treat cause
Blood transfusions

Splenectomy
Genetic counselling

Sickle Cell Disease

Sickle Cell Disease

Autosomal recessive mutation in B-globin gene Hb SS Sickles if low ph/low o2/ infection/dehydration

Sickled RBC stick in blood vessels

Bones: pain, necrosis Lungs: infarct, SOB Spleen: auto-splenectomy Brain: stroke

Eyes
Skin: leg ulcers

Treatment

Reverse sickling conditions: O2, IVF, Abx, Analgesia Blood transfusions

Hydroxyurea [increases HbF]

Prophylaxis re auto-splenectomy Genetic counselling

Malignancies

Myeloma

Malignancy of plasma cells

Presenting Features
Lytic bone lesions:

Pain

Pathological fractures
Hypercalcaemia

Paraprotein:

Immunoparesis

Renal failure
Hyperviscosity

Amyloidosis

On investigation
Normochromic normocytic anaemia Raised CRP/ESR, Ca increased, ALP NORMAL Serum electrophoresis M band [paraprotein]

Urine electrophoresis may show BJP

Bone marrow aspirate/trephine: raised plasma cells x-rays lytic lesions

Treatment
Chemotherapy

Treat complications

Lymphoma
Malignancy of lymphoid cells

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

On investigation
LN biopsy, bone marrow biopsy, CT scan, PET scan
Staging: Ann Arbor

Treatment

Chemotherapy or radiotherapy

Leukaemias

Acute [differentiation and apoptosis] vs Chronic [apoptosis]

Transformation Lympho vs Myelo

Presenting features: BM failure, systemic symptoms

Ix: Bloods, BM,cytogenetics Tx: Chemotx, supportive, BM transplant

Clotting Disorders

Haemophilia
A deficiency factor V111 B deficiency factor 1X C deficiency factor X1 X linked recessive

Presenting features:

joint deformities haematuria excess bleeding after trauma/surgery

Treatment:

factor transfusions lifestyle advice eg 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
Antiphospholipd syndrome venous, arterial, miscarriages

Family history, young age, recurrent, unusual site Anticoagulation, Advice eg OCP

Thrombocytopenia

BM failure
Splenic sequestration ITP TTP Defective VWF-cleaving protein [fever, fluctuating cns, haem anaemia, thrombocytopenia, RF]

HUS

Tx plasma exchange, FFP, steroids, splenectomy

DIC
Causes: sepsis, obstetric, malignancy, trauma, burns
Widespread activation of clotting cascade [clotting], consumption of clotting factors [bleeding] and fibrin webs [haemolytic anaemia].

Ix: raised APTT and d-dimer, low fibrinogen, low platelets , low Hb [schistocytes]
Treat the cause ASAP, may need to transfuse blood components

Failure

Pancytopenia
Bone marrow failure leukaemia/myeloma/myelofibrosis, drugs, idiopathic, viruses, inherited
Anaemia, Thrombocytopenia, Leukopenia

Hypocellular bone marrow

Low reticulocytes

Neutropenia
BM failure
Chemotherapy Sepsis Viral Ab Low threshold for abx

Replacement

Blood transfusion reactions

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

Shocked
SOB Increased RR, decreased BP, increased HR Skin rash Sense of impending doom, agitation, chest/abdo pain Airway obstruction

Management
If in doubt, stop transfusion
ABC management

Call lab
Send FBC, U and E, clotting, blood cultures, urine [intravascular haemolysis], return the bag of blood CXR

Plus, depending on reaction...

Tx of anaphylaxis

Tx of sepsis
02 Paracteamol Clorphenamine Furosemide

Prevention
Importance of careful blood sample labelling
Wristband and safety checks

Regular monitoring throughout transfusion

Bone Marrow Replacement

Destroy host BM.....
Transplant allogeneic stem cells....

Repopulate BM....
Graft versus leukaemia But: Graft versus host Infections Relapse

Summary

Anaemias: microcytic [iron deficiency, thalassemia,]

macrocytic, haemolytic [sickle cell]

Malignancies: myeloma, lymphoma, leukaemia Clotting Disorders: haemophilia. thrombophilia,

thrombocytopenia, DIC

Failure: pancytopenia, neutropenia Replacement: transfusion reactions, bone marrow

replacement

Learning points

Fe def anaemia consider occult malignancy

Thalassemias: anaemia and extramedullary haematopoiesis Always check and treat B12 def before folate def

G6PD def exacerbated by fava beans

Sickle cell tx the sickling conditions

ALP normal in myeloma

 Reed-sternberg cells in HL
Acute leukaemias [differentiation and apoptosis], Chronic leukaemias [apoptosis] Joint disorders in Haemophilia Antiphospholipid antibody triad TTP and VWF DIC treat the cause

 Pancytopenia anaemia, thrombocytopenia, leukopenia

Neutropenia low threshold for abx If suspect blood transfusion reaction, stop the transfusion

GVHD in BM transplant

The End