Haematology Flashcards
What is HITT syndrome?
Heparin-induced thrombocytopenic thrombosis
platelet antibodies cause plts to thrombose vessels: loss of limb or life
Types of disease associated with B cell deficiencies
Defective antibody response = increased susceptibility to opportunistic infections caused by extracellular organisms
Types of disease associated with T cell deficiencies
Defective cell-mediated immunity = increased susceptilibity to opportunistic infections caused by intracellular organisms
Commonest immunodeficiency
IgA (1 in 700 Caucasians)
patients prone to sinopulmonary infections and bowel colonisation with Giardia, Salmonella, other enteric organisms
Example primary B cell deficiency
IgA deficiency
lots of weird congenital ones
Example primary T cell deficiency
DiGeorge (thymic hypoplasia)
Example primary mixed T and B deficiency
SCID (severe combined immune deficiency)
Example secondary B cell deficiency
Myeloma
Example secondary T cell deficiency
AIDS
Hodgkin’s and Non-Hodgkin’s lymphoma
Drugs, eg steroids, ciclosporin, azathioprine
Example secondary mixed B and T cell deficiency
CLL Post-bone marrow transplantation Post-chemo/ radiotherapy Chronic renal failure Splenectomy
What is amyloidosis?
the pathological deposition of abnormal extracellular fibrillar protein (amyloid) in tissues
can’t be broken down
can be systemic or localised
can be inherited (rare)
Figures for neutropenia
lower than 2.5 (1.5 if black/ Middle Eastern)
severe is termed ‘agranulocytosis’
vulnerable to opportunistic infection (Gram-positive skin organisms and Gram-negative gut infections)
Causes of neutropenia
Reduced granulopoiesis
Accelerated granulocyte removal: autoimmune, SLE, Felty’s, infection
Drug-induced neutropenia
Part of a general pancytopenia
B symptoms
weight loss, pyrexia, night sweats
What is Hodgkin’s characterised by
Painless lymphadenopathy + presence of large binucleate cells within them (Reed-Sternberg cells)
lymph nodes often within upper half of body (then spreads via lymphatic sx to below diaphragm)
Incidence of Hodgkins
15-20 years, then 40-60 years
Incidence NHL
Middle/later life
Difference acute and chronic leukaemias
Acute: numerous immature blast cells - rapid disease progression
Chronic: large numbers of precursor cells that are more differentiated than blast cells - slower disease progression
Then differentiated into myeloid (granulocytes) or lymphocytic leukaemia
Main features of leukaemias
Bone marrow failure: anaemia, haemorrhage, infection
Gout (increased cell turnover)
Metastasis
Incidence of acute leukaemia
ALL: most common in children (also occurs in middle-age - worse prognosis)
AML: more common in adults
What is the Philadelphia chromosome associated with?
CML
Stages of CML
Chronic phase: anaemia + splenomegaly - responsive to chemo
Accelerated phase: more difficult to control - emergence + dominance of a more malignant clone of myeloid cells
Blast crisis phase: transformation to acute leukaemia, usually AML - often rapidly fatal (timing unpredictable)
Difference in presentation of AML and CML
In CML the neutrapenia, lymphopenia and thrombocytopenia are uncommon - so not haemorrhaging or infection
Ditto in CLL not common until later stages
Most common leukaemia in adults
CLL
Clinical features of multiple myeloma
Bone pain, esp backache and pathological fractures
Anaemia
Repeated infections: deficient antibody levels and bone marrow failure
Abnormal bleeding tendency
Renal impairment (Bence-Jones or hypercalcaemia)
Causes of splenomegaly
Infection
Congestion
Pre-hepatic: thrombosis of hepatic, splenic or portal vein
Hepatic: longstanding portal hypertension
Post-hepatic: raised venous pressure, eg RHF
Neoplasm (usually secondary)
Haematological disorders
Immune disorders: Felty’s, amyloidosis, sarcoidosis
HYPERSPLENISM
Enlarged spleen causing decrease in pancytopenia
often accompanied by compensatory hyperplasia of bone marrow - situation rectified by splenectomy
What can cause splenic infarcts?
Emboli from heart - can be septic if associated with IE
Local thrombosis - eg sickle cell, malignant infiltrates
Causes macrocytic anaemias
Megaloblastic anaemias (B12/ folate deficiency) Haemolytic anaemias (new immature RBCs are large)
Causes normocytic anaemias
anaemia of chronic disease
hypoplastic anaemias
Causes microcytic anaemia
Fe deficiency
thalassaemia
Crises of sickle cell disease
Sequestration crises: pooling of RBCs in liver and spleen - death from rapid fall in Hb
Infarctive crises: brain, retinopathy, ARDS, cor pulmonale, haematuria, bone necrosis
Aplastic crises: infection with parvovirus B19 which targets erythrocyes and lyses them - rapid fall in Hb
Common sites of infarction in SCD
Femoral head
spleen
skin (ulcers)
Clinical features of chronic haemolysis in SCD
Anaemia
Jaundice + gallstones
Fe overload
Blood group types in UK (most common to least common)
O A B AB
Clinical features of ABO incompatibility
Massive intravascular haemolysis leading to collapse, hypotension, lumbar pain
DIC may be triggered
Store reserves for Vit B12 and folate
Folate: 50-100 days
B12: several years
Where is B12 and folate absorbed?
B12: terminal ileum (after binding to IF)
Folate: Jejunum
Causes B12 deficiency
Pernicious anaemia: autoimmune atrophic gastritis
Congenital lack of IF
Surgical gastrectomy
Surgical removal or disease of terminal ileum
Bacterial overgrowth (competes for B12)
Veganism: rare
Causes of folic acid deficiency
Malnutrition
Malabsorption
Increased requirements: pregnancy, lactation, haemolysis, malignancy, extensive psoriasis
Drugs (anticonvulsants, methotrexate)
Clinical features of Fe-deficiency anaemia
Anaemia Angular cheilitis Atrophic glossitis Oesophageal webs hypochlorhydia Koilonycia Brittle nails Pica
Causes DIC
Infection: sepsis, viral, malaria Malignancy Obstetric complications: amniotic embolus, placental abruption, retained fetus Anaphylaxis Burns, major surgery, major trauma Liver disease
How is Fe transported/ stored?
Transported on transferrin, stored bound to ferritin
Neurological manifestations of B12 deficiency
Peripheral neuropathy
Subacute combined degeneration of the cord
Dementia
Causes of congenital haemolysis
Presentation
Hereditary spherocytosis
Thalassaemia
SCD
G6PD
Pallor, jaundice, splenomegaly
What is hereditary spherocytosis?
AD transmission
Defect in cell membrane causing increased cell fragility
What is G6PD?
glucose-6-phosphate dehydrogenase deficiency
X-linked
normally generates NADPH, needed for maintaining healthy Hb so can withstand stress
need to avoid drugs that precipitate haemolysis
Inheritance of haemophilias
X-linked recessive
Girls carry
Boys suffer
Signs and symptoms of polycythaemia
facial plethora, bleeding, splenomegsaly, bruising
headaches, dizziness, pruritus after bathing, LOC, gout
What cancerous transformations can result from polycythaemia?
Myelofibrosis, AML
What is myelofibrosis vs myelodysplasia?
MYELOFIBROSIS: clonal proliferation of haematopoietic stem cells, leading to bone marrow fibrosis
MYELODYSPLASIA: clonal disorder of bone marrow, producing morphologically/functionally abnormal cells - worse prognosis with 1/3 turning to AML
Signs of myelofibrosis
Management
Pallor, bruising, massive splenomegaly, oral thrush, systemic symptoms
Supportive: blood transfusion
Can also use hydroxycarbamide, thalidomide, splenectomy
Signs of myelodysplasia
Management
features of anaemia, bacterial infection, bleeding
supportive: transfusions, abx
in young patients can consider allogenic bone marrow transplant which can be curative
Type I hypersensitivity
Immediate, eg anaphylaxis
Type II hypersensitivity
cytotoxic
Type III hypersensitivity
immune complex disorders
Type IV hypersensitivity
Delayed hypersensitivity
What is serum?
Plasma without clotting factors
Sites of haematopoeisis
Bone marrow
Extramedullary: liver, spleen
Stem cell lineages
MYELOID STEM CELLS Proerythroblasts > erythrocytes Megarkaryocytes > platelets Myeloblasts > neutrophils, eosinophils, basophils Monoblasts > monocytes
LYMHOID STEM CELLS
NK cells
Lymphocytes T, B
How to manage mild allergy to blood transfusion?
Slow transfusion, antihistamine
(eg rash, itch, urticaria)
occurs immediately
How to manage ABO incompatible transfusion
Stop transfusion, inform lab, IV fluids
Manage DIC
occurs within minutes
How to manage febrile non-haemolytic transfusion
Slow transfusion, paracetamol
occurs within hours
How to manage bacterial contamination of blood products
Stop transfusion, sepsis 6
inform lab
occurs within 24h
How to treat TRALI (transfusion-related acute lung injury)
stop transfusion, oxygen, treat ARDS
(acute SOB, Cough, normal CVP/ JVP)
occurs within 6-24h
How to treat TACO
slow transfusion, oxygen, IV furosemide
(acute SOB, raised CVP/ JVP)
occurs within 6-24h
What is HSCT
Haematopoietic stem cell transplant
Allogenic: usually HLA-matched, requires high-dose chemo (destroys malignant cells + induces temporary immunosuppression)
Autologous: harvested prior to therapy then re-infused post-chemo
WHO anaemia
below 13 in men
below 12 in women
Diagnosing Fe-deficiency anaemia
Microcytic anaemia
Ferritin (<12 ng) - although as an acute phase protein could be falsely elevated
Gold standard: Prussian blue staining of bone marrow biopsy
(Consider testing for coeliac)
Managing iron-deficiency anaemia
Oral supplements: may take 2 months for Hb to normalise
IV iron if not responsive
What is sideroblastic anaemia?
Excess Fe deposition in RBC precursors, forming ringed sideroblasts in bone marrow
Congenital or acquired (chronic infections, SLE, drugs, lead poisoning)
Clinically indistinguishable from other anaemias but iron studies will show high Fe levels (then bone marrow studies)
Generally supportive treatment/ treat underlying cause
Pyridoxine (B6) may be helpful in treating congenital forms
Antifolate drugs
methotrexate
phenytoin
trimethoprim
What further investigation should be offered when pernicious anaemia is identified?
OGD: susceptibility to gastric cancers
Replace B12 or folate first?
B12: prevent exacerbation of neurological symptoms
Diagnosis of aplastic anaemia
Hypocellular bone marrow and 2 of:
Hb < 10
Neut < 1.5
Plts < 50
Mx hereditary spherocytosis
Folate replacement
Splenectomy (usually after age 6)
Blood film: G6PD
Heinz bodies and Blister (bite) cells
Blood film: pyruvate kinase deficiency
Prickle cells
What is the Coombs test - what are the types?
Detects presence of antibodies
DAT (Direct Coombs): haemolytic anaemias, transfusion reactions
detects antibodies bonded to the RBC
IAT (Indirect Coombs): cross-matching, prenatal rhesus testing
Detects antibodies in plasma
Classifying bleeding disorders
VESSEL WALL DISORDERS
PLATELET DISORDERS: thrombocytopenia or platelet dysfunction
COAGULATION DISORDERS: congenital or acquired
Distinguishing clotting and coagulation disorders
Clotting (ie platelets): bruising, purpura, mucosal membranes. Occurs spontaneously
Coagulation: generally haemarthroses or haematomas - occurs within hours/ days
Understanding the coagulation screen: bleeding times
Gives info about platelets: is there platelet dysfunction or vWB disease
Understanding the coagulation screen: APTT
gives info about the intrinsic pathway
helpful to monitor heparin therapy, haemophilia, DIC
Understanding the coagulation screen: PT, INR
gives info about the extrinsic pathway
helpful for monotoring warfarin therapy, liver disease, DIC
Understanding the coagulation screen: fibrinogen levels
final common pathway
helpful in liver disease, DIC
Congenital and acquired examples of vessel wall disorders
HHT, Ehlers-Danlos
Scurvy, vasclitis (Henoch-Schonlein), infection (meningococcal rash)
Difference in LMWH and UFH with heparin-induced thrombocytopenia
Much more common in UFH, typically occurs within 5-10 days of commencement
HAEMOPHILIA A
X-linked
Factor VIII deficiency (intrinsic pathway)
Mx haemophilia A
Severe bleeds: give factor VIII IV
Mild bleeds: IV or intranasal desmopressin (DDAVP)
stimulates release of vWF > increases Factor VIII levels
Things to avoid in haemophilia A
contact sports!
NSAIDs
IM injections
HAEMOPHILIA B (CHRISTMAS DISEASE)
Factor IX
DDAVP has no effect
Findings on coagulation test in vWD
Both prolonged PT and APTT
Smudge cells
CLL - fragile lymphocytes
The most common indications for irradiated blood products
- Those at risk of transfusion associated with graft versus host disease such as neonates
- Those receiving purine analogues based chemotherapy
- Hodgkin’s lymphoma
- Immunodeficiency states
- Post bone marrow transplants
Blood tests to support assumption that haemolysis was causing jaundice in patient?
Low haptoglobin
High LDH
