Haematology Flashcards
What are the indications of blood transfusions
- active bleeding in trauma or surgery or anything else
- SCD or thalessemia
- leukaemia
Hb is less than 80 and the patient is symptomatic
What is FFP
Frozen plasma
Is done to replace coagulation factors
Can be given in TTP, or to reverse warfarin or severe chronic liver disease
When is platelet transfusion required
When platelets are below 50 + active bleeding
Shouldn’t be transfused in patients with TTP or drug induced thrombocytopenia (heparin)
Ocular and neurosurgery
What is cryoprecipitate
Used to replace VIII and fibrinogen. After a massive haemorrhage
Or can be congenital fibrinogen deficiency
Transfusion reaction presentations
Pruritus
Jaundice
Shock
Renal fialaure
Flank pain
Haemoglobiinuria
Fever
Tachypneoa
Tachycardia
Hypotension
Treatment for AHTR
Fluid resus ‘
Correct electrolytes
What is Febrile non haemolytic transfusion reaction
No haemolysis occurs and fever occurs due to endogenous release of pyrogens
Give anti-pyretics
Transfusion complications on lungs
TRALI - acute noncardiogenic pulmonary oedema within 6 hours of receiving blood products
Neutrophil activation which releases o2 species that damages pulmonary vasculature + extravastion of fluid
- diuretics not helpful in this as not heart related. Steroids helpful as this is immune mediated and ventilation
TACO - (within 12 hours) patient already has underlying heart failure in which transfusion rate is not adjusted leading to circulatory overload. The heart cannot tolerate this overload which will cause hypertension leading to pulmonary oedema. Raised JVP
Treatment - respiratory support and diuretics
Anaphylactic transfusion reaction
Symtoms occur within 4 hours of transfusion
Caused by release of histamine by mast cells
Managed with steroids and fluids?
Septic transfusion reactions
Within 4 hours symptoms of sepsis occur
Most common organisms are staph a. And gram negatives
Treat with vancomycin and aminoglycosides
What occurs in vessel injury
BV constriction
Platelet activation
Activation of coagulation cascade
Clotting is down regulated by fibrinolysis, Protein C and S, anti-thrombin III
How to differentiate between petechiae, purpura and ecchymosis
Petechaie - less than 2mm
Purpura - 2mm to 1cm
Ecchymosis >1cm
Bleeding into deep tissues, joints and muscles suggest what
Coagulation factor deficiencies
What drugs can cause thrombocytopenia
Amiodarone
Carbamazepine
NSAIDs
Tamoxifen
What is ITP: immune thrpmbocytopenic purpura
Autoimmune condition mainly affecting women in which immune system attacks platelets targeting the GP IIb/3a complex. Trapped within the spleen and removed by splenic macrophages
Mild - gums, nose and heavy periods (might cause anaemia)
- no organomegaly should occur or lymphadenopathy
20-40s age and presents suddenly
Steroids treatment of choice
What is TTP
Rare disorder : Pentad
Thrombocytopenia (as platelets are used in making micro-thrombi)
RBC fragmentation
Kidney failure
Neurological dysfunction
Fever
VW protein is released from endothelial cells when required for platelet aggregation. In this disease ADAMTS13 ( a protease which cleaves VW protein when not needed) is deficient meaning lots of VW protein can clump together leading to micro thrombi. Micro thrombi cause micro vascular injury affecting all the above systems within the body. Presence of microthrombi can damage RBC)
Petechaie
Fever
Confusion
Headaches
Coma
What is the normal PT time and what pathway does it measure
10 to 14 seconds
Extrinsic pathway
What is normal PTT time and which pathway does it meausre
Intrinsic
25-38
What causes prolonged PT time
Defieciency in factor 12
Factor 7
Vitamin k deficiency 10 9 7 2
Liver disease
Causes of prolonged PTT time
Low factor 8,9,10 + 11
Von willebrand disease
haemophilia A + B
Haemophilia A
Low factor 8
X-linked
Haemophilia B
- low factor 9
X-linked
What is haemophilia C
Low factor 11
Treated by FAP
Role of VW protein
Is a glycoprotein that acts to platelet adhesion and helps to carry factor 8
In disease:
Platelet levels are normal, PT normal
PTT is prolonged and VW low. Factor 8 will also be low
What is VW disease treated with
Tranexamic acid?
What is the definition of haematocrit
Of the centrifuged sample what proportion of the blood is made up of red blood cells
What are the causes of microcytic anaemia
Iron deficiency anaemia
Thalessemia
Congenital sideroblastic anaemia
Anaemia of chronic disease
Lead poisoning
What can cause iron deficiency anaemia
Menorrhagia
Pregnancy
GIT malignancies
Oesophagitis
GORD
Coeliac disease
Hookworm - and schistosomiasis
Low iron diet - vegans
What is transferrin
A protein which is responsible for the transport of iron through out the body
What is ferritin
A protein which stores iron
What would the FBC picture look like in microcytic anaemia
Microcytic and hypochromic cells
Decreased MCV
Decreased MCH
Decreased ferritin
Decreased iron
Increased transferrin* and TIBC
Blood film - anisocytosis (RBC are different sizes) + poikilocytosis (RBC are different shapes).
- variable depending on cause of microcytic anaemia
Causes of normocytic anaemia
CKD
Haemolytic anemia
Aplastic anaemia
Anaemia of chronic disease
Acute blood loss
Pregnancy
Hypothyroid
What can cause haemolytic anaemia
Glucose 6 phosphate deficiency (enzyme that protects the RBC from oxidative stress and destruction)
Hereditary spherocytosis - Rbc are sphere shaped and more fragile + prone to haemolysis
Haemolytic disease of the newborn
Sickle cell disease
Warm antibody autoimmune haemolytic anaemia - at higher temperatures plasma cells attack RBC causing their destruction - mainly IgG
Cold antibody autoimmune haemolytic anaemia - IgM at lower temperatures attach to RBC causing them to agglutinate and undergo destruction
What are Heinz bodies
Most commonly seen in G6P deficiency - when the body detects damaged Hb it tries to remove it from the cell leaving behind a small round blue black body known as a Heinz body
WAIHA is usually associated with what condition
CLL
CAIHA is usually associated with which conditions
Lymphoma
Mycoplasma
EBV injections
Which groups of women are at higher risk of having a baby with a NTD
BMI over 30
Previous child with NTD
FHX
Taking anti-epileptics
Diabetes
Coeliacs
Thalessemia
What does FBC look like in normocytic anaemia
Decreased hb
Normal MCV
Normal or increased ferritin
Increased bilirubin
Check reticulocyte count
What can cause G6P deficiency
X linked condition - thus affects males more
Anti- malarials
Sulfa drugs ( sulfonamides, sulphasalazine and sulfonylureas)
Causes of macrocytic anaemia
FAT RBC
Megaloblastic - b12 defieicny, folate defeciency and secondary to methotrexate + pernicious anaemia
Non-megaloblastic - alcohol, liver disease, hypothyroid, pregnancy, reticulocytosis, myelodysplasia and cytotoxic drugs
What does the FBC picture look like for macrocytic anaemia
Decreased HB
Increased MCV
Decreased B12 and folate
On blood film hypersegmented neutrophils
What happens to TIBC in anaemia of chronic disease
It is Low. In comparison to in iron deficiency anaemia TIBC is high
key regulator in ACD is hepcidin, a protein produced by the liver in response to inflammation.
1️⃣ Hepcidin blocks iron release from macrophages and hepatocytes
Iron remains trapped in storage and is unavailable for erythropoiesis.
This leads to low serum iron despite adequate iron stores.
Causes of hypo proliferative (reticulocyte count) normocytic anaemia
Leukaemia
Aplastic anaemia
Pure red cell aplasia
Other BM failure syndromes eg parvovirus infection in SCD
What kind of investigations would you carry out to find the causes of microcytic anemia
Faecal occult blood test
Endoscopy
Colonoscopy
TTG-IgA test
Flow cytometry - diagnostic for paroxysmal nocturnal haemoglobinuria
Transvaginal ultrasound - may reveal cause of menorrhagia
What is thalessemia
Autosomal recessive condition which leads to insufficient haemoglobin production. Affects production of alpha or beta chains .
Most common in Mediterranean, Middle Eastern and Southeast Asians.
Electrophoresis is diagnostic test
Alpha chains coded for via gene on chromosome 16
Beta chains coded for by gene on chromosome 11
What is an important thing to consider in normocytic anaemia
Whether reticulocyte count is hypo or hyperproliferative
What causes a hyperproliferatve normocytic anaemia
( high production of of rBCS and reticulocyte in response to increased destruction or loss of RBC)
- haemolytic anaemia caused by
Drugs - penicillin, levodopa, cephalosporins
Infections - CMV, toxoplasmosis, leishmania, malaria
Transfusion reactions
Burns
Microangiopathic haemolytic anaemias - HUS, TTP + DIC
What kind of anaemia does SCD cause
Normocytic hyperprolierative anaemia
Etiology of SCD
Autosomal recessive condition in which an amino acid substitution leads to production of HbS which in deoxygenated states polymerises causing the characteristic sickle shape and is very rigid.
Causes vaso-occlusive crises and haemolysis. Can also get aplastic crisis where there is a sudden reduction in production of RBC, reticulocyte, WBC and platelets.
Acute chest syndrome - pain, dyspnoea, low sats, infiltrates on CXR
Sequestration crisis - pooling of blood in the spleen and lungs
Diagnosed by electrophoresis
How to treat SCD crisis
Exchange transfusion??
For recurrent crises patient should be started on hydroxycarbamide
Acute chest syndrome = give antibiotics, oxygen and analgesia
Acute painful crises = IV morphine, fluids and oxygen
What test checks for autoimmune haemolytic anaemias
Coombs test/ antiglobulin test
Direct test = detects antibodies stuck to surface of RBC
Indirect = detects free floating antibodies in blood
What are Howell jolly bodies
Red cells which still have nuclear fragments
Often seen in megaloblastic anaemias, hyposplenism and SCD
What can cause macrocytic megaloblstic anaemia
B12 or B9 deficiency
Malnutrition
Alcohol abuse
Vegan diets
Low protein diets
Pregnancy
Gastric surgery
Anti-folate drugs
Anti-epileptics
Anti-convulsants
Oral contraceptives
Metformin
Causes of macrocytic normoblastic anaemia
Alcohol abuse
Liver disease
Congenital bone marrow failure syndromes
Myelodysplastic syndrome
Hypothyroid
Pregnancy
What is Myelodysplastic syndrome
Neoplasm of the bone marrow which affects the stem cells that give rise to the various cell lines. Leads to pancytopenia, anaemia, thrombocytopenia and leukopenia.
Can be idiopathic or secondary to insults to the BM through chemotherapy (alkylating agents*), radiation or exposure to benzene
What is hereditary haemorrhagic telangiectasia
A type of bleeding disorder:
Fragile dilated capillaries develop on the skin of the lips, nose and fingers which rupture easily
Epistaxis occurs more frequently in these patients
What is ehlers Danos syndrome
Defect in collagen which makes the blood vessels more weaker and elastic which means the person is at higher risk of:
Easily bruising
Aortic regurgitation
Aortic dissection
Subarachnoid haemorrhage
Mitral valve prolapse
What is pseudoxanthoma elasticum
When elastic fibres of blood vessels become mineralised due to calcium deposits
Examples of platelets disorders:
Decreased marrow production (aplastic anaemia or suppression due to cytotoxic drugs or RT)
Bernard soulier disease - platelets are very large and lack protein on surface which allows aggregation to occur
Glanzmanns thromboasthenia - low levels of glycoprotein IIb/IIIa which acts as a receptor for fibrinogen. This interaction normally allows aggregation to occur
thrombotic thrombocytopenic purpura - clotting occurs in small vessels in absence of vascular
injury causing microthrombi to form. Platelets are used up.
Excessive destruction of platelets in immune/idiopathic thrombocytopenic purpura, heparin. SLE + CLL, DIC and HUS
What is von wille brands disease
Deficiency in Von wille brand factor which is required for platelets to adhere to the endothelium
Also acts as a carrier for factor VIII
What is haemophilia A
Factor 8 deficiency
X linked recessive condition. Mainly in males but offspring sons will not be affected and daughters will be carriers
May lead to haemarthorosis (bleeding into joints) or haematomas into muscles leading to nerve palsies or compartment syndrome
What is haemophilia C
Deficiency in factor 11
1 unit of RBC is transfused in a non emergency situation over how long
90- 120 mins
Those with hf - 3 hours
1 unit of RBC increases. HB by
10-15g/L
1 unit of platelets increases count by
20
Indicated when levels are below 30. (Normal is >100 to 400)
When is the use of fresh frozen plasma indicated
Correct clotting defects (eg DIC)
When is cryoprecipitate used
Replaces fibrinogen and factor 8 in massive haemorrhages
How do acute haemolytic reactions present after transfusion
Fevers
Rigours
Hypotension
Tachycardia
Rashes
Pruritus
Red urine
Bleeding
Jaundice
Dyspnoea
Decreased o2 sats
Examples of delayed reactions that occur after transfusion
Infections
Iron overload
Graft vs host disease (donors T cells attack the hosts healthy cells)
Post transfusion purpura
What is Haptoglobin
Protein produced by the liver which binds to free Hb released from RBC during lysis. It forms a complex which is processed by the liver and removed from the body.
In haemolytic situations levels of haptoglobin become depleted as more is bound to free Hb
What cells do myeloid progenitor cells give rise to
1) mast cells
2) megakaryocyte —> thrombocyte
3) erythrocytes
4) granulocyte —> basophils, neutrophils and eosinophils
5) monocyte —> macrophage + dendritic cell
What cells do lymphoid progenitor cells give rise to
1) B cell —> plasma B cell
2) T cell
3) NK cell
4) dendritic cell
What is the most common blood cancer in children
Acute lymphoid leukaemia
What is haemochromatosis
Condition in which iron overload occurs.
Most common is hereditary condition which is inherited in an autosomal recessive fashion. There is increased iron absorption which leads to depositions in liver, pancreas, heart and skin leading to liver disease, heart failure, diabetes and skin discolouration
Secondary might be caused by transfusions required in the following disorders: thalessemia, Sickle cell and hereditary spherocytosis
What causes anaemia of chronic disease and how is it treated
Presents as a normocytic normochromic anaemia
Thought to be related to levels of inflammation affecting levels of EPO
Ferritin levels are high but iron + transferrin is low
Treated with EPO stimulating agent. Can’t be treated with iron as wont be incorporated (+ stimulate erythropoiesis)
What common infection can result in haemolytic anaemia as a complication
Pneumococcal pneumonia
Conditions causing relative polycethaemia
Dehydration
Smoking
Hypertension ? Don’t know why
What are secondary causes of polycythemia
Increased EPO production in renal cell carcinoma
Paraneoplastic syndromes
Chronic hypoxia in COPD and high altitude
What are secondary causes of thrombocythemia
Bleeding
Inflammation
Infection
Malignancy
Splenectomy
Indications of BM aspiration + trephine biopsy
Pancytopenia
Lymphoma
Leukaemia
Myeloma
Why are levels of LDH increased in anemia and haemolysis
Enzyme found within RBC
So when rbc are destroyed prematurely in megaloblastic anaemias and during haemolysis enzyme is released
In ineffective erythrpoeisis there might be hypoxia which might lead to higher levels of this enzyme which is part of anaerobic pathway of respiration
Indication of hydroxocobalamin injections
Pernicious anaemia B12 deficiency
Giving folate in b12 deficiency might lead to
Subacute combined degeneration of the cord
What is ALL
Acute lymphoblastic leukaemia
A form of leukaemia in which the bone marrow produces lots of immature lymphocytes ( B + T cells)
Symptoms include
Fatigue, SOB, fever, easy bruising, bone pain, swollen lymph nodes and weight loss and lack of appetite
Signs:
Lymphadenopathy, hepatosplenomegaly, nuchal rigidity
Risk factors:
- chromosomal aberrations like downs
- previous chemo or RT
- high levels of radiation
- genetic
Occurs in children most commonly, peak in mid 30s and 80s
Treatment of ALL
- induction chemo (to get rid of immature blasts)
- adjunct meds to prevent toxicity to other organs
- rituximab
- prophylactic antimicrobials
-haematopietic growth factor
Who does CLL affect
Most common leukaemia
Affects males more than females
Median age of diagnosis is 70
What are the symptoms of CLL and pathophysiology
Affects mature lymphocytes which are functionally abnormal (mostly B cells) - accumulate in the BM preventing normal BM function
Causes:
- chromosomal abnormalities and mutations in proteins involving tyrosine kinase pathway
Risk factors:
- age
- FHX
- agent orange exposure from Vietnam war
B cells might produce abnormal antibodies that might lead to autoimmune haemolytic anaemia, ITP
Treated with chemoimmunotherapy (tyrosine kinase inhibitors)
What organs can leukaemias infiltrate
Bone marrow —> bone pain
Thymus —> palpable mass and airway compression
Liver + spleen —> hepatosplenomegaly
Lymph nodes —> lymphadenopathy
Meningeal infiltration —> headaches, vomiting, nerve palsies + nuchal rigidity
What labs would you request for investigation of leukaemia
Blood count
Blood smear/film
BM smear
Immunophenotyping
What is AML:
Affects myeloid lineage with rapid production of immature blasts that are unable to mature into neutrophils, RBC, platelets. This leads to BM failure
Risk factors:
Age 60 peak
RT or chemo
Downs
Myeloproliferative disorders such as PRV or thromobocythemia
Radiation or benzene exposure
On smear presence of Auer rods
Treated with chemo
Retinoic acid treatment for promyelocytic anaemia
What is richter syndrome
Transformation of CLL or small lymphocytic lymphoma to high grade diffuse large B cell lymphoma
Which leukaemia may progress to aggressive lymphoma (diffuse large B cell lymphoma)
CLL
What is CML
Form of leukaemia in which there is increased myeloid cells. This is caused by a genetic abnormality - formation of the Philadelphia chromosome (9+22 translocation) which results in BCR-ABL gene which produces increases in protein called tyrosine kinase —> uncontrolled growth
Has stages:
1) chronic phase
2) accelerated ophase
3) blast phase (behaves like an acute leukaemia)
Risk factors:
-age
-radiation and benzene exposure
Treatment:
- tyrosine kinase inhibitors like imatinib
What is myeloma
Terminally differentiated neoplastic plasma cells which produce antibodies uncontrollably. Produces lots of fragments + light chains (paraproteins) IGA and IGG
Associated with osteolytic bone disease, renal failure and anaemia. Leads to amyloidosis and hyper viscosity syndrome (heart has to work harder)
Symptoms: CRABBI
Hypercalcemia
Renal failure
Anaemia
Bone pain/lesions
Bleeding
Infections
Investigations:
-electrophoresis
- bence jones proteins in urine
MRI - for bony lesions
Treatment:
Chemo, RT, immunotherapy + transplants
What is first line therapy for hypercalcemia
IV 0.9% saline
What is tumour lysis syndrome
A complication of chemo in which cancer cells die and release toxins which the body is not able to get rid of as quickly.
Hyperuricemia, hyperphopshatemia, hyperkalemia, uraemia, hypocalcemia and acute renal failure.
IV rasburicase used to treat this.
Allopurinol used as prophylaxis
What is lymphoma
Malignancy of the lymphatic tissues and lymph nodes affecting lymphocytes. Usually starts off in a node or tissue (spleen, thymus + other organs) and may spread to BM + other parts of body.
Hodgkins - characterised by presence of reed sternberg cells (giant cells with more than 1 nucleus arranged in a mirror fashion (looks like owl eyes) )
Occurs in early adulthood
Non Hodgkins - classified at B or T type (most common type 90%) with B cell more common. There are a lot of types within these two categories
Affects older people >60
What staging system is used for Hodgkin lymphoma
Ann arbor
Looks at symmetry of lymph node involvement
Types of Hodgkin lymphoma
Nodular sclerosing - most common. Occurs more in young women affecting lymph nodes of central chest - good prognosis
Mixed cellularity - many different WBC types - good prognosis
Lymphocyte rich - m>w. Has many normal lymphocytes along side reed sternberg cells. Best prognosis
Lymphocyte depleted - occurs in those with HIV/AIDS. Replacement of normal cells with R/S cells - worst prognosis
Risk factors for Hodgkin’s lymphoma
Older age
Males
Family history
Infections: HIV, HEP C, EBV, HHV-8, h.pylori, C.jejuni.
Autoimmune disease: hashimotos,coeliac, Sjögren’s syndrome, RA + SLE
Investigations for lymphoma
FBC
Imaging - CT + PET
Lymph node biopsy
Treatment regime for Hodgkins AVBD: or BEACOPP
Doxorubicin (Adriamycin)
Vinblastine
Bleomycin
Dacarbazine
Bleomycin
Etoposide
Doxorubicin
Cycklophasmide
Vincristine/oncovin
Procarbazine
Prednisolone
Examples of B cell non Hodgkins lymphomas
Burkitts lymphoma (associated with EBV + malaria) aggressive
Diffuse large B cell lymphoma (most common but aggressive)
Mantle cell lymphoma (aggressive)
Follicular lymphoma (non-aggressive)
CLL
Marginal zone lymphoma
Examples of T cell non Hodgkin’s lymphoma
Adult T cell lymphoma
Cutaneous T cell lymphomas (formation of itchy plaques)
Treatment of non Hodgkin’s lymphoma RCHOP
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine/oncovin
Prednisolone
Examples of myeloproliferative disorders
PRV (excessive RBC caused by JAK-2 mutation)
Essential thrombocythemia (excessive platelets which can block vessels and flow. Or can cause excessive bleeding as all might be used in clotting)
ET might progress to PRV, myelofibrosis or AML
Signs and symptoms of PRV
PE
DVT
Splenomegaly
Excessive bleeding
Kidney stones and gout (high RBC turnover causes high urate levels)
Stomach ulcers (high RBC levels leads to immune response and release of histamine which acts on parietal cells to secret more acid)
Examples of JAK inhibitor
Ruxolitinib
Treatments for PRV
Venesection
Low dose aspirin
Allopurolol
Ruxolitinib
BM transplant
Treatment for ET
Aspirin
Interferon alpha (stops platelets dividing)
Hydroxyurea 9reduces platelet count)
Ruxolitinib
Chemo
Plateletpheresis (machine removes platelets
What is myelofibrosis
Most aggressive MP disorder: caused JAK-2 =, CALR and MPL mutation.
BM produces abnormal stem cells that become inflamed and make scar tissue. This stops production of other blood cells. RBC low, WBC + P may increase at first but will suddenly drop
Anaemia, fevers, night sweats, weight loss, splenomgealy (massive) and easy bruising
Treatments for myelofibrosis
JAK inhibitor
Blood transfusions
Chemo
Splenectomy if speeen too damaged
Androgens can boost RBC production
What is myelodysplasia
Blood cancer where BM stem cells don’t mature and die leading to pancytopenia. Can progress to AML
Causes include:
- fanconi anaemia
- diamond black fan anaemia
- previous chemo = RT
- exposure to heavy metals
Treatment for myelodysplasia
Blood transfusions + platelet
Antibiotics
Chemo
Stem cell transplants
What is fanconi anaemia
Rare autosomal disorder in which there is impaired DNA repair machinery which leads to genetic damage —> pancytopenia
