Haematological Disease Flashcards
What are the three main functions of the blood?
- Transport nutrients
- Removal of waste
- Transport host defences
What is the function of red blood cells?
Carrying oxygen in bloodstream
What are the two main plasma proteins?
- albumin
- globulin
What is meant by, FBC?
Full blood count
What is meant by, RBC?
Red blood cells
What is meant by, RCC?
Red cell counts
What is meant by, WCC?
White cell count
What is meant by, PLT?
Platelets
What is meant by, HCT?
Haematocrit
What is meant by, MCV?
Mean cell volume
What condition is characterised by low levels of Hb in the blood?
Anaemia
What condition is characterised by low WCC?
Leukopenia
What condition is characterised by low platelets?
Thrombocytopenia
What condition is characterised by all cell counts being reduced?
Pancytopenia
If there are multiple low levels of cell counts what does this suggest?
Bone marrow failure
What condition is characterised by raised Hb count in the blood?
Polycytheamia
What condition is characterised by raised WCC in blood?
Leukocytosis
What condition is characterised by raised platelets in blood?
Thrombocythaemia
What are the two cancers of the blood?
Leukaemia
Lymphoma
What blood malignancy is described:
Neoplastic proliferation of white cells, usually disseminated.
Leukaemia
What blood malignancy is described:
Neoplastic proliferation of white cells, usually a solid tumour.
Lymphoma
Name 4 chronic malignancies that stem from a lymphoid lineage?
- Chronic lymphocytic leukaemia
- Hodgkin’s lymphoma
- Non-Hodgkin’s lymphoma
- Multiple myeloma
Name an acute malignancy of lymphoid lineage?
Acute lymphoblastic leukaemia
Name an acute malignancy of myeloid lineage?
Acute myeloid leukaemia
Name two chronic malignancies of myeloid lineage?
- Chronic myeloid leukaemia
- Myeloproliferative disorders
What is porphyria?
An abnormality of haem metabolism
Why is acute intermittent porphyria important for dentists to be aware of?
Acute attacks can be triggered by medicines including LA.
What is the main symptom of an acute porphyria episode?
Severe abdominal pain
What are the clinical side effects of porphyria?
- photosensitive rash
- Neuropsychiatric disturbances (motor and sensory changes, seizures)
- hypertension and tachycardia
What are the two causes of haemoglobin reduction in the blood?
- Inability to make Haem (usually an iron deficiency)
- Inability to make the correct globin chains (e.g. thalasseamia, or sickle cell)
What factor is the greatest indicator as to the cause of anaemia?
The size of the red blood cells (MCV)
What is meant by haematinics? Give three examples.
Things used to make red blood cells.
Examples: iron, vitamin B12, folic acid (folate).
Give three examples of sources of iron?
- meat
- green leafy vegetable
- iron tablets
What does achlorhydria mean?
Absence of hydrochloric acid in the gastric secretions (lack of stomach acid)
What drugs can induce achlorhydria?
Proton Pump Inhibitors
What food group is high in vitamin B12?
Meat and dairy products
What are 3 reasons as to why vitamin B12 absorption may be reduced?
- Problems with production of intrinsic factor in the stomach
- Problem with dietary B12
- Disease of the terminal ileum (such as Crohn’s disease)
What individuals are most likely to have vitamin B12 deficiency due to lack of dietary intake?
Strict vegans
Gives two examples where lack of intrinsic factor causes vitamin B12 deficiency?
- autoimmune stomach disease (pernicious anaemia)
- gastric disease
Give an example of when absorption failure results in folic acid deficiency?
- jejunal disease (coeliac disease)
What can be the consequnece of folic acid deficiency in a mum, for a foetus?
Neural tube defects (such as spinobifida)
What are the two main diseases considered where abnormal globin chains cause anaemia?
- Thalassimia
- Sickle cell disease
At the very early stages of pregnancy, where is haemoglobin managed and formed?
Liver and spleen
What disease is described?
Where little to no haemoglobin is produced and there is genetic mutation of globin chains.
Thalassaemia
What are the two different types of Thalassaemia?
- Alpha chains
- Beta chains
What are the 5 clinical effects of Thalassaemia?
- Chronic anaemia
- Marrow hyperplasia
- Splenomegaly
- Cirrhosis
- gallstones
What is the management of Thalassaemia?
Blood transfusions and prevention of iron overload
What disease is characterised by abnormal globin chains that change the shape of RBC in low oxygen environements?
Sickle cell anaemia
What can be the consequence of change in shape of red blood cells in low oxygen environments (sickle cell anaemia)?
Red blood cells cannot pass through capillaries so blocking circulation and causing tissue ischaemia. This can lead to pain and necrosis of the tissue.
Guide two examples of haemoglobinopathies?
- Thalassaemia
- Sickle cell anaemia
What does a raised blood cell volume indicate?
Deficiencies in B12 or folic acid
What is a small shaped red blood cells usually indicative of?
- Iron deficiency
OR - Thalasseamia
What will tell us if anaemia is associated with normal or reduced number of RBC’s?
Red cell count
What is usually the cause of anaemia, when there are normal red cells?
Chronic GI bleeding
What is the usual cause of anaemia, presenting with abnormal red cells?
- autoimmune
- hereditary (e.g. sickle cell)
In what anaemic conditions would MCV of RBC be microcytic?
- iron deficiency
- thalasseamia
In what anaemic conditions would MCV of RBC be macrocytic?
- B12 deficiency
- folate deficiency
What term is used to describe red blood cells that appear pale under the microscope, due to there being less Hb in the cells?
Hypochromic
What term is used to describe red blood cells that vary in size, some very big cells and some very small cells in the same sample?
Ansiocytic
What cell type if released early into the circulation to replace losses of red blood cells in anaemia?
Reticulocytes
What are the signs of anaemia?
- pale
- tachycardia
What are the symptoms of anaemia?
- tired and weak
- dizzy
- shortness of breath
- palpitations
What can be an oral sign of iron deficiency?
Smooth tongue (glossitis) and angular chelitis
What can be an oral sign of vitamin B12 deficiency?
‘Beefy’ tongue
What is another term for hidden bleeding?
Occult bleeding
What investigations are required for anaemia due to GI blood loss?
- faecal occult blood
- endoscopy
What is the replacement treatmnet for iron deficiency?
200mg FeSO4 3x daily for 3 months
What is the replacement treatmnet for B12 deficiency?
1mg IM vit B12 x6
What is the replacement treatmnet for folate deficiency?
5mg folic acid daily
What are the three main treatment modalities for anaemia?
- replace haematinics
- transfusions
- erythropoietin
What are common dental symptoms of deficiency states, such as iron deficiency?
- mucosal atrophy
- candidiasis
- recurrent oral ulceration
- sensory changes
What is the normal level of Hb in the blood for males and females?
Males: 14 to 18 g/dl
Females: 12 to 16 g/dl
What is the normal value of RCC in the blood for males and females?
Males 4.0 to 5.9 x1012/L
Females 3.8 to 5.2 x1012/L
What is the normal value of WCC in the blood?
4,500 to 11,000 WBC’s per micro litre (4.5 to 11.0 x10*9/L)
What is the normal value of red cell MCV in the blood?
80-100fl
What is the normal value of platelet count (PLT) in the blood?
150,000-450,000 platelets per micro litre of blood
What ferritin level indicates iron deficiency?
<30 micrograms/L
What is an important cause of anaemia in females?
Menstrual blood loss
name three types of antithrombotic medication and give an example for each.
- Injectable anticoagulation (e.g. heparins)
- Oral anticoagulation (e.g. coumarin, non-coumarin)
- Antiplatelet medication (e.g. aspirin/clopidegril)
What injectable drug allows rapid control of anticoagulation (for example during operations) in hospital base settings?
Unfractionated heparin
What injectable drug is very useful for patients who have a short term issue with hyper-caoguability? (E.g. individuals who have recently recovered from C-section which makes them more prone to coagulation and DVT)
Low molecular weight heparin
Name 5 anticoagulants.
- warfarin
- apixaban
- edoxaban
- rivaroxaban
- dabigatran
Name 4 anti-platelets.
- low dose aspirin
- clopidegrol
- dipyridamole
- ticagrelor
What dental procedures should be undertaken with caution if a patient has a medical condition which may cause them to bleed?
- extractions
- minor oral surgery
- implants
- periodontal surgery
- biopsies
What 5 conditions involve blood clots forming too readily on or in the circulation, and are indications for a patient to be taking anticoagulants?
- Atrial fibrillation
- deep vein thrombosis
- Heart valve disease
- Mechanical heart valves
- Thrombophilia
What anticoagulant is a coumarin?
Warfarin
What anticoagulant is a direct thrombin inhibitor?
Dabigatran
What anticoagulants are factor Xa inhibitors?
- apixaban
- rivaroxaban
- edoxaban
What commonly used anticoagulant is described as a vitamin K antagonist?
Warfarin
What is the action of warfarin?
Inhibits production of vitamin K dependent clotting factors 2,7,9 and 10.
What does INR stand for?
International normalised ratio
What does INR measure?
How long it takes for your blood to clot.
What is a normal INR reading?
2-3
What is a normal INR reading in individuals with a prosthetic valve and who are at higher risk of DVT?
3-4
How often should a patients INR be checked?
Every 4-8 weeks
What precautionary steps must be taken for patients on warfarin who require dental procedures likely to cause haemorrhage?
- INR and FBC blood test within 72 hours of treatment
- treat early in the day and week
- INR must be less than 4 to proceed with caution
What drug should you assume everything interacts with and always check the BNF?
Warfarin
Name three drug types that should be avoided if dental patients are taking warfarin?
- Aspirin
- NSAIDs
- Azole antifungal drugs (e.g. fluconazole)
What is the most likley cause of haemorrhage due to warfarin intake?
Trauma, such as a hip/bone fracture following a fall.
What does NOAC’s stand for?
New oral anticoagulants
What are the main advantages of NOAC’s over warfarin?
- no need to monitor action as they have predictable bioavailability
- rapid onset of action, working within a few hours of dose
What is the disadvantage of NOAC’s compared to warfarin?
Short duration of action, so their effect is lost within a day
What is the specific function of NOAC’s?
Act by preventing the effect of factor X
Name 4 NOAC’s and how often they must be taken daily.
- Rivaroxaban - once daily
- Apixaban - twice daily
- Edoxaban - once daily
- Dabigatran - once daily
Why does apixaban have a higher dosage daily compared to other NOAC’s?
Because it has a very short half-life
If a low risk dental procedure is being carried out, is NOAC dosage required to be changed?
No
If a higher risk dental procedure is to be carried out, is NOAC dosage to be changed?
Yes, miss/delay morning dose
How soon after a high risk treatment should the patient start taking their NOAC again?
Restart dose immediately after treatment for once daily
It’s an IANB safe to give to a patient who is taking NOAC’s or warfarin?
Yes
For what disorders, is it unsafe to give an IANB?
Inherited coagulation defects/blood disorders
How long post extraction should an individual with high bleeding risk be kept to assess their bleeding?
20 mins
What class of antibiotics should not be prescribed when a patient is taking a NOAC, due to drug interactions? name two examples of antibiotics from this class.
Macrolides.
1. Erythromycin
2. Clarithromycin
Other than Macrolides, what two other drugs have interactions with NOACs and should therfore be avoided?
- NSAIDs
- carbamazepine
Name the three drugs grouped as the standard antiplatelet therapy?
- Low dose aspirin (75mg)
- Clopidegrol
- Dipyridamole
What are the two main functions of antiplatelet drugs?
- Inhibit platelet aggregation
- Inhibit thrombus formation in the arterial circulation
Should aspirin ever be stopped for a dental procedure?
No
What prescribed drug interactions are relevant for clopidegrol?
Avoid erythromycin/ Fluconazole as this may reduce efficacy
What prescribed drug interactions are relevant for ticagrelor?
Clarithromycin may increase the antiplatelet effect
What is an inherited bleeding disorder?
An acquired defect which affects the coagulation of the blood
What factors within the blood does an inherited bleeding disorder affect?
- Coagulation cascade
- Platelets
- A combined deficiency
What is the name of the inherited bleeding disorder characterised by too little clot formed in the coagulation cascade?
Haemophilia
What is the name of the inherited bleeding disorder characterised by too much clot formed in the coagulation cascade?
Thrombophilia
What inherited bleeding disorders cause a deficiency in the coagulation factor, VIII?
Haemophilia/haemophilia A
Von willebrands disease
What inherited bleeding disorders cause a deficiency in the coagulation factor, IX?
Christmas disease/haemophilia B
What type of inheritance does haemophilia A&B have?
Sex-linked recessive
What sex chromosome has a defective gene in haemophilia A&B?
X chromosome
What sex is more likely to be affected by haemophilia A & B?
Males
What does the severity of Haemophilia depend on?
The amount of factor produced (1u is normal)
What does DDAVP stand for?
Desmopressin
How does DDAVP temporarily boost the amount of factor VIII present within the circulation, to treat mild/carriers of haemophilia A?
It doesn’t have affects on coagulation cascade itself, instead displaces protein (factor VIII) from binding to walls of blood vessels, allowing VIII to move into circulation.
What is the function of tranexamic acid?
Inhibitor of fibrinolysis (keeps any clot that is formed)
What would be the appropriate management of very mild cases of haemophilia A?
Oral tranexamic acid
How can severe and moderate haemophilia A be managed?
Use of recombinant factor VIII (medication)
How would severe and moderate haemophilia B be managed?
Use of recombinant factor IX (medication)
How would mild and carriers of haemophilia B be managed?
Use of recombinant factor IX (medication)
What is another name for haemophilia B?
Christmas disease
What are coagulation factor inhibitors?
Antibodies which develop to factor VIII and IX
What inheritance does von willebrands disease have?
Autosomal dominant (not transmitted by the X chromosome)
What is von willebrands disease?
An inherited bleeding disorder caused by deficiency of a plasma coagulation factor (von willebrands factor)
What other coagulation factor is reduced upon deficieny in von willebrands factor?
Factor VIII
How many types of von willebrands disease are there?
3
What types of von willebrands disease have a dominant mild inheritance?
Type 1 and 2
What type of von willebrands disease has an inheritance of recessive severe?
Type 3
What is the management of severe and moderate von willebrands disease?
DDAVP
What is the management of mild/carriers of von willebrands disease?
Mild cases may only require tranexamic acid
What is the incidence in the UK of haemophilia A?
1:10,000
What is the incidence in the UK of haemophilia B?
1:50,000
What is the incidence in the UK of von willebrands disease?
1:100-500
What is the incidence in the UK of factor XI deficiency?
1:50,000
What does degree of bleeding risk depend on?
Baseline coagulation factor activity (higher factor activity gives less risk)
How often should a haemophilia patient, be reviewed at a haemophilia centre dental unit?
Every 2 years
What are the 5 main high risk bleeding risk procedures for someone with an inherited bleeding disorder?
- administration of LA
- extractions
- minor oral surgery
- periodontal surgery
- biopsies
What local anaesthesia is safe in patients haemophilia?
- buccal infiltration
- intraligamentary injections
- intra-papillary injections
What local anaesthesia is dangerous in patients with haemophilia?
- inferior alveolar nerve block
- lingual infiltration
- posterior superior nerve block
What is the post-op management of someone with severe/moderate haemophilia?
Patients should be observed overnight following surgery
What is the post-op management of someone with mild/carriers of haemophilia?
Patients must be observed for 2-3 hours after surgery
What is Thrombophilia?
Increased risk of clots developing
What can be the life-threatening consequences of thrombophilia?
- pulmonary thromboembolism
What bleeding condition is caused by reduced platelet numbers?
Thrombocytopenia
What bleeding condition is caused by normal number of platelets but with abnormal functions?
Qualitative disorders
What bleeding condition is caused by increased platelet numbers?
Thrombocythemia
What must the platelet count be greater than for dental treatment to proceed safely in primary care for someone with thrombocytopenia?
100x10^9/L
What is the most likley cause of thrombocythemia ?
Usually patients who are on aspirin to prevent clot formation
Name three inherited (rare) qualitative platelet disorders?
- Bernard soulier syndrome
- Hermansky pudlak
- Glanzmann’s thromboasthenia
Name 4 acquired platelet disorders?
- cirrhosis
- drugs
- alcohol
- cardiopulmonary bypass
Why might an individual require a blood transfusion?
- Where one or more components of the blood has to be replaced quickly
- Where the bone marrow cannot produce blood cells
What system has core surface markers for red blood cells?
ABO system
What blood system is important for maternal and foetal compatibility?
D system (rhesus)
What are the two main indications for blood transfusion?
- Blood loss
- Specific production problems (e.g. RBC, platelets, plasma proteins)
What are the 4 main stages in the blood transfusion process?
- Sample taken from patient
- Tested against known blood types
- Patient sample tested against selected donated sample
- Successfully matched blood given to patient
What are the 4 ABO blood groups?
- group A
- group B
- group AB
- group O
What ABO blood group is described:
- Anti-B antibodies in plasma
- A antigen in red blood cells
Group A
What ABO blood group is described:
- No antibodies in plasma
- A and B antigens in red blood cells
Group AB
What ABO blood group is described:
- Anti-A antibodies in plasma
- B antigen in red blood cells
Group B
What ABO blood group is described:
- Anti-A and Anti-B antibodies in plasma
- No antigens in red blood cells
Group O
What are the three main blood transfusion complications?
- Incompatible blood leading to fever, jaundice and death.
- Fluid overload leading to heart failure
- Transmission of infection (e.g. BBV’s, bacterial infections)
Define, clonal proliferation of lymphocytes arising in a lymph node or associated tissue?
Lymphoma
What are the two types of lymphoma?
1 Hodgkin’s lymphoma
2. Non-Hodgkin’s lymphoma
Which type of lymphoma is most common?
Non-Hodgkin lymphoma (ratio of 6:1)
Define, a disseminated tumour of white cells within the circulation that can spill over into tissues?
Leukaemia
What are the main symptoms of lymphoma?
- fever
- swelling of the face and neck
- lump in neck, armpits or groin
- excessive night sweats
- breathlessness
- weakness
- itchiness of skin
How many stages of disease are there for lymphoma?
4 stages
What investigations are required to stage lymphoma?
CT imaging or MRI
What three factors are considered when staging lymphoma?
- Number of nodes involved and site
- Extra-nodal involvement
- Systemic symptoms
What are characteristics of lymphadenopathy?
- painless
- typically cervical
- fluctuates in size
- pain with alcohol use notable
What lymphoma stage is described?:
Single lymph node region or single extralymphatic site.
Stage 1
What lymphoma stage is described?:
Two or more sites, same side of diaphragm or contiguous extralymphatic site.
Stage 2
What lymphoma stage is described?:
Both sides of the diaphragm or spleen, or contiguous extralymphatic site.
Stage 3
What lymphoma stage is described?:
Diffuse involvement of extralymphatic sites +/- nodal disease
Stage 4
What type of lymphocyte makes up majority (85%) of non-Hodgkin lymphomas?
B-cells
What microbial factors are strongly implicated in lymphoma?
- EBV, HIV, H.pylori
Name three autoimmune diseases mainly associated with lymphoma?
- Sjögren’s syndrome
- RA
- Peptic ulcer disease
What is the presentation of NHL?
- Lymphadenopathy (“invisible”)
- Extra-nodal disease (oropharyngeal involvement, waldeyers ring)
- Symptoms of marrow failure
NHL is an aggressive disease with poor prognosis. True or false?
True
Define, a malignant proliferation of plasma cells?
Multiple myeloma
What are the three main features of multiple myeloma?
- Monoclonal paraprotein in blood and urine
- Lytic bone lesions
- Excess plasma cells in bone marrow
What are the main symptoms of multiple myeloma?
- infection
- bone pain/ fracture
- renal failure
- amyloidosis
What are the 4 treatments of haematological malignancies?
- Chemotherapy
- Radiotherapy
- Monoclonal antibodies
- Haemopoietic stem cell transplantation
What is meant by induction as part of treatment for haematological malignancies?
Initial chemotherapy a person receives before undergoing additional cancer treatment
What is meant by remission as part of treatment for haematological malignancies?
Where the patient is effectively normal bone marrow and no evidence of disease
What is meant by maintenance & consolidation as part of treatment for haematological malignancies?
Where a patient requires treatment at a low-level over many years
What is meant by relapse as part of treatment for haematological malignancies?
Where an individual will relapse after treatment and the process of induction will be started again.
What cells are targeted in chemotherapy?
Cells with high turnover
What are the common side effects of chemotherapy?
- hair loss
- nausea
- vomiting
- tiredness
What are the two main risks of radiotherapy?
- Cytotoxic effect of ionising radiation (adjacent healthy tissue will also be irradiated)
- Risk of inducing late cancers
What is an increasingly effective way of targeting cancer treatment to particular cells?
Monoclonal antibodies
What does “Allogenic” mean, in regards to Haemopoietic stem cell transplant?
From a live donor
What does “Autologous” mean, in regards to Haemopoietic stem cell transplant?
From the patient
Haemopoietic stem cell transplant is a high risk procedure. 1. What is the mortality rate for such a procedure, and 2. what are the potential consequences for the patient?
- 10% mortality
- Life-threatening infection, graft-versus-host disease, graft failure and total marrow failure
What is meant by “graft-versus-host disease”?
Where new bone marrow after transplantation starts to attack the individual and casue tissue damage
The earlier a haematological cell line turns neoplastic, what is the effect on malignancy?
The more potentially aggressive the malignancy
What are the three main characteristics of cancer cells?
- Uncontrolled proliferation
- Loss of apoptosis
- Loss of normal functions/products
What type of leukaemia is the most serious and life-threatening?
Acute leukaemia
What condition describes a group of cancers of the bone marrow which prevent normal manufacture of the blood and therefore result in:
1. Anaemia
2. Infection
3. Bleeding
Leukaemia
What is meant by “neutropenia”?
Infection
What is meant by “thrombocytopenia”?
Bleeding
What is the pathogenesis of leukaemia?
The bone marrow will gradually be replaced by the leukaemic cells and this prevents the patient from being able to maintain normal blood haemostasis
What are usually the clinical features of leukaemia ?
- Anaemia
- Neutropenia
- Thrombocytopenia
- Lymphadenopathy
- Splenomegaly/hepatomegaly
- Bone pain
What is meant by Splenomegaly?
An enlarged spleen
What is meant by hepatomegaly?
Enlargement of the liver
Why does Splenomegaly or hepatomegaly present in leukaemia?
Red cells are reprocessing at a higher rate
What are the progressive symptoms of anaemia?
- breathlessness
- tiredness
- easily fatigued
- chest pain/angina
What are the clinical signs of anaemia?
- Pallor
- Signs of cardiac failure (ankle swelling, breathlessness)
- Nail changes (e.g. brittle nails)
What condition often presents after chemotherapy and increases you risk for infection?
Neutropenia
What are symptoms for neutropenia?
- recurrent infection
- unusual severity of infection
What are the clinical signs of neutropenia?
- unusual patterns of infection and rapid spread
- will respond to treatment but recur
- signs of systemic involvement (fever, rigors, chills)
If a child presents in the dental practice with swollen and bleeding gums, what should be suspected?
Leukaemia
What bleeding symptoms can be associated with leukaemia?
- bruises easily or spontaneously
- minor cuts fail to clot
- gingival bleeding or nose bleeds
- menorrhagia (heavy periods)
What form of leukaemia is most common in children?
Acute lymphoblastic leukaemia
What is the most common form of leukaemia?
Chronic lymphocytic leukaemia
What type of leukaemia has slow progression, and is mostly asymptomatic and discovered on routine blood tests
Chronic lymphocytic leukaemia
What leukaemia is characterised by presentation of the “Philadelphia” chromosome?
Chronic myeloid leukaemia
When the GP does Mrs Smith’s haemoglobin (Hb) level, it is 100g/L (normal range 115-165g/L). Other full blood count readings are within normal range. What is your provisional diagnosis?
Normocytic anaemia
List the signs and symptoms of symptoms of normocytic anaemia?
- glossitis
- pallor
- conjunctiva
- dizzy
- fatigued
- tachycardia
- shortness of breath
What are oral symptoms of anaemia induced by iron deficiency?
- angular chelitis
- ulceration
What does INR stand for?
International normalised ratio
What ratio does INR measure?
It measures the ratio of the patients prothrombin time to a normal control sample (measures how long it takes for blood to clot)
When is the best time for a patient to have their INR checked prior to dental appointment?
24 hrs prior
After removing roots surgically for an extraction, the patient starts bleeding profusely, what can you do to address this?
- Use local haemostatic measures
- Consider packing with haemostatic material and suturing