Diseases of the blood Flashcards
What are the four main components of blood
Plasma
WBC’s
RBC’s
Platelets
What makes up plasma
Proteins
ions
water
nutrients
wasres
gases
What do these mean:
Leuko
Erythro
Thrombocyto
Pan / poly
Leuko – white blood cell
Erythro – red blood cell
Thrombocyto – platelet
Pan / poly – all blood cells
What indicates excess of
Cytosis
What does the ending penia mean
Lack of
How can cell sizes be written
Microcytic – small cell size
Normocytic - normal cell size
Macrocytic – large cell size
What is the purpose of blood
Transportation (oxygen from lungs to tissues, hormones, nutrients, waste to liver and kidneys)
Clotting (more in Coagulation lecture)
Immune (B cells, T cells…)
Temperature regulation
What are the two origin sites of blood cells
Myeloid
Lymphoid
What is the life span of rbc
120 days
What is anaemia
Low haemoglobin in the blood
How many haem molecules does each RBC have
270 million
What are the causes of anaemia
Impaired production
Increased breakdown (haemolysis)
Increased demand
Increased blood loss
What causes impaired production anaemia
Issue with the marrow:
-Congenital aplasia
-Medication side effects
Lack of EPO
-Severe CKD
Lack of “raw materials”
-Iron
-Vitamin B12
-Folic acid
How does haemolysis cause anaemia
Issue with the RBC
-G6PD deficiency
-Hereditary spherocytosis
Issue with haemoglobin
-Thalassaemia
-Sickle cell disease
Immune driven
-Autoimmune haemolysis
What causes increased demand leading to anaemia
Pregnancy
Growth phases (children)
Why can acute bleeding , menstrual bleeding and gastrointestinal losses (cancer) all cause anaemia
increased blood loss
What are symptoms of anaemia
Tiredness
Shortness of breath
Dizziness
Palpitations (angina if severe)
What are visual indicators of anaemia
Pale skin
Conjunctival pallor
What classical signs of anaemis can we see as dentists
Angular cheilitis
Koilonchyia (spoon shaped nails-iron deficiency)
What subsequent deficiencies can anaemia cause
Iron
Folate
Vit B12
What are the causes of iron deficiency anaemia
Reduced dietary intake
Impaired absorption – in duodenum
Increased loss – menstrual, GI bleeding etc.
Increased demands – pregnancy, growth
What can cause reduced iron absorption
Inflammation in duodenum
-Coeliac disease**
Lack of stomach acid
-Proton pump inhibitor (omeprazole)
Where is the main site of iron absorption
Duodenum
What causes a Vit B12 deficiency
Reduced intake
Impaired absorption
Medication side effect (metformin)
What are the symptoms of Vit B12 deficiencies
Anaemia symptoms
Peripheral neuropathy
Visual changes
Results in a macrocytic anaemia
How can most deficiencies be managed/treated
Oral supplementation
IV supplementation
Intra-muscular supplementation
What is required for Vit B12 absorption
Intrinsic factor
Where is Vit B12 absorbed
Ileum
Why might Vit B12 absorption be impaired
Pernicious anaemia ***
Gastrectomy
Crohn’s disease (inflammation in ileum)
Following bowel surgery
What is pernicious anaemia
Autoimmune condition
Commonly middle-aged patient
Antibodies destroy parietal cells in stomach
Can also target intrinsic factor itself
No intrinsic factor
No absorption of vitamin B12 in ileum
IM supplementation (3 monthly)
Where is folic acid absorbed
Jejunum
What can cause folic acid deficiency
Dietary (found in leafy vegetables)
Medications (methotrexate, phenytoin)
Alcohol excess
Bowel inflammation
What do we need folic acid for
folic acid has important role in foetal development
Spina bifida
What is ferritin
the molecule in which iron is stored in cells
How can anaemia be tested for
Blood tests
Full blood count
Haematinics (ferritin, folate, B12)
May consider endoscopy/colonoscopy if suspicious of GI bleeding
Blood in stool, weight loss, older patient
When will the mean red blood cell volume be <80 (microcytic)
-Iron deficiency
-Thalassaemia
-Lead poisoning
When are RBCs often normocytic (80-100)
-Bleeding
-Kidney disease
-Anaemia of chronic disease
What size of RBC’s would often be present with B12 deficiency and folic acid deficiency
Macrocytic (>100)
What is thalassaemia
Genetic defect in the protein chains which make up haemoglobin (autosomal recessive)
Alpha globin (x2)
Beta globin (x2)
Meaning there is alpha or beta thalassaemia
What effect does thalassaemia have on RBCs
RBCs are more fragile, therefore the spleen detects and destroys damaged RBCs
Microcytic anaemia
How is thalassaemia managed
Monitoring (minor)
Blood transfusions
Splenectomy
Bone marrow transplant
What are the properties of sickle cell anaemia
Genetic condition, results in crescent-shaped RBCs
Autosomal recessive
Crescent shape = more fragile and easily destroyed
Screening – newborns
Reduced severity of Malaria
Higher incidence in African, Caribbean populations
How is sickle cell anaemia managed
Avoid triggers
Antibiotic prophylaxis
Specialist medications
Blood transfusions
Bone marrow transplant
How can anaemia manifest within the oral environment
Angular cheilitis
Mucosal atrophy
Glossitis - smooth or ‘beefy’ (tongue)
Recurrent aphthous stomatitis (ulcers)
Candidal infections
Oral dysaesthesia
What is the universal donor
Group O
What is the universal recipient
Group AB
How long does a blood transfusion take
3-4 hours
What is cross-matching
Sample taken from recipient and tested against donor’s blood
What are the complications of blood transfusions
Transfusion associated fever
-Benign
Incompatible blood (e.g. giving Group B blood to a Group A recipient)
-Haemolysis
Fluid overload -> heart failure
-TACO (transfusion associated circulatory overload)
Anaphylaxis
Infection (rare)
What are the normal ranges of Haemoglobin g/L in adults blood
Male: 135-180
Female: 115-160
What are the normal adult ranges of WBCs in blood x10^9/L
4-11
How many platelets should adults have in their blood x10^9/L
150-400
What is the normal MCV (mean cell volume) within adult blood
78-100
What is leukaemia
A group of blood cancers
-particular line of stem cells in the bone marrow
-unregulated production
Bone marrow produces high amount of immature “-blast” cells
-Loss of marrow function
Blast cells propagate, displace normal cell development
What is caused by platelet deficiency
Easy bleeding
What is caused by WBC deficiency of dysfunction
Impaired immunity
What are the subtypes of leukaemia
Acute lymphoblastic – most often kids <5years old
Down syndrome = risk factor
Acute myeloid leukaemia – in adults
Chronic lymphocytic leukaemia – older adults, slow proliferation
Chronic myeloid leukaemia – Philadelphia chromosome
What are some non-specific symptoms of leukaemias
Fatigue
Fever
Weight loss
Easy bruising
Easy bleeding
Abnormal infections
Lymphadenopathy
How is leukaemia diagnosed
via blood tests, bone marrow biopsy and scans
What are the main managment methods of leukaemia
Mainly chemotherapy
Targeted therapies (monoclonal antibodies e.g. Rituximab)
Bone marrow transplant (immunosuppression +++)
What does this blood test indicate
Result Normal range
Hb 107 115 - 160
WCC 6.8 4.0 - 11.0
Platelets 378 150 - 400
MCV 105 78 - 100
Ferritin 67 10 - 300
Folate 10.4 >4.0
B12 98 180 - 1000
Macrocytic anaemia secondary to B12 deficiency
What cells will chemotherapy target aside from Fast-growing cancer cells
Oral mucosa
Gut mucosa
Hair cells
Why is chemotherapy used
Halts or slows the growth of cancer cells, which grow and divide quickly
What are the general side effects of chemotherapy
Hair loss
Nausea, vomiting, diarrhoea
Infertility
Bone marrow suppression
Immunosuppression
Cardiac toxicity
Oral mucositis
Depression / anxiety
What is lymphoma
Cancer affecting the white blood cells in the lymphatic system
The lymph nodes become abnormally large (painless)
What are the two main types of lymphoma
Hodgkin’s lymphoma (20-40 year old)
Non-Hodgkin lymphoma (most common)
What is the key presenting symptoms of lymphoma
Lymphadenopathy
-Non-tender
-Rubbery
-Pain with alcohol
What is the difference between acute and chronic leukaemia
Acute - raid and more severe
Chronic - slow less treatment required
What are common constitutional/Bsymptoms of lymphadenopathy
Fever
Night sweats
Weight loss
Fatigue
Itching
Cough
Shortness of breath
Abdominal pain
Recurrent infections
How is lymphoma diagnosed
Lymph node biopsy***
Reed-Sternberg cells (in Hodgkin’s lymphoma)
-“Owl’s eyes”
Scans (CT, MRI, PET)
How can lymphoma be managed
Chemotherapy
Radiotherapy
Targeted therapy
-Rituximab – targets B cells (CD 20)
Stem cell transplant
What is myeloma
Cancer affecting the plasma cells
B cells which produce antibodies
What protein is overproduced with myeloma
“paraprotein”
causes organ/tissue impairment
present in urine (Bence-Jones protein)
In whom is myeloma most common
70+ year olds
What are the key symptoms/affects of myeloma
Calcium (increased)
Renal impairment
Anaemia
Bone lesions
-Pathological fractures
How does myeloma present
Unexplained fever
Weight loss
Fatigue
Anaemia
Renal impairment
Bone pain (back pain)
Pathological fractures**
Very rarely can present in mouth
What is the management of myeloma
No cure
Management focuses on disease control
Chemotherapy
Stem cell transplant
Bisphosphonates ***
What are the Oral manifestations of haematological malignancy
Easy bleeding (Platelets - thrombocytopenia)
-Petechiae
-Haemorrhage (e.g. after extraction)
-Spontaneous gingival bleeding
Low immunity (WBC – leukopenia/neutropenia)
-Candidosis
-Herpes simplex virus
Anaemia (RBC)
-Pallor
Gingival swelling
-Acute myeloid leukaemia
Presentation of myeloma in mandible (rare
What are the stages of lymphoma
Stage 1 - one lymphadenopathy
Stage 2 - two on once side of diaphragm
Stage 3 - groups across diaphragm
Stage 4 - widespread metastasis
What are oral side effects of chemotherapy
Mucositis
Dry mouth – caries risk, taste disturbance, dysphagia
Infection (fungal, viral) – vulnerable**
Easy bleeding (thrombocytopenia)
Within the oral cavity what can radiotherapy cause
Dry mouth
Osteoradionecrosis of jaw (if in way of beam)
Fibrosis = trismus
What are the main side effects of treatment for cancers
Fungal infections (reduced salivary flow and immunosuppression)
Xerostomia (reduced salivary flow)
Caries (high calorie dietary supplements and reduced salivary flow)
Osteonecrosis (anti-resorptives, anti-angiogenics and immunosuppressive effects)
Bleeding tendencies (Thrombocytopenia)
How can dental health be optimised prior to the patient starting of chemotherapy
Dental assessment
OPT radiograph
Removal of hopeless teeth / teeth that may cause issues / infection
Removal and stabilisation of caries
Removal of traumatic edges
Toothbrushing instruction
Fabrication of mouthguard
High fluoride toothpaste
Fluoride varnish
Dietary advice
Prepare patient for expected oral side effects
Completion of treatment at least 10 days before chemotherapy
How long before starting chemotherapy should dental work be completed
At least 10 days
When a patient is undergoing chemotherapy how can oral health be optimised
Hygienist support
Maintenance of oral hygiene
Ongoing caries prevention
Assess and manage mucositis
Provision of saliva substitutes
Avoid any elective dental treatment
What is the common name for candidosis
Thrush
What is mucositis
Ulceration of mucosal cells
What are the steps in clotting
Injury
Vascular phase
Platelet phase (primary haemostasis)
Coagulation phase (secondary haemostasis)
Clot formation and stabilisation
Clot dissolution
What factors are released from the vessel lining after injury
ADP (platelets)
Tissue factor
Endothelins
What specifically aside from injury attracts platelets
Exposed collagen, ADP and endothelins
What is fibrinolysis
Clot breakdown
What is the difference between intrinsic and extrinsic coagulation cascade
Intrinsic - in bloodstream
Extrinsic - in vessel wall
What is the result of both intrinsic and extrinsic coagulation cascade
Fibrin clot
What medications affect platelets (clotting)
Aspirin
Clopidogrel
Dipyridamole
Ticagrelor
What medications affect anticoagulants (clotting)
Warfarin
Edoxaban
Rivaroxaban
Apixaban
Dabigatran
What injectable medication affects clotting
Heparin
Why are patients prescribed blood thinners
Coronary disease – to prevent an MI or stroke
Peripheral artery disease – to reduce symptoms
Prosthetic heart valves – to prevent a clot
Atrial fibrillation – to prevent a stroke
Pulmonary embolism/Deep vein thrombosis – to treat or prevent
Following surgery or pregnancy
What is the lifespan of platelets
7-10 days
How does aspirin reduce platelet aggregation
inhibits COX enzyme, to reduce production of thromboxane A2, thereby reducing platelet aggregation
When would a patient be taking 75mg of aspirin daily
Coronary artery disease (secondary prevention)
Transient ischaemic attack (secondary prevention)
What is a 300mg dose of aspirin prescribed/given for
Given in acute MI/stroke
How does Warfarin affect clotting
inhibits the production of vitamin K, which is essential in formation of coagulation factors II, VII, IX, X (2, 7, 9, 10)
What substances will warfarin interact with
Metronidazole
Fluconazole
NSAIDs
Alcohol
Grapefruit
What should be continuously monitored when taking warfarin
INR – International Normalised Ratio
What doesDOAC stand for
Direct Oral Anticoagulants
What are some examples of DOACs
Edoxaban, rivaroxaban, apixaban
Dabigatran
How do DOACs affect clotting
inhibits factor Xa
Dabigatran also inhibits free thrombin
Why are DOACs preferable over warfarin
Do not require monitoring
Less interactions
Faster onset
Fixed dosage
Shorter offset
Do direct oral and injectable anticoagulants have the same affact on clotting
Yes both affect formation offactor Xa and thrombin
What procedures pose a high risk for post op bleeding complications
Complex extractions (adjacent extractions or more then 3 at once)
Gingivalrecontouring
Biopsies
Flap raising surgery:
Periodontal surgery
Preprosthetic surgery
Perriradicular surgery
Dental implant surgery
What should you doif a patient on blood thinners needs dental surgery/procedures
Consult with patient’s prescribing specialist/GP if unsure***
Consult with more senior dentist if unsure***
Delay dental treatment until anticoagulant finishes (if planned)
Plan treatment for early in the week
Plan treatment for early in the day
“Atraumatic” surgery, staged
Consider packing and suturing
Ensure bleeding has stopped
Give excellent post-operative instructions
Advise the patient to take paracetamol, unless contraindicated, for pain relief rather than NSAIDs such as aspirin, ibuprofen, diclofenac or naproxen
What should be done if the patients INR is below 4 on warfarin within the 24 hrs before procedure
Treat without interrupting medication
What is the recommendation if the patient’s INR levels are 4 or above on warfarin
Delay invasive treatment or refer if urgent
What DOACs require the morning dose to be delayed or missed prior to dental treatment
Apixaban or dibigatran (miss)
Rivaroxaban (delay)
What are inherited bleeding disorders
Von Willebrand disease
Haemophilia A
Haemophilia B
What are acquired bleeding disorders
`Liver disease
Thrombocytopenia
How does liver disease result in bleeding disorder
Reduced platelet number and function
-Thrombopoeitin (TPO) hormone which stimulates platelet production is produced in liver
Impaired production of coagulation factors
I, II, V, VII, IX, X, XI, and XIII
What is the meaning of thrombocytopenia (breakdown)
Thrombo - clot
cyto - cell
penia - low
What is thrombocytopenia
Low platelets
What diseases cause reduced production of platelets (thrombocytopenia)
B12 deficiency
Folic acid deficiency
Liver disease
Leukaemia
Chemotherapy
What is the most common inherited cause of abnormal and prolonged bleeding
Von Willebrand Disease
Autosomal dominant inheritance - familial
What are the differences between types of von willebrand disease
Type 1(autosomal dominant) involves a partial deficiency of VWF and is the most common and mildest type
Type 2 (autosomal dominan) tinvolves the reduced function of VWF
Type 3 (autosomal recessive) involves a complete deficiency of VWF and is the most rare and severe type
What causes the abnormal bleeding with Von willebrand disease
Impaired platelet aggregation
Impaired transport of factor VIII to wound
How does DDAVP/desmopressin act to reduce bleeding
Works by increasing vWF production and factor VIII production
What treatments can be used to carry out dental procedures on Von Willebrand patients
tranexamic acid oral/mouthwash (if mild disease and low risk procedure)
DDAVP/desmopressin (if more likely to cause bleeding)
Von Willebrand factor concentrate (if severe disease and high risk procedure)
What is haemophilia
X-linked recessive (primarily affects males)
Rare
Haemophilia A – deficiency factor VIII
Haemophilia B – deficiency factor IX
Spontaneous bleeding (into joints) and significant bleeding following minor trauma
What separates mild, moderate and severe haemophiliacs
mild (6-40% factor)
moderate (2-5%)
severe (<1%)
What blood products are given before treatments of haemophiliacs
Haemophilia A – use of DDAVP/desmopressin (mild) or factor VIII concentrate (moderate/severe)
Haemophilia B – requires use of factor IX concentrate (DDAVP not effective)
How long before a procedure should blood products be given to patients with bleeding disorders
within 30 mins to an hour of treatment
When are those with haemophilia prone to bleeding
Severe - frequent spontaneous bleeds (should have all treatments carried out at a hospital)
Moderate - may have spontaneous bleeds (managed same as severe)
Mild - bleed after trauma or surgery
When administering local anaesthetic to those with bleeding disorders what should be avoided where possible
try to avoid inferior alveolar nerve block = risk of bleeding from muscle – haematoma, airway compromise
buccal infiltration, intra-papillary injections and intra-ligamentary injections preferred
What blood tests are related to clotting
Full blood count
Liver function test (Most coagulation factors are made in liver)
INR (Compares how long it takes patient’s blood to clot compared to a laboratory standard)
Coagulation screen
What are the variation of results seen from an INR blood test
Higher number = longer to clot
Healthy person on no medication = 1
Usual range for patients on warfarin = ~2 – 4
Normally should be <4 for dental treatment
What is the name for clotting too much
Thrombophilia
What elements of the clotting cascade prevent ‘over-clotting’
Protein C
Protein S
Antithrombin
What diseases/disorders are associated with clotting too much
Antiphospholipid syndrome
Protein C / Protein S deficiency
What is a pulmonary embolism
Blood clot in lung
What is a deep vein thrombosis
Blood clot in limbs (often leg)
What are symptoms of a deep vein thrombosis
Calf swelling and tenderness
Dilated superficial veins
Colour change
Oedema
What are the risk factors of thrombophilia
Previous DVT/PE
Prolonged immobility (long haul flight, long hospital stay)
Plaster cast
Combined oral contraceptive pill / HRT
Surgical operation (particularly orthopaedic)
Acutely unwell (sepsis)
Cancer
Dehydration
Pregnancy
Why do most thrombophiliacs become bleeding risks for dentists
Treated with anticoagulants
