Haematology Flashcards
What is haemopoiesis
The physiological developmental process that gives rise to the cellular components of blood
What are the characteristics of haemopoietic stem cells
Self renewal
High proliferative potential
Differentiation potential for all lineages
Long term activity throughout the lifespan of the individual
What are the two types of haemopoietic lineages
Myeloid
Lymphoid
When and where does haemopoiesis happen in utero
Day 27 in the aorta mesonephros region, expands rapidly at day 35, then disappear at day 40 when the haemopoietic stem cells migrate to the foetal liver which becomes the subsequent site of haemopoiesis
What are the functions of blood cells
Oxygen transport
Coagulation (haemostasis)
Immune response to infection
Immune response to abnormal cells (senescent, malignant etc)
What is anaemia
Reduced red cells
What is polycythaemia
Raised red blood cells
What are the functions of white blood cells (leukocytes)
Immunity and host defence
What are the types of white blood cells
Granulocytes: -Neutrophils -Eosinophils -Basophils Moncytes Lymphocytes
What is neutropenia
Decrease numbers of neutrophils
What is eosinophilia
Increased numbers of eosinophils
What is basophilia
Increased numbers of basophils
What is monocytosis
Increased numbers of monocytes
What is lymphocytosis
Increased numbers of lymphocytes
What is lymphopenia
Decreased numbers of lymphocytes
What are the four main subdivisions of haematology clinical practice
Coagulation
Malignant
Non-malignant
Transfusion
What are the diagnostic tests in haematology
Full blood count
Blood film (or smear)
Coagulation screen
What does the full blood count test
Haemoglobin conc Red cell parameters -MCV (mean cell volume) -MCH (mean cell Hb) White cell count (WCC) Platelet count
What does a coagulation screen do?
Tests measure the time taken for a clot to form when plasma is mixed with specified reagents
What parts of coagulation cascade can be assayed
- Prothrombin time
- Activated partial thromboplastin time
- Thrombin time
How is bone marrow aspirated
Under local anaesthetic, liquid marrow is aspirated from the posterior iliac crest of the pelvis and a trephine core biopsy is then taken with a hollow needle
What is the sensitivity of a test
Defined as the proportion of abnormal results correctly classified by the test
Expresses the ability to detect a true abnormality
What is the specificity of a test
Defined as the proportion of normal results correctly classified by the test
Expresses the ability to exclude an abnormal result in a healthy person
How do the cells in iron deficiency anaemia present
Small, pale red cells
Low MCV and MCH
Variable size and shape- long thin pencil cells
What is leucodepletion
When whole blood is filtered before further processing to remove white cells
How is a unit of red blood cells kept healthy during storage
Plasma is replaced by a solution of electrolytes, glucose and adenine
What is the raise in a patients Hb expected to be after a unit of RBC transfusion
10g/L
How much iron is in one unit of packed RBC
200-250 mg of iron
How is a unit of RBC stored
At 4 degrees C for up to 35 days from collection
What is the therapeutic dose of RBC
10-20ml/kg of recipient
What is the usual transfusion time
1.5-3 hours
Why are red blood cells transfused
Significant bleeding
Acute anaemia
Chronic anaemia
To restore oxygen carrying capacity
What types of anaemia can be treated without blood transfusion
Iron deficiency B12 and folate deficiency Renal disease (erythropoietin treatment)
How many units of pooled platelets are in a single pack
4-6 units which each come from different donors as one unit of platelet comes form one unit of whole blood
What are aphaeresis platelets
Platelets that have been removed through an apheresis machine that collects platelets and returns all other blood constituents to the donor
The amount of platelets collected this way is equivalent to 4-6 units of pooled platelets
How much will a therapeutic dose of platelets raise patients platelets
20-60x 10^9/L
What is the platelet count per therapeutic dose
3 x 10^11
How are platelets stored
Room temperature (22 degrees C) on an agitator Shelf-life 5 days from collection
What is the usual transfusion time
30 mins/unit
What is the limiting factor for the shelf life of platelets
The risk of contamination by bacteria from the donor’s arm that grow at the conditions of storage and can be transmitted to the recipient
Why are platelets transfused
To treat bleeding due to severe thrombocytopenia (low platelets) or platelet dysfunction
To prevent bleeding in patients with thrombocytopenia or platelet dysfunction
What is fresh frozen plasma
Contains all clotting factors at physiological levels
What is the therapeutic dose of fresh frozen plasma
12-15 ml/kg (4-6 units for average adults)
How is fresh frozen plasma stored
-30 degrees C for up to 36 months
What is the volume of 1 unit of fresh frozen plasma
300ml
What is the usual transfusion time of fresh frozen plasma
30 mins/unit
Why is fresh frozen plasma transfused
To replace clotting factors in patients with multiple factor deficiencies:
- to treat significant bleeding in patients with abnormal clotting results
- to correct abnormal clotting results prior to invasive procedures
When should you not transfuse FFP
To treat single factor deficiencies
To correct abnormal clotting results in patients that are not bleeding
To reverse warfarin
What are some acquired coagulopathies
Liver disease
Disseminated intravascular coagulation
Massive haemorrhage
How is warfarin anticoagulation reversed
Prothrombin complex concentrate (factor IX complex)
What is cryoprecipitate
Extracted from FFP during thawing
Contains fibrinogen, von Willebrand, factor VIII, factor XIII
Therapeutic dose: 10-15ml/kg (6-10 units)
Used as a concentrated source of fibrinogen in acquired coagulopathies
What are causes of anaemia
Haematinic deficiencies Secondary to chronic disease Haemolysis Alcohol, drugs, toxins Renal impairment - EPO Primary haematological/ marrow disease: -Malignant -Haemoglobin disorders (sickle etc) -Aplasia -Congenital
What are the classifications of anaemia based on MCV
Macrocytic
Normocytic
Microcytic
What types of anaemia fall in to Macrocytic
- B12, Folate, metabolic (thyroid/liver disease)
- Marrow damage (booze, drugs, marrow disease)
- Haemolysis (due to reticulocytosis)
What types of anaemia fall in to normocytic
Anaemia of chronic disease/inflammatory
What types of anaemia fall in to microcytic
Iron deficiency
Haemoglobin disorders
Sometimes chronic disease
How is iron balanced
No excretion - limited absorption Controlled at the level of the gut mucosa Most iron is thus re-cycled Absorbed in duodenum Transported by transferrin Stored in ferritin/ haemosiderin
Where can iron be found in diet
Pretty much everything
Should not be iron deficiently anaemic if eating a balanced diet
What is the management of iron deficiency disorder
Establish that there is low iron
Establish the cause
Treat the iron and the cause
How is low iron established
FBC, indices and film Ferritin levels tell if iron deficient % hypochromic cells Serum iron/ TIBC Marrow
What are the main causes of iron deficiency
Blood loss from anywhere (gut/ PV/ PU/ respiratory tract etc)
Malignancy
Increased demand (pregnancy/ growth)
Reduced intake (diet/ malabsorption)
How is iron deficiency treated
Oral iron
IM iron
IV iron
What is megaloblastic anaemia
A characteristic cell morphology caused by impaired DNA synthesis
What are the most common causes of thrombocytopenia
Drugs, alcohol, toxins ITP Autoimmune disease Liver disease and/or hyperslenism Pregnancy Haematological/ marrow disease Infections acute or otherwise: -HIV -Acute sepsis -Viral infection (EBV) Disseminated intravascular coagulation Range of congenital conditions Many others
What is ITP
Common Immune thrombocytopenic purport Immune disorder Occurs on its own or as part of: -Other autoimmune disease -Lymphomas/ CLL -HIV Can be acute/ chronic/ relapsing
How does ITP present
Bruising or petechiae or bleeding Platelet count: <10 urgent/ might be bleeding <20 a worry <30 need treatment especially if having surgery No definitive test
How is ITP treated
Steroid is first line IV immunoglobulin Immunosuppressives or splectomy Thrombosis-mimetics: -Eltrombopag -Romiplostin
What is the outcome of ITP therapy
Usually rapid response Can relapse after therapy Rarely life-threathening Commonly recurrent Some difficult refractory causes
What is TTP
Thrombotic thrombocytopenia purpura Rare but urgent diagnosis Most are immune ADAMTS-13/VWD Suspect if thrombocytopenia and: -Fever -Neurological symptoms -Haemolysis (retics/ LDH) Seek evidence of microangiopathy: -Blood film fragments
How is TTP treated
Plasma exchange with FFP/plasma
Steroids
(Vincristine)
(Rituximab)
What are the causes of megaloblastic change
B12 and/ or folic acid deficiency Alcohol Drugs: -cytotoxics -folate antagonists -N20 Haematological malignancy Congenital rarities: -Transcobalamin deficiency -Orotic aciduria
How do B12 and Folate cause anaemia
DNA consists of purine/pyrimidine bases
Folates are required for their synthesis
B12 is essential for cell folate generation
So low folate or B12 starves DNA of bases
Where can vitamin B12 be found in the diet and how is it absorbed
Loads in most diets but only from animal sources Absorption: -gastric parietal cells -intrinsic factor -receptors in terminal ileum Stores sufficient for some years
Who has b12 deficiency
Nutritional: vegans Gastric problems: -pernicious anaemia (autoimmune) -Gastrectomy Small bowel problems -terminal ileum resection/ Chrons -Stagnant loops/ jejunal diverticulosis -Tropical sprue/ Fish tapeworm
Where can folic acid be found and absorbed
Mainly in green vegetables, beans, peas, nuts and liver
Required intake needs decent daily diet
Absorbed in upper small bowel
4 months body stores
Why do patients have folic acid deficiency
Mainly dietary/ malnutrition Malabsorption/ small bowel disease Increased usage: -pregnancy -haemolysis -inflammatory disorders Drugs/ alcohol/ ITU
What are the features common to B12 or folate deficiency
Megaloblastic anaemia Can have pancytopenia if more severe Mild jaundice Glossitis/ angular stomatitis Anorexia/ weight loss Sterility
What is haemolysis and the causes
Shortened red cell life Causes: -Things wrong inside the red cell -Things wrong with the red -cell membrane -Things wrong external to the red cell
Why are anticoagulants used
Prevention of venous thromboembolism Prevention of stroke in AF Treatment of DVT/PE etc Mechanical valve patients Arterial thrombosis/ limb ischaemia
What are the common anticoagulants
Heparin Fondaparinux Vitamin K antagonists: Warfarin Sinthrome ( Acenocoumoral) DOACs ( Direct Oral Anticoagulants): -Rivaraoxaban -Apixaban -Edoxaban -Dabigatran
What is heparin
Derived from pigs
Mode of action:
Increases ability of antithrombin to bind to and irreversibly switch off thrombin (IIa) and Factor Xa
What are the potential complications of heparin
Skin/allergic reactions
Osteoporosis
Heparin induced thrombocytopenia
How does heparin induced thrombocytopenia present
drop in platelet count >50% from baseline usually 5-10 days after starting heparin can be associated with thrombosis Calculate 4Ts score (timing, level, thrombosis, other causes) and if > 3 send HIT screen, stop heparin, start argatroban
What is fondaparinux
Synthetic pentasaccharide, given subcutaneously
Binds to antithrombin and inhibits Xa activity
Half life 17-20 hours if normal renal function
Bleeding- stop treatment and general haemostatic measures
No specific antidote
Critical bleeding- consider rFVIIa
How is warfarin monitored
By INR
What is INR
Prothrombin ratio
Prothrombin ratio = Patient’s prothrombin time/ mean normal prothrombin time
What are the problems with oral anticoagulants
React with many drugs
Food interactions- vitamin K containing
Alcohol
What are the characteristics of the ideal anticoagulant
- Oral administration
- No requirement for routine coagulation monitoring and dose adjustment
- Wide therapeutic window: high efficacy in preventing thrombosis; low bleeding risk
- Rapid onset of action
- Predictable pharmacokinetics and pharmacodynamics
- Minimal interactions with foods and other drugs
- Ability to inhibit free and clot-bound coagulation factors
- Low non-specific binding
- Availability of an antidote
- No unexpected toxicities
- Acceptable costs
What are the benefits of DOACs
Uniform dose in most patients
No need for routine monitoring
Minimal interactions with drugs and foodstuffs
What are the cons of DOACs
Contraindications: -Renal impairment -Women of child bearing age -Extremes of body weight >120 kg Management of bleeding Lab issues Adherence Special populations: -Mechanical valves -antiphospholipid syndrome Peri-operative management
What are the indications for measuring anticoagulant drug levels
Bleeding Need for emergency surgery/procedure Question of adherence Recurrent thrombosis Renal impairment Potential drug interactions Extremes of weight
What is aspirin
Inactivates platelet cyclooxygenase reducing thromboxane A2
Irreversible effect, lasts 4-5 days
No reversal agents
Give 2-3 adult doses of platelets in critical bleeding
What are the acquired bleeding disorders
Vitamin K deficiency Liver disease Renal disease Major haemorrhage DIC
What are the causes of vitamin K deficiency
Obstructive jaundice
Prolonged nutritional deficiency
Broad spectrum antibiotics
Neonates (classical 1-7 days)
How is vitamin K deficiency treated
IV/Oral Vitamin K 10mg for 3-5 days
How is haemostasis impaired in liver disease
- Thrombocytopenia (production or hypersplenism)
- Platelet dysfunction (plasmin induced cleavage of surface glycoproteins)
- Reduced plasma concentration of all coagulation factors (reduced synthesis) except FVIII
- Delayed fibrin monomer polymerisation due to altered fibrinogen glycosylation (xs sialic acid)
- Excessive plasmin activity
How is bleeding in liver disease treated
Platelet transfusions
FFP or prothrombin complex concentrate
Cryoprecipitate or fibrinogen concentrate
Endoscopy if GI bleed
NB above transfusions may not correct clotting tests completely.
How does bleeding in renal disease present
Symptoms: (30-50% of CRF patients)
Easy bruising, petechia, gum bleeding, nosebleeds, excessive bleeding from venepuncture/lines
ICH bleeds, retroperitoneal bleed, pericardial tamponade, GI bleeds
Patients with uncontrolled high BP and on dialysis Increased risk of ICH
What are the causes of bleeding in renal disease
Anaemia
Drugs accumulating in renal failure can bind to platelets and block their receptors
Uremia
How is bleeding prevented in renal disease
Correction of anaemia- EPO and transfusions
Avoidance of antiplatelet drugs for at least 7 days prior to procedures
Dialysis
DDAVP pre procedures
Tranexamic acid pre procedures (not if urinary tract and risk of haematuria)