Haematology Flashcards
1
Q
Basics of haematology:
Characteristics of red blood cells (erythrocytes)?
A
- Life span = 120 days
- No nucleus or cell organelles
- Biconcave shape
- Contains haemoglobin
2
Q
Basics of haematology:
Functions of red blood cells?
A
- Transport O₂ to tissues
- Transport CO₂ to the lungs for elimination
- Involved in acid-base homeostasis
3
Q
Basics of haematology:
Types of white blood cells?
A
- Neutrophils
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils
4
Q
Basics of haematology:
Neutrophil characteristics and functions?
A
Characteristics:
- Around 60% of total WCC
- Polymorphic lobulated nucleus
- Have specific protease-containing granules
Function:
- Acute inflammatory response
- Phagocytosis
5
Q
Basics of haematology:
Lymphocyte characteristics?
A
- Around 25-33% of total WCC
- Mononuclear cell with round, densely staining nucleus
- Small, pale cytoplasm
- Includes T cells (∼80%), B cells (∼15%), and natural killer cells (∼5%)
6
Q
Basics of haematology:
Lymphocyte functions?
A
T cells: - Adaptive (cellular) immune response Differentiate into: - Cytotoxic T cells (CD8+) - Helper T cells (CD4+) - Regulatory T cells
B cells:
- Adaptive (humoral) immune response
- Differentiate into plasma cells → antibody production
- Can act as antigen-presenting cells
NK cells:
- Innate immune response
7
Q
Basics of haematology:
Monocyte characteristics and functions?
A
Characteristics:
- Around 5% of total WCC
- Kidney-shaped nucleus
- Mononuclear cell
Functions:
- Differentiates into macrophage
- Phagocytosis
8
Q
Basics of haematology:
Eosinophil characteristics and functions?
A
Characteristics:
- Around 1-3% of total WCC
- Bilobate nucleus
- Large eosinophilic granules
Functions:
- Defence against parasitic infections
- Production of enzymes and proteins e.g. histaminase
- Phagocytosis of immune complexes
9
Q
Basics of haematology:
Basophil characteristics and functions?
A
Characteristics:
- Around 0-0.75% of total WCC
- Dense, basophilic granules of heparin and histamine
Functions:
- Mediates allergic reaction
- Synthesis and release of leukotrienes
10
Q
Basics of haematology:
What are macrophages?
A
- Phagocytic cells located in peripheral tissues (e.g. Kupffer cells in the liver)
Functions:
- Phagocytosis of pathogens, old RBCs, and cellular debris
- Antigen-presentation
11
Q
Basics of haematology:
What are mast cells?
A
- Differentiate from basophils
- Contain heparin and histamine
- IgE binds to cell membrane → degranulation → allergic reaction
12
Q
Basics of haematology:
What are dendritic cells?
A
- Phagocytic white cells that differentiate from either lymphoid or myeloid precursors
Functions:
- Phagocytosis
- Antigen-presentation
- Links innate and adaptive immune response
13
Q
Basics of haematology:
Where is erythropoietin produced?
A
Endothelial cells in the peritubular capillaries of the kidneys
14
Q
Basics of haematology:
Stages of red blood cell development?
A
- Haematopoietic stem cell
- Proerythroblast
- Erythroblast
- Normoblast
- Reticulocyte
When reticulocytes enter the bloodstream they begin to mature into erythrocytes over 1-2 days.
15
Q
Basics of haematology:
What factors affect the number of reticulocytes seen on a blood film?
A
- Increased reticulocytes indicates increased erythropoiesis (e.g. due to haemolysis)
- Decreased reticulocytes indicate decreased erythropoiesis (e.g. due to aplastic anaemia)
16
Q
Basics of haematology:
What are the two white cell lineages?
A
- Myeloid line
- Lymphoid line
17
Q
Basics of haematology:
Stages of lymphocyte production?
A
- Lymphopoiesis in the bone marry
- T lymphocytes mature in the thymus
- B lymphocytes mature in the bone marrow
18
Q
Basics of haematology:
Stages of thrombopoiesis?
A
- Occurs in bone marrow
- Myeloid precursor cell → megakaryoblasts → megakaryocytes → platelets
About 1/3 of the body’s platelets are stored in the spleen
19
Q
Basics of haematology:
Platelet characteristics and function?
A
- Lifespan 8-10 days
- Contain dense granules (serotonin, histamine) and alpha granules (vWF, fibrinogen, fibronectin, platelet factor IV)
20
Q
Erythrocyte morphology and haemoglobin:
What are the two types of erythrocyte dysmorphia
A
- Anisocytosis (RBCs of varying size)
- Poikilocytosis (RBCs of varying shape)
21
Q
Erythrocyte morphology and haemoglobin:
What are dacryocytes? What are they seen in?
A
- Teardrop-shaped RBCs
- Seen in some conditions where there is bone marrow infiltration, primarily 𝗺𝘆𝗲𝗹𝗼𝗳𝗶𝗯𝗿𝗼𝘀𝗶𝘀
- Also seen in 𝘁𝗵𝗮𝗹𝗮𝘀𝘀𝗮𝗲𝗺𝗶𝗮
Da𝗖𝗥𝗬ocytes = tear-shaped
22
Q
Erythrocyte morphology and haemoglobin:
What factors contribute to sickle cell formation?
A
- Sickle cell anaemia gene mutations
- Hypoxia and conditions related to hypoxia worsen sickling (e.g. acidosis, high altitude)
23
Q
Erythrocyte morphology and haemoglobin:
What are schistocytes? What are they seen in?
A
- Fragmented red blood cells
- Seen in microangiopathic haemolytic anaemia (e.g. haemolytic uraemic syndrome, DIC, TTP)
- Also seen when there’s mechanical damage to RBCs (e.g. artificial valves, extracorporeal circulation)
24
Q
Erythrocyte morphology and haemoglobin:
What are macrocytes? What are they seen in?
A
- Large, spherical RBCs
- Seen in megaloblastic anaemia (e.g. B₁₂ deficiency, folate deficiency)
25
Erythrocyte morphology and haemoglobin:
| What are spherocytes? What are they seen in?
- Small, spherical RBCs - no central pallor as no concavity
- Seen in haemolytic anaemias (e.g. 𝗵𝗲𝗿𝗲𝗱𝗶𝘁𝗮𝗿𝘆 𝘀𝗽𝗵𝗲𝗿𝗼𝗰𝘆𝘁𝗼𝘀𝗶𝘀, autoimmune haemolytic anaemia, haemolytic transfusion reaction)
26
Erythrocyte morphology and haemoglobin:
| What are target cells? What are they seen in?
- Cells with a bullseye appearance (dark outer ring, pale ring inside that with a dark centre; normally there's only the two 'rings')
- Seen in haemoglobinopathies e.g. thalassaemia
- Seen post-splenectomy
- Sometimes seen in liver disease
27
Erythrocyte morphology and haemoglobin:
| What are Heinz bodies? What are they seen in?
- Inclusion bodies of iron-containing, denatured DNA
| - Classically seen in glucose-6-phosphate dehydrogenase (G6PD) deficiency anaemia
28
Erythrocyte morphology and haemoglobin:
| What are ringed sideroblasts? What are they seen in?
- Perinuclear ring of iron in the mitochondria of erythroblasts. Detected in a bone marrow film.
- Seen in sideroblastic anaemia
29
Erythrocyte morphology and haemoglobin:
| What are Howell-Jolly bodies? What are they seen in?
- DNA inclusions that 𝗱𝗼 𝗻𝗼𝘁 contain iron
| - Seen in asplenism (normally they are detected and destroyed in the spleen; in asplenism, they can accumulate)
30
Erythrocyte morphology and haemoglobin:
| What is the normal composition of a haemoglobin molecule in an adult?
- HbA1 (the main adult haemoglobin): ααββ (95-98%)
| - HbA1c: glycosylated Hb (seen in diabetes mellitus)
31
Erythrocyte morphology and haemoglobin:
| What is the composition of fetal haemoglobin? What is physiologically different compared with adult Hb?
- HbF (fetal haemoglobin): ααγγ
| - Has a higher affinity for O₂ so it can extract it from the maternal circulation
32
Erythrocyte morphology and haemoglobin:
| What changes to haemoglobin structure occur as people get older?
- 𝗔lpha is 𝗔lways there
| - 𝗚amma 𝗚oes, and 𝗕ecomes 𝗕eta
33
Erythrocyte morphology and haemoglobin:
| What does a shift to the right on the oxygen-haemoglobin dissociation curve mean?
- Lower affinity for O₂ → ↑dissociation of O₂ from Hb → ↑tissue oxygenation
34
Erythrocyte morphology and haemoglobin:
| Causes of a shift to the right on the oxygen dissociation curve?
- ↑ PCO₂
- Fever
- High altitude
- Exercise
- Acidaemia
35
Erythrocyte morphology and haemoglobin:
| What does a shift to the left on the oxygen-haemoglobin dissociation curve mean?
- Higher affinity for O₂ → ↓dissociation of O₂ from Hb → ↓tissue oxygenation
36
Erythrocyte morphology and haemoglobin:
| Causes of a shift to the left on the oxygen dissociation curve?
- ↑ CO
- ↑ Methemoglobin
- ↑ Fetal haemoglobin (HbF)
- ↑ pH
- ↓ PCO₂
- ↓ Body temperature
37
Anaemia:
| Causes of microcytic anaemia?
- Iron deficiency anaemia
- Lead poisoning
- Late-stage anaemia of chronic disease
- Sideroblastic anaemia
- Thalassaemia
38
Anaemia:
| Causes of normocytic anaemia?
- Haemolytic anaemia
- Acute blood loss
- Aplastic anaemia
- Anaemia of chronic disease
39
Anaemia:
| Causes of macrocytic anaemia?
- Vitamin B₁₂ deficiency
- Folate deficiency
- Phenytoin
- Liver disease
- Alcohol use
40
Anaemia:
Clinical features?
(General features)
- Pallor
- Fatigue
- Exertional dyspnoea
- Pica (craving for ice, dirt)
- Worsening of angina pectoris
Features of a hyperdynamic state:
- Bounding pulse
- Tachycardia/palpitations
- Flow murmur
41
Anaemia:
| Investigation of microcytic anaemia?
Iron studies:
- ↓ Ferritin OR normal/↑ ferritin and ↑ TIBC: iron deficiency anaemia
- Normal/↑ ferritin and ↓ TIBC: anaemia of chronic disease
Peripheral blood smear:
- Reticulocyte count is important
- Other dysmorphic red cells (e.g. spherocytes)
Bone marrow biopsy if sideroblastic is anaemia suspected
In older patients, IDA warrants colonoscopy/gastroscopy to investigate for GI malignancy
42
Anaemia:
| Investigation of macrocytic anaemia?
Peripheral blood smear:
- Hypersegmented neutrophils = megaloblastic anaemia (B₁₂/folate)
- Serum B₁₂
- Serum folate
43
Anaemia:
| What is aplastic anaemia?
Pancytopenia caused by bone marrow insufficiency
44
Anaemia:
| Causes of aplastic anaemia?
- Idiopathic in 50%
- Drugs (e.g. chemotherapy, carbamazepine)
- Radiation
- Viruses (e.g. parvovirus B19, HBV)
- Fanconi anaemia (autosomal recessive disorder causing bone marrow failure, 50% develop AML or MDS)
45
Anaemia:
| Causes of iron deficiency anaemia?
- Excessive blood loss: menorrhagia, GI bleeding
- Inadequate dietary intake: vegans/vegetarians higher risk
- Poor intestinal absorption: e.g. coeliac disease
- Increased iron requirements: e.g. growth spurts, pregnancy
46
Anaemia:
| Features of iron deficiency anaemia?
- Fatigue, SOBOE
- Palpitations
- Pallor
- Koilonychia (spoon-shaped nails)
- Hair loss
- Atrophic glossitis
- Angular stomatitis
47
Anaemia:
| Investigation of iron deficiency anaemia?
History:
- Changes in bowel habit
- Menstrual history
- Dietary changes
- Medication history
- FBC
- Iron profile (ferritin, TIBC, transferrin saturation)
- Blood film - ?poikilocytosis/anisocytosis
- Endoscopy - ?malignancy (all males or post-menopausal women with unexplained IDA should get 2ww)
48
Anaemia:
| Management of iron deficiency anaemia?
- Treat underlying cause if appropriate
- Encourage iron-rich diet (meat, green leafy vegetables)
- Oral ferrous sulfate - should continue for 3 months after iron profile normalises to replenish iron stores
- May require parenteral iron in malabsorption or if oral iron is not tolerated
49
Thalassaemia:
| What is thalassaemia?
- A group of hereditary haemoglobin disorders causing mutations in the α- or β-globin chains (alpha or beta thalassaemia)
- It is further classified based on the number of alleles affected (α-globin is coded by four alleles, β-globin is coded by two alleles) - the number of deficient alleles directly correlates to the severity of the disease (minor/intermedia/major)
50
Thalassaemia:
| Epidemiology?
- β-thalassaemia more common in Mediterraneans
| - 𝗔lpha thalassaemia commoner in 𝗔sians and 𝗔fricans
51
Thalassaemia:
| Clinical features of beta thalassaemia?
```
Minor variant (1/2 defective allele):
- Unremarkable symptoms (low risk of haemolysis or splenomegaly)
```
Major variant (2/2 defective alleles):
- Severe haemolytic anaemia requiring frequent transfusions
- Growth retardation
- Hepatosplenomegaly
- Skeletal deformities (high forehead, prominent zygomata and maxillae)
- Infection with parvovirus B19 → aplastic crisis
52
Thalassaemia:
| Clinical features of alpha thalassaemia?
```
Silent carrier (1/4 defective allele):
- Asymptomatic
```
Alpha thalassaemia trait (2/4 defective alleles):
- Mild haemolytic anaemia with normal RBC
Haemoglobin H disease (3/4 defective alleles):
- Jaundice and anaemia at birth
- Chronic haemolytic anaemia that may require transfusion
- Hepatosplenomegaly
- Symptoms generally less severe than beta thalassaemia major
Hb Bart's → hydrops fetalis (4/4 defective alleles):
- Intrauterine ascites and hydrops fetalis (fetal heart failure)
- Incompatible with life (die in-utero or shortly after birth)
53
Thalassaemia:
| Diagnosis?
- FBC
- Peripheral blood smear (PBS; shows teardrop and target cells)
- Haemoglobin electrophoresis (identifies which chains are present)
- Diagnosis confirmed with genetic testing
54
B₁₂ deficiency:
| Causes?
Malabsorption:
- ↓intrinsic factor
- Reduced uptake of B₁₂-IF complex e.g. due to chronic alcoholism, coeliac disease, Crohn's
Inadequate intake:
- Anorexia nervosa
- Vegan diet (occurs after years of inadequate intake)
Increased demand:
- Pregnancy
- Breastfeeding
- Tapeworm infection
55
B₁₂ deficiency:
| Pathophysiology?
- B₁₂ is an important co-enzyme in DNA synthesis
| - Low B₁₂ → impaired DNA synthesis → immature, large, nucleated RBC formation (megaloblasts)
56
B₁₂ deficiency:
| What is pernicious anaemia?
- Type of B₁₂ deficiency caused by autoantibodies against intrinsic factor/gastric parietal cells
- Results in impaired B₁₂ absorption in the terminal ileum
- Associated with other autoimmune disorders
- Increased risk of gastric cancer
57
B₁₂ deficiency:
| Symptoms?
- General signs and symptoms of anaemia
Neurological disturbances (usually symmetrical):
- 𝗣𝗲𝗿𝗶𝗽𝗵𝗲𝗿𝗮𝗹 𝗻𝗲𝘂𝗿𝗼𝗽𝗮𝘁𝗵𝘆: glove and stocking symptoms
- B₁₂ maintains myelin so deficiency → subacute combined degeneration of the spinal cord; affects 𝗱𝗼𝗿𝘀𝗮𝗹 𝗰𝗼𝗹𝘂𝗺𝗻𝘀 (paraesthesia, impaired proprioception, loss of vibration sense), 𝗹𝗮𝘁𝗲𝗿𝗮𝗹 𝗰𝗼𝗿𝘁𝗶𝗰𝗼𝘀𝗽𝗶𝗻𝗮𝗹 𝘁𝗿𝗮𝗰𝘁 (spastic paresis) and spinocerebellar tracts (ataxia)
- Reversible dementia
N.B: neurological manifestations of B₁₂ deficiency are hard to localise; the trio of peripheral neuropathy, and dorsal column and lateral CST involvement should prompt suspicion.
𝗦ubacute 𝗖ombined 𝗗egeneration = 𝗦pinocerebellar tract, 𝗖orticospinal tract, and 𝗗orsal column
58
B₁₂ deficiency:
| Investigations?
- anti-IF antibodies
- anti-parietal cell antibodies
- MRI if subacute combined degeneration suspected
59
B₁₂ deficiency:
| Management?
Primary care:
- Encourage dietary intake
- IM hydroxocobalamin (frequency depends on features)
60
Folate deficiency:
| Causes?
- Poor intake
- Poor absorption
- Increased demands
- Drugs (e.g. phenytoin, trimethoprim)
61
Folate deficiency:
| Symptoms?
- Anaemia
- Glossitis
- Maternal deficiency → fetal neural tube defects
Does not cause neurological symptoms
62
Folate deficiency:
| Investigation?
- FBC
- ↑homocysteine
- If folate deficiency is suspected, ALWAYS rule-out B₁₂ deficiency
63
Folate deficiency:
| Management?
- Folate supplementation (at risk women should start supplementation pre-conception)
- Always treat any coexisting B12 deficiency BEFORE folate (treat deficiencies in alphabetical order), otherwise it can cause subacute combined degeneration
64
Haemolytic anaemia:
| What are the two types?
- Intrinsic haemolytic anaemia: increased destruction of RBCs due to a defect within the RBC
- Extrinsic haemolytic anaemia: increased destruction of normal RBCs
65
Haemolytic anaemia:
| Causes of intrinsic haemolytic anaemia?
- Thalassaemia
- Sickle-cell anaemia
- G6PD deficiency
- Hereditary spherocytosis
66
Haemolytic anaemia:
| Causes of extrinsic haemolytic anaemia?
- HELLP syndrome
- Malaria
- Hypersplenism
- Chronic lymphocytic leukaemia
- ABO/Rh incompatibility
67
Haemolytic anaemia:
| What is the direct Coombs test (DAT; direct antiglobulin test)? What does a positive result indicate?
- A laboratory investigation that tests for the presence of antibodies and/or complement proteins bound to the surface of RBCS
- A positive result indicates that the patient's RBCs have autoantibodies/complement proteins adhered to them which are causing haemolysis (e.g. autoimmune haemolytic anaemia)
𝗗𝗶𝗿𝗲𝗰𝘁 Coombs test = antibodies 𝗱𝗶𝗿𝗲𝗰𝘁ly bound to RBCs
68
Haemolytic anaemia:
| What is the indirect Coombs test? What does a positive result indicate?
- A laboratory investigation that tests for the presence of free autoantibodies circulating in the patient's serum
- Used to screen for rhesus sensitisation
- Positive result indicates freely circulating anti-RBC antibodies that may be responsible for neonatal haemolysis or a transfusion reaction
69
Glucose-6-phosphate dehydrogenase deficiency:
| Pathophysiology?
- G6PD is an enzyme involved in synthesising glutathione, an important antioxidant
- In G6PD deficiency there is an impairment of this process, resulting in an increased susceptibility to oxidative damage
- As a result, increased levels of oxidative free radicals can trigger haemolytic crises
70
Glucose-6-phosphate dehydrogenase deficiency:
| Triggers of haemolytic crisis?
- 𝗙𝗮𝘃𝗮 𝗯𝗲𝗮𝗻𝘀 (commonly tested)
- 𝗔𝗻𝘁𝗶𝗺𝗮𝗹𝗮𝗿𝗶𝗮𝗹 𝗱𝗿𝘂𝗴𝘀
- Bacterial and viral 𝗶𝗻𝗳𝗲𝗰𝘁𝗶𝗼𝗻𝘀 (most common)
71
Glucose-6-phosphate dehydrogenase deficiency:
| Inheritance pattern?
- X-linked recessive
| - Commoner in African and Mediterranean people
72
Glucose-6-phosphate dehydrogenase deficiency:
| Diagnosis?
Blood smear:
- 𝗛𝗲𝗶𝗻𝘇 𝗯𝗼𝗱𝗶𝗲𝘀 (inclusion bodies of denatured DNA)
Direct measuring of G6PD activity is diagnostic
73
Glucose-6-phosphate dehydrogenase deficiency:
| Management?
Educate patient and avoid triggers
74
Hereditary spherocytosis:
| What is it?
- Autosomal dominant defect of red blood cell cytoskeleton
- Commonest hereditary haemolytic anaemia in Northern Europeans
- Normal biconcave shape of RBC replaced by spherical-shaped RBC
- Red blood cell survival decreased as destroyed by spleen
75
Hereditary spherocytosis:
| Clinical features?
- Anaemia
- Jaundice
- Splenomegaly (sphere shaped cells get trapped in capillaries)
- Gallstones
- Raised mean corpuscular haemoglobin concentration (MCHC)
76
Hereditary spherocytosis:
| Diagnosis?
- Patients with family history, typical clinical features, and typical laboratory findings (spherocytes, raised MCHC) don't require further investigation.
- If the diagnosis is equivocal, EMA binding test is used
77
Hereditary spherocytosis:
| Management?
Acute haemolysis:
- Supportive care
- Transfusion if necessary
Chronic management:
- Folate supplements
- Splenectomy is definitive management
- Before splenectomy, vaccinate against S. pneumoniae, N. meningitidis, H. influenzae type B.
78
Hereditary spherocytosis:
| Complications?
- Haemolytic crisis (usually after viral infection)
| - Aplastic crisis (after 𝗽𝗮𝗿𝘃𝗼𝘃𝗶𝗿𝘂𝘀 𝗕𝟭𝟵 infection; shows low reticulocyte count)
79
Sickle cell anaemia:
| What is it?
- Autosomal recessive mutation on chromosome 11 resulting in the formation of an abnormal haemoglobin chain (HbS)
- Provides some degree of protection against malaria
80
Sickle cell anaemia:
| Genetics?
- Heterozygous (HbSA): one sickle cell allele and one normal → sickle cell trait
- Homozygous (HbSS): two sickle cell alleles → sickle cell disease
81
Sickle cell anaemia:
| Clinical features of sickle cell trait (heterozygous)?
Painless gross haematuria due to renal necrosis often the only feature
82
Sickle cell anaemia:
| Clinical features of sickle cell disease (homozygous)?
- Acute haemolytic crisis (e.g. splenic sequestration crisis, aplastic crisis)
- Increased risk of infection (e.g. osteomyelitis)
- Painful vaso-occlusive events (e.g. priapism, acute chest syndrome)
83
Sickle cell anaemia:
| Diagnosis?
Haemoglobin electrophoresis
84
Sickle cell anaemia:
| Crisis management?
- Supportive care (opiates, IV fluids, oxygen)
- Consider antibiotics
- Blood transfusion if needed
85
Sickle cell anaemia:
| Chronic management?
- Hydroxyurea (prevents painful episodes)
| - Pneumococcal vaccine every 5 years
86
Polycythaemia:
| Causes of primary polycythaemia?
Polycythaemia rubra vera
87
Polycythaemia:
| Causes of secondary polycythaemia?
- COPD
- High altitude (e.g. altitude training)
- Obstructive sleep apnoea
- Renal cell carcinoma → EPO secretion
88
Polycythaemia:
| Genetics of polycythaemia rubra vera?
- JAK2 gene mutation (95% of cases)
- ↑ tyrosine kinase activity
- Causes myeloid proliferation (without need for EPO)
89
Polycythaemia:
| Clinical features of polycythaemia rubra vera?
- Hyperviscosity → VTE
- Plethora
- Pruritus (worse in warm water)
- Hypertension
- Splenomegaly
90
Polycythaemia:
| Investigation of suspected polycythaemia?
- FBC
- Blood film
- JAK2 mutation
- Serum ferritin
- Renal and liver function tests
91
Polycythaemia:
| Diagnosis of polycythaemia rubra vera?
WHO, 2016:
All major criteria or 2/3 major and one minor criterion:
Major:
1. Evidence of increased RBCs
2. Bone marrow biopsy
3. JAK2 mutation
Minor:
- Decreased EPO levels
92
Polycythaemia:
| Management of polycythaemia rubra vera?
- Aspirin reduces VTE risk
- Venesection to keep haemoglobin in normal limits
- Chemotherapy (hydroxyurea)
93
Polycythaemia:
| Prognosis of polycythaemia rubra vera?
- Thrombotic events are common cause of death
- 5-15% of patients progress to myelofibrosis
- 5-15% of patients progress to acute leukaemia
94
Haemostasis:
| What is primary haemostasis?
The formation of a platelet plug following vascular injury
1. Platelets bind to vWF at the site of the injury
2. Platelets change shape and activate more platelets
3. Platelet aggregation
95
Haemostasis:
| What is secondary haemostasis?
The formation of a stable platelet plug by creating a fibrin meshwork (i.e. the coagulation cascade)
96
Haemostasis:
| What systems inhibit haemostasis (to prevent hypercoagulability)?
- (activated) protein C and protein S (inhibit factor 5 & 8)
| - Antithrombin (degrades thrombin and factors 9 & 10)
97
Von Willebrand Disease:
| What is von Willebrand Disease?
Autosomal dominant bleeding disorder caused by deficiency or dysfunction of von Willebrand Factor (vWF)
98
Von Willebrand Disease:
| Pathophysiology?
- Deficiency or dysfunction of vWF leads to impaired platelet adhesion → impaired primary haemostasis
- Also factor ↓VIII activity so secondary haemostasis is impaired
99
Von Willebrand Disease:
| Clinical features?
- Often asymptomatic
- Bruising
- Epistaxis (nosebleeds)
- Bleeding from gums and gingiva
- Prolonged bleeding from minor injuries
- GI bleeding
- Menorrhagia
100
Von Willebrand Disease:
| Diagnosis?
↑ bleeding time
↑/- APTT
Normal PT
Clotting factors:
↓ factor VIII
↓ vWF
101
Von Willebrand Disease:
| Management?
- Tranexamic acid for mild bleeding
- Desmopressin (increases vWP release)
- Factor VIII
