Lecture 9/10 - Disorders of haemostasis Flashcards
Four causes of defective haemostasis with abnormal bleeding
- Abnormalities of the vessel wall (vascular system)
- Thrombocytopenia
- Disordered platelet function (thrombocytopathy)
- Defective blood coagulation
How are vessel wall abnormalities characterised?
Characterized by easy bruising and purpura (bleeding into the skin or mucous membranes)
What are vascular and platelet bleeding disorders associated with?
Associated with bleeding from the mucous membranes and into the skin
Where is bleeding often located in Coagulation disorders?
Bleeding is often into joints or soft tissues
Vascular building disorders: what are the characteristics and what is the pathology?
Characteristics:
* Easy bruising
* Spontaneous bleeding from small vessels
Pathology:
* Abnormality in blood vessels
* Bleeding and other haemostasis tests usually normal
Hereditary haemorrhagic Telangiectasia: how many people are affected, is it a dominant or recessive illness, where are the defects in the genome, what are they symptoms, and what are the treatments?
Uncommon - approx. 1.2 million worldwide (equally between men and women)
Autosomal dominant
Defects in at least 3 genes but only 1 gene is the cause in any one family
Abnormally formed blood vessels: Arteriovenous malformations
Symptoms mild - severe:
* Telangiectases - dilated microvascular swellings, easy to rupture (90-95%: at least a few telangiectasias on the skin of the face and/or hands by middle age)
* nose, tongue and lips (90-95% nosebleeds by adulthood at varying frequencies)
* Nosebleeds and gastrointestinal blood loss.
* Chronic iron deficiency is frequent
* 20-25%: bleeding in the stomach or intestines, but rarely before 50 y.old.
Treatment: embolization, laser treatment and tranexamic acid (prevents fibrinolysis)
Acquired vascular defects: what causes them, and what can they be characterised as?
Wide variety of causes: incl. infections, drug reactions, trauma, old age and steroid use.
Vascular purpura can be categorized as such:
- Purpura simplex - common benign disorder, in women of childbearing age.
- Senile purpura - old age, due to the loss of skin elasticity and atrophy of vascular collagen, mainly on the forearms and hands
- Infection-associated purpura - bacterial and viral infections, e.g. measles can cause purpura from vascular damage by the organism.
Thrombocytopenia: what is it and what are the three main causes of it?
Deficiency in platelet numbers (defined as a low platelet count with values less than 150 x 109/L)
3 main causes of thrombocytopenias:
* Failure of platelet production
* Increased destruction of platelets
* Sequestration (abnormal distribution) of platelets
Platelet production failure: what is it the most common cause of, what is it usually caused by, and how do we diagnose it?
Most common cause of thrombocytopenia
- Usually part of bone marrow failure - aplastic anaemia/leukaemia (deficiency in blood cells produced)
- drug/viral-induced toxicity
Clinical history, peripheral blood count, blood film, and bone marrow examination
Increased destruction of platelets: what is it usually caused by and what does it result in?
Autoimmune response - autoantibodies attach to platelet surface
Autoimmune (idiopathic) thrombocytopenia purpura (ITP) in two disease categories: chronic ITP and acute ITP
Chronic ITP: what are the general features, what causes it, and what happens to platelet lifespan?
Relatively common in young women 15-60 years old, often asymptomatic or have an insidious onset of bleeding?
Autoantibodies (mostly IgG) in plasma and on platelets which make them get destroyed by macrophages in the spleen and liver.
((((Antibodies: glycoprotein IIb/IIIa or Ib)))
Platelet lifespan considerably reduced: as little as a few hours
Acute ITP: general features, what causes it, and what two ways does it usually lead to?
Children under 10
The majority is abrupt following vaccination or viral episode as the IgG antibody attaches to the viral antigen and is absorbed onto the platelet surface, causing a dramatic fall in platelet count (may be less than 20 x 109/L)
- Spontaneous remissions usual
- The minority of cases develop chronic ITP
Sequestrian of platelets: how many platelets are in the spleen normal and how many platelets are in the spleen when splenomegaly occurs?
Normally, the spleen contains ~30% of all platelets
Splenomegaly: up to 90% of platelets sequestered in the spleen - thrombocytopenia
Thrombocytopathy: what is it, when is it diagnosed, and what is it caused by?
Disorders of Platelet Function
Considered when clinical signs and symptoms of thrombocytopenia but in the presence of a normal platelet count
Inherited and Acquired disorders:
* Inherited disorders - rare but capable of producing defects at each of the different phases of the platelet reaction (activation, adhesion, secretion, aggregations).
* Acquired disorders - much more common
Antiplatelet drugs (Aspirin): what do they do, what do they result in, and what is their effect of them?
Irreversibly inactivates the enzyme cyclooxygenase (COX), preventing the production of thromboxane A2 from arachidonic acid
Result: inhibition of platelet aggregation
Significantly extends the bleeding time which may cause haemorrhage in patients with thrombocytopenia
Haematological malignancy: what does it do and what may it be caused by?
Causes platelets to function incorrectly
- acute myeloid leukaemia
- any myeloproliferative disorders and myeloma
Platelet disorder diagnosis
- Initial blood count and blood film examination
- Bone marrow biopsy - thrombocytopenic patients, ascertain failure of platelet production
- Blood count: within normal limits - other tests performed to detect abnormal platelet function
- Prolonged bleeding time detected - defect usually acquired and should be evident in clinical investigation
- Patients with hereditary defects require further testing to define the specific abnormality
Haemophilia a
The most common hereditary clotting factor deficiency
Factor VIII deficiency
30-100 per million of a population
X-linked recessive disorder - all males with the defective gene suffer, sons of haemophiliac men are (usually) non-sufferers but their daughters will be carriers (or sufferers)
Can be spontaneously mutated
Clinical features of factor VIII level in bleeding severity: what are the symptoms and what are deaths mainly caused by?
Severity of bleeding is related to the factor VIII level
Clinical features of severe haemophilia:
* Bleeding into joints and less frequently muscles
* Knees, elbows and ankles are most commonly affected by bleeding
* The majority of bleeds require treatment
* Presenting symptoms: pain in affected areas
Intracranial bleeding: the main cause of death from the disease
High death rate: HIV-contaminating factor VIII observed in the USA and Europe in the last two decades
