Abnormalities of haemostasis Flashcards
Appreciate how minor bleeding abnormalities are common
Easy bruising 12% Gum bleeding 7% Frequent nosebleeds 5% Bleeding after tooth extraction 2.5% Post operative bleeding 1.4% In women Menorrhagia 23% Post partum bleeding 6%
Family history 44%
When is bleeding also common
After removing tonsils (tonsillectomy)
e.g % of easy bruising, frequent bruising and epistaxes are increased in patients with no known bleeding disorders and comparable to statistics in those with known bleeding disorders
however the severity is not comparable (i.e the % of epistaxes lasting greater than 10 mins is very low in those with no known bleeding disorders).
This highlights how the bleeding history is the most important investigation.
What are the key elements of a significant bleeding history
Epistaxis not stopped by 10 mins compression or requiring medical attention/transfusion.
Cutaneous haemorrhage or bruising without apparent trauma (esp. multiple/large).
Prolonged (>15 mins) bleeding from trivial wounds, or in oral cavity or recurring spontaneously in 7 days after wound. Spontaneous GI bleeding leading to anaemia.
Menorrhagia requiring treatment or leading to anaemia, not due to structural lesions (e.g fibroids) of the uterus.
Heavy, prolonged or recurrent bleeding after surgery or dental extractions.
When is primary haemostasis sufficient
In small blood vessels- bleeding is stopped without the need for a fibrin meshwork.
Summarise the causes of abnormal haemostasis
Lack of a specific factor
Failure of production: congenital and acquired
Increased consumption/clearance
Defective function of a specific factor
Genetic defect
Acquired defect – drugs (anti-platelet drugs or anti-coagulants), synthetic defect, inhibition
Summarise platelet adhesion in primary haemostasis
Can attach to collagen indirectly via VWF- platelet binds to VWF via Glp1b
Can attach to collagen directly via Glp1a
This leads to platelet activation, leading to release of ADP and thromboxane
The platelets then aggregate, via fibrinogen and Ca2+
Platelets bind to fibrinogen via Glp2b/3a
Describe a low number of platelets as a disorder of primary haemostasis
Low numbers: “thrombocytopenia”
Bone marrow failure eg: leukaemia, B12 deficiency (megaloblastic anaemia- cells grow and grow without means of synthesising new DNA- thus they cannot divide)- both of these ‘clog’ up the bone marrow and interfere with normal haemostasis.
Accelerated clearance eg: immune (ITP)- making lots of platelets- but they are destroyed in the circulation, DIC.
Pooling and destruction in an enlarged spleen
Describe the pathogenesis of auto-ITP
Auto-Immune Thrombocytopenic Purpura (auto-ITP)
Purpura means bruising
Antiplatelet antibodies
Sensitised platelet
Sensitised platelets cleared by the macrophages in the reticulo-endothelial system (especially in the spleen)
Summarise the mechanisms and causes of thrombocytopenia
Failure of platelet production by megakaryocytes
- Shortened half life of platelets
- Increased pooling of platelets in an enlarged spleen
(hypersplenism) + shortened half life
Describe an impaired function of platelets as a cause of a disorder in primary haemostasis
Impaired function
Hereditary absence of glycoproteins or storage granules
Acquired due to drugs: aspirin, NSAIDs, clopidogrel
These drugs can be given to prevent strokes, but increased risk bleeding will be a major side effect.
State three hereditary platelet defects
Glanzmann’s Thrombasthenia – absence of GlpIIb/IIIa (prevents platelet aggregation)
Bernard Soulier Syndrome – absence of GlpIb (prevents binding to von Willebrand factor)
Storage Pool Disease – storage granules are not able to release adequately (no release of ADP,ATP, serotonin or Ca2+ from dense granules)
What is a distinctive feature of thrombocytopenia
Petechiae
Describe VWD as a disorder or primary haemostasis
Von Willebrand disease
Hereditary decrease of quantity +/ function (common)
Acquired due to antibody (rare)
What are the two functions of VWF in primary haemostasis
VWF has two functions in haemostasis
Binding to collagen and capturing platelets
Stabilising Factor VIII
Factor VIII may be low if VWF is very low
Describe the genetic defects in VWF
VWD is usually hereditary
Deficiency of VWF (Type 1 or 3)
VWF with abnormal function (Type 2)
Type 3 - complete absence – autosomal recessive
the other 2 are AD
Describe problems with the vessel wall as cause of primary haemostasis
The vessel wall
Inherited (rare) Hereditary haemorrhagic telangiectasia Ehlers-Danlos syndrome and other connective tissue disorders
Blue sclera, especially seen in females.Atypical ears: prominent “winged”, small, round, lobeless, lobe attached to face, ears with different shapes: kidney shape, “Dumbo ears”, “Mr. Spock ears”, soft ears, with bent helix.Abnormal nose: with a lump in the union of the bone and the cartilage, nasal septum deviation,
Acquired: Scurvy, Steroid therapy, Ageing (senile purpura), Vasculitis - can all thin the blood vessel and make it weak.
Summarise the disorders of primary haemostasis
Platelets
Thrombocytopenia
Drugs
Von Willebrand Factor
Von Willebrand disease
The vessel wall
Hereditary vascular disorders
Scurvy, steroids, age
What is the key function of primary haemostasis
Formation of the platelet plug
Describe the pattern of bleeding in disorders of primary haemostasis
Typical primary haemostasis bleeding: Immediate Prolonged bleeding from cuts Epistaxes Gum bleeding Menorrhagia Easy bruising Prolonged bleeding after trauma or surgery
The primary platelet plug isn’t strong enough to stop the bleeding
Summarise the other key features of disorders in primary haemostasis
Thrombocytopenia – Petechiae
Severe VWD – haemophilia-like bleeding- due to loss of stabilisation of FVIII
Purpura and petechiae
Summarise the different tests available for the disorders of primary haemostasis
Platelet count, platelet morphology
Bleeding time (PFA100 in lab)
Assays of von Willebrand Factor
Clinical observation