Disorders of Haemostasis Flashcards
What is abnormal bleeding?
- Easy bruising (e.g. w/o apparent trauma)
- Gum bleeding
- Frequent nosebleeds (and duration >10 min)
- Bleeding after tooth extraction
- Post operative bleeding
- Heavy, prolonged or recurrent bleeding after surgery or dental extractions.
- 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.
In women - Menorrhagia (e.g requiring treatment)
- Post partum bleeding
- Family history
What categories of causes can cause problems with 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, synthetic defect, inhibition
(more commonly due to drugs than do to genetic defects)
What factors are important for platelet aggregation?
ADP, thromboxane
-> the first step in primary heamosuasis is adhesion and then the platelets are activated more which leads to aggregation.
How do platelets bind to WVF and collagen
WVF: Glp1b / Gp1b
Collagen: Glp1a, GPVI, alpha1beta1
Name some disorders of primary haemostasis related to thrombocytes
Low numbers: “thrombocytopenia”
- BM failure eg: leukaemia, B12 deficiency
- Accelerated clearance eg: immune (ITP), DIC.
- pooling and destruction in an enlarged spleen
Impaired function
- Hereditary absence of glycoproteins or storage granules
- Acquired due to drugs: aspirin, NSAIDs, clopidogrel
What are the 3 main factors that can cause problems with primary haemostasis?
- platelets
- WVF
- Vessel Wall
auto-ITP
Autoimmune thrombocytopenic purpura
- very common cause of thrombocytopenia
- ABs cover the platelet and then it is phagocytksed by macrophages.
What are the 3 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
Hereditary platelet defects
- missing surface glycoproteins (Gp2b/3a; Gp1b)
- missing granules (i.e. dense granules)
Examples:
- Glanzmann’s thrombasthenia (recessive severe bleeding)
- Bernard Soulier syndrome (GPIB binding to VWF is impaired)
- Storage Pool disease (problem with dense granule release)
VWF - what can lead to problems with haemostasis
VWD:
- Hereditary decrease of quantity +/ function (common)
- Acquired due to antibody (rare)
VWD is usually hereditary
- Deficiency of VWF (Type 1 (not recessive, you don’t make enough) or 3 (recessive, you don’t make any))
- VWF with abnormal function (Type 2)
What are the functions of VWF in haemostasis?
- Binding to collagen and capturing platelets
- Stabilising Factor VIII
- Factor VIII may be low if VWF is very low
Problems with the vessles leading to problems with primary haemostasis
Inherited (rare) Hereditary haemorrhagic telangiectasia Ehlers-Danlos syndrome and other connective tissue disorders
Acquired:
- Scurvy
- Steroid therapy
- Ageing (senile purpura)
- Vasculitis
Ehlers-Danlos syndrome
(stretchy velvety skin. 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)
Briefly summarise the disorders of primary haemostasis
Platelets
- Thrombocytopenia
- Drugs
Von Willebrand Factor
- Von Willebrand disease
The vessel wall
- Hereditary vascular disorders
- Scurvy, steroids, age
Summarise the typical features of primary haemostasis disorders
Typical primary haemostasis bleeding:
- Immediate
- Prolonged bleeding from cuts
- Epistaxes
- Gum bleeding
- Menorrhagia
- Easy bruising
- Prolonged bleeding after trauma or surgery
- Mucotaneous: gums, nose, menstrual bleeding.
Thrombocytopenia – Petechiae
Severe VWD – haemophilia-like bleeding
Tests for disorders of primary haemostasis
- Platelet count, platelet morphology
- Bleeding time (PFA100 in lab)
- Assays of von Willebrand Factor
- Clinical observation
FVI
activated factor V
What are the effects of haemophilia on thrombin production
- very reduced thrombin production
- thrombogram curve Is a lot flatter
Why is coagulation important in injuries?
- The role of the coagulation cascade is to generate a burst of thrombin which will convert fibrinogen to fibrin
- Deficiency of any coagulation factor results in a failure of thrombin generation and hence fibrin formation
- platelet plug is enough for small injuries but for bigger ones you need fibrin.
- The primary platelet plug is sufficient for small vessel injury
- In larger vessels it will fall apart
- Fibrin formation stabilises the platelet plug
Summarise disorders of coagulation
Deficiency of coagulation factor production
- Hereditary failure of production
- Factor VIII/IX: haemophilia A/B - Acquired
- Liver disease
- Dilution
- Anticoagulant drugs – warfarin
Increased consumption
- Acquired
- Disseminated intravascular coagulation (DIC)
- Immune - autoantibodies (very rarely there are ABs to clotting factors)
Consumption
- Disseminated intravascular coagulation
increased consumption
- Generalised activation of coagulation – Tissue factor
- Associated with sepsis, major tissue damage, inflammation
- Consumes and depletes coagulation factors
- Platelets consumed
- Activation of fibrinolysis depletes fibrinogen
- Deposition of fibrin in vessels causes organ failure
DIC - how do you treat it?
- treat DIC by treating the underlying cause
- you can support by replacing these things but you cannot turn the process off without removing the cause
Name 4 coagulation factor deficiencies and what problems they cause.
Factor VIII and IX (Haemophilia)
- Severe but compatible with life
- Spontaneous joint and muscle bleeding
Prothrombin (Factor II)
- Lethal
Factor XI
- Bleed after trauma but not spontaneously
Factor XII
- No excess bleeding at all
=> not all factor deficiencies are the same.
Acquired coagulation disorders - coagulation factor production
Liver failure – decreased production
- Most coagulation factors are synthesised in the liver
Dilution
- Red cell transfusions no longer contain plasma
- Major transfusions require plasma as well as rbc and platelets (otherwise you have a dilutional effect)
Anticoagulant drugs
- e.g. warfarin
Summarise DIC
= disseminated intravascular coagulation
- commonly seen with sepsis, obstetric problems, cancer.
- there is an unregulated activation of the coagulation system
- all the clotting factors are being used up, platelet activation
- blood clots form in small vessels
- fibrin in organs can cause organ failure
- because all coagulation factors are used up you get bleeding
- you have uncontrolled coagulation and bleeding
- treat it by treating the cause.
