Lecture 9 - Bleeding Disorders part 2 Flashcards
What are purapura?
Bleeding into the skin due to reduced platelet count
What are ecchymoses?
Large purapura
What are Petechiae?
Small pinpoint sites of bleeding from capillaries
What are key factors to take into consideration for a clinical assessment?
- Location of bleeding; mucosal, joints/muscles, skin, GI tract
- Pattern of bleeding: frequency, severity, predisposing events
- Recent drug history
- Family history
What tests can be done to do a haemostatic assessment?
- Platelet count and morphology
- Coagulation screen: APTT, PT, fibrinogen (TCT)
- Plateley functioning test: PFA-100
- specialst assays - e.g. vWF, platelet function, coagulation factor assays
What can cause bleeding?
- Defective vessel wall (only a small number of conditions)
- Platelet disorders: e.g. Thrombocytopenia, where the bleeding increases progressively if <100e9/L (ref range: 150-400e9/L). Or there can be defective platelet function, which can be due to drugs inhibiting their function or from inherited conditions.
- vWF disease, where circulating vWF have a reduced production (type l), or were abnormal vWF are produced (type ll)
- Or bleeding can be caused by defective coagulation (Many conditions, inherited or acquired)
What are some aquired vascular disorders
- Easy bruising - women and childeren
- Purapura of old age (Senline purapura) - this is caused by atrophy of the supporting connective tissue, and results in bruising in the skin
- Purapura from prologed steroid medication, due to reduced anabolism of supporting connective tissue and continued catabolism - causing the tissue turnover to be unbalanced
- Scurvy - caused by defective collagen production due to lack of vitamin C, causing vascular fragility
- Severe atheroscleoris which weakens the arterial wall - this can cause an aneurysm which may rupture, causing a massive arterial haemorrhage
Desribe how purapura can occur in association with an infection
Purapura can occur due to vascular damage from immune complexes. IgG+antigen+complement complexes get trapped in the basement membrane of vessels, leading to inflammation.
Briefly describe what happens in a PFA-100
Platelets are activated by collagen-adrenalin (or collagen-ADP) coating in tubing, causing adhesion.
This causes the platelets to have a release reaction, this causes synthesis of thromboxane A2, which activates more platelets.
Activation of the GPllb-lla receptor results in aggregration of large numbers of platelets to produce a platelet plug that occludes the lumen
What are the four causes of thrombocytopenia?
- Reduced production - Hereditary or acquired (much more common)
- Shortened survival - acquired disorders are common. There can be activation/consumption of platelets by coagulation, antibodies etc
- Dilutional - Massive transfusion. Commonly occurs after 5-10L volume replacement. Dilutional thrombocytopenia is treated with transfusion of platelet concentrates.
- Sequestration in the spleen - 30-80% of platelets pool in pathologically enlarged spleen (uncommon)
In relation to bleeding, what can occur in acute and chronic severe liver disease?
- Reduced production of Vitamin K-dependant faactors is the dominant effect (ll, Xll, lX, X))
- Thrombocytopenia is quite commonly caused by this aswell
What effects does a reduced production of vitamin K dependant coagulation factors due to liver disease have?
- It increases PT & APTT (reduced thrombin burst)
- It reduces antithrombin, Protein C & S partly corrects thrombin burst
- in servere cases fibrinogen is reduced
- Reduced clearance of t-PA by liver may result in increased fibrinolysis
What are the main causes of thrombocytopenia?
- Reduced production
- Reduced survival
- Haemodilution after massive haemorrhage
- Splenic sequestration
Describe how a clot is broken down
(Plasminogen is bound tightly to fibrin)
t-PA is secreted by endothelial cells, and this binds to fibrin and activates plasminogen to plasmin. This results in an unstable clot that is cleaved to FDPs from fibrin.
PAI-1 inactivates t-PA
How is fibrinolysis prevented?
Tranexamic acid blocks the binding of tPA and plasminogen to fibrin resulting in a stable clot
What does factor Vlll bind to to prevent it from breakking down
Factor Vlll binds to vWF because its not very stable by itself
What’s the difference between type 1 and 2 Von Willebrand Disease?
Type 1 - reduced production of vWF protein
Type 2 - Production of abnormal protein
What can occur to Factor Vlll in vWD?
There will be a mild reduction in FVlll since vWF is needed as a carrier protein for FVlll
(FVlll stability is enhanced by vWF)
How can vWD present clinically?
Mucosal bleeding: frequent and prolonged epistaxis, heavy and prolonged menstruation
Easy bruising: Increased size and frequency of bruises
Prolonged bleeding: From cuts/ wounds/ dental treatment/ surgery
What are the diagnostic tests for vWD?
- Can do a bleeding time and PFA-100 test, checking to see if they’re prolonged
- They may be normal or reduced vWF antigen (Reduced amount = type 1, normal amount of vWF protein but abnormal function = type 2)
- vWF functional acitivtiy will always be reduced
- Mildly reduced Factor Vlll
How can we treat vWD?
There are two parts to the treatment.
Firstly we boost or inject vWF/FVlll. This gives a temporary benefit for 2-8h. We can also inject desmopressin which boosts the endothelial release vWF. OR we can give them blood product (FVlll-vWF biostate)
In the second part of treatment we inhibit fibrinolysis. We use transexamic acid (Cyklokapron)
Describe some features of haemphilias
Haemophilia is an X-linked recessive disorder. This results in reduced functional levels in FVlll (Haemophilia A), or FlX (Haemophilia B)
Males are mainly effected (since X-linked disoder) Females rarely affected, as they would need to be homozygous
How may haemophilia present in the clinic?
- Most present with joint bleeding (haemoarthrosis), which results in arthritits unless FVlll levels maintain at adequate levels during daytime in childhood
- Muscle bleeding (resulting in muscle fibrosis and calcification if not treated)
- Bleeding in kidney, brain, skin (Bruises) etc
The increased bleeding in haemophilia is caused by a reduced thrombin burst, as the fibrin strands are thinner and weaker than normal and are easily disrupted physically & by fibrinolysis
