Week 3 - C - Bleeding disorders - Primary&Secondary Haemostasis - Vascular/Platelet (reduction/destruction)/V.W.D - DIC/Liver/VitK/Hameophilia Flashcards
What are the components of the normal haemostatic system?
* Formation of platelet plug - primary haemostasis * Formation of fibrin clot - secondary haemostasis * Fibrinolysis * Anti-coagulant defenses This is the 4 main stages of haemostasis (not homeostasis) Once a clot is formed we start breaking it down almost immediately (fibrinolysis)
When there are problems with haemostasis, it is mainly due to primary or secondary haemostasis failure What is primary haemostasis again? (How does it occur)
Endothelial damage occurs IN response collagen and vWF are exposed on the endothelial surface and these cause platelet adhesion to the site of injury When the platelets adhere, they release chemicals which cause other platelets to come to the site of injury and this is known as platelet aggregation
Once formed platelet plug this is secondary haemostasis, clotting factors come to the positively charged platelet surface (due to the calcium on it) What is the internal pathway? What is the external pathway?
The internal pathway is where thrombin acts to amplify the clotting cascade by feeding back to increase Factors VIIIand IX (Factors VIII,IX,XI,XII) The external pathway is where there is tissue factor released from the site of damage which promotes factor VII activation (Factors VII,V,X,II)
What are the different categories of the causes of primary haemostasis failure again?
Vascular causes - vessel wall - eg endothelial injury or collagen deficiency Platelets - there is a reduced number of reduced function Von willebrand disease
What are the symptoms of primary haemostasis failure?
Symptoms - generalized bruising and purpura Epsitaxis, GI bleeds, conjunctival bleeds (cunjuctival injection), and menorrhagia Also can have intracranial bleeds if complete failure Vascular & platelet disorders lead to prolonged bleeding from cuts, bleeding into skin (bruising and purpura) and bleeding from mucous membranes (epistaxis, gums, menorrhagia) Coagulation disorders cause bleeding into joints and muscles
How can collagen deficiency occur? What are the two ways for the collagen deficiency? One is rarely seen nowadays
Collagen deficiency can occur as senile purpura - collagen content decreases with age - less platelet adherance - commonly seen bruising on extensors in response to minor trauma VitC deficiency causes a condition known as scurvy - vit C is needed for synthesis of collagen - rarely seen nowadays
As mentioned, collagen disorders are a cause of primary haemostasis dysfunction - senile pupura or scurvy These are acquired Can also have hereditary disorders Name two hereditary conditions associated with vacular abnormalities leading to bleeding? (tall people and stretchy people)
This could be Marfans syndrome and Ehlers Danlos syndrome
What is the different mutation in Ehlers danlos and marfan syndrome? What are the different features?
Ehlers danlos syndrome - usually a mutation causing abnormal collagen and elastin formation - most autosomal dominant - the defect results in very stretchy skin and also increases vascular fragility so easy bruising and abnormal wound healing Marfan syndrome - due to a mutation in the firbillin gene - autosomal dominantn - tall people with long extremities, lens and retinal detachmenet, tension pneumotorax and cardiac abnoramlities, pectus abnormalities
Most commonly vascular abnormalities are acquired vasculitis e.g. Henoch schonlein purpura What is henoch schonlein pupura? and what are the features of the disease?
It is a small vessel vasculitis mediated by IgA that is typically self limiting It produces classicial purpura on the buttocks and extensor surfaces and normally occurs in children Children may also present with abdo pain due to GI bleeds
Platelet disorders were the next cause of failure of formation of the platelet plug They can be due to reduced number of reduced fucntion Reduced number covers both increased destruction and decreased production What is decreased production due to? What is low platelets known as?
This is due to marrow problems Eg aplastic anaemia, marrow infiltration (eg malignancies or Myelofibrosis), marrow suppression (cytotoxic drugs/radiotherapy) Low platelets - thrombocytopenia
What are causes of an increased destruction of the platelets?
These would be Disseminated intravascular coagulation Autoimmune - eg immune thrombocytopenic purpura Hypersplenism HUS - haemolytic ureamic syndrome - endothelial damage triggers platelet consumption Thrombotic thrombocytic purpura - uses up platelet as well
Both HUS and TTP come under microagniopathic haemolytic anaemia (MAHA) What is this MAHA? What are 4 conditions that cause it?
Microangiopathic haemolytic anaemia is when there is intravascular haemolysis + red cell fragmentation (shcistocytes) Caused by DIC, HUS, TTP, Prosthetic heart valves
How does immune thrombocytopenic purpura occur? What is seen in the bone marow in patients with this condition?
This conditions occur because anti-platelet antibodies bind to to the platelets causing them to be removed by the reticuloendothelial system (Mostly spleen but also in liver) - typically occurs a couple of weeks post-infection In the bone marrow it is normal to see increased megakaryocyte numbers as they are trying to produce platelets to combat the shortage IMportant to rule out secondary causes
What is the treatment of ITP? Is there splenomegaly in ITP? Remember the spleen is removing the antibody bound platelets hence the thrombocytopenia Why are platelets not given when the platelet count reaches very low levles?
The treatment is none if mild If symtpomatic or platelets <20x10^9/L start the patient on prednisolone (IV steroids) Spleen is not enlarged in this condition Platelet transfusions are not given unless splenectomy has been carried out as they are quickly destroyed by the circulating anti-platelet antibodies Splenectomy considered in those unresponsive to steroids
Disseminated intravascular coagulation was another cause of primary haemostatic failure (be aware this affects both primary and secondary) How does DIC work?
DIC occurs where all the blood clotting factors and platelets are used up due to widespread activation of coagulation due to the release of procagulants into the circulation Fibrin strands fill small vessels and haemolyse passing red blood cells resulting in red cell fragments on blood film DIC causes numerous clots usually in small vessels and since both platelets and clotting factors are used up, bleeding occurs
Hypersplenism is the other cause of thrombocytopenia How is the platelet count reduced here?
Usually hypersplenism occurs due to splenomeglay as there is an increased blood cell flow into the spleen which then as it is bigger breaks more cells down resulting in penia
What is the usual cause of reduced function of the platelets? These are drug effects
Usually due NSAIDs They affect the ability of platelets to function and form a proper plug NSAIDs prevent the release of TXA2 by inhibiting the enzyme COX (cycloxygenase) meaning platelet aggregation is impaired
Vascular - Marfans, Ehlers Danlos, Scurvy, Senile purpura Reduced number - marrow failure, DIC, ITP, Hypersplenism Reduced function - aspirin Lets now talk about VWD What are the main functions of vWF? What is the inheritance of VWD?
The main mode of action of von willebrand factor are: To bring platelets into contact where there has been endothelial damage and to make the platelets bind together as well as binding to factor VIII in the blood preventing it form destruction in the circulation VWD is most commonly an autosomal dominant inheritance pattern
What are the two main types of von willebrand disease?
Type 1 where there is a deficiency of VWF - accounts for 80% of cases - quantitative deficiency and Type 2 where wVF is produced but is abnormal - qualitative deficiency Von Willebrand disease (vWD) is the most common hereditary blood-clotting disorder in humans.
In 80% of people it is just a problem producing vWFIn the second type they produce vWF that doesn’t work properly and they tend to have a greater bleeding tendency The main role of vWF is in primary haemostasis Therefore will see a primary bleeding As it will cause a primary bleeding, what are the symptoms?
Will have prolonged bleeding from cuts, bleeding into the skin (purpura and bruising) and bleeding from mucous membranes - bleeding after dental extraction, menorrhagia, epistaxis
What tests are carried out for diagnosis of von willebrand disease?
Because vWF carries factor VIII around, this factor will fall with vWF and therefore with vWF disease, will end up with a prolonged APPT time Prolonged APTT and decreased Factor VIII concentration Prolonged bleeding time Platelets are a normal level
What is the treatment of VWD in patients with mild bleeding? What is given to patients who have major bleeds or who are having surgery>
In patients with mild bleeding - desmopressin (an anti diuretic) can be given to treat the disease (desmopressin stimulates the release of vWF) In heavy bleeding or prep for surgery - vWF containing factor VIII concentrates can be given to the patient
Thrombocytopenia is the commonest cause of primary haemostatic failure Can be caused by vascular defects and vWD also Secondary haemostasis failure is due to mutliple clotting factor deficiencies or single clotting factor deficiencies State two causes of each?
Multiple clotting factor deficiencies - Vit K deficiency, DIC or liver failure Single clotting factor deficiencies - Hameophila A or B
Secondary haemostasis disorders tend to bleed into joints and muscles What are the two tests used to measure a basic coagulation screen? How are they carried out?
Prothrombin time Activated partial thromboplastin time Blood is taken from a patient into a citrate (anticoagulant) containing test tube to prevent the blood clotting * When ready to test: * PT - TF is added to test the extrinsic pathway factors (VII,V,X,II) * APTT -Kaolin is added to test the intrinsic pathway factors (VIII,IX,XI,XII)
