Formative of the Week 2 Flashcards
A student has cut himself after peeling vegetables. He has been investigated and has a thrombocytopenia. Why is his platelet count low?
Failure of production or increased destruction
Failure of production - bone marrow failure (lymphomas, leukemias, metastatic cancer) - if this is the cause, note that platelets do not fall in isolation, usually get a pancytopenia.
Increased destruction - methotrexate, autoimmune thrombocytopenia purport, hypersplenism - if this is the cause, usually an isolated thrombocytopenia
Why are platelets so important?
Platelets are involved in primary haemostasis
How are platelets normally formed in my body?
They bud off megakaryocytes
What clinical signs and symptoms may I have had on my body because of my thrombocytopenia?
Bleeding
Haemorrhage
Mucosal bleeding (epistaxis, GI bleed)
Excessive bleeding from cuts
Purpura
Fundal haemorrhages in eyes
What are the main causes of problems with primary haemostasis?
Von willebrand disease
Impaired platelet function (anti platelet medications like aspirin, clopidogrel, NSAIDs in younger people)
Low platelet count
Vasculitis
How would I initially have been investigated if I had problems with primary haemostasis?
Platelet count (only screening for primary haemostasis)
Platelet function (history - drugs that interfere with platelet function)
What is haemophilia?
A genetic condition that leads to a problem with secondary haemostasis and the blood clotting factors
X-linked recessive disorder, so males mostly affeced
Factor VIII deficiency - Haemophilia A
Factor IX deficiency - Haemophilia B
In what way does having haemophilia affect haemostasis?
Compromises secondary haemostasis so that you cannot form fibrin mesh on top of platelet plug. Cannot clot in larger bleeds
Why would I not have prolonged bleeding following a superficial cut with a knife if I have haemophilia?
The disorder does not involve primary haemostasis and platelets, which is what would be fixing the bleeding in this case. Normal platelet count means small bleeds can be fixed
In what way would my clinical symptoms and signs in haemophilia differ from a friend with thrombocytopenia?
Spontaneous bleeding, swelling
Haemarthroses in knees and ankles
Recurrent bleeds in same joint (target joint)
What blood tests would be useful in identifying the abnormality in blood clotting system in haemophilia?
APTT and PT, APTT is affected in haemophilia
factor VIII and IX serum assay can distinguish between factors VIII and IX
A 28 year old barman presents to A&E because he is concerned about major bruising that has developed over his shoulder and chest wall after a fight.
On examination he is noted to have blood shot eyes as well as bruising over his shoulder. In addition, his liver is noted to be enlarged.
On further questioning he admits to an alcohol intake of 60-70 units per week
How has his haemostasis been affected?
Problem with primary and secondary haemostasis with thrombocytopenia (primary haemostasis) and prolonged APTT and PT (secondary haemostasis
A 28 year old barman presents to A&E because he is concerned about major bruising that has developed over his shoulder and chest wall after a fight.
On examination he is noted to have blood shot eyes as well as bruising over his shoulder. In addition, his liver is noted to be enlarged.
On further questioning he admits to an alcohol intake of 60-70 units per week
Why is his platelet count low?
Alcohol in large quantities can have a toxic effect on bone marrow and reduced production. Often usually diet is poor in alcoholics and low in folic acid - megaloblastic anaemia + pancytopenia
Low platelets in liver disease - when liver becomes cirrhotic, blood cannot get into liver, and this causes portal hypertension. Blood backs up into spleen -> hypersplenism -> increase destruction of platelets because of hypersplenism secondary to liver disease
A 28 year old barman presents to A&E because he is concerned about major bruising that has developed over his shoulder and chest wall after a fight.
On examination he is noted to have blood shot eyes as well as bruising over his shoulder. In addition, his liver is noted to be enlarged.
On further questioning he admits to an alcohol intake of 60-70 units per week
Explain the coagulation abnormalities
Cirrhotic liver does not create clotting factors that is needed.
Blood clotting factors made in the liver, not only vitamin K dependent ones. If liver is not synthesising proteins then all coagulation factors dry down. Failure of synthesis due to liver disease
What role does vitamin K play in haemostasis?
Vitamin K is important in clotting factor II, VII, IX and X synthesis (1972)
Vitamin K is involved in enzyme reaction that leads to carboxylation of these clotting factors
They need to be carboxylated in order to become negatively charged. platelets are phospholipids and negatively charged, platelets release calcium to stick to that, positively charged surface and coagulation factors need negative charge to sit on positive.
How may the body become deficient in vitamin K dependent coagulation factors?
Poor diet (green leafy vegetables, bacterial synthesis produces half of vitamin K)
Malabsorption (Crohn’s - vitamin K is a fat soluble vitamin and needs bile salts to be absorbed)
Gallstones can prevent absorption of vitamin K
Cancer at head of pancreas wraps around biliary tree and causes obstructive jaundice
Haemorrhage disease of the newborn (babies don’t get vitamin K in breast milk, don’t get bacterial synthesis because clean bowels)
Warfarin (antagonist of vitamin K)
Mrs McIvor is a 64 year old woman who has been
Admitted for an elective cholecystectomy. She has longstanding hypertension and has been plagued by varicose veins since she had a DVT after her fourth child. She is 1.64m tall and weighs 100kgs.
What is a thrombus?
A blood clot
What is the difference between an arterial and venous thrombosis?
Venous thrombosis - low pressure system and stasis of blood.
Arterial thrombosis - high pressure system, atherosclerosis.
How does arterial thrombosis happen?
Hypertension, smoking, high cholesterol, obesity -> damage to endothelial wall under high pressure, cholesterol in wall, atherosclerosis. IF plaque ruptures, platelets stick to that and occlude vessel. Platelet rich thrombus (anti platelet agents prevent that)
What pathological mechanisms increase the risk of venous thrombosis
Virchow’s triad - vessel wall (valvular) damage, hyper coagulability (increased level of coagulation factors - in particular acute phase proteins in infection, malignancy; VIII, tissue factor, fibrinogen) and stasis of blood
How would you assess Mrs McIver’s thrombotic risk ?
Mrs McIvor is a 64 year old woman who has been
Admitted for an elective cholecystectomy. She has longstanding hypertension and has been plagued by varicose veins since she had a DVT after her fourth child. She is 1.64m tall and weighs 100kgs.
Previous DVT (damage to valves causes high risk)
obesity (immobility)
Adipose cells - secrete cytokines Il-6 and pushes up coagulation factors (hypercoaguability). Going fr a surgery. Hypertension
What does thromboprophylaxis mean and what options for post-operative thromboprophylaxis would you consider in Mrs McIver’s case ?
Heparin
What clinical signs you would look for if you
were concerned that Mrs McIver had developed a DVT and why might this be a problem ?
Unilateral red swollen warm leg
Do an USS scan for DVT
How does heparin work?
Blocks factors II and Xa
Activates antithrombin 3 (natural anticoagulant - binds to thrombin which is essential for haemostasis and fibrin clot)
Antithrombin switches off haemostasis when we have achieved that. Heparin potentiates natural reaction
LMWH - potencies antithrombin, and inhibits factors Xa (don’t need to monitor). Heparin works in minutes
