Bleeding Disorders Flashcards
What are the 3 common things that can be affected that cause abnormal bleeding?
1 - blood vessel disorders
2 - platelet disorders
3 - coagulation disorders (clotting factors)
Although uncommon, what is Hereditary Haemorrhagic Telangiectasia as a form of blood vessel disorder?
- Haemorrhagic = violent bleeding
- Telangiectasia = end of blood vessels dilate
- blood vessel dilated and swell casuing bleeding
- common in skin and mucous membranes
- present with nose or GI tract bleeds
Inherited collagen abnormalities can cause dysfuctional blood vessels. What happens in this instance?
- Ehlers Danlos Syndrome is one of most common
- small blood vessels are weak and can rupture
Scurvy is an acquired disorder that can affect blood vessels. How can scurvy cause this?
- hypertophy of fragile blood vessels
What is the most commonly acquired cause of dysfuctional blood vessels?
- ageing
- collagen loses it properties and blood vessles become damaged
What is the normal range for platelets?
- 150-400 x109/L
- collagen is exposed to blood and activates platelets
- this triggers coagulation cascade
What is thrombocytopenia?
- low platelet count <150
- BUT symptoms wont present until <10
In relation to bleeding, what do patients with platelet disorders generally present with?
- superficial
- epitaxis (nose bleeds), GI tract bleeds, bruising
- petechial rash (red dots on skin)
What are the 4 most common causes of acquired platelet dysfunction?
- bone marrow disorders (dysfunctional platelets)
- immune thrombocytopenia (low platelets)
- drug related (damaged platelets)
- disseminated intravascular coagulation (DIC)
What is immune thrombocytopenic purpura?
- immune cells attack platelets, reducing their numbers
Does immune thrombocytopenic purpura affect young or older people more?
- more common in children who have good outcomes
- adults less affected but need more support to recover
What are the treatment options for patients with chronic immune thrombocytopenic purpura?
- steroids
- immunoglobulins
- occasionally splenectomy
Drugs are the most common causes of acquired platelet dysfunction. What drugs have been linked with this?
- drugs (asprin, clopidogral, NSAIDs)
Glanzmann’s thrombocytopenia is an inherited cause of platelet disorders. How does this affect platelet function?
- leads to Gp 2b/3a deficiency
- Gp 2b/3a binds fibrinogen
Bernard-Soulier syndrome is an inherited cause of platelet disorders. How does this affect platelet function?
- leads to Gp1b deficiency
- Gp1b binds to Von Willebrands factor
What is haemophilia?
- genetic disorder
- affects bodies ability to make blood clots
What is the most common inherited blood coagulation abnormality?
- haemophilia
- BUT generally not that common
Haemophilia A (which is the more common form) Haemophilia B are the 2 most common inherited blood clotting abnormality. What factors are affected in each?
- Haemophilia A = Factor VIII (8) deficiency
- Haemophilia B = Factor IX (9) deficiency
What does X linked recessive mean?
- a mutation in a gene on the X chromosome that will always causes the phenotype to be always expressed in males
Are men and women equally affected by haemophilia?
- no
- women can only be carriers
- if men have one gene they have disease
- men cannot transmit disease
What are some of the common presenting symptoms of haemophilia?
- spontaneous bleeding into joints and muscles
- joint disease
- famility history 1:3 chance
The activated partial thromboplastin time (APTT) is a test to determine clotting pathways. What aspects of the clotting cascade can the APTT test assess?
- intrinsic pathway
- used to assess heparin efficacy
The prothrombin time (PT) is a test to determine clotting pathways. What aspects of the clotting cascade can the PT test assess?
- extrinsic pathways
- important with epithelial surfaces due to tissue factor
- used to assess the efficacy of warfarin
What is does the international normalised ratio (INR) mean in clotting function?
- patients prothrombin time (PT) is compared with normal (PT)
What is the thrombin time (TT) test?
- measures of the time taken for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added
What is bleeding time?
- patient has a superficial cut
- time taken for bleeding to stop
In a patient with haemophilia they are likley to have a prolonged activated partial thromboplastin time (APTT), generally what factors from the coagulation cascade cause this?
- factors VIII (8), IX (9), XI (11) and XII (12)
- haemophilia A and B are affected factors 8 and 9, respectively
- all from intrinsic pathway
In a patient with haemophilia they are likley to have a normal prothrombin time (PT), why is this?
- haemophilia is caused by dysfunctional factors VIII (8) and IX (9)
- prothrombin time (PT) does not measure this
In haemophilia disease, do all patients have the same levels of factors VIII (8) and IX (9)?
- no
- severe haemophilia = <1%
- moderate haemophilia = 1-5%
- mild haemophilia = >5%
How is haemophilia generally treated?
- recombinant DNA used to create factors VIII (8) and IX (9)
- replace missing factors
What is the Von Willebrand Disease?
- common genetic condition that impairs blood clotting
- Von Willebrand factor helps blood cells stick together (clot) when you bleed.
What is the most common blood clotting abnormality?
- Von Willebrand disease (VWD)
What does autosomal dominant mean?
- only one form of mutated gene is required to cause disease
What are the 2 main roles of the Von Willebrand factor?
1 - binds platelets to subendothelial collagen
2 - carries VIII in the plasma
How can Von Willebrand disease present?
- Mucocutaneous bleeds
- nosebleeds
- menorrhagia
In Von Willebrand disease what can we expect to see in the activated partial thromboplastin time (APTT = intrinsic) and prothrombin time (PT = extrinsic)?
- prolonged APTT due to VIII
- normal PT
In Von Willebrand disease what can we expect to see in regards to platelets?
- normal or low platelet number
- defective platelet function
How can we treat Von Willebrand disease?
- Desmopressin (DDAVP) = increases synthesis/release
- Anti-fibrinolytics (eg Tranexamic acid) = reduce thrombus breakdown
- Plasma products need to be replaced vWF and Factor VIII
What is the most common acquired coagulation disorders?
- chronic liver disease
- synthesis of clotting proteins is reduced
Which factors in the coagulation cascade are dependent on vitamin K?
- 1972 was the diSCo era
- factors 2, 7, 9 and 10
- proteins S and C
Vitamin K is an important fat soluble vitamin which most people consume enough of. Even if a patient is consuming sufficient vitamin K, what can cause you to have low levels?
- fat malabsorption as vit K is fat soluble
- biliary obstruction means no bile to digest fat
What is Disseminated Intravascular Coagulation (DIC)?
- disease that causes abnormal blood clotting
- clotting becomes over active
What is the most common cause of Disseminated Intravascular Coagulation (DIC)?
- scepticaemia (blood infection)
In addition to septicaemia, what other diseases can cause Disseminated Intravascular Coagulation (DIC)?
- Acute promyelocytic leukaemia
- Cancer, Trauma
- Pregnancy complication
What is the most common trigger that sets off Disseminated Intravascular Coagulation (DIC)?
- increased tissue factor (TF)
- TF triggers clotting factors
In Disseminated Intravascular Coagulation (DIC) what would we expect to see in activated partial thromboplastin time (APTT) and prothrombin time (PT)?
- both would be prolonged
In Disseminated Intravascular Coagulation (DIC) what would we expect to see in figrinogen and platelet numbers?
- both would be low
In Disseminated Intravascular Coagulation (DIC) what would we expect to see in a d-dimer test?
- d-dimer is a breakdown product of blood clots
- this would be increased in DIC
How can we treat Disseminated Intravascular Coagulation (DIC)?
- treat the underlying cause (antibiotics for septicaemia)
- treat with coagulation factors
