Lecture 4 - Bleeding and coagulation abnormalities Flashcards
Catagorise the different types of coagulation abnormalities.
Lack of platelets (thrombocytopenia)
*Idiopathic thrombocytopenia (ITP)
Disorders of platelet function
*inherited – Bernard Soulier disease & Glanzmann’s thrombasthenia
*acquired – aspirin, renal failure, haematological diseases
Vascular bleeding disorders (purpuras)
*inherited - Hereditary Haemorrhagic Telangiectasia (HHT), Inherited connective tissue disorders
*Henoch-Schonlein purpura, scurvy, senile purpura
What is thrombocytopenia?
Thrombocytopenia
Defined as a platelet count fewer than 100 x109/L (normal range 140-360 x 109/L)
Symptoms: spontaneous bleeding from mucous membranes (e.g. gums/nose)
Causes:
* Failure in production: e.g. marrow disease.
* Increase in destruction: immune-mediated (ITP – next slide)
* Abnormal distribution: Increased pooling in the spleen (not where should be)
* Dilution: massive transfusion
Give an example of a throbocytopenia.
Autoimmune (idiopathic) Thrombocytopenia Purpura (ITP)
Purpura: rash of purple spots under the skin caused by vessel haemorrhage
Symptoms: Petechiae (red spots on skin), nose bleeds
Cause: Development of antibodies against platelet self-antigens. Platelets destroyed in spleen and liver.
Acute: frequent children post viral infection or vaccination - can resolve on its own
Chronic: develop antibodies to IIb/IIIa. Platelets destroyed in spleen and liver.
Important to rule out leukaemia
Treatment can include a spleen as it is the site of platelet destruction
Describe the disorders (causes) of the inherited disorders of platelet function.
Normal -
* Binding of GP Ib-IX-V and GP IIb/IIIa receptors on platelets causes adhesion to basement membrane
* GP IIb/IIIa also participates in platelet cross-linking to form clot
(More info on previous lecture)
Bernard Soulier disease -
* Deficiency of GP Ib-IX-V receptor meaning incompetent binding of platelet to vWF
* Loss of platelet adhesion
Glanzmann’s thrombasthenia -
* Loss of function of GP IIb/IIIa receptor meaning there is binding to vWF but the adhesion is not firm and fibrin bridges don’t form.
* Loss of platelet aggregation
Symptoms: Bleeding gums, bruising, menorrhagia
Give the cuases of aquired disorders of platelet function.
- Aspirin
- Renal failure
○ uraemia – high levels of creatinine and urea in blood. Results in abnormal platelet adhesion, activation and aggregation - Haematological diseases
○ abnormal bone marrow function (e.g. leukaemia)
○ anaemias
○ complications from chemotherapy or transfusions
- Renal failure
Symptoms: Bleeding or bruising more easily
Describe asprin’s mechanism of action.
- platelet activation needs production of thromboxane A2, which is made via phospholipid pathway
- aspirin irreversibly inhibits cyclooxygenase 1 = prevents conversion of arachidonic acid to endoperoxides and thromboxane A2 - blocks downstream pathways
Irreversible - affects for lifetime of platelet
platelet aggregation is inhibited for lifetime of platelet
- aspirin irreversibly inhibits cyclooxygenase 1 = prevents conversion of arachidonic acid to endoperoxides and thromboxane A2 - blocks downstream pathways
Describe the inherited vascular bleeding disorders.
Vascular bleeding disorders (purpuras) - inherited
Hereditary Haemorrhagic Telangiectasia (HHT)
* Autosomal dominant mutation in genes associated with angiogenesis
* Increases vessel friability = solid substance break into smaller pieces under contact
* Symptoms: Small blood vessel swellings; Telangiectasia on skin (type of purpura), on: mucous membranes, internal organs, GI haemorrhage
Inherited connective tissue disorders (rare)
* Lack of connective tissue support for blood vessels or abnormal collagen = disrupted vessel structure & ineffective platelet adhesion
○ e.g. Marfan syndrome - flexible joints
* Symptoms: Easy bleeding
Describe the aquired bascular bleeding disorders.
Henoch-Schonlein purpura
* Systemic vasculitis (inflammation of blood vessels) resulting in blood vessel bursting
* IgA attacks blood vessels, often after respiratory infection
* Affects skin, joints, bowels, kidneys
* Symptoms: Raised rash, joint pain, blood in urine
Scurvy
* vitamin C deficiency (needed for collagen production)
* Symptoms: Petechiae, poor wound healing
Senile purpura
* Symptoms: Skin bruising in elderly
Due to tissue atrophy, loss of connective tissue (e.g. collagen)
List all the coagulation disorders.
Inherited coagulation disorders:
1. Haemophilia (factor VIII deficiency, haemophilia A)
2. Factor IX deficiency (Haemophilia B, Christmas disease)
3. Von Willebrand’s disease
4. Other inherited coagulation disorders caused by defects in coagulation factors
5. Fibrinogen abnormalities
Acquired coagulation disorders
6. Disseminated Intravascular Coagulation (DIC)
7. Vitamin K deficiency
8. Liver disease
9. Acquired haemophilia
10. Thrombophilia
What is Haemophilia A
- X-linked - recessive
- Factor VIII (antihaemophilic factor) deficiency
- Affects 30-100 per million people. Most common haemophilia
- Often family history but 1/3 of cases arise from spontaneous mutations
- Symptoms: Excessive bruising and bleeding during operations
- Prolonged APTT test (intrinsic pathway)
- Bleeding time and PT/INR normal
*RBC count and haemoglobin can be low in patients with haemophilia after prolonged or heavy bleeding but normally the CBC is normal.
What is haemophilia B
- X linked – recessive
- Factor IX (Christmas factor) deficiency
- Affects 3-4 per 100,000 people
- Symptoms: Clinical features same as Haemophilia A
- Prolonged APTT test (intrinsic pathway)
*Bleeding time and PT/INR normal
What is von Willebrand’s disease
- vWF Promotes adhesion of platelets to subendothelial matrix and carries factor VIII.
- vWD = reduced level or abnormal function of vWF
- Low amounts of factor VIII = abnormal platelet adhesion
- Symptoms: Spontaneous bleeding (nose bleeds, menorrhagia etc.)
*APTT prolonged
Describe the causes of other inherited coagulation disorders.
- caused by defect in other coagulation factors (V, VII, XI, XIII)
- Fibrinogen abnormalities (less protein or abnormal protein)
- Disorders of inhibitors of coagulation pathway = clots get too big, aggregation tests will be faster than usual
e.g. thrombophilia (too much factor II)
What is Disseminated intravascular accumulation?
Disseminated intravascular accumulation
* Widespread intravascular fibrin formation = Coagulation factors and platelets used up
* Symptoms: Bleeding, large vessel thrombosis, haemorrhagic tissue necrosis
* Causes: Widespread endothelial damage e.g. incompatible blood transfusion, septicaemia, viral infection, malignancy, surgery, burns …
* FDPs = fibrin degradation products have anticoagulant activity = risk of severe bleeding
* Poor tissue perfusion = risk of gangrene
* APTT, PT/INR and TT increased
Treated with FFP
Describe Vitamin K deficiency.
Vitamin K needed for formation of factor II, VII, IX and X
* Derived from intestinal flora and vegetables in diet
* Fat-soluble vitamin absorbed through lining of gut, bile needed for fat absorption
* Cause: Malabsorption; malnourishment; warfarin therapy (inhibits vit K)
Haemorrhagic Disease of the Newborn
* Newborns have sterile gut (no intestinal flora)
* Breast milk low in vitamin K
* Liver cells immature
* Symptoms: Easy bruising, blood in stool or urine
Vitamin K now given to newborns via subcutaneous injection
