Bleeding disorders Flashcards
What two categories of bleeding disorder are there
Bleeding
Thrombosis
What categories of bleeding are there?
Primary haemostasis failure
Secondary haemostasis failure
What components of primary haemostasis can be defective?
Collagen (vessels)
Platelets
von WIllebrand Factor
What general symptoms can collagen defects cause?
East bruising and bleeding into the skin
Rarely bleed from mucous membranes
What are some hereditary collagen defects?
Marfans
Hereditary haemorrhagic telangiectasia (HHT)
How is hereditary haemorrhagic telangictasia (HHT) inehrited?
Autosomally
Describe HHT
Capillary dilation gives small red dots that blanch- mainly in nose and GI tract
What are some symptoms of HHT?
Epistaxis
GI bleeds- lead to iron deficient anaemia
What are some acquired causes of collagen defects?
Vasculitis Scurvy Senile purpura Steroid induced Infection- Meningococcal septicaemia Henoch–Schönlein purpura
Describe Henoch-Schonlein purpura
Type III hypersensitivity (immune complex) caused but acute URTI.
Ab against cell wall
What are some symptoms of Henoch–Schönlein purpura?
Mainly in children
Purpura in legs and buttocks, abdo pain, arthritis, hematuria, glomerulonephritis
What infection classically gives purpura due to damage to cell walls?
Meningococcal septicaemia
What symptoms characterize platelet defective/deficient primary haemostatic failure?
Purpura and mucosal bleeding.
How may platelets cause uncontrolled bleeding?
Reduced number (thrombocytopenia) Reduced platelet function
What does the platelet count look like in patients with reduced platelet function?
Normal or increased
How does the bleed time change in patients with reduced platelet function?
Prolonges
What are some hereditary causes of reduced platelet function?
Glanzmann’s thrombasthenia
Bernard–Soulier syndrome
Storage pool disease
Describe Glanzmann’s thrombasthenia
Lack GPIIb-IIIa on platelets therefore fibrinogen cannot bind and cause aggregation.
Describe Bernard–Soulier syndrome
Lack GPIb therefore cannot bind to vWF.
What are some acquired causes of reduced platelet function?
Drugs- Aspirin, NSAIDs
Renal failure- Urea can interfere with platelet function
What is a reduced platelet number called?
Thrombocytopenia
What is the commonest cause of primary haemostatic failure?
Thrombocytopenia
Is thrombocytopenia usually hereditary or acquired?
Acquired
How do you investigate thrombocytopenia?
Bone marrow biopsy
What can cause thrombocytopenia?
Reduced platelet production
Increased platelet destruction
Hypersplenism
How can hypersplenism cause thrombocytopenia?
Sequester platelets there
What can cause decreased platelet production?
Bone marrow failure
What can increase platelet destruction?
Coagulopathy
Immune destruction
What coagulopathies can cause increased platelet destruction?
Disseminated intravascular coagulation (DIC)
Thrombotic thrombocytopenic purpura (TTP)
Describe thrombotic thrombocytopenic purpura
Platelet consumption leads to profound thrombocytopenia.
What causes thrombotic thrombocytopenic purpura?
Endothelial damage and microvascular thrombosis (due to inability to degrade vWF).
What are some risk factors for thrombotic thrombocytopenic purpura?
Pregnancy Oral contraceptive SLE Infection Clopidogrel
What are some symptoms of TTP?
Purpura Fever Fluctuating cerebral dysfunction Haemolytic anaemia with red cell fragmentation/Haemolytic Urea Syndrome (HUS) Renal Failure
How do you diagnose TTP?
Normal coag screen
Raised lactic dehydrogenase (LDH)- Due to haemolysis
How do you treat TTP?
Plasma exchange
Cryoprecipitate and FFP
Pulsed intravenous methylprednisolone
What immune conditions can cause a thrombocytopenia?
Immune thrombocytopenic purpura (ITP)
Post-transfusion purpura (PTP)
Describe post-transfusion purpura (PTP)
Alloantibodies against platelets
2-12 days after transfusion
Mainly in women immunised by pregnancy
Describe immune thrombocytopenic purpura (ITP)
Immune destruction of platelets by macrophages
What are the types of immune thrombocytopenic purpura (ITP)?
Child
Adult
Describe ITP in children
Onset 2-6YO
Acute onset with mucosal bleeding- sometimes following viral infection.
Severe but rarely life threatening.
Describe ITP in adults
More chronic than in children.
More common in women and associated with other autoimmune disease (SLE, thyroid and autoimmune haemolytic anaemia), malignancy and infection.
How do you treat ITP in children?
Only treat in very symptomatic
Short course high-dose prednisolone
i.v. IgG
How do you treat IPT in adults?
Oral prednisolone 1mg/kg body weight body weight
Splenectomy
i.v. IgG
Platelet transfusion- only in extreme cases
What are the symptoms of ITP?
Easy bruising, purpura, epistaxis and menorrhagia are common
Major haemorrhage is rare
Splenomegaly is rare
How do you diagnose ITP?
Blood count normal bar for thrombocytopenia
Normal or increased numbers of megakaryocytes
Platelet antibodies
In what two ways can vWF be affected to cause a thrombocytopenia?
Decreased volume
Decreased function
Describe hereditary vWF defects causing thrombocytopenia
Autosomal dominant
Common
Variable severity
Form Ab against vWF
What is a secondary haemostasis failure also known as?
Coagulopathy
What are the two categories of coagulopathy?
Multiple clotting factor deficiency
SIngle clotting factor deficiency
Are multiple clotting factor deficiencies normally inherited or acquired?
Acquired
How do you test for multiple clotting factor deficiencies?
Prolonged PT and APTT
What are some causes of multiple clotting factor deficiencies?
Disseminated intravascular coagulation (DIC)
Liver failure
VK deficiency
Warfarin therapy
How can warfarin therapy cause multiple clotting factor deficiencies?
Antagonised VK
Which coag factors are needed for VK to make?
II, VII, IX, X, Protein C and Protein S
Where do we get VK from and how is it absorbed?
Diet (green leafy veg)
Bowel bacteria
Absorbed in upper intestine and needs bile salts
What can cause VK deficiency?
Poor dietary intake
Malabsorption- Antibiotic therapy and obstructive jaundice
Vitamin K antagonists (warfarin)
What are some symptoms of VK deficiency?
Bruising
Haematurea
GI bleed
Cerebral bleed
How do you treat a VK deficiency?
Phytomenadione (vitamin K1) 10mg IV for minor bleed
What is VK deficiency called in newborns?
Haemorrhagic disease of the newborn
What is Haemorrhagic disease of the newborn?
VK deficiency of newborn
Treat with VK shot
Describe Disseminated intravascular coagulation (DIC)
Excessive and inappropriate activation of the haemostatic system- primary, secondary and fibrinolysis- that then leads to bleeds.
What can cause DIC?
- Malignant disease
- Septicaemia (e.g. Gram-negative and meningococcal)
- Haemolytic transfusion reactions
- Obstetric causes (e.g. abruptio placentae, amniotic fluid embolism)
- Trauma, burns, surgery
- Other infections (e.g. falciparum malaria)
What organs are most commonly affected in DIC?
Brain, skin and kidneys
What are some symptoms of DIC?
Acutely ill and shocked
No bleeding at all to profound haemostatic failure with widespread haemorrhage
Bleeding may occur from the mouth, nose and venepuncture sites and there may be widespread ecchymoses
Thrombotic events
How do you diagnose DIC?
Clinical Prolonged PT, APTT and TT Reduced fibrinogen High levels of D-Dimer Severe thrombocytopenia Fragmented RBC
How do you treat DIC?
Treat underlying condition
Maintain blood volume and tissue perfusion
Transfusions of platelet concentrates, FFP, cryoprecipitate and red cell concentrates is indicated in patients who are bleeding
Do NOT use tranexamic acid!!!
What things in the history suggests a generalised haemostatic defect?
Bleeding from multiple sites
Spontaneous bleeding
Excessive bleeding after injury
What things suggest a platelet bleeding disorder?
Easy bruising
Spontaneous bleeding from small vessels
Bleed into skin- purpura (petechiae and ecchymoses (bruise))
Bleeding often occurs from mucous membrains
What things suggest a coagulopathy disorder?
Bleeding after surgery or injury
Haemoarthrosis and haemotomas
What lab tests can be used to investigate a bleeding disorder?
Blood count/film
Bleed time
Coagulation tests
What are some coagulation tests?
Prothrombin time (PT) Activated partial thromboplastin time (APTT) Thrombin time (TT)
How is blood stored for a coagulation test?
Blood collected in citrate (neutralizes Ca ions to prevent clotting)
Describe thrombin time test
Add thrombin to plasma
Normal 12-14s
Prolonged in fibrinogen deficiency, heparin etc
Describe Activated partial thromboplastin time test
Add surface activator, phospholipids and Ca to plasma.
Normal 30-50s
Measures V, VIII, IX, X, XI, XII, prothrombin and fibrinogen. Not dependent on VII.
Intrinsic coagulation
Describe Prothrombin time test
Add tissue factor (thromboplastin) and Ca to plasma.
Normal 12-16s
INR
Measure of extrinsic coagulation pathway (V, VII, X, prothrombin and fibrinogen)
Prolonged if problems with coag factors, liver disease or warfarin
Most sensitive.
What are thrombotic disorders?
Excessive coagulation
What two categories of thrombotic disorder are there?
Arterial/platelet
Venous/coagulation
What are some risk factors for developing an arterial thrombotic disorder?
Hypertension
Smoking
High cholesterol
Diabetes
What is the underlying condition precipitating an arterial thrombotic disorder?
Atherosclerosis
Describe atherosclerosis
Damage to endothelium and foamy macrophages. Forms plaques rich in cholesterol.
Where does atherosclerosis normally form?
Areas of turbulence- bifurcations
What are some forms of stable atherosclerosis?
Stable angina
Intermittent claudications
What are some forms of unstable atheroclerosis?
Plaque ruptures and platelets are recruited causing acute thrombosis.
Unstable angina, MI and stroke.
How do you treat an arterial thrombotic disorder?
Treat underlying cause
Antiplatelets
Thrombolysis
Name four antiplatelets
Aspirin
Clopidogrel
Dipyridamole
Abciximab
How does aspirin work?
Inhibits COX which is needed to produce Thromboxane A2 (platelet agonist)
What are some side effects of aspirin?
Bleeds
Gastric ulcers
Bronchospasm
How does clopidogrel work?
ADP receptor antagonist
How does Dipyridamole work?
Phosphodiesterase inhibitor- reduces cAMP production which is second messenger in platelet activation.
How does Abciximab work?
Inhibits GPIIb/IIIa preventing aggregation.
How can you treat bleeding associated with antiplatelets?
PLatelet transfusion
What enhances thrombolytic therapy?
Aspirin
Give some examples of thrombolytic drugs
Streptokinase
Alteplase
Reteplase
Describe streptokinase
Helps to convert plasminogen to plasmin.
Can develop antibodies against it.
Can lead to haemorrhage.
What are alterplase and reteplase?
Plasminogen activators
What are some risk factors for a venous thrombosis?
Virchow’s triad:
Stasis
Vessel wall damage (blood clot damages valves leading to stasis and more damage)
Hypercoagubility (increased tissue factor, vWF and VIII)
What can increase hypercoagubility?
Age, pregnancy, malignancy, genetics, oestrogen therapy and trauma
What are some venous thrombosis embolic conditions?
Deep venous thromboses
Pulmonary Embolism
What are some risk factors for developing a venous thrombotic event?
Age Obesity Pregnancy Oestrogen therapy Previous event Trauma/surgery Malignancy Paralysis Infection Thrombophilia
What are the symptoms of a DVT?
Hot swollen and tender limb with pitting oedema.
Can lead to ulceration
What are the symptoms of a PE?
Pleuritic chest pain
CV collapse and death
Hypoxia
Right heart strain
What are thrombophilias?
Defects of haemostasis leading to predisposition to arterial or venous thrombosis.
Give an example of an acquired thrombophilia
Antiphospholipid syndrome
Describe antiphospholipid syndrome
Ab activate primary and secondary haemostasis.
Ab specific for anionic phospholipids and prolong coag time (Lupus anticoagulants).
What are the symptoms of antiphospholipid syndrome?
Recurrent thromboses- arterial and venous
Recurrent foetal loss
Mild thrombocytopenia
How do you treat antiphospholipid syndrome?
Aspirin
Warfarin
When should you screen for a hereditary thrombophilia?
Vt<45
Recurrent VT events
Family history of Vt or thrombophilia
Give some examples of hereditary thrombophilia
Factor V Leiden Prothrombin 20210 mutation Antithrombin deficiency Protein C deficiency Protein S deficiency
Describe Factor V Leiden
Mutant form of FV resulting in impaired inactivation by PC.
Describe prothrombin 20210 mutation
Results in excessive prothrombin.
Interaction with FV Leiden and contraceptive pill.
Describe antithrombin deficiecy
Autosomal dominant
Many mutations
Acquired from: surgery/trauma and contraceptive pill.
Get recurrent thrombotic episodes starting from a young age.
Describe protein C and S deficiency
Autosomal dominant
Venous thrombosis before age 40
Are single clotting factor defects acquired or hereditary?
Hereditary and rare
Give two examples of single clotting factor defect conditions?
Haemophilia
von WIllebrand Disease
How is haemophilia inherited?
X-linked
Describe haemophilia
Repeated prolonged bleed from medium to large vessels
No primary abnormality
How do clotting tests present in haemophilia?
Normal PT, prolonged APTT
What two forms of haemophilia are there?
Haemophilia A
Haemophilia B
What causes haemophilia A?
Factor VIII deficiency
What causes haemophilia B?
Factor IX deficiency
What are some symptoms of severe haemophilia?
Frequent spontaneous bleeding from early life.
Haemarthrosis are common
Bleed into muscle common
What can recurrent hemarthrosis cause?
Deformities
Give some symptoms of moderate haemophilia
Severe bleeding following injury
Occasional spontaneous bleeds
Give some examples of mild haemophilia
Bleeding only after injury or surgery
How do you treat haemophilia A?
IM administration of factor VIII concentrate Synthetic vasopressin (desmopressin )
How do you treat haemophilia B?
Factor IX concentrates
Prophylactic doses are given twice a week
Desmopressin is ineffective
What is a complication of haemophilia A?
VIII Ab
What are haemophiliacs vaccinated against?
Hep A and B
What do haemophiliacs not get if they have HIV?
Kaposi sarcoma
Which is more common: haemophilia A or B?
A
Describe von Willebrand disease
Platelet and VIII dysfunction due to loss or abnormal vWF.
What are the three forms of vWD?
Type 1
Type 2
Type 3
Describe Type 1 vWD
Partial quantitative deficit in vWF.
Autosomal dominant
Give some symptoms of Type 1 vWD
Bleeding follows minor trauma or surgery
Epistaxis and menorrhagia
Describe Type 2 vWD
Qualitative abnormality in vWF
Autosomal dominant
Give some symptoms of Type 2 vWD
Bleeding follows minor trauma or surgery
Epistaxis and menorrhagia
Describe Type 3 vWD
Complete vWF deficit
Autosomal recessive
Give some symptoms of Type 3 vWD
Severe bleeding
Haemoarthrosis rare
How do you treat vWD
Desmopressin
vWF- only for symptom treatment
