Bleeding Disorders Flashcards
List the 4 main types of acquired bleeding disorder.
List the 4 main types of inherited bleeding disorders.
ACQUIRED: Disseminated intravascular coagulation (DIC) Drug effects (e.g. warfarin, DOACs) Coagulopathy in liver disease Lupus anticoagulant
INHERITED: Clotting factor deficiencies (e.g. haemophilia A/B) Von Willebrand factor deficiency Platelet disorders Thrombophilia
What are the 3 main features of disseminated intravascular coagulation (DIC)?
Microthrombi, due to inappropriate activation of coagulation cascade
Fragmentation anaemia, due to RBC damage by microthrombi
Bleeding, due to exhaustion of coagulation cascade
Describe the pathophysiology of DIC. (3)
- Systemic activation of coagulation causes:
a. Intravascular fibrin deposition, causing:
- Thrombosis of small vessels
- Organ failure
b. Depletion of platelets and clotting factors, causing:
- Bleeding
List 5 possible causes of DIC.
Sepsis Malignancy Massive haemorrhage Severe trauma Pregnancy complications, e.g. -Pre-eclampsia -Placental abruption -Amniotic fluid embolism
Which investigations would you do for DIC? (7)
Investigate underlying cause
Coagulation tests:
- PT
- APTT
- TCT
Blood tests:
- FBC
- Blood film
- D-dimers
How would you treat DIC? (7)
Treat underlying cuase Fresh frozen plasma Platelet transfusion Heparin (if thrombotic phenotype) Antithrombin concentrate Protein C concentrate Activated protein C
What is the most significant side effect of warfarin?
Bleeding complications
What could you do if your patient is on warfarin, and their INR is too high? (5)
- Stop warfarin
- Reduce warfarin dose
- Give vitamin K (oral/IV)
- Give vitamin K dependent coagulation factors (2, 7, 9, 10)
- Give prothrombin complex concentrates (e.g. beriplex, octaplex)
List the 4 vitamin K dependent clotting factors.
2, 7, 9, 10
What type of drug is dabigatran? Outline its effect on:
a) PT
b) APTT
c) TCT
Which other test could you do to check dabigatran levels?
Direct factor 2a (thrombin) inhibitor
PT - no change
APTT - affected if very high levels of dabigatran
TCT - affected by slight changes in dabigatran levels
Ecarin clot time (ECT) - add snake venom to patient’s plasma; time taken for it to clot
What type of drug is rivaroxaban? What is its effect on:
a) PT
b) APTT
What other test could you do to check rivaroxaban levels?
Direct factor 10a inhibitor
PT - sensitive, dose depend change
APTT - weak, non-linear effect
Anti-10a assay - but calibration curve is still being established
In liver disease, why might you also see coagulopathy? (3)
Decreased clotting factor synthesis in liver
Vitamin K deficiency (e.g. poor diet, obstructive jaundice)
Poor clearance of activated coagulation factors
Describe the features of coagulopathy in liver disease. (5)
DIC Hypersplenism Low WBC Low platelets Decreased thrombopoietin synthesis
What is lupus anticoagulant?
What is its effect on:
a) PT
b) APTT
c) APTT 50:50
What other test could you do to detect lupus anticoagulant?
Phospholipid dependent antibody - i.e. binds to phospholipids
PT - normal
APTT - prolonged
APTT 50:50 - only partial correction
DRVVT ratio (dilute Russell's viper venom time) - snake venom added to plasma -Results: prolonged (BUT corrected by excess phospholipid)
What are the main clinical features of antiphospholipid syndrome? (3)
Which antiphospholipid antibodies might be present? (3)
FEATURES:
Antiphospholipid antibodies
Thrombosis
Recurrent miscarriage
ANTIPHOSPHOLIPID ANTIBODIES:
Lupus anticoagulant
Anti-cardiolipin antibodies
Beta 2 glycoprotein 1 antibodies
Describe the pathophysiology of antiphospholipid syndrome. (3)
- Antiphospholipid antibodies disrupt the Annexin V shield and expose phospholipids
- This causes continuous activation of the clotting cascade
- This leads to thrombosis
What is haemophilia A caused by?
How is it inherited?
Factor 8 deficiency
X-linked recessive inheritence
How would you classify haemophilia A>
HINT: there are 3 levels of severity.
Mild:
- Factor 8: 6-40 iu/dL
- Surgical bleeding
Moderate:
- Factor 8: 2-5 iu/dL
- Minor trauma bleeds
Severe:
- Factor 8: <1 iu/dL
- Spontaneous bleeds
In haemophilia, what would the following coagulation tests look like?
a) PT
b) APTT
Why?
PT - normal
APTT - prolonged
BECAUSE:
Haemophilia A is a factor 8 deficiency
Factor 8 is in the intrinsic pathway
APTT measures the intrinsic pathway, BUT PT only measures the extrinsic pathway (therefore isn’t affected)
How would you treat haemophilia A? (5)
Patient/doctor education
Desmopressin (DDVAP)
Replacement therapy, e.g.
- Recombinant produced factor 8 concentrate
- FFP
- Plasma derived factor 8 concentrate
What is haemophilia B caused by?
Factor 9 deficiency
Describe the features of Von Willebrand factor deficiency. (4)
Mucosal type bleeding pattern
Decreased VWF levels
Decreased platelet aggregation
Decreased factor 8
How would you classify VWF deficiency?
HINT: there are 3 categories, but one of them has 4 subcategories.
Type 1 - partial quantitative VWF deficiency
Type 2 - qualitative VWF defiency:
- 2A: absence of HMW VWF multimers
- 2B: increased affinity for platelet GPIb-V-IX
- 2M: decreased platelet dependent function NOT caused by lack of HMW VWF multimers
- 2N: increased affinity for platelet GPIb-V-IX
Type 3 - almost complete VWF deficiency
List 5 possible causes of thrombophilia.
Anticoagulant deficiencies, e.g.
- Antithrombin
- Protein C
- Protein S
Specific gene mutations, e.g.
- Factor 5 Leiden mutation
- Prothrombin gene mutation
