Hypercoagulable states - BB Flashcards
Virchow’s triad
Endothelial damage
Stasis of blood
Hypercoagulability
Natural anticoagulants made by endothelial cells
NO, prostaglandins, antithrombin, tPA, APC
Reasons why malignancy may cause hypercoagulable state:
- Some tumours produce pro-coagulants (TF)
1b. Adenocarcinomas - some data that mucin is thrombogenic - Normal cells may produce pro-coagulants (in reaction to the presence or growth of the tumour)
- Decreased activity, surgery and bed rest of the patient
Why does pregnancy cause hypercoagulable state?
- Possible evolved to protect against blood loss at delivery
- Many clotting factor level changes
- – increased fibrinogen
- – decreased protein S
- Foetus obstructs venous return - pooling of blood in lower extremities (stasis)
- – Hence DVT common
Why does oral contraceptive cause hypercoagulable state?
Oestrogen increases production of coagulation factors
Elevated presence of which amino acid causes hypercoagulable state
Homocysteine
Why does elevated homocysteine cause a hypercoagulable state?
High levels may cause - A+V clots
- Endothelial injury
- Activation of some clotting factors
What causes elevated homocysteine?
Deficiencies:
- Folate
- B12
- B6
Homocystinuria - (cystathionine beta synthase deficiency)
Why does nephrotic syndrome cause a hypercoagulable state?
Multiple mechanisms - main one is:
- loss of anti-clotting factors in the urine (antithrombin III)
Inherited hypercoagulable states (thrombophilia)
x4
- Factor V Leiden Mutation
- Prothrombin gene mutation
- Antithrombin deficiency
- Protein C/S deficiency
Factor V Leiden Mutation - how it works
Abnormal factor V - not inactivated by APC:S
Means that factor V remains active for longer -=> causing hypercoagulability
Genetics of factor V leiden mutation
Point mutation in factor V gene
Results in:
- single amino acid substituion
- guanine to adenine change
Occurs at position 506 on factor V molecule
Prothrombin gene mutation genetics:
Prothrombin 20210 gene
- guanine to adenine change in prothrombin gene
- occurs at position 20210
Heterozygous carriers have 30% increase in prothrombin
Homozygous carriers have even higher
ATIII deficiency (antithrombin) 2 types:
- Inherited due to gene mutations (number of different mutations can cause)
- Acquired deficiency
a- Liver disease (impaired production)
b- Nephrotic syndrome (Protein losses including ATIII)
c- DIC (consumption of both anti-/coagulant factors)
Typical presentation of antithrombin III deficiency
Heparin resistance
- escalating dose with little to no change in PTT
- Because no ATIII for heparin to work on