B7 - Disorders of homeostasis Flashcards

Question

Disseminated Intravascular Coagulation (DIC)

Answer 1

- Systemic process where the blood is exposed to procoagulant factor (e.g. tissue factor) Massive thrombin generation, widespread coagulation, followed by fibrinolysis and depletion of clotting factors

Answer 2

``` - Causes ○ Acute § Sepsis § Severe trauma § Complications of pregnancy (amniotic fluid embolism, placental abruption, fetal death in utero) § Snake bite § Acute leukaemia (particularly promyelocytic) ○ Chronic (compensated) § Cancer ```

Answer 3

○ Bleeding (64%), including spontaneous bleeding from cannula sites ○ Renal dysfunction (25%) ○ Hepatic dysfunction (19%) ○ Respiratory dysfunction (16%) ○ Shock (14%) ○ Thromboembolism (7%) ○ Central nervous system involvement (2%)

Answer 4

- Too little breakdown, too much clot formation - Risk factors - Virchow's Triad ○ Endothelial injury ○ Abnormal blood flow ○ Hypercoagulability (too many clotting proteins, to thicker blood flow) - Clinical features of deep vein thrombosis ○ Usually in leg ○ Usually red swollen and painful

Answer 5

○ Presentations to ED with suspected DVT: 20% have DVT and 80% have other cause ○ DVT cannot be safely diagnosed or excluded on history/exam alone ○ Diagnosis involves § Assessment of pre-test probablity of DVT - clinical prediction guide □ D dimer - measures broken down fragments of cross linked fibrin from a clot ® Any reason for having activated thrombosis will increase D dimer measurement ® If your D dimer is normal, DVT can be excluded ® If D dimer is high it is not necessarily DVT □ Ultasonography USS

Answer 6

○ Endothelial injury ○ Abnormal blood flow ○ Hypercoagulability (too many clotting proteins, to thicker blood flow)

Answer 7

- At the time that the clot is broken down all the fibrin strands are cross linked - Cross linked fragments of broken down blood clot are measured with d dimer

Answer 8

- Plasmin breaks down cross-linked fibrin to d-dimers (product of fibrinolysis) - Occur after a thrombin has formed - Found in VTE and post-operatively, DIC, infection, malignancy, trauma - Not specific and cannot be used to confirm a diagnosis of DVT Why measure D-dimer - High negative predictive value, low positive predictive value

Answer 9

- Chest pain, shortness of breath, cough, palpitations, syncope, differential diagnosis ○ Chest infection ○ Cardiac failure ○ Malignancy

Answer 10

- Usually starts in the calf veins - Majority is symptomatic DVT are proximal - Pulmonary embolism (PE) usually arise from proximal DVT - some of the clot breaks of and travels to cause a PE - ~ 50% of untreated symptomatic proximal DVT are expected to cause symptomatic PE - ~10% of symptomatic PE are rapidly fatal - ~30% of untreated symptomatic non-fatal PE will have a fatal recurrence

Answer 11

- Relieve symptoms - Prevent PE (DVT patients) - Prevent death (PE patients) - Prevent recurrence - Prevent complications - post-phlebitic syndrome (DVT), pulmonary hypertension (PE) - Anticoagulation is the mainstay of treatment

Answer 12

- Genetics encode how much we produce - Major inhibitor of thrombin, Xa and other serine proteases in coagulation cascade e.g. Ixa - Heparin cofactor ○ Slowly inactivates thrombin in abense of heparin ○ More potent in presence of haperin - Active sites ○ Reactive centre - cleaved by thrombin ○ Heparin binding iste - Inherited autosomal dominant, variable clinical penetrance ○ One acquired defective copy of the gene is sufficient - Acquired causes include liver disease, warferin theraoy, protein loss (e.g. nephrotic syndrome), DIC

Answer 13

- Heparin cofactor ○ Slowly inactivates thrombin in abense of heparin More potent in presence of haperin

Answer 14

- Inherited autosomal dominant, variable clinical penetrance ○ One acquired defective copy of the gene is sufficient

Answer 15

- Vitamin K dependant protein synthesised in the liver - Autosomal dominant inheritance - Anticoagulant effect only after activation to activated protein C (aPC) - aPC inactivates Va and VIIIa - Effect markedly enhanced by protein S - aPC also has anti-inflammatory action, protects endothelial barrier function and enhances fibrinolysis

Answer 16

- Autosomal dominant I heritance of deficiency - Vit K dependant - Co factor for protein C system - Acquired deficiency in pregnancy, OCP, liver disease, certain drugs, HIV infection

Answer 17

- Point mutation in factor 5 gene - Arginine to glutamine at position 506 - Protein C is unable to inactivate factor V - 'activated protein C resistance' - factor 5 is not switched off by protein C like it should be - Only 5% of heterozygotes for FVL will experience VTE - Risk factor, does not mean these people will have problems with clotting

Answer 18

- Prothrombin is the precursor for thrombin - G20210A transition in 3' untranslated region of gene is risk factor for thrombosis - Heterozygous carriers have 30% higher plasma prothrombin levels - Mechanism: altered mRNA processing or decay rate - Risk factor for blood clotting, does not necessarily mean this people will have clotting issues

B7 - Disorders of homeostasis Flashcards

(42 cards)