Haematology Flashcards

Question

What is fibrinolysis?

Answer 1

the breakdown of a clot whereby fibrin is degraded by plasmin plasminogen --> plasmin (protease) much slower than coagulation/ clot formation and hence allows vessel to heal. activated by tissue plasminogen activator (tPA) which is slowly released from damaged tissue which converts plasminogen to plasmin

Answer 2

by product of breakdown of fibrin clot

Answer 3

This is a medical management whereby the fibrinolysis pathway is utilised to breakdown a life threatening clot. (P.E, MI, limb ischaemia, stroke) e.g. thrombolytic drugs include alteplase, streptokinase

Answer 4

Diagnostic test to evaluate the haemostatic process in whole blood to aid transfusion therapies provides a evaluation of clot formation, stabilisation and dissolution a sample of blood is rotated and causes blood to clot which changes the viscoelastic properties of the sample which can be measured by resistance to rotation

Answer 5

R time = stimulation until beginning of clot formation. determined by clotting factors. if prolonged need FFP K time = time for width of graph to reach a certain point and is a measure of time taken to reach a particular firmness of clot. determined by fibrinogen. hence if prolonged give cryoprecipitate alpha angle = rate of clot formation. determined by fibrinogen. if low give cryoprecipitate max amplitude (MA) - max extent of clot. determined by platelets. if low give platelets LY30 - lysis at 30mins - measures clot breakdown. if high give TXA

Answer 6

disseminated intravascular coagulopathy widespread activation of clotting cascade microclots and depletion of clotting factors so bleeding. infection/ sepsis trauma malignancy transfusion placental abruption/ amniotic fluid embolism.

Answer 7

high APTT, PT , TT low platelets low fibrinogen high d dimer

Answer 8

Also mention TXA = which promotes thrombosis by blocking the conversion of plasminogen to plasmin and hence the breakdown of fibrinogen. these are all active drugs - can also mention replacement of certain products (platelets, factors) to improve thrombosis

Answer 9

Can be classified via mechanism. Their mechanism works through inhibiting platelet activation and aggregation through various platelet receptors most of these acts via Gi to activate platelets. Activation - P2Y12 receptor (ADP receptor) = clopidogrel, prasugrel, ticagrelor - Thromboxane receptor = reduced thromboxan production via COX inhibitors. - phosphodiesterase inhibitors = Dipyramiole (increases cAMP , opposite to Gi) Aggregation and activation - GPIIb/IIIa receptor = tirofiban

Answer 10

can be divided into two broad groups - parental and oral parenteral - direct thrombin (F2a) inhibitors = Bivalirudin - indirect thrombin inhibitors = unfractionated heparin, LMWH (enoxaparin, dalteparin), fondaparinux oral anticoagulants - coumarins = warfarin - direct Xa (DOAC) = apixaban, edoxaban, rivaroxaban. - direct thrombin (IIa) = dabigatran

Answer 11

ADP receptor anatagonist works via inhibiting platelet activation through irreversible antagonism. commonly used in high risk CVS events such as MIs and Strokes, stents or peripheral vascular disease to prevent further thrombosis and ischaemia. 75mg OD is usually given but often a loading dose of 300mg. Pharmacodynamics: - It reduces platelet activation and thus has some side effects related to this bleeding & bruising (type A reaction) - it can also lead to thrombotic thrombocytopenia pupura - rare side effect where platelets form small clots throughout the body and platelet levels are depleted. (type B) pharmacokinetics.. - It is taken orally and absorbed from GI tract - mostly broken down by esterases but some converted to active form. - prodrug and converted to active form by CYP450 - genetic polymorphisms - some people cant convert to prodrug v. well. - omeprazole also inhibits this conversion - 98% PB - renal excretion.

Answer 12

commonly used antiplatelet - irreversible COX inhibitor COX1 > COX2 used for pain, antiplatelet actions in prevention and treatment of MI, strokes, PVD and also for its antipyretic effects. can be given PO, PR usually 75mg or 300mg loading dose in acute setting (has a quicker onset) pharmacodynamics: - COX inhibition results in less prostaglandins (pain and inflammation), less thromboxane (less platelet activation) - thus side effects can be type A - bleeding, bruising, GI ulceration, renal dysfunction and worsening of asthma (leukotrienes) - or type B - allergy, reyes disease in children pharmacokinetics: - absorbed from stomach and intestine - pKa 3.5, acid. acidity of stomach promotes absorption. - 80% PB - converted to salicyclates in liver and GIT - renal excretion.

Answer 13

Phosphodiesterase inhibitor inhibits platelet activation Main role is in stroke prevention and treatment. particularly when clopidogrel is contraindicated.

Answer 14

tirofiban IV infusion, very short half life used for coronary stenting

Answer 15

Heparin is an endogenous molecule normally produced by mast cells and works via binding ATIII to potentiate its inhibition of factor 2,10, 9.11 and 12. It has now mostly been replaced by LMWH due to monitoring issues however still used in special circumstances e.g. acute limb ischaemia and vascular surgery. given as IV infusion and requires close monitoring of APTT and platelet count. Issues: - type A - bleeding - type B - hypotension with large IV bolus, hypersensitivity, osteoporosis, and heparin induced thrombocytopenia.

Answer 16

This comes in 2 forms type 1 = non immune, mild, self resolves, no need to stop infusion. develops few days after. type 2 = immune mediated - IgG antibodies to platelet factor 4 (PF4) which results in platelet activation and destruction which inturn causes strokes and bleeding. , severe and develops on day 5-10. can be distinguished by timing, level of platelet drop and is there is thrombosis.

Answer 17

protamine sulphate. heparin is very negatively charged and acidic and can be neutralised by protamine which is basic and positively charged.

Answer 18

LMWH is a newer form of heparin which has been fractionated and hence smaller. IT also binds and potentiates ATIII however due to its size is limited to actions only on 2a and 10a. it has become popular due to its more predictable nature and thus doesnt need monitoring and its improved side effect profile. given subcutaneously and needs adjustments in obesity and renal failure. its downfalls - cant be reversed by protamine (or atleast only slightly) - can be underdosed in obesity - factor Xa levels can be checked in those where underdosing may occur

Answer 19

heparins because they dont cross placenta - although LMWH much more favoured in comparison to unfractionated due to monitoring and HITT aspirin low dose can also be used and is used for pre-eclampsai avoid warfarin - teratogenic avoid DOACs

Answer 20

Commonly used oral anticoagulant. although more recently, its role is being replaced by newer agents such as the DOACs. It is a coumarin based molecule Works via inhibition of Vitamin K epoxide reductase. This inhibition prevents the reduction of vitamin K such that it cannot be replenished for its use in carboxylation of clotting factor and hence their activation It mostly affects the production of factors 10, 9, 7 and 2 but also protein C and S It only affects the synthesis of new clotting facotrs and hence takes around 3-5 days to work and should be bridged by LMWH. Also this bridging is useful as initially the inhibition of protein C and S gives pro-coagulant effects It is taken orally and titrated to the INR and the range of INR depends on indication e.g. AF is 2-3 whereas a mechanical valve is 3-4. pharmacodynamics - bleeding - N&V & diarrhoea - teratogenic pharmacokinetics - good oral absorption -metabolised by CyP450 and subject to inducer/inhibitors. - many DDI = plasma protien binding (NSAIDs, phenytoin), CYP450 inhibitors (erythromycin) inducers ( phenytoin, COCP)

Answer 21

stop warfarin high INR no bleed - oral vit K bleeding, mild = vitamin K IV major bleed = Prothrombin complex concentrate (beriplex) or FFP

Answer 22

apixaban, edoxaban, rivaroxaban indicated in venous thrombosis e.g. P.E, DVTs, prophylaxis for AF

Answer 23

Dabigatran = monoclonal Ab rivaroxaban and apixaban = Andexanet alpha

Answer 24

these are drugs that promote breakdown of fibrin clot. normally plasminogen --> plasmin. this step is activated by tissue plasminogen activator. plasmin cleaves fibrin. there are a number of drugs that mimic tPA including streptokinase, alteplase

Answer 25

anti-fibrinolytic agent blocks conversion of plasminogen to plasmin to prevent breakdown of fibrin aims to prevent/ help with haemorrhage used in major trauma and traumatic brain injuries after CRASH 2 and 3 studies. also often used in orthopedic surgery.

Answer 26

The Classical (Cascade) Model of Hemostasis * clotting cascade The Cell-Based Model of Hemostasis * newer model incorporates the role of cells (especially platelets and endothelial cells)

Answer 27

iron - around 3g (4g in male) ferritin - males up to 400ng/ml females 15-150ng/ml transferrin - normal saturation of iron around 20-50%

Answer 28

ferritin is the intracellular storage protein for iron. used as a marker of iron deficiency/ overload transferrin is the mechanism for transport of iron in the blood.

Answer 29

mostly in liver, bone marrow and spleen

Answer 30

absorbed from duodenum and upper jejunum absorbed as Fe2+ and enhanced by vit C hepcidin is a protein made by the liver that inhibits absorption for regulation old damaged RBC are engulfed by macrophages and the iron in them is recycled.

Answer 31

excess loss * menorrhagia, GI malignancy insufficient production * dietary - iron lack * malabsorption - low stomach acid

Answer 32

no - mensturation, venepuncture e.g. for haemochromatosis

Haematology Flashcards

(58 cards)