haemostatic problems Flashcards
What is haemostasis?
Coagulation- conversion of soluble proteins into insoluble polymer- coagulation cascade- positive feedback (fibrinogen into fibrin polymer)
Platelets interact with cascade
What is the coagulation cascade?
Extrinsic pathway- measured via prothrombin time or international normalised ratio- subendothelial collagen (tissue factor)
Intrinsic pathway- measured via activated partial thromboplastin time- negatively charged phospholipids from endothelial trauma (endothelia bursts to release phospholipids) and Factor XII
Final common pathway
How is coagulation measured?
Blood collected in citrate which chelates Ca2+ (Ca2+ is clotting factor IV for both pathways)
In lab, an excess of Ca2+ is added to overcome citrate to measure coagulation time
What is prothrombin time (PT)?
Add tissue factor to measure extrinsic pathway of coagulation, will also measure final common pathway
Factors that are measured- I, II, VII, X
What factors does Warfarin inhibit?
II, VII, IX, X
What is international normalised ratio (INR)?
Ratio of-
Patients PT:normal PT
Under specific lab conditions
Used to assess warfarins effect
Patients extrinsic pathway is 2x as long under these conditions
What is the activated partial thromboplastin time (APTT)?
Add phospholipid, silica and Ca2+ to measure
Measures intrinsic pathway + final common pathway
Factors measured- I, II, V, VIII, IX, X, XI, XII
Can also measure warfarins effect
If APTT is raised but PT and INR normal= potential haemophilia
What is Haemophilia A and B?
Haemophilia A- deficiency of Factor VIII
Haemophilia B- deficiency of Factor IX
What are some important congenital disorders?
Haemophilia A
Haemophilia B
Von Willebrands- shortage of VW Factor which is important in platelet adhesion and binds to factor VIII to stop breakdown in blood (raised APTT and bleeding time)
What are some important medical conditions?
Liver/kidney disease- bleed more
Cardiac disease- due to drugs
Cancer- due to drugs/myelosupression
Immune thrombrocytopenic purpura (ITP)- acquired bleeding problem
How might liver disease affect bleeding?
Produces most coagulation factors
Maybe compromised due to cancer, cirrhosis, jaundice, paracetamol overdose (PT marker of failing liver)
How might kidney disease affect bleeding?
Related to platelet function, not no
Ca metabolism related
Prolonged bleeding time
Kidney failure- dialysis (will be heparanised, don’t take teeth out)
What drugs should be known for bleeding?
Warfarin
Aspirin
Clopidogrel
Heparin
NOACs- Novel oral anticoagulants, such as, Dabigatran, Rivaroxaban, Apixaban
How does aspirin affect bleeding?
Highly first pass metabolised by liver
So needs to affect hepatic portal vein before reaching liver
Irreversible inactivation of COX enzyme within platelets
This prevents Thromboxane A2 formation so platelets can’t aggregate
Must wait 7 days of discontinuation to form platelets before treatment
What is the Arachidonic acid pathway?
Arachidonic acid is turned into prostaglandins/prostacyclins (pain and gastric regulation) and thromboxane A2 (platelet aggregating factor) by COX 1,2,3
Therefore positive feedback as platelet bursts and thromboxane A2 release for more aggregation