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
How does warfarin affect bleeding?
Factors II, VII, IX and X are inactive until the cofactor Vit K is turned into Vit K Epoxide to make them active
Vit K Epoxide Reductase turns Vit K Epoxide back into Vit K, warfarin blocks this enzyme which stops reaction
Reversal= add more Vit K in emergency (2-10mg)
How does heparin affect bleeding?
Given subcutaneously as a prophylactic measure
Binds to and activates Antithrombin III (which inhibits Factor X and II of final pathway)
Reversal agent= protamine sulphate
How does Clopidogrel affect bleeding?
P2Y12 is a receptor on platelets inv. in platelet aggregation and linking to fibrin meshwork
Clopidogrel is a P2Y12 inhibitor
How can you avoid haemorrhage?
Warfarinised patient- check INR within 72hrs to be <4 and avoid ID blocks
Antiplatelets medication (aspirin, Clopidogrel, dipyridamole)- fine as long as only one med Multiple eg. Aspirin + Clopidogrel = check w haematologist
Haemophilia/VWB- liaise w haematologist, who will give recombinant factor VIII/IX or DDAVP (releases stores of factor VIII from vascular endothelia into circulation), tranexamic acid mouthwash afterwards
If 3 or more teeth/surgical extraction= 1x a day med (take med 4hrs after), 2x a day (miss morning dose)
What are the types of haemorrhage?
Primary- as soon as tooth removed due to bleeding disorder/local cause
Reactionary- within 48hrs (not immediate) due to anaesthetic wear off, exercise, alcohol, heat etc
Secondary- 1 week after due to infection (tonsillar bed after tonsillectomy)
What are standard measures for extraction?
Firm pressure/ bite on gauze
Compress socket
Post op instructions
What are further measures for extraction?
Bone bleed- haemostatic pack in socket (surgicel- resorbable oxidised cellulose helps clot form) (gelatin sponge- absorbs up to 45x weight in blood and expands for pressure)
Gingival bleed- suture (compress gingival blood supply, prevents pack from falling out)
Ongoing bleed- tranexamic acid on gauze to bite down/reversal of anticoagulant
Ongoing bleed after this- accept v small ooze for a few days if bleeding disorder
Bleed of unknown cause-coagulation screen (APTT and PT), full blood count, factor assay
LA contains adrenaline which is a vasoconstrictor- can be readministered
What should be measured for warfarin?
APTT and PT prolonged Factors II and X in final common PT- Factor VII in extrinsic APTT- Factor IX in intrinsic Linear relationship between APTT and PT, only one needs to be measured so PT which is affected more
What does bleeding time measure?
Platelet function
What should be measured for aspirin?
Bleeding time prolonged
What should be measured for Von Willenbrands Disease?
Prolonged APTT and bleeding time
VWB factor supports factor VIII
So if less VIII, prolonged intrinsic pathway so prolonged APTT
Influences platelet function
What should be measured for haemophilia?
APTT prolonged
Deficiency in Factors VIII or IX
Measured through APTT
What other names for DDAVP are there?
Desmopressin
Synthetic Vasopressin
Synthetic ADH
ADH and vasopressin are same hormone but has different effect depending on conc
