Haematology Flashcards
Discuss haemostatic/sealant agents.
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Physical agents / Passive Topical
- Dry matrix
- oxidised regenerated cellulose - Surgicell (mesh) or Fibrillar (fleece)
- gelatin matrix - Gelfoam, Surgifoam, Spongostan
- microporous polysaccharide spheres - Arista, PerClot (powders)
- microfibrillar collagen - Avitene (powder or foam sheet)
- Bone wax and putty
- External agents
- chitosan - HemCon bandage or Chitoflex
- kaolin-based - Quickclot
- Nustat
- Dry matrix
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Biologically active topicals
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topical thrombin
- combined with gelatin - Gelfoam plus, Floseal
- fibrin sealant
- Tisseel (liquid - fibrinogen, factor XII, thormbin, calcium), Tachosil (gelfoam sponge + thrombin + fibrinogen)
- tranexamic acid
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topical thrombin
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Tissue adhesives and sealants
- fibrin sealant (above)
- cyanoacrylate - Dermabond, Histoacryl
- albumin-based - Bioglue
- Polyethylene glycol hydrogel - Coseal
- Urethane-based - TissueGlue
POTENTIAL ALGORITHM FOR BLEEDING
- Localised bleeding = matrix application
- Cellulose (Surgicel)
- Porcine gelatin (Gelfoam)
- Polysaccharide spheres (Arista, Perclot)
- Localised bleeding but more significant = above agents impregnated with thrombin
- Floseal
- Gelfoam Plus
- Diffuse bleeding = spray sealant
- Vascular: PEG polymer (Coseal) or albumin+glutaraldehyde (Bioglue) or Cyanoacrylate (Omnex)
- Colon: fibrin sealant (Tisseel)
- Diffuse bleeding from discrete area: TachoSil
What is the massive transfusion protocol?
A system designed to rapidly replace blood producs at an approximate 1:1:1 ratio in a patient who is exsanguinating.
(Massive transfusion is defined as either replacement of >1 blood volume in 24 hours or replacement of >50% of blood volume in 4 hours)
Aim in a massive transfusion scenario is to:
- Recognise and assess blood loss
- Restoration of intravascular volume and Hb levels
- Control of bleeding by surgical or radiological means
- Correction of other parameters eg coagulopathy
At our institution the MTP is activated for massive bleeding with either shock or ABC ≥2 or abnormal coagulopathy
- 2g TXA IV bolus (if not yet given - if 1g given pre-hospital consider further 1g)
- Ensure crossmatch sample delivered to blood bank
- Give 2 units O-neg or type specific RBC
- Trauma: add 2 units FFP or thawed plasma
- Ring blood bank to activate MTP
- MTP Box ONE:
- 2 whole blood OR 2 RBC + 2 FFP
- Trauma: add 3 cryoprecipitate (or 4g FC) + 1 pack platelets
- MTP Box TWO
- 4 RBC + 4 FFP
- 1 platelets
- MTP BOX THREE
- 4 RBC + 4 FFP
- 3 units cryoprecipitate
- MTP BOX FOUR
- 4RBC + 4FFP
- 1 platelets
- and alternate 3&4
- check at time of box 1 and repeat every 30mins: coags, FBC, ABG, calcium
- Additional treatment thresholds:
- PR >1.5 or aPTT >40, consider additional 4 units FFP
- fibrinogen <1.5g/L, consider additional 3 units cryo or 4 units FC
- if platelets <75 x 109 consider additional 1 pack platelets
- if ionised Ca <1.2mmol/L give 10mL calcium ** this is important
Recombinant factor VIIa is out
Thromboelastography (TEG) or rotational thromboelastometrey (ROTEM) can be used as adjuncts if available
ABC score is a massive bleeding score - 1 point each for penetrating injury, SBP ≤90, HR ≥120, positive E-FAST - positive if ≥2/4
What are the commonly used anti-platelet drugs?
How do they work?
-
Aspirin
- Irreversibly acetylates a serine residue which inhibits COX-1 > COX-2 (irreversible non-selective COX inhibitor)
- Prevents production of TXA2 which is pro-coagulant and pro-platelet.
- Effects last for duration of platelet’s life - 7 days
- Reversal - platelet transfusion
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Dipyridamole
- Phosphodiesterase inhibitor; prevents cAMP breakdown, reduced Calcium, reduced platelet shape change/activation.
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Clopidogrel/Ticagrelor
- P2Y12 blocker; prevents ADP to ATP-dependent platelet aggregation.
- Platelet transfusion less effetive than it is for aspirin reversal
What are the pros and cons of UFH versus LMWH?
In the setting of anticoagulation:
UFH
- Half life of 60-90 minutes
- Less reliably metabolised so IVI best with measurement of ApTT
- Higher risk of HIT
- Heparin infusion beneficial in renal failure as close monitoring and control available.
- Higher bleeding risk (5%) cf LMWH
LMWH (depolymerised Heparin)
- Has largely superceded UFH
- Higher anti-Xa activity due to depolymerization
- Lower risk HIT
- Worse in underweight patients and renal failure
Outline the key points in anticoagulation in pregnancy.
- LMWHs are the anticoagulant of choice in pregnancy
- Do not cross placental interface
- Warfarin is teratogenic
- The half life of LMWH is shorter in pregnancy so twice daily dosing is preferred
Provide an overview of haemostasis
Arteriolar vasoconstriction
- Reflex neurogenic mechanism augmented by endothelin (a potent endothelial-derived vasoconstrictor)
Primary haemostasis - formation of the platelet plug
- subendothelial ECM exposed
- platelet adhesion and activation (ie shape change and secretory granule release) by binding to exposed ECM
- platelet-ECM adhesion = mediated through vWF which acts as a bridge between platelet receptors (mostly glycoprotein Ib) and exposed collagen
- platelet aggregation - secreted products (ADP and thromboxane A2)recruit other platelets to form a temporary haemostatic plug
Secondary haemostasis - activation of coagulation cascade
- release of tissue factor (aka thromboplastin/factor II), a membrane-bound lipoprotein procoagulant factor synthesised by endothelium activates the cascade by activating factor VIIa
- coagulation culminates in thrombin generation & conversion of circulating fibrinogen to insoluble fibrin
- thrombin also induces additional platelet recruitment & granule release
- polymerised fibrin and platelet aggregates together form a solid, permanent plug
Clot stabilisation and absorption - activation of counter-regulatory mechanisms
- Counter-regulatory mechanisms are set into motion to limit VTE/restrict the haemostatic plug to the site of injury
- t-PA etc eventually resorb plug
Provide and overview of the coagulation cascade
An orchestrated pathway where sequential activation of key enzymes eventually leads to fibrin maturation.
Likened to a dance, that takes place on a phospholipid surface in the presence of calcium…
- tF activates VII to VIIa…
- Which activates X to Xa…
- Activated Xa then accelerates the activation of II (Prothrombin) to IIa (Thrombin)
- Thrombin converts fibrinogen to fibrin.
What is in Prothrombinex?
What is the dose?
Prothrombinex®-VF is a sterile freeze-dried powder containing purified human coagulation factors II, IX and X and low levels of factors V and VII.
25-50IU/kg for haemorrhage.
What is DIC?
- Disseminated intravascular coagulation is a potentially life-threatening condition associated with a state of paradoxical haemorrhage and microthrombosis.
- Identifying DIC and the underlying condition responsible for it are critical to proper management.
- In DIC, the processes of coagulation and fibrinolysis become abnormally (and often massively) activated within the vasculature, leading to ongoing coagulation and fibrinolysis.
- Inciting factors include:
- LPS endotoxins
- Amniotic fluid
- Widespread tissue factor release
- Widespread release of DAMPS, PAMPS
- Acute haemolytic transfusion reaction
- Once widespread exposure to procoagulant factor is initiated, microvascular thrombosis, widespread fibrinolysis, and end-organ damage occurs.
What is thromboelastography?
Describe a thromboelastogram.
- TEG is a method of testing dynamic coagulation using a sample of blood either spun around a needle (ROTEM), or with a needle spun within it (TEG) to measure the speed and strength of clot formation.
- R = reaction time (citrated kaolin test) = time taken for coagulation factors to initiate clot formation
- if prolonged (>9min): give FFP 2-4u or prothrombinex 25-35u/kg
- MA = max amplitude - strength of clot formed by fibrinogen crosslinking with platelets
- 2 types - CFF MA (uses citrated functional fibrinogen, measures fibrinogen only) and CRT MA (citrated rapid TEG, measures fibrinogen and platelets)
- CFF MA <20mm = give cryoprecipitate of fibrinogen
- CFF normal and CRTMA <52mm = give platelets
- K = achievement of certain clot fimness
- alpha angle = kinetics of clot development (should be >55 degrees
- LY30 = percent lysis 30mins after MA (should be <2.2%)
- ?TEG-ACT activated clotting time?
What is in Cyroprecipate?
What is in Fresh Frozen Plasma?
What is in Prothrombinex?
Cryoprecipitate
- Fibrinogen
- vWF
- Factor VIII
- Factor XIII
FFP
- All coagulation factors except platelets
Prothrombinex
- Factor II
- Factor IX
- Factor X
- Low levels of factors V and VII
Classify the causes of coagulation disorders.
- Inherited
- Haemophilia A - XLR VIII deficiency
- Haemophilia B - XLR IX deficiency
- von Willebrand’s disease - low on vWF and VII
- Acquired
- Immune-mediated - SLE antiboides
- Vitamin-K deficiency
- Liver disease
- DIC, Massive transfusion
Categorise VTE risk in general sugery.
High risk (should all get VTEP unless contraindications):
- Major abdominal surgery
- Resectional cancer surgery
- Arthroplasty surgery
- Previous VTE and any surgery
Low risk (VTEP if additonal risk factors)
- Any other surgery
- Note any additional risk factors
- Immobility
- Hyperoestrogenic
- Inflammation
- Obesity
- Family history
What are the contraindications to VTE prophylaxis?
Absolute:
- Previous reaction to anti-coagulants e.g. HIT
- Active bleeding
Relative:
- Previous GI or intracranial bleed
- Liver disease
- Caution in renal disease
- High falls risk
- Palliative outlook
What scoring systems are validated for pre-operative classification of VTE risk?
- Very low risk: Caprini score 0
- corresponding to an EBL <0.5 percent
- Low risk: Caprini score 1 to 2
- corresponding to an EBL of about 1.5 percent
- Moderate risk: Caprini score 3 to 4
- corresponding to an EBL of about 3 percent
- High risk: Caprini score ≥5
- corresponding to an EBL of at least 6 percent