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
-
Biologically active topicals
-
topical thrombin
- combined with gelatin - Gelfoam plus, Floseal
- fibrin sealant
- Tisseel (liquid - fibrinogen, factor XII, thormbin, calcium), Tachosil (gelfoam sponge + thrombin + fibrinogen)
- tranexamic acid
-
topical thrombin
-
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
-
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
Discuss VTE prophylaxis
- VTE rates depend on
- type of procedure performed and duration
- positioning, type of anaesthesia
- time to perform procedure
- pre-op immobility (eg hip fractures)
- post-op mobility
- whether surgery involves potential trauma to veins (eg knee surgery)
- critically ill states eg extesnive burns, multiple trauma
- and also individual risk factors eg
- previous history of VTE
- hypercoagulable disorders
- cancer
- use of oestrogens & HRT
First establish risk of postop VTE - Caprini score: v low (EBR <0.5%), low (EBR 1.5%), moderate (EBR 3%) or high risk (EBR ≥5%) groups - Caprini score
Also consider bleeding risk
- low bleeding risk - general, abdominal-pelvic, bariatric, vasc and thoracic surgery that is uncomplicated have beeding rates <2%
- high bleeding risk - cardiac surgery, major trauma esp brain and spine; also include those in whom consequences of bleeding are potentially devastating
V low thrombosis risk: early ambulation (healthy young pts undergoing minor outpaitnet procedure eg breast biopsy, nasal polyp removal)
Low thrombosis risk (baseline risk 1.5%, Caprini 1-2 if general abdo/pelvis surgery, eg appendix, lap chole, vein ablation) - mechanical methods
Moderate or high risk (baseline risk 3-6%, Caprini 3/4/5; moderate includes bariatric surgery, high risk includes abdominal-pelvic surgery eg distal colorectal surgery, major trauma) - combined prophylaxis (unless bleeding risk high)
Duration: in most cases VTE continued til pt becomes fully ambulatory or until hospital discharge; if tps have prolonged periods of immobility between ambulatory periods should prob receive continued or additional methods of prophylaxis, sepsec bc risk fo VTE doesn’t drop to zero upon ambulation but may be sustained beyond day of surgery. 10-14 days of thromboprophylaxis may be indicated in high risk surgical pts, including those with cancer. Extended pharmacologic VTE prophylaxis beyond discharge not routinely recommended in most nonorthopedic surgical pts except for those who undergo major abdominal and/or pelvic surgery for cancer - extended VTE offered for up to 12weeks post discharge. Optimal duration unknown but is typically recommended beyond 10 days and for a period of 3-4 weeks for high-risk pts who undergo major abdominal and/or pelvic surgery for cancer.
Preventative measures include:
- lifestype modification
- smoking cessation
- weight loss
- pre-op ambulation or exercise
- mechanical VTE prophylaxis
- TEDs (10-20mmHg for prophylaxis)
- sequential calf compressors intra-op and post-op
- work in two ways: 1) reduce pooling and aid in returning blood to central circulatoin by replicating calf pump mechanism (prevent stasis), and 2) trauma from the compression of the SCDs acts to enhance fibrinolysis and therefore prevent and lyse small clots
- pharmaceutical VTE prophylaxis
- LMWH - can give empiric weight-based dose or tailor dose to anti-factor Xa levels aiming for 0.2-0.5IU/mL, consider continuing for 28 days if high risk
- unfractionated heparin
- direct Xa inhibitors
- may be given pre, intr, and post-op
- in high risk pts may be continued post-op for 5-30 days
Commonly used antithrombotic medications:
- enoxaparin
- LMWH, derived from UFH
- more predictable dose response and fewer haemorrhagic side effects
- potentiates antithrombin III
- heparin
- mixture of sulphated glycosaminoglycans with mixed activity against multiple coagulation factors as well as potentiating AT-III
- higher rates of HIT
- rivaroxaban/Apixaban
- not as widely used, main application is in ‘extended duration’ VTEP, often in orth
- direct Xa inhibitors
- aspirin and warfarin do not have an established role in VTE prophylaxis
