Haem - VTE Flashcards
Why does venous thromboembolic disease matter?
Venous thromboembolism is an important complication of hospital admission
and of critical illness, and as such is a major cause of potentially preventable
morbidity and mortality. An estimated 25% of patients who have one or more
risk factors will develop a DVT. Pulmonary embolism complicates approximately
one third of cases of DVT, and may be life-threatening. Critically ill patients are
at particular risk of thrombosis due to their acute and chronic illness, immobility,
interventions including organ support and central venous access, sedation and
paralysis.
Tell me about the pathophysiology of VTE
Virchow’s triad describes three factors that are necessary to be present in order for a thrombus form:
1 Perturbation in blood flow, e.g. stasis or turbulence
2 Injury to the vascular endothelium
3 Alterations in blood coagulability
Typically, venous thrombosis occurs following vascular trauma, in response to an indwelling venous device, or in regions of poor flow. Platelets and fibrin are
deposited, and the clot grows rapidly (in the direction of flow). It may occlude
the vein distally, causing the acute presentation of venous congestion (most
commonly of the limbs in a DVT) or pulmonary infarction, or even obstructive
shock with RVF in massive PE. Endogenous fibrinolysis then breaks down the clot over a period of time, but this may be incomplete and result in chronic venous
insufficiency.
What are the risk factors for VTE?
Venous stasis
- Immobility, including anaesthesia >30 mins
- Long travel
- Varicose veins
Endothelial injury -
- Indwelling devices
- Surgery
- Trauma
- Burns
Hypercoagulabilty
- Malignancy
- Pregnancy and puerperium
- Obesity
- Medical conditions (stroke, IBD, nephrotic syndrome (loss of ATIII),
history of VTE, HIT)
- Drugs (combined oral contraceptive, hormone replacement therapy, chemotherapy)
- Smoking
- Ageing
- Thrombophilia (factor V Leidin, activated protein C resistance, antiphospholipid syndrome, antithrombin and protein C and
S deficiencies)
How would you classify pulmonary embolism?
Pulmonary embolism can be classified on the basis of haemodynamic stability:
Massive PE
Acute PE with one or more of the following:
i Sustained hypotension
SBP <90 mmHg for at least 15 min or requiring inotropic support
Not due to a cause other than PE, e.g. arrhythmia, hypovolemia, sepsis, or LVF
ii Pulselessness
iii Persistent profound bradycardia (heart rate <40 bpm with signs or symptoms
of shock)
Submassive PE
Acute PE without systemic hypotension (i.e. SBP ≥90 mmHg) but with either
RV dysfunction or myocardial necrosis
PE may also be classified according to clinical severity, and is based on the
estimated in-hospital or 30-day mortality:
High-risk – suspected or confirmed PE in the presence of shock or sustained
hypotension
Not high-risk – suspected or confirmed PE in the absence of shock or sustained
hypotension
What are the echocardiographic findings in acute
pulmonary embolus?
Acute PE may lead to RV pressure overload and dysfunction, which can be
detected by echocardiography. Right ventricular dilatation is found in 25% of
cases of PE and is used to risk stratify the disease.
McConnell’s sign (reduced RV free wall contractility with sparing of the apex)
has a high positive predictive value for PE even in the presence of respiratory
disease.
In suspected cases of high-risk PE, the absence of echocardiographic signs of RV overload or dysfunction can help to exclude PE as the cause of the haemodynamic
instability.
Do you know of any guidelines for the treatment of
high-risk PE?
The ESC recommend that treatment of pulmonary embolus is coordinated with
MDT input including that of an interventional cardiologist with the following
approach:
1 Haemodynamic and respiratory support
2 Anticoagulation
– IV UFH is the preferred mode of initial anticoagulation
3 Primary reperfusion therapy
i Thrombolysis is first line
ii Surgical embolectomy in patients with contraindications to systemic
thrombolysis or in whom initial thrombolysis has failed to improve the
haemodynamic status
iii Percutaneous catheter-directed treatment if available
Is there any evidence for thrombolysis in submassive PE?
The PEITHO trial (NEJM, 2014) was a multi-centre, randomised, double-blind
comparison of thrombolysis with a single bolus of IV tenecteplase plus
heparin compared to placebo plus heparin. Patients with acute PE were
eligible for the study if they had objective (biochemical or radiographic)
evidence of RV dysfunction. There was a significant reduction in the composite
endpoint of cardiovascular decompensation plus all-cause mortality
within seven days of randomisation. However, there was a significantly
higher rate of major bleeding complications including intracranial haemorrhage
in the intervention arm, highlighting the need to improve the safety of
thrombolytic therapy. Using reduced dose tPA or catheter-delivered localised thrombolysis may be helpful.
What methods are available to help prevent venous
thromboembolic disease?
1 General measures
– Mobilisation
– Hydration
2 Non-pharmacological
– Anti-embolism stockings – reduce venous stasis in legs
Caution with arterial insufficiency, limb fractures, cellulitis and neuropathy
– Sequential calf compression devices (SCCDs)
3 Pharmacological
– LMWH – caution in renal failure
– UFH – bd dosing, similar efficacy
– NOACs – dabigatran (IIa), rivaroxaban (Xa) – licensed for use in thromboprophylaxis
following TKR/THR
– Regional anaesthesia peri-operatively
Tell me about heparin
Heparin is a large polysaccharide (5–40 kDa) and is a naturally occurring anticoagulant that exerts its action by binding to endogenous antithrombin III. This complex then inhibits factor Xa and IIa (thrombin). Unfractionated heparin has a predictable effect on the activated partial thromboplastin time (APTT) when administered intravenously (which is used to monitor therapeutic anticoagulation with heparin), although less so when given subcutaneously. UFH is cleared rapidly by the reticuloendothelial system.
Low molecular weight heparins are short chain polysaccharides (<8 kDa) and
work in a similar manner to UFH, although exhibit limited antithrombin activity.
There is a lower risk of bleeding and complications including HIT and osteoporosis when compared with UFH. LMWHs are renally excreted and their dose should be adjusted in renal impairment. LMWHs require no monitoring (anti-Xa assay may be performed if overdose/accumulation are suspected) and are given on a once daily basis for prophylaxis against VTE.
Protamine may be given to reverse the action of UFH (1 mg will neutralise
100 units of UFH). It must be given slowly to avoid pulmonary vasoconstriction
and hypotension. Protamine may partially reverse the effects of LMWH, but the effects are inconsistent.
What are the causes of an isolated APTT rise, and what would you do in this situation?
The causes of an isolated rise in APTT are:
1 Haemophilia A (factor VIII deficiency)
2 Haemophilia B (factor IX deficiency)
3 Factor XI deficiency
4 Factor XII deficiency
5 Heparin therapy
6 Antiphospholipid syndrome (the antibodies can have a variable effect on the
clotting screen)
7 Artifact
Appropriate action:
1 Review the patient – history, examination, review the notes and drug chart
2 Repeat the APTT and perform a full coagulation screen
– It is important to realise that the results from a clotting screen can be
greatly affected simply by alterations in the volume of blood placed in the
bottle (due to the dilutional effect on the anticoagulant)
3 Request a heparinase test
4 Perform a clotting factor assay
5 Request an antiphospholipid screen (anticardiolipin antibodies and lupus
anticoagulant)
What are the contraindications to the use of heparin?
1 Documented allergy to heparin
2 Previous history of HIT (caution)
3 Active major bleeding or risk of serious re-bleeding including intracranial
haemorrhage or recent ischaemic stroke
4 Platelets <50 x 109/l, coagulopathy
5 Recent neuraxial block/catheter removal
– Heparin may be given >4 hours after uncomplicated neuraxial blockade or
epidural catheter removal
– Neuraxial anaesthesia should be avoided for 12 hours after prophylactic
LMWH has been given
How might your approach to VTE prophylaxis differ in a multiply injured trauma patient who is at high risk of bleeding and of developing VTE?
The patient should be managed using an ABCDE approach, treating abnormalities
as they are found and ensuring all steps are taken to stop the bleeding.
Other measures include:
1 Involve haematology early
2 SCCDs +/– anti-embolism stockings if appropriate
3 Consider IVC filter or Angel® Catheter
The Angel® Catheter is a retrievable IVC filter that can be placed via the femoral
vein on the ICU in a manner similar to CVC insertion. It is intended for use in
patients in whom anticoagulation is contraindicated or in whom the risk of VTE
is very high, e.g. pelvic trauma
Importantly, the emphasis in these patients may change quickly from the management
of life-threatening haemorrhage, to prevention and management of
life-threatening thromboembolism. Any decision with regards to whether to
anticoagulate or not should be carefully documented in the notes and communicated
to the patient and their relatives.
What is HIT?
Heparin-induced thrombocytopenia is a life-threatening prothrombotic complication
of heparin therapy. There are two types:
1 Type I
– Non-immune mediated
– More common (10–20% of patients on heparin)
– Occurs early in treatment – within three days
– Platelet count 100–150 x 109/l
494 Chapter 88: Venous Thromboembolism and Heparin-Induced Thrombocytopenia
– No bleeding/thrombotic complications
– Resolves spontaneously
2 Type II
– Immune mediated – IgG to heparin/platelet factor 4 complex causes platelet
activation and results in arterial and venous thrombosis
– ~0.6% of patients treated with heparin – >10 times more common with UFH
than LMWH
– Occurs 5–10 days after starting treatment
– Platelets fall to ~50 x 109/l or by >50%
– Thrombosis occurs in 20–50%
– Skin necrosis occurs in up to 20%
How do we diagnose HIT?
The pre-test probability of HIT is calculated (the 4 Ts, see Table 88.2), and on this basis a HIT screen maybe carried out after consulting a haematologist. The HIT screen may
be functional (measure heparin-dependent platelet activation by the heparin/PF4
antibody) or use immunoassays (measure antibody level in the blood; however, only
5–30% of patients with heparin/PF4 antibodies will have clinically relevant HIT).
How is HIT managed?
1 HIT is a prothrombotic state and although heparin should be immediately
withdrawn, an alternative anticoagulant should be introduced:
– Argatroban (direct thrombin inhibitor) – first line, IV, half-life ~20 minutes,
only licensed for use in HIT
– Dabigatran (direct thrombin inhibitor)
– Danaparoid (indirect Xa inhibitor) – LMWheparinoid + dermatan sulphate +
chondroitin sulphate
– Fondaparinux (indirect Xa inhibitor) – synthetic heparin pentasaccharide
– Lepiridun and bivalirudin are no longer used in the UK
2 Avoid giving platelets as this will worsen the condition (cf. TTP)
3 Warfarin will worsen the skin necrosis – only consider once plts >150
4 Avoid reintroduction of heparin for 100 days to minimise the risk of
thrombosis
– Does not contraindicate the use of UFH/LMWH but caution is advised – no
IgM antibodies are produced, so the body does not retain immunological
memory
– In extreme circumstances it is possible to measure the antibody titre to
assess response and timing of reintroduction of heparin
In exceptional circumstances, e.g. the patient post-cardiothoracic surgery who
needs to return to theatre, it is possible to use heparin but the patient should be
anticoagulated using an alternative agent immediately post-operatively.
