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Thrombosis - Coagulation Disorders - Venous Thrombosis Diagnosis and…
Thrombosis - Coagulation Disorders - Venous Thrombosis Diagnosis and Treatment
THombosis
Arterial
Fhx
Hypercholesteria
Venous
RF
Oestrogen
Imobility
3.
Venous Thrombosis
Types
Deep venous thrombosis 60%
Lower limb or upper limb DVT
Thrombosis at unusual sites
Mesenteric vein thrombosis
GOnadal vein thrombosis
Renal vein thrombosises
Pulmonary embolism 35%
Cerebral thrombosis 2%
Pathogenesis
Virchow's Triad
Venous stasis
Vessel injury
Hyper coagulation
eg pregnancy
Natural Hx
DEvelopment of DVT is dynamic
Majority initiate in calf veins - may be asymptomatic
Approx half calf vein DVT resolve spontaenously within 72 hr
Approx 1 in 6 will extend into proximal vein - popliteal vein - above knee vein
Symptoms uncommon until extension into proximal veins
Symptomatic DVT more likely to extend than asymptomatic
Risk of embolisation increased with proximal extentino
Epidemiology
Risk of Pulmonary Embolism
Difficult to estimate risk of PE in untreated proximal DVT but may be as high as 50%
Risk of embolism is highest during acute phase
40-50% of pt with symptomatic proximal DVT have evidence of PE on imaging
Incidence
2-3/ 1,000 people per year
11,000 cases in IRE per year
Approx 1.1 mil in the EU every yer
10 mil globally per yr
Risk Factors
Provkoing -> RF that can be identified
Provoking RF
Increasing age
Fhx VTE
Thrombophilia
Surgery
Trauma
Hospital admission
Cancer
Immobility
OCP
Pregnancy
Central venous catheters
Unprovoked
Idiopathic 50%
Circumstance of how the clot formed decides anticoagulation treatment
DVT
Clinical Features
1. Pain 97%
2. Oedma 86%
3. Warmth 72%
Progressive symptoms
Commonest in lower limb
Dilated superficial veins - Dilated, tortured and elongated
Blood from deep veins redirected to superficial
Unilateral oedema / swelling
Difference in calf measurements
Pain of tenderness elicited on palpation
Signs of underlying pathology - eg malignancy
Investigation
History
Signs
Bloods
Won't diagnose
Routine checklist before anticoagulation
FBC
Renal
Liver
BAseline PT
APTT
Imaging
Doppler ultrasound
Lower sensitivity for calf vein DVT
May fail to identify iliac vein thrombi
MR venogram may be helpful for proximal events
Can only go as far as groin
PE
Clinical Features
Dyspnoea 75%
Pleuritic chest pain 66%
Infarct lung tissue and inflammation of pleural membrane - catch when breathing in
Cough 37%
Orthopnoea 28%
Haemopytsis 13%
Palpatation
Presyncopal symptoms
Syncope, collapse
Physical Findings
Tachypnoea
Evidence of DVT
Tachycardia
Chst exam - often non specific abnormalities
CArdiovas exxm - evidence of right ventricular compromise
Investigations
Bloods
BEfore coag
FBC
Biocem
Coag
ABG
Hypoxaemia
Resp alkalosis
ECG
NSR
Sinus tachycadia
Often non specific ST/T wave changes
Classical SI / QIII/ TIII
Large S wave in lead I, Q wave in lead III and inverted T wave in lead III
Signs of right ventricular strain rare (<10%)
CXR
Non specific changes
Area of oligohaemia - Westermark sign
Absence of alternative pathology
CT Pulmonary Angiogram
Has repalced VQ imaging as modality of choice
Newer CT tech allows higher resolution imaging with lower radiation exposure
May identify alternative pathologies
VQ may be useful in certain contexts
eg contrast allergy, rebal disease, CTPH
Role of D-Dimer
Definition
D-Dimers generated when crosslinked fibrin is cleaved by plasmin
Increased in Conditions
VTE
DIC
PET / HELLP
Post op states
Burns
Malignancy
Infx
Pregnancy
Test Value
Good sensitivity for VTE
Poor specificity for VTE
NPV
Rule out test should have high NPV
Management of VTEQ
Anticoagulation Regieme
Initial 0-7 days
Long term 7days - 3 months
Extended 3months to indefinite
NB
Oral acute phase dosing with DOAC Dabigatran and Edoxaban start with LMWH for 5 days
Apixiban and Rivaroxaban have an increased dose for first 7 days(Apix) and 21 days (riv)
Choice of Agents
Take into account clinical circumstances and pt pref
Risk of drug accumulation in renal failure with LMWH and DOACs
BE aware of dif acute phase dosing for DOACs
Dabigatran and Edoxaban not licenced for initial treatment of VTE and Must have initial period of anticoagulation with heparin
Agents
Heparin
Extended Suration Anticoagultaion
Isolated Below Knee DVT
Massive PE
Recurrence
Epi
30% at 10yr no plateu
Highest in first 2 years after VTE
Risk Of Recurrence
Type of DVT
Following surgery
1% per year
3% after 5 yr
Following non-surgical reversible risk factor
5% per yr
15% after 5 yr
Unprovoked
10% per year
30% after 5 yr
Second unprovoked
15% per year
45% after 5 year
Pt Factors
Gender
Persistenly elevated D-Dimer
Evidence of residual thrombosis
Ethnicicty
Risk of recurrence predicted by circumstance of VTE not by duration on anticoagulation or thrombophilia
Complications
Early
Clot extension
Embolisation
Bleeding from anticoagulation
Death - 15% of PE
Late
Recurrence
Post-thrombotic sundrome (10% DVT)
Chronic thromboembolic pulmonary hypertension CTEPH (up to 3% of PEs)
Hospital Aquire Thrombosis (HAT)
Epi
More than 100 fold increased incidence
Leading cause of hospital aquired disability worldwide - beats HAP, catheter related blood stream infx and ADRs
Accounts for 60-70% of all VTE events
Similar no. on medical and surgical wards
With increased age, aquired RF are of greater importance than genetic
Cancer Associated Thrombosis CAT
Epi
4-7 fold increased risk of VTE
12% of ambulatory pt with cancer
20% of all cases of VTE in cancer pt
Cancer pt who develop VTE have 3x increased risk of death
VTE is second leading cause of mortalityin cancer pts
Pathophysiology
Tumour cell processes
Expression of Tissue factors and Cancer Procoagulant
Mechanical compression
Direct vessel invasion (tumour thombus)
Host response to Malignancy
Inflammatory response
Thrombocytosis
Tx mediated effects
Surgery
Venous catheters
Immobility
Drugs
Bleomycin
Cisplatin
Hormonal therapies
Radiation
Pt factors
Age
BMI
Smoking
PMhx
Fhx
Managment
Agents of Choice
LMWH
Direct FXa Inhibitors
Edoxaban
Rivaroxaban
Apixaban
Duration of tx
Minimum 6 months
Extended tx
Setting of ongoing active malignancy
Increased risk of Bleeding in Pt w/ Cancer
Bleeding from tumour sites
Surgical bleeding
Myelosuppresion (chemo, BM infiiltration, radiotherapy)
DIC
Medical co-morbidity
Poor performance status
Cancer Diagnosis after VTE
Est 10% pts with
unprovoked VTE
will be diagnosed with cancer within 1 yr
Large scale epidemiological studies suches SIR of 2.1 - 4.6 in 12 months following unprovoked VTE
Risk highest in first 6 months and reduces to 1.1 after 1 year
Results of Extensive Screening
Most common cancers identified are pancreas, ovary, liver and brain
40% identified cancers are metastatic at time of diagnosis
Cancer assocaited VTE has worse prognosis than similar cancers without VTE (1 yr survival 13% vs 36%)
Increased screening increases pick up
Even with extensive screening 1/3 are missed
Survival not improved with extensive screening
Role Of Screening
Limited screening (hx, physical exam, basic labs, ix per pt symptoms) as effective as CT
No evidence that earlier detection leads to improved outcomes
Risks associated with screening -
indicentalomas,
Unnecessary biopsy
Interruption of anticoagulation
Resource utilisation
Antiphospholipid Syndrome
Definition
Autoimmune multisystem disorder
Characterised by persistent presence of antiphospholipid antobodies and clinical complications
Risk
Recognised increased risk for both venous and arterial thrombosis
Majority cases primary but can occur in assocaition with underlying systemic autoimmune disorder - particularly SLE
Diagnosis - Sapporo Criteria