VTE.pdf

VENOUS
THROMBOEMBOLISM
Baffa A GwaramFMCP
Clinical Haematology unit, Dept of Medicine,
AKTH, Kano.

What is thrombosis
• Thrombosis is the formation or presence of a blood clot in the
cardiovascular system formed during life from the constituents of
blood
• Thrombosis can result in -
Local obstruction of the circulation
Embolisation of clot
Consumption of haemostatic factors (if extensive)
• Venous thrombosis may occur in the deep veins of the limbs
presenting as Deep Vein Thrombosis (DVT) with consequent
embolisation to the lungs resulting in Pulmonary Embolism (PE)
Fac of Int Med, NPMCN, Rev Course 30th July, 2022

Other materials that may embolise to the lung
• Fat (after fracture of long bones)
• Amniotic fluid (post partum)
• Air (e.g. from disconnected central venous lines)
• Tumour (tumour invasion of venous system)
• Infected vegetations (tricuspid endocarditis)
• Foreign materials (drug contaminations injected by abuses)

Venous thromboembolism
• Venous thromboembolism (VTE) is a spectrum of thrombotic
disorders presenting as Deep Vein Thrombosis (DVT) and Pulmonary
Embolism (PE)
• Most patients presenting with PE has asymptomatic DVT and most
patients presenting with symptoms of DVT alone has asymptomatic
PE
• Annual incidence 1/1000 increasing with age
• Case fatality rate 1-5%

Epidemiology
• The actual incidences of DVT and PE are difficult to ascertain because
they are easily missed and large community or regional data are
lacking
• Most epidemiological studies described the incidence of VTE among
hospitalized patients, who have a higher risk of developing DVT
• Autopsy incidence of PE is 10-25% and that of DVT is 20-35%
• The incidence in Sudan was 9.6% and 12% in Malaysia
• Hospital studies in Nigeria revealed that DVT was seen in 0.6% and
2.2% of cases while VTE has a prevalence of 2.9%

Epidemiology
• A review by Tyler et al of venous thrombosis in blacks revealed that:
-The overall incidence of VTE is 30% to 60% higher in blacks than
in whites
-The overall incidence of PE is higher for blacks, as is the
proportion of VTE patients who have a PE.
-Pregnancy-associated VTE rates are also higher in blacks than in
other groups.
• Commonest predisposing factor from Nigerian studies - malignancies
(autopsy); recent surgery and obesity (clinical and laboratory
diagnosis); CVA and malignancies (review of clinic experience)

Pathophysiology
• In 1840 the German pathologist Rudolf
Virchow observed the high frequency of post
partum thrombosis
• He deduced that the major cause of
thrombosis are at least one of the following
three factors-
stasis
hypercoagulability
vessel wall injury
• These factors are otherwise called Virchows’
triad

Pathophysiology
• Thrombus formation may occur in arteries and veins but differ in their
pathophysiology
• Arterial thrombi occur in relatively damaged vessels and are rich in
platelets with minimal fibrin
• Venous thrombi occur in relatively preserved vessels, and are rich in
red blood cells and fibrin with minimal amount of platelets

Risk factors
Patient risk
-Previous VTE
-Immobilization
-Obesity
-Age > 40yrs and esp > 60yrs
-Cancer ±chemotherapy/radiotherapy
-Severe infection
-Respiratory disease
-Heart failure
-Known thrombophilias
-Pregnancy/Pueperium
-Use OCPs/HRT
Procedural risk
-Major orthopaedic surgery to lower limb
-Abd or pelvic surgery lasting 30min under GA
-Major trauma especially hip fracture
-Central Venous/Femoral catheterization

Risk factors
Other risks
-Hypertension
-Diabetes mellitus
-Smoking
-Air travel
-Neurological disease with extremity paresis
-Hospitalization for acute medical illness
-Antiphospholipid syndrome
-HIV infection
-Varicose veins and Superficial vein thrombosis
-Current and past history of thrombophlebitis
-Individuals with a Non-O blood group
Thrombophilias
-Factor V Leiden mutation,
-Antithrombin deficiency
-Protein C deficiency
-Protein S deficiency,
-Dysplasminogenemia,
-Dysfibrinogenemia
-Increased levels of TAFI
-Elevated levels of factor VIII, IX, XI

VTE classification
DVT
• Proximal or Distal
• Superficial or Deep
• Below knee or Above knee
PE
• Acute or Chronic
• Central or Peripheral
• Massive or submassive

Clinical presentation (DVT)
• DVT may be asymptomatic in about 50% of patients and only about
25% of those that present with compatible symptoms are confirmed
on objective testing.
• Common symptoms that are associated with DVT include
Pain in the affected limb due to vein wall inflammation and venous
distension
Redness and warmth due to vein wall inflammation and shunting of
blood from obstructed deep vein to superficial veins
Swelling is mainly due to venous out flow obstruction
• Common signs include – Tenderness
Warmth
Erythema
Cyanosis
Pedal oedema (usually pitting)
Palpable cord (palpable thrombosed vein)
Superficial venous dilatation

Clinical presentation (DVT)
• Some important clinical examination signs associated with DVT are
(although some have questionable clinical use due to risk of
dislodgement of thrombus)
• Homans sign is present if sudden dorsiflexion of ankle joint with knee
flexed to 30° produces discomfort in the upper calf
• Laurels sign denotes worsening of pain along the course of
thrombosed vein by coughing or sneezing
• Lowenbergs sign is positive if after inflation of sphygmomanometer
cuff around the calfs, pain is experienced in affected calf at a lower
pressure than the unaffected calf

Clinical presentation (PE)
• This depend on the number, size and distribution of the emboli; small
emboli may be asymptomatic, whereas large emboli are often fatal
• Dysnoea, tachypnoea (RR > 20/min) and pleuritic pain are three
cardinal features of PE. (absence of these symptoms makes PE
unlikely)
• Other symptoms of cough, haemoptysis, apprehension, palpitations,
sweating, syncope are associated
• Signs include pyrexia; cyanosis; tachycardia; hypotension; ↑jvp;
pleural rub and effusion

Clinical presentation (PE)
• Acute massive
• Sub-acute presentation
• Acute minor with infarction
• Silent – acute minor without infarction
• Chronic thromboembolic pulmonary hypertension
• Atypical – AF, Seizure, altered sensorium, syncope, abd pain,
wheezing, fever, productive cough

Differentials (DVT)
• Deep venous thrombosis need to be differentiated from other clinical
conditions that may present with similar clinical findings like
cellulitis arterial occlusion,
superficial thrombophlebitis neuropathy
lymphedema varicose veins
chronic venous insufficiency arthritis
• The most common differential diagnosis found in some studies are
muscle related (40%), cellulitis (3%),
leg swelling in paralysed leg (9%) venous reflux(8%)
lymphatic (8%) bakers cyst (5%)
unknown (26%)

Differentials (PE)
• MI
• Unstable angina
• Pneumonia, Bronchitis, COPD excerbations
• CCF
• Asthma
• Pericarditis
• Primary pulmonary Hypertension
• Rib fracture
• Pneumothorax

Diagnosis
Investigation of suspected VTE is now frequently on combination of
clinical assessment (pretest probability {PTP} score) and result of D-
dimer measurement

Clinical probability (PTP) asses. score for DVT(Well’s score)
Active cancer (treatment ongoing or within previous 6/12 or palliative) 1
Paralysis, plaster cast 1
Bed > 3/7 or surgery within 4/52 1
Tenderness along deep vein distribution 1
Entire leg swollen 1
Swollen calf (measured >3cm difference between limbs) 1
Pitting oedema in symptomatic leg 1
Collateral veins 1
Alternative diagnosis likely -2
• Total score – 0 = low
1-2 = moderate

Clinical predictions rule for PE – Well’s Rule
Variable Score
DVT 3.0
PE more likely 3.0
HR > 100 1.5
immobilization or surgery x 4/52 1.5
Previous DVT or PE 1.5
Haemoptysis 1.0
Cancer 1.0
Total score: <2.0 = low pretest probability
2.0 to 6.0 = moderate pretest probability
> 6 = high pretest probability

PPT for PE
• A simple pragmatic approach -
Patient has clinical features compatible with PE - (a)
Absence of another diagnosis – (b)
Presence of major risk factor – (c)
• High probability = (a) + (b) + (c) = CTPA
• Moderate probability = (a) + (b) or (c) = CTPA or high sensitivity
D-dimer, and CTPA only if D-dimer is +ve
• Low probability = (a) = D-dimer and CTPA if +ve

VTE – Work up (D-dimer)
• D-dimer is a FDP that is produce in high quantity during thrombosis,
however not specific
• False +ve D-dimer results are seen in infection, inflammation,
malignancy, tissue trauma, pregnancy, postoperative state, DIC, AF,
acute MI, acute CVD, HbSS
• Can be used to exclude thrombosis

VTE – Work up (Doppler ultrasound)

VTE – Work up (CTPA-Computed tomography pulmonary angiography)
-rapid spiral images taken
-definitive non-invasive test
-most widely used for diagnosis or exclusion

VTE – Work up (Chest X-ray)
-Elevation of hemidiaphragm + areas of linear atelectasis → PE
-Pleural effusion with wedge-shaped peripheral opacities in pulmonary
infarction (Hampton’s hump)
-Area of under perfusion + few vascular markings (Westermark sign)
-Enlarged pulmonary artery:- feature of PHTN in Chronic
thromboembolic disease

VTE – Work up (Chest X-ray)
Westermark sign Hampton’s hump

VTE – Work up {Ventilation Perfusion scan (V/Q)}

VTE – Work up (ECG)
• Right heart strain + depression of ST-segment and T wave in V1-V3 +
RAD + S1Q3T3 pattern → massive PE

VTE – Work up
• Pulmonary angiogram
Diagnostic features:- -intraluminal filling defects
-abrupt cut off of vessels
-peripheral pruning
-reduced perfusions
• Venography
• Troponin
• Magnetic resonance imaging (MRI) - for pregnant women
• Echocardiography
• Arterial blood gases
• Others – FBC, E/U&Cr, PT, PTTK, INR, LFT

Covid-19 and VTE
• Thrombotic complications are frequent in COVID-19 and contribute
significantly to mortality and morbidity
• Pulmonary thrombosis appears to be common in COVID-19
pneumonia and takes two forms, proximal pulmonary emboli and/or
distal thrombosis
• Vaccines also has some reports of increase risk of thrombosis
• The coronavirus family have been shown to enter cells through
binding ACE-2, found mainly on alveolar epithelium and endothelium
• Activation of endothelial cells is thought to be the primary driver for
the increasingly recognised complication of thrombosis

Covid-19 and VTE
• The high rate of pulmonary thrombosis in COVID-19 conceivably lies
in the confluence of three processes:
-The intense endothelial inflammation leading to “in situ”
thrombosis, including microvascular thrombosis
-Altered pulmonary blood flow in response to the parenchymal
process, disturbing Virchow's triad within the lung
-Classical DVT to PE transition
• Hypercoagulability in sepsis that may be upregulated in COVID-19
include: immune-mediated thrombotic mechanisms; complement
activation; macrophage activation syndrome; antiphospholipid
antibody syndrome; hyperferritinemia; renin-angiotensin system
dysregulation.

Treatment
• Immediate full anticoagulation is mandatory for all patients suspected
of having DVT or pulmonary embolism
• Diagnostic investigations should not delay empirical anticoagulant
therapy
• Long-term anticoagulation is critical to the prevention of recurrence
of DVT or pulmonary embolism (ACCP GUIDELINES)

Treatment
• Therapeutic dose of LMWH for 3-5 days
• Loading dose of oral VKA (warfarin) when diagnosis is confirmed with
prediction of daily maintainance dose of target INR 2.5 (concomitant)
• Oral anticoagulation for 3-6 months for 1st episode of VTE (extended
if recurrent)
• Compression stockings
• If massive PE thrombolysis is 1st line of treatment
• IV bolus of UFH (10000iu) recommended after thrombolysis in
massive PE followed by LMWH
• LMWH alone for non massive PE
• Vena cava filters/ Thrombolectomy

Treatment
Anticoagulation medications include the following: –
• Unfractionated heparin
• Low-molecular-weight heparin (dalteparin, enoxaparin, tinzaparin)
• Warfarin
• Factor Xa Inhibitors (rivaroxaban, apixaban, Fondaparinux)
• Direct thrombin inhibitor (Dabigatran)

Treatment
Thrombolytic agents used in managing PE include the following:
•Streptokinase
• Urokinase
• Reteplase
• Alteplase

Risk assessment and thromboprophylaxis
• Decision and choice of prophylactic intervention depend on patient,
procedural and bleeding risks
• Patient and procedural risks (see risk factors)
• Bleeding risk factors –
-Surgery – eye, neuro, others
-Haemophilia and other bleeding disorders
-Thrombocytopaenia
-Recent cerebral haemorrhage
-Severe liver disease
-Peptic ulcer
-Endocarditis

Risk assessment and thromboprophylaxis
• Methods of prevention of VTE - Mechanical- IPC & GCS
Pharmacological – UFH & LMWH
• UFH 5000iu 2-3 times daily reduces the risk of VTE by > 50%
• LMWH in equally or more effective with lower risk of bleeding
• The combination of GCS and heparin is more effective than either
alone

Approach to prevention
• Identifying patient VTE risk factors during admission
• Identifying patient contraindications to pharmacologic prophylaxis
during admission
• Ordering risk-appropriate VTE prophylaxis
• Reassessing VTE risk status and contraindications during
hospitalization

Prognosis
• Depends on 2 factors: -the underlying disease state
-appropriate diagnosis and treatment.
• Approximately 10% of patients with PE die within the first hour, and
30% die from subsequent embolic episode
Anticoagulant treatment decreases mortality to less than 5%
• The deaths occurred due to cardiac disease, recurrent pulmonary
embolism, infection, and cancer
• The risk of recurrent PE due to the recurrence of proximal venous
thrombosis
• Approximately 17% of patients with recurrent PE were found to have
proximal DVT.

Take Home Message
• DVT and PE are the same disease
• Assigning pretest probability for VTE is an essential step in diagnosis
• DVT & PE can be diagnosed or excluded in many but not all patients
using noninvasive means
• VTE can be safely managed with heparin for at least 5 days with
simultaneous warfarin without a loading dose
• Always consider VTE prophylaxis in in-patients

References
• John H. Derick. Stedman’s concise medical and allied health dictionary. Illustrated (1997)
third edition. Williams and Wilkins
• Jack Hirsh, Mark A Crowther. Venous Thromboembolism. In Hoffman Hematology: Basic
principles and practice, Ronald H, Edward J. B, Sanford J.S, Bruce F, Harvey J.L, Leslie E.S,
Philip M. (Editors). Third edition (2000), Churchill Livingstone inc. p2075-2088
• Dennis A. Gastineau. Initiation and control of coagulation. In manual of Clinical
Hematology, Joseph J. Mazza (Editor). Third edition (2002), Lippincott, Williams and
Wilkins. P 355-368
• Cunningham IGE, and Yong ND. Incidence of post–operative deep vein thrombosis in
Malaysia. Br. J. Surg. 1974; 61: 482–3.
• Osime U, Lawrie J, Lawrie H. Post operative deep vein thrombosis incidence among
Nigerians. Niger Med J. 1976 Jan; 6:26-8.
• Clinical practice guideline for the prevention of venous thromboembolism in patients
admitted to Australian hospitals 2009. National Health and Medical Research Council.
Page 9-56.
• R Parakh, VV Kakkar, AK Kakkar. Management of Venous Thromboembolism. Journal of
association of physicians India. January 2007; 55:49-70

References
• Drew P et al. Oxford handbook of clinical haematology, third edition (2009)
• Jack Hirsh and Agnes Y. Y. Lee. How we diagnose and treat deep vein thrombosis. Blood
Journal. 2002; 99:3102-3110
• Watila M.M, Nyandaiti Y, Balarabe SA, Ibrahim A, Alkali NH, Gezawa ID, Bwala SA. Medical
complications among stroke patients at the University of Maiduguri Teaching Hospital,
Northeastern Nigeria. Journal of Medicine and Medical Science March 2012; 3:189-194,
• Goldhaber S. Pulmonary embolism and deep vein thrombosis. www.thelancet.com
• Pistolesi M. Pulmonary Embolism, in Respiratory Medicine (ERS Handbook). 332-335.
(2010)
• Prospective Investigation of Pulmonary Embolism Diagnosis Study. J Nucl Med. 1995. Dec
36 (12) 2380 -7 (Medline)
• Keeling D et al. The diagnosis of DVT in symptomatic outpatients and the potential for
clinical assessment and D-dimer assay to reduce the need for diagnostic imaging. Brit J
Haeatol,124,15-25 (2004)
• Baglin T P et al. Guidelines on use of vena cava filters. Br J Haematol, 134,590-5(2006)

References
• Tyler W Buckner, Nigel S Key. Venous Thrombosis in Blacks. Circulation. 2012 Feb
14;125(6):837–9.
• Sotunmbi PT, Idowu AT, Akang EEU, Aken'Ova YA. Prevalence of venous
thromboembolism at post-mortem in an African population: a cause for concern. Afr J
Med Med Sci. 2006 Sep;35(3):345–8.
• Okunade MA, Kotila TR, Shokunbi WA, Aken'Ova YA. Venous thromboembolism in
Ibadan: A five year experience (1986-1990). Niger Q J Hosp Med. 1998 Jan 1;8(2):80–2.
• Ahmed SG, Tahir A, Hassan AW, Kyari O, Ibrahim UA. Clinical Risk factors for deep vein
thrombosis in Maiduguri - Nigeria. Highl Med Res J. 2003 Jan 1;1(4):9–16.
• Thomas C Hanff et al. Thrombosis in COVID-19. Am J Hematol 2020 Dec;95(12):1578-
1589.
• Laura C. Price, Colm McCabe, Ben Garfield, Stephen J. Wort. Thrombosis and COVID-19
pneumonia: the clot thickens! European Respiratory Journal 2020 56: 2001608; DOI:
10.1183/13993003.01608-2020
• Guideline for management of Venous Thromboembolism in Nigeria by the Nigerian
Society for Hematology and Blood Transfusion (2018)

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