This document discusses venous thromboembolic disease (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Some key points: - PE is a common cause of death and VTE can result in long-term disability. Risk factors include hospitalization, surgery, trauma, and reduced mobility. - VTE has variable and non-specific symptoms, making it difficult to diagnose. Imaging tests like ultrasound, CT, and pulmonary angiography are used to confirm diagnosis. - Treatment involves anticoagulation to prevent clot extension and recurrence. Therapy is typically divided into acute, maintenance, and long-term phases. Anticoagulation is effective but carries

1. Venous Thromboembolic Disease
• Dr. Mazen Al Zo’ubi, MD, JMB, JRB
• Rheumatology and Internal Medicine Senior Specialist

2. INTRODUCTION
PE is the 3rd most common cause of cardiovascular death after M.I and
CVA.
PE and DVT result in the post-thrombotic syndrome, which is a major
cause of long-term disability.
VTE (the term describing both conditions), is multicausal, often arising
as a result of transient provoking factors, or in individuals with a
heritable or acquired predisposition, but in up to 50% of people no
cause can be established.

3. WHY CLINICIAN MUST BE
VERY FAMILIAR WITH VTE
It is common, particularly in those
• admitted to hospital or
• who have had surgery or
• suffered trauma or
• have other causes of reduced mobility
It is life-threatening
• underdiagnosed
• over diagnosed
• fatal complications
It is preventable
• PE is the most common avoidable cause of death in patients
admitted to hospital,
• and the single leading direct cause of death during pregnancy
and the puerperium

4. WHY CLINICIAN MUST BE
VERY FAMILIAR WITH VTE
It can be difficult to diagnose
• the clinical features and routine initial investigations,
particularly for PE, are often non-specific, and this
leads to diagnostic delays with potentially serious
consequences
Its treatment can be hazardous
• anticoagulant therapy, which may be long-term, is
effective but carries the risk of major, even fatal,
bleeding, and can be particularly challenging in
patients with co-morbidities
It is a significant cause of morbidity
• long-term sequelae are frequent and significantly
impair quality of life.

5. PATHOGENESIS
OF
THROMBOSIS
Thrombosis is the pathological process by which a blood clot or
thrombus forms within a blood vessel, mostly as a result of fibrin
formation with a variable contribution from platelets and other cells.
This differentiates it from physiological haemostasias, the process in
which a fibrin-rich blood clot occurs outside the endothelium as a
result of injury.
Thrombi form on, and are attached to, the vessel wall but emboli
may break off and occlude vessels downstream.
Arterial clots are described as white thrombi and venous clots as red
thrombi, reflecting the contribution that platelets, and fibrin, make
to the former, and fibrin and red cells to the latter.

6. FACTORS
INFLUENCING
THROMBOSIS
The importance of the individual components
of Virchow’s triad varies between arterial and
venous thrombosis:
Turbulence and vessel-wall
dysfunction caused by
atheromatous plaques are
factors in arterial thrombosis.
Stasis and hypercoagulability
are more relevant in the
pathogenesis of venous
thrombosis.
Virchow’s triad:
changes in blood
flow (stasis or
turbulence)
vessel wall
dysfunction
changes in blood
components,
leading to
hypercoagulability.

7. DEFINITIONS
• Most often, venous thrombosis originates in the deep
veins of the leg
• Process starts within the pocket of one of the valves that
line the veins
• Where flow may be turbulent and localized hypoxia may
develop, resulting in endothelial dysfunction.
Deep vein thrombosis
• The thrombus may remain localized to the leg veins or
• may embolize through the circulation to result in a
pulmonary embolus
Pulmonary embolus
• Episodes of venous thrombosis arise in other sites,
such as the upper limb, the cerebral venous
sinuses and the splanchnic veins (hepatic, portal
and mesenteric veins)
• A minority (about 10%)
• Should raise the suspicion for secondary cause.
Unusual-site thromboses

8. EPIDEMIOLOGY
VTE incidence is 1 per 1000 per year overall and is age-dependent
Clinically, about 60% of episodes of VTE present with DVT and the other 40% with
PE, with or without accompanying features of DVT
Uncommon in childhood
Affects around 1 per 10 000 young adults per year and 1 per 1000 middle-aged
adults per year, and approaches an incidence of 1 in 100 elderly adults per year
(aging)
About 10% of patients who died in hospital did so from PE (hospitalization)
Over 5% of people will develop one or more episodes of VTE during their lifetime
(history of VTE).

9. RISK FACTORS CLASSIFICATIONS
Durability
Persistent
Age
Obesity
Ethnicity
Transient
Surgery
Hospitalization
Trauma
Mechanism
Stasis-related
factors
Surgery
Pregnancy
Hypercoagulability
Cancer
OCPs
APS
Degree
Strong risk
factors
•Risk 10–50-fold
Major surgery
Moderate risk
factors
Risk 3–10-fold
Pregnancy
Weak risk
factors
Risk up to 3-fold
Obesity

10. The severity of presentation
depends on both:
1. the thrombus burden and
2. the individual’s
cardiopulmonary
reserve.

11. DIAGNOSIS
• most patients (>80%) who present with suspected VTE
have the diagnosis excluded rather than confirmed.
Unfortunately, the differential
diagnosis of suspected DVT or PE is
very wide,
• the majority of people who die from PE probably do so
because earlier warning signs were missed rather than
because of sudden collapse and death, or failure of
treatment.
The clinical features are often non-specific

12. DIFFERENTIAL DIAGNOSIS
Deep vein thrombosis
• Ruptured Baker’s cyst
• Musculo-tendinous
• trauma, hematoma, myositis, tendonitis
• Superficial vein thrombosis
• Post-thrombotic syndrome
• Cellulitis
• Osteoarthritis, osteomyelitis, synovitis, fracture,
tumor
• Acute arterial occlusion
• Lymphoedema
• Congestive cardiac failure and hypoalbuminemia
• usually cause bilateral leg swelling
Pulmonary embolism
• Chest infection/pneumonia
• Exacerbation of chronic obstructive pulmonary
disease
• Asthma
• Pneumothorax
• Congestive cardiac failure
• Acute coronary syndrome
• Costochondritis
• Musculoskeletal pain or rib fracture
• Aortic dissection
• Pericardial tamponade
• Lung cancer
• Primary pulmonary hypertension
• Anxiety/hyperventilation

13. INITIAL INVESTIGATIONS
ECG
CXR
ABGs
Biomarkers of cardiac injury

14. ECG
There is an S wave in lead I,
a Q wave in lead III and an
inverted T wave in lead III
(the S1, Q3, T3 pattern).
There is sinus tachycardia
(160 beats/min) and an
incomplete right bundle
branch block pattern (an R
wave in AVR and V1 and an
S wave in V6).

15. CXR
• This may be normal
• More often shows non-specific
abnormalities, including atelectasis,
parenchyma abnormalities, cardiomegaly,
elevation of the hemidiaphragm or a pleural
effusion.

16. ABGs
Blood gases typically show hypoxia and
hypocapnia, but again these are non-specific
findings and are not always present
Also shows respiratory alkalosis

17. BIOMARKERS OF CARDIAC INJURY
Plasma levels of brain natriuretic peptide (BNP) or
its precursor, amino-terminal pro-BNP, may be
elevated because of stretching of the right ventricle
Troponin may be increased because of right
ventricular injury due to strain, but once
again these findings are non-specific

18. RISK STRATIFICATION
Wells score for DVT two-level

19. RISK STRATIFICATION
Wells score for PE two-level

20. DVT
APPROACH

21. PE
APPROACH

22. MANAGEMENT
The aim of treatment in the initial phase is to
prevent thrombus extension and hence reduce the
risk of embolization; the goal thereafter is to prevent
thrombus recurrence.
Anticoagulant therapy is the standard treatment for
VTE. It is traditionally divided into three phases:
the acute phase,
lasting 5–10 days
a maintenance phase,
lasting a minimum of
3 months
a long-term phase
beyond this.

23. MANAGEMENT

24. End Of Part One

25. Pulmonary Arterial Hypertension
• Dr. Mazen Al Zo’ubi, MD, JMB, JRB
• Rheumatology and Internal Medicine
Senior Specialist

26. Definitions
Pulmonary hypertension (PHTN):
is a group of conditions with
increased mean pulmonary
arterial pressure (mPAP) > 25 mm
Hg at rest as measured by right
heart catheterization (RHT).
Pulmonary arterial hypertension
(PAH): is specifically to group 1
PHTN defined as mPAP > 20 mm
Hg, pulmonary artery wedge
pressure (PAWP) ≤ 15 mm Hg,
and pulmonary vascular
resistance (PVR) ≥ 3 Wood units.

27. Classification Of Pulmonary Hypertension
Group 1
•pulmonary arterial
hypertension (PAH)
1
Group 2
•pulmonary
hypertension due
to left heart
disease
2
Group 3
•pulmonary
hypertension due
to lung diseases
and/or hypoxia
3
Group 4
•pulmonary
hypertension due
to pulmonary
artery obstructions
4
Group 5
•pulmonary
hypertension with
unclear and/or
multifactorial
mechanisms
5

28. Pulmonary
Arterial
Hypertension
Types
idiopathic
Group 1.1
heritable, with mutations identified in several genes
Group 1.2
drug- and toxin-induced
Group 1.3
disease-associated
Group 1.4
PAH in long-term responders to calcium channel blockers
Group 1.5
PAH with overt features of pulmonary venous/capillary involvement
Group 1.6
persistent pulmonary hypertension of the newborn
Group 1.7

29. Epidemiology
Mean age at diagnosis 50-65
years.
Reported prevalence 15-60 per
1,000,000 adults for PAH.
Reported incidence 5-10 per
1,000,000 adults for idiopathic
PAH (group 1.1) .

30. Risk factors
• Drugs and toxins considered to be definite risk factors
• Aminorex
• Fenfluramine
• Dexfenfluramine
• Drugs and toxins considered to be possible risk factors
• alkylating agents
• Amphetamine
• bosutinib
• Interferon reported to induce pulmonary arterial
hypertension in case report of patient with multiple
sclerosis

31. Pathogenesis
The different groups are
characterized by variable amounts
of hypertrophy, proliferation and
fibrotic changes in distal
pulmonary arteries.
Pulmonary venous changes are
seen in pulmonary venoocclusive
disease and PH groups due to left
heart disease, and the vascular
bed may be destroyed in
emphysematous or fibrotic areas
seen in lung disease.
In chronic thromboembolic
pulmonary hypertension,
organized thrombi are seen in the
elastic pulmonary arteries.
Patients with PH with unclear
and/or multifactorial mechanisms
have variable pathological
findings.
Patients with progressive PH
develop right ventricular
hypertrophy, dilation, heart
failure and death.

32. History
Symptoms
• dyspnea
• fatigue
• weakness
• angina
• syncope (or near
syncope)
• abdominal
distension
• chest pain
• peripheral edema
• palpitations
Disease course
• progressive
breathlessness
• chest pain may
occur with exertion
• exertional dizziness
and syncope (with
development of
right ventricular
dysfunction)
• peripheral edema
• ascites (may develop
later in disease
course)
Medication
history
• aminorex
• fenfluramine
• dexfenfluramine
• benfluorex
• chemotherapeutic
agents
• interferon alfa and
interferon beta
• amphetamine-like
medications
• L-tryptophan
Social history
• cocaine
• methamphetamines
• Alcohol
• HIV infection

33. Physical Examination
May be unremarkable in early
disease
With progression symptoms
and signs of right heart
failure will appear

34. Diagnosis
CXR
• can help
exclude
moderate-to-
severe lung
diseases or
pulmonary
venous
hypertension
due to left
heart disease
2DE
• Consider in
suspected
pulmonary
hypertension
• estimate
pulmonary
pressures by
determining the
tricuspid
regurgitation jet
velocity
• exclude other
causes of PH,
such as left
heart disease or
shunt (contrast
required to
detect shunt)
• assess right
ventricular
function
HRCCT
• Consider in all
patients with
pulmonary
hypertension
V/Q scan
• recommended
in patients with
unexplained
pulmonary
hypertension
ECG
• may provide
suggestive
evidence for
pulmonary
hypertension
but absence of
findings does
not rule out
pulmonary
hypertension
PFT
• identify
contribution of
underlying
airway or
parenchymal
lung disease
RHC
• indicated in all
patients with
PAH to confirm
diagnosis and
determine
severity, which
can influence
the choice of
therapy
prescribed
Vasoreactivity
test
• indicated in
patients with
idiopathic PAH,
heritable PAH,
and PAH
associated with
anorexigen use
to detect
patients who
can be treated
with high-dose
calcium channel
blockers

35. Complications and Prognosis
• Right ventricular dysfunction/right heart failure
• Ascites
• Tachyarrhythmia, commonly atrial flutter and atrial fibrillation
• Pulmonary arterial hypertension (PAH)associated with high morbidity
and mortality, but prognosis varies by underlying condition

36. General
Management
Physical activity. Patients should be encouraged to remain physically active but
avoid exertion that precipitates severe dyspnoea, chest pain or pre-syncope.
Pregnancy. Patients with PAH have a very high mortality rate during pregnancy
(30–50%) and should be counselled against conception. Contraception may
include barrier methods, progesterone-only pill or Mirena coil.
Travel. During plane travel, supplementary oxygen at 2L/min may be
appropriate for patients with reduced functional class and with resting hypoxia
of less than 8kPa.
Vaccination. Vaccination should be given for influenza and pneumococcal
pneumonia.
Elective surgery. Epidural anesthesia may be preferable to a general anesthetic.

37. Pharmaceutical
Management
Oral anticoagulation. There is evidence to support the use of oral anticoagulation in patients
with IPAH, heritable PAH and PAH due to anorexigens.
Diuretics. These are used in patients with right heart failure and fluid overload.
Digoxin. This may be helpful in patients with tachyarrhythmias.
Calcium-channel blockers. These can be effective in high doses in selected patients with IPAH
who demonstrate a response to a vasodilator challenge. Right heart catheterization should
be repeated in 3–4 months to assess response to therapy.
Prostanoids. Prostacyclin is a potent vasodilator that also inhibits platelet aggregation and
cell proliferation. They provide symptomatic relief and can improve exercise capacity.
Endothelin receptor antagonists. Endothelin-1 is a potent vasoconstrictor and mitogen that
binds to endothelin A and B receptors in the pulmonary vasculature. Both dual antagonists
(bosentan) and selective A receptor antagonists (sitaxentan, ambrisentan) can improve
symptoms, exercise capacity and haemodynamics in patients with IPAH.