FAKULTAS KEDOKTERAN

UNIVERSITAS MUSLIM INDONESIA Makassar,12 April 2019

LAPORAN PBL
MODUL VASKULAR
BLOK KARDIOVASKULAR

OLEH:
KELOMPOK 15
M. Farizan Atjo (11020160032)
Ainunnisa Muhammad (11020170003)
Miftahul Janna (11020170042)
Moh. Yusril (11020170052)
Muhammad Fakhri (11020170069)
Muh. Fadil Asrar (11020170055)
Jihan Adjdjibiyan S. Azzubaidi (11020170105)
Indah Setiyani Ulum (11020170134)
Andi Bau Syatirah Ninnong M (11020170138)
Hernita (11020170152)
TUTOR: dr. Nurfachanti, M.Kes
FAKULTAS KEDOKTERAN
UNIVERSITAS MUSLIM INDONESIA
MAKASSAR
2019
SCENARIO 3
A 42 year old man came to the Public Health Service with complaint of swelling
in the left leg with severe redness on the last 1 day. Patient often feel cramps and
sometimes feel numb and accompanied by pain. The patient’s occupational history
is an expedition driver between provinces.
On physical examination blood pressure was 120/80 mmHg. Pulse 92x/minute,
respiratory rate 20x/minute, temperature: 36,80C. Examination of the extremities
found redness as high as 1/3 proximal tibia with erythema accompanied by pitting
edema. Normal popliteal arterial pulsation

Keywords
1. 42 years old man
2. Swelling in the left leg with severe redness on the last 1 day
3. Feel cramps and feel numb
4. Patient is an expedition driver between provinces
5. Blood pressure: 120/80 mmHg, Pulse: 92x/minute, RR: 20x/minute,
Temperature: 36,80C
6. Extremities found Redness as high as 1/3 proimal tibia with erythema and
pitting edema. Normal A. Popliteal Pulsation

Question :
1. How is the mechanism of Edema?
2. How to difference disease cause by Artery and Vein?
3. What is relation between activity and swelling in the leg?
4. Why the patient feel cramp and numb?
5. How to diagnose the patient based on scenario?
6. What is the differential diagnose in the scenario?
7. What is the first treatment based on the scenario?

Answer :
1. How is the mechanism of Edema?
Edema is excessive fluid accumulation between body cells or in
various body cavities, this condition is often encountered in daily clinical
practice that occurs as a result of imbalance of factors that control the
transfer of body fluids, including the capillary hemodynamic system
causing sodium and water retention, kidney disease and the transfer of
water from intervascular to intertotal.
Edema occurs in conditions where there is an increase in
hydrostatic capillary pressure, increased capillary permeability or
increased intertial osmotic pressure, or a decrease in plasma osmotic
pressure. The kidneys have a central role in maintaining body fluid
homeostasis by controlling the volume of extracellular fluid through
regulation of sodium and water excretion. Antidiuretic hormones are
secreted in response to changes in blood volume, tonicity and blood
pressure to maintain balance of body fluids.1

Edema can be caused by:

a. Inflammation, namely edema as a result of an increase in vascular
permeability with the disappearance of exudates that are rich in
protein.
b. Non-inflammation, namely edema caused by changes in hemodynamic
pressure on the capillary wall (also called hemodynamic edema).
c. Lymphadema secondary to reduced lymphatic drainage.

Edema can be divided into:

a. Local Edema
Local edema is if there is swelling on one side of the body. Local
edema usually occurs due to local causes, such as insect bites, skin
allergies, blockage of blood vessels in the area, and so on. Local edema
is usually more mild and not fatal.
b. Edema General
General edema is when swelling occurs in more than one part of
the body. General edema usually occurs due to interference or failure
of an organ in the body. Examples: heart failure, kidney failure, liver
failure, tumors, cancer and so on.

General related mechanisms:

 a. Decrease in colloid osmotic pressure.
If the plasma protein in the blood is thinning, the inward strength
decreases which allows movement into the tissue. This results in
accumulation of fluid in the tissue with a decrease in central plasma
volume.
b. Increased capillary hydrostatic pressure.
The most common cause of increased capillary pressure is
congestive heart failure where increased systemic venous pressure is
combined with an increase in blood volume. This manifestation is
characteristic for right ventricular failure or right heart failure. If this
pressure exceeds 30mm, pulmonary edema occurs.
c. Increased capillary permeability.
Direct damage to blood vessels, such as burn injury, can cause
increased permeability of endothelial relationships. Local edema can
occur in response to allergens, such as bee stings.
d. Lymphatic Obstruction.
The most common cause of lymphatic obstruction is surgical
removal of lymph nodes and blood vessels to prevent the spread of
malignancy.
e. Excess water and sodium.
In congestive heart failure, cardiac output decreases when the
strength of the contraction decreases. To compensate, an increase in the
amount of aldosterone causes sodium and water retention. Plasma
volume increases, as does intervascular capillary venous pressure. This
failed heart is unable to pump up this venous return, and fluid is forced
into the interstitial.2,3

2. How to difference disease cause by Artery and Vein?

Artery
Severe pain, burning, fatigue, cramps, or tingling in the affected
area, symptoms appear in various activities, improve with rest, other
symptoms are found lesions especially in the peripheral area, parasthesia,
paralysis, raynaud or cyanosis if you get exposure to cold temperatures the
most common area is in the fingers and toes, but is rarely found on the
tongue, nose and ear lobe.4
 Vein
Deep vein thrombosis can appear with the first symptoms found,
namely edema that is more often unilateral, then can be accompanied by
pain and itching or ulcers which improve with elevation of the foot
position, in some patients it is found that symptoms can be aggravated
during activities.4

3. What is relation between activity and swelling in the leg?

Sitting for too long, such as when driving or on an airplane. When
our feet are in a stationary position for quite a long time, our leg muscles
do not contract so that the muscle pump mechanism does not go well. 5
In 1856 virchow first discovered the pathogenesis of DVT and
pulmonary embolism known as Virchow trias (stasis, hypercoagulability
and injury)
a. Stasis (the presence of slow blood flow) is a condition of
immobilization of one's activities, for example lying more than 3 days
or legs hanging more than 7 hours (when sitting) slow flowing blood
gives more opportunities for freezing (thrombus), loose thrombus
following venous blood flow to the right heart and after reaching the
pulmonary circulation
b. damage to the vein wall
c. the state of blood easily freezes

So it can be concluded that the effect of patient activity as a driver

patient lacks leg muscle contractions, causing DVT (deep vein
thrombosis),chronic vein insufficiency that can lead to swelling in the leg
because In the condition of a blocked vein (congestion), an increase in
intra-vascular hydrostatic pressure (the pressure that pushes blood to flow
in the vasculature by the work of the heart pump) causes permeation of
plasma fluid into the interstitium space. This plasma liquid will fill
between the loose connective tissue and body cavity (edema).5,6
4. Why the patient feel cramp and numb?
Cramp
A cramp is a sudden, involuntary muscle contraction or over-
shortening; while generally temporary and non-damaging, they can cause
significant pain, and a paralysis-like immobility of the affected muscle.
Onset is usually sudden, and it resolves on its own over a period of several
seconds, minutes or hours. Cramps may occur in a skeletal muscle or
smooth muscle. Skeletal muscle cramps may be caused by muscle fatigue
or a lack of electrolytes such as low sodium, low potassium or low
magnesium. Cramps of smooth muscle may be due to menstruation or
gastroenteritis.
Muscle contraction begins with the brain setting off action
potentials, which are waves in the electrical charges that extend along
neurons. The waves travel to a group of cells in a muscle, letting calcium
ions out from the cells' sarcoplasmic reticula (SR), which are storage areas
for calcium. The released calcium lets myofibrils contract under the power
of energy-carrying adenosine triphosphate (ATP) molecules. Meanwhile,
the calcium is quickly pumped back into the SR by fast calcium pumps.
Each muscle cell contracts fully; stronger contraction of the whole muscle
requires more action potentials on more groups of cells in the muscle.
When the action potentials stop, the calcium stops flowing from the SR
and the muscle relaxes. The fast calcium pumps are powered by the
sodium gradient, or the pent-up sodium ions that rush out from the SR.
The sodium gradient is maintained by the sodium-potassium pump. A lack
of sodium would prevent the sodium gradient from being strong enough to
power the calcium pumps; the calcium ions would remain in the
myofibrils, forcing the muscle to stay contracted and causing a cramp. The
cramp eventually eases as slow calcium pumps, powered by ATP instead
of the sodium gradient, push the calcium back into storage.
Cramps can occur when muscles are unable to relax properly due
to myosin proteins not fully detaching from actin filaments. In skeletal
muscle, ATP levels must be large enough to bind to the myosin heads for
 them to attach or detach from the actin and allow contraction or relaxation;
the absence of enough levels of ATP means that the myosin heads remains
attached to actin. The muscle must be allowed to recover (resynthesize
ATP), before the myosin proteins can detach and allow the muscle to relax.
Skeletal muscles work as antagonistic pairs. Contracting one skeletal
muscle requires the relaxation of the opposing muscle in the pair.7

Numb
Numbness is most often caused by damage, irritation or
compression of nerves. A single nerve branch, or several nerves, may be
affected, as with a slipped disc in the back or carpal tunnel syndrome in
the wrist. Certain diseases, such as diabetes, which can damage the
longest, most sensitive nerve fibers (such as those going to your feet), can
also cause numbness.
Usually, the affected nerves are located on the periphery of your
body. Only rarely is numbness caused by problems in your brain or spinal
cord. Numbness alone is only rarely associated with potentially life-
threatening disorders, such as strokes or tumors.7

5. How to diagnose the patient based on scenario?

ANAMNESIS
Symptoms felt by patients are dependent on vascular disease
suffered by patients. In patients with arterial disease, symptoms can be
caused by stenosis, blockage, or sometimes aneurysm, whereas venous and
lymphatic disease should be suspected in patients with swelling, venaises,
veins, or local inflammation in the legs. the subsequent swelling must be
distinguished from the causes of venous and lymphatic disease, trauma,
inflammation or heart failure, cirrhosis, nephrotic syndrome and others.
Venous and lymphatic disease Deep venous thrombosis can appear
with symptoms of swelling that are often unilateral. An uncomfortable
feeling can arise. Risk factors for thrombosis such as the period of
immobility.

Scenario:
 A 42-year-old man came to the public health with a complaint
swelling in the left foot with redness weighing in the last 1 day. Frequent
patients feel cramps and sometimes like numbness and pain. History the
patient's job was an expedition driver between provinces.

PHYSICAL EXAMINATION
1. Vital signs: blood pressure 120/80 mmHg, pulse 92x / minute,
breathing 20x / minute, temperature: 36.8 0 C.
2. Inspection: symmetry, changes in skin appearance and edema, skin
color (on examination of extremities found redness as high as 1/3
proximal tibia with erythema accompanied by pitting edema.)
3. Palpation: pulsations in the upper and lower limbs. Asymmetricity,
intensity pressure suppression and weakening of the pulse can lead to
peripheral arterial disease
a. Examination of Allen
b. Thoracic outlet maneuver
c. Signs of homan: an examination is performed by bending the
patient's knee and forcibly pushing the ankle into a dorsiflexion
position. The presence of calf pain with this maneuver indicates
thrombosis in the vein.
Normal popliteal arterial pulsation.

SUPPORTING INVESTIGATION
 Duplex examination of the extremity veins can evaluate the
presence of non-invasive thrombosis in the deep vein
 Magnetic resonance angiography (MRA)8

6. What is the differential diagnose in the scenario?

Varicose veins
Definition
Varicose veins are veins that are dilated due to increased venous
pressure. Varicose veins are a manifestation of venous insufficiency, where
venous blood flow is refluxed due to damage to the venous valve.

Etiology
 The veins function to drain blood from the entire body back to the
heart. To reach the heart, the muscles of the lower extremities must
contract to squeeze and pump blood from the lower extremity veins back
towards the top (heart) against the effects of gravity. Veins have many one-
way valves to prevent blood from returning down (reflux). If the venous
valve is damaged so that the blood pumped from the lower extremity to
the heart partially returns to the bottom and accumulates causing venous
pressure to increase.
Lower extremity venous damage resulting in backflow or reflux as a
result of:
a. Venous hypertension
b. Deep vein thrombosis
c. Obesity
d. Leg immobility
e. Pregnancy
f. Often standing or sitting for long periods of time due to lifestyle or
profession
g. The aging process

Pathogenesis
Valve failure in the superficial vein is most commonly caused due
to increased pressure in the blood vessels by venous insufficiency. Another
possible cause of venous valve failure is the direct trauma to the vein in
the presence of a valve abnormality due to thrombosis. If the superficial
vein is exposed in the presence of high pressure in the blood vessels, these
veins will be dilated and then continue to enlarge until the vein valves
from one another cannot meet each other. Failure in one vein valve will
trigger failure of the other valves. An increase in excessive pressure in the
superficial venous system will cause dilatation of the vein
local. After several venous valves fail, the function of the vein to drain
blood up and into the deep vein will be disrupted. Without functional
valves, venous blood flow will flow due to pressure and gravity gradients.

Clinical features
Varicose veins are classified as:
a. Primary varicose veins, due to superficial venous abnormalities of the
lower extremities
b. Secondary varicose veins, due to abnormal venous insufficiency,
which includes edema, skin pigmentation, and ulcers.

Primary varicose veins occur when the superficial venous system

valves (v. Saphena magna, v. Saphena parva and v. Perforantes) fail to
close properly, so that reflux will occur downward and chronic venous
dilatation occurs, while v. Profunda is still normal. Secondary varices
occur as a result of the v. Profunda system experiencing thrombosis /
thrombophlebitis, deep venous obstruction due to tumor / trauma or the
presence of an arterovenous fistula, which initially is normal and then
compensates for widening of the superficial vein.

Physical examination:
a. Crash at night lower limb muscles (legs)
b. The legs get tired quickly when walking
c. Swelling and heaviness in the legs
d. Clinical features of venous insufficiency (edema, pain, discoloration,
to ulcers)
e. Itching of the legs
f. Tingling in the legs
g. Widening of the blue or dark purple veins that appear on the skin

Supporting investigation
• Brodie-Tredelenburg test
Shows back blood flow through the incompetence of superficial
venous valves and branches associated with veins in the legs. The patient
is lying down, the affected limb is elevated 45 ° to empty the vein. Then
tourniquet is placed around the upper limb and the patient is asked to
stand. If venous filling is <30 seconds distal to tourniquet, the perforator
vein and vein are incompetent. If when the tourniquet is released, blood
will fill and flow quickly from the top to the superficial vein, meaning the
superficial vein valve is incompetent.
• Test Perthes
A tourniquet is placed in the middle of the thigh in a standing
position. If the varicose vein disappears after 5 minutes of walking, the
inner vein and perforator vein are competent. If the blood vessels are not
able to empty themselves but instead pain and distension when walking,
meaning there is incompetence or obstruction.
• Venous Duplex Imaging
Can detect reflux in the superficial vein, perforator vein or deep
vein.
• Venous plestimography
To detect changes in venous blood volume in the limbs, normal
<2mL / s,> 4mL / s is abnormal.
• Computed Tomographic or Magnetic Resonance Venography
Can be used to assess venous anatomy, blockage of veins.
• Venography
Contrast is injected into the venous system to identify reflux in the
venous flow system.

Governance
1. MPFF (Micronized Purified Flavonoid Fraction)
Dosage of 1000 mg / day for 6 weeks
 To improve venous vascular tone, improve microcirculation
and lymphatic flow thereby reducing swelling.
 Reducing leukocyte adhesion thereby reducing inflammation
2. Compression stocking
 It is useful to press the edge of the vein wall towards the lumen
so that the center of the valve approaches and reflux decreases
in addition to increasing the pressure of the paravascular tissue
and muscle contraction, thereby increasing venous tone.
 Stocking is used while on the move, and released during sleep
 Use of stockings below the knee
3. Treatment of venous sclerosing.
4. Endovenous radiofrequency or laser ablation therapy.
5. Surgery by means of ligation or vein stripping9

Chronic Veins Insufficiency

Introduction
Chronic venous insufficiency (CVI) describes a condition that
affects the venous system of the lower extremities, with venous
hypertension causing various pathologies, including pain, edema, skin
changes, and ulcerations. CVI often indicates the more advanced forms of
venous disorders, including manifestations such as hyperpigmentation,
venous eczema, lipodermatosclerosis, atrophie blanche, and healed or
active ulcers.

Epidemiology
The importance of CVI is related to the number of persons afflicted
and the socioeconomic impact of its more severe manifestations.
Varicose veins have an estimated prevalence between 5% and 30%
in the adult population, with a female:male predominance of 3:1, although
a more recent study supports a higher male prevalence. CVI was more
common with increasing age; however, there was no significant sex
difference. The rate of varicose vein development may be estimated from
the Framingham Study, which found an annual incidence of 2.6% in
women and 1.9% in men. The prevalence of varicose veins is higher in
developed, industrial countries than in underdeveloped countries. Risk
factors found to be associated with CVI include age, sex, a family history
of varicose veins, obesity, pregnancy, phlebitis, and previous leg
injury.9 There are also environmental or behavioral factors associated with
CVI, such as prolonged standing and perhaps a sitting posture at work.
The overall prognosis of venous ulcers is poor, because delayed
healing and recurrent ulceration are very common. The socioeconomic
impact of venous ulceration is dramatic because of an impaired ability to
engage in social and occupational activities, reducing the quality of life
and imposing financial constraints.

Venous Pathophysiology
Normal Venous Anatomy and Function
The peripheral venous system functions as a reservoir to store
blood and as a conduit to return blood to the heart. Proper functioning of
the peripheral venous system depends on patency of vessels containing a
series of 1-way valves and muscle pumps. In the erect position, blood that
enters into the lower extremity venous system must travel against gravity
and other pressures to return to the central circulation.
The veins of the lower extremity are divided into superficial, deep,
and perforator veins. The superficial venous system is located above the
muscular fascial layer. It is composed of an interconnecting network of
veins and several truncal superficial veins, including the great saphenous
vein (GSV) and small saphenous vein, as well as several accessory veins,
which may develop pathology contributing to CVI. The deep venous
system is located below the muscular fascia and serves as collecting veins
and the outflow from the extremity. The deep veins of the lower extremity
consist of axial veins, which follow the course of the major arteries, and
intramuscular veins, including venous sinusoids and plexi. The perforating
veins traverse the anatomic fascial layer to connect the superficial to the
deep venous system.
The valves within the veins are essential in assuring that blood
flows in the correct direction, particularly while in the upright posture.
There is a series of 1-way bicuspid valves located throughout the deep and
superficial veins that open to allow flow toward the heart but close to
prevent the return of blood toward the feet. There are 4 phases of valve
function which include opening, equilibrium, closing, and closed. The
critical factors to valve function are axial vertical of blood flow opening
the valve and vertical velocity in the valve cups that increases mural
pressure relative to the luminal pressure leading to valve closure. The
frequency of these venous valves increases from the proximal to distal leg
to prevent an increase pressure within the distal veins because of
gravitational effects. In addition, perforating veins also contain valves that
only allow blood flow from the superficial to the deep veins.
The valves function in concert with venous muscle pumps to allow
the return of blood against gravity to the heart. Contraction of the muscle
pumps, primarily in the calf, force blood out of the venous plexi to ascend
up the deep venous system. The valves prevent blood from being forced
more distally within the deep system or through perforator veins into the
superficial system. Immediately after ambulation, the pressure within the
veins of the lower extremity is normally low because the venous system
has been emptied by the muscle pump action (Figure 1). Relaxation of the
muscle pump then allows blood to refill to the deep venous system. With
prolonged standing, the veins become distended as the vein fills via
antegrade flow, allowing the valves to open and pressure to increase.
Contraction of the muscle pump will again empty the veins and reduce
venous pressure.

Figure 1. Illustrative ambulatory foot venous pressure

measurements during exercise and at rest over time in the standing
position. A, Normal venous pressure. The resting standing venous pressure
in ≈80 to 90 mm Hg. The pressure drops to ≈20 to 30 mm Hg (or >50%
decrease) with calf exercise. The return in pressure is gradual, with refill
taking >20 seconds. B, Abnormal venous pressure with venous reflux. The
resting standing pressure is usually higher than normal. The drop in
pressure with exercise is blunted (<50% decrease). The return in venous
pressure to the resting level is rapid because of a short refill time (<20
seconds). C, Abnormal venous pressure with venous obstruction. Resting
standing venous pressure is usually higher than normal. There is minimal-
to-no drop in pressure with exercise.

Venous Pathophysiology and Dysfunction

Venous pathology develops when venous pressure is increased and
return of blood is impaired through several mechanisms. This may result
from valvular incompetence of axial deep or superficial veins, perforator
veins, venous tributaries, or venous obstruction, or a combination of these
mechanisms. These factors are exacerbated by muscle pump dysfunction,
most notably of the calf muscles. These mechanisms serve to produce
global or regional venous hypertension, particularly with standing or
ambulation. Contributing to the macrocirculatory hemodynamic
disturbances are alterations within the microcirculation. Unabated venous
hypertension may result in dermal changes with hyperpigmentation;
subcutaneous tissue fibrosis, termed “lipodermatosclerosis”; and eventual
ulceration.
Dysfunction or incompetence of the valves in the superficial
venous system also allows retrograde flow of blood, which is called
“reflux” and serves to increase hydrostatic pressures. Valve failure of the
superficial veins may be primarily because of pre-existing weakness in the
vessel wall or valve leaflets or secondary to direct injury, superficial
phlebitis, or excessive venous distention resulting from hormonal effects
or high pressure. Failure of valves located at the junctions of the deep and
superficial systems, at the saphenofemoral and saphenopopliteal junctions,
can be a source of reflux leading to CVI. Incompetence of the valves of the
superficial veins with reflux has been shown in ≤90% of patient presenting
the CVD with reflux in the GSV, accounting for 70% to 80%, and in ≈84%
of those presenting with venous ulcers.
Dysfunction of the valves of the deep system is most often a
consequence of damage from previous deep vein thrombosis. The damage
to the valves of the deep veins leads to rapid refilling by pathologic
retrograde venous flow and may even reduce the blood volume exiting the
limb. The venous pressure immediately after ambulation may be slightly
elevated or even normal, but the veins refill quickly with the development
of high venous pressure without ongoing muscle contraction (Figure 1).
Dysfunction of the deep vein valves has been shown to increase the rate of
progression of venous disease with a higher rate of venous ulceration
formation.
Failure of the valves in the communicating perforator veins may
also allow high pressure to enter into the superficial system. Perforator
valve incompetence allows blood to flow from deep veins backward into
the superficial system with force because of the high pressures generated
by the muscle pump action. This excessive local pressure can produce
dilatation of the superficial veins and their valve cusps with secondary
failure of the valves. This may result in a localized cluster of dilated veins
that ascends up the leg.
In addition, reflux may also occur in venous tributaries in the
absence of any truncal superficial or deep vein or perforator vein
reflux. The most common tributaries with reflux are in communication
with the GSV (≈60%), small saphenous vein (≈20%), or both (≈10%). This
process of isolated tributary reflux may contribute to progression of
disease within the other superficial or deep venous segments.
Obstruction of the deep veins may limit the outflow of blood,
causing increased venous pressure with muscle contraction, and lead to
secondary muscle pump dysfunction. Venous obstruction may result from
an intrinsic venous process, such as chronic deep vein thrombosis or
venous stenosis, or because of extrinsic compression. Venous outflow
obstruction plays a significant role in the pathogenesis of CVI.
Postthrombotic venous obstruction, as with deep vein valve dysfunction,
has a high rate of venous ulceration development and more rapid
progression of disease.
Dysfunction of the muscle pumps may lead to ineffective emptying
of venous blood from the distal lower extremity. This rarely occurs as a
primary disorder with neuromuscular conditions or muscle-wasting
syndromes. However, muscle pump dysfunction often occurs with severe
reflux or obstruction. Because of ineffective venous emptying, the
immediate postambulatory venous pressure will be nearly as high as the
pressure after prolonged standing. Muscle pump dysfunction appears to be
a significant mechanism for the development of complications such as
venous ulcers.
Changes in the hemodynamics of the large veins of the lower
extremity are transmitted into the microcirculation and lead to the
development of venous microangiopathy. In addition, dysfunction of the
microvenous valves seems to be play a key role and may occur
independent of the macrovenous dysfunction. These hemodynamic
perturbations contribute to the development of microangiopathic findings,
with elongation, dilation, and tortuosity of capillary beds; thickening of
basement membranes with increased collagen and elastic fibers;
endothelial damage with widening of interendothelial spaces; and
increased pericapillary edema with halo formation; however, normal
interendothelial junctions have also been found in advance CVI.39 The
abnormal capillaries with increased permeability and high venous pressure
lead to the accumulation of fluid, macromolecules, and extravasated red
blood cells into the interstitial space. There have been several postulated
mechanisms for the development of venous microangiopathy, including
fibrin cuff formation, growth factor trapping, and white blood cell
trapping, but further work in this area is needed to better define this
pathophysiology.

Clinical Manifestations
CVD represents a spectrum of conditions ranging from simple
telangiectases or reticular veins to more advanced stages, such as skin
fibrosis and venous ulceration. It is important to realize that the same
clinical manifestations may result from different pathogenic mechanisms,
including incompetent valves, venous obstruction, muscle pump
dysfunction, or a combination. The major clinical features of CVI are
dilated veins, edema, leg pain, and cutaneous changes in the leg. Varicose
veins are dilated superficial veins that become progressively more tortuous
and enlarged (Figure 2A). They may develop bouts of superficial
thrombophlebitis, recognized by painful, indurated, inflamed areas along
the varicose vein. Edema begins in the perimalleolar region and ascends
up the leg with dependent fluid accumulation. Leg discomfort is often
described as heaviness or aching after prolonged standing and is relieved
by elevation of the leg. This discomfort is thought to be produced by
increased intracompartmental and subcutaneous volume and pressure.
There may also be tenderness along varicose veins because of venous
distention. Obstruction of the deep venous system may lead to venous
claudication (or intense leg discomfort with ambulation). Cutaneous
changes include skin hyperpigmentation because of hemosiderin
deposition and eczematous dermatitis (Figure 2B). A fibrotic process may
occur in the dermis and subcutaneous fat termed “lipodermatosclerosis.”
There is an increased risk of cellulitis, leg ulceration, and delayed wound
healing (Figure 2C). In addition, protracted CVI may also contribute to the
development of lymphedema, representing a combined process.

Figure 2. Manifestations of chronic venous insufficiency. A,

Extensive varicose veins involving the thigh and leg. B,
Hyperpigmentation and severe lipodermatosclerosis with leg edema.
Notice healed ulcers in the gaiter region of the medial leg. C, Medial
malleolar venous ulcers. Notice concomitant eczema and
lipodermatosclerotic skin.

Diagnosis of CVI
A complete history and physical examination are important to
establish a proper diagnosis of CVI and may be assisted by noninvasive
testing. Invasive testing may also be used to establish the diagnosis but is
typically reserved for assessing disease severity or if surgical intervention
is being contemplated. The methods used to assess CVI are described
below, but comprehensive overviews have been published previously.

Physical Examination
The physical examination not only aids in establishing a diagnosis
but plays an important role in helping to guide therapy in CVI. Visual
inspection and palpation may reveal evidence of venous disorders. The
skin is examined for prominent, dilated superficial venous abnormalities,
such as telangiectasis, reticular veins, or varicose veins. The surface is
inspected for irregularities or bulges to suggest the presence of dilated
tortuous veins. The distribution of these varicose veins may follow the
course of the affected superficial vein, such as the GSV and small
saphenous vein. This evaluation should include positioning in the upright
posture to allow for maximal distention of the veins. Additional skin
findings may be seen, such as hyperpigmentation, stasis dermatitis,
atrophie blanche (or white scarring with a paucity of capillaries), or
lipodermatosclerosis. The presence of edema and its severity is assessed.
The edema seen in CVI is dependent and usually pitting; however, it may
become more resilient to palpation if protracted. There is often relative
sparing of the forefoot to help distinguish the etiology of other causes of
edema, such as lymphedema. An early finding of venous congestion
includes calf fullness or increased limb girth, so the calf muscle
consistency should be assessed, and measurement of the limb girth should
be performed. There is no universally agreed on scale for grading the
severity of edema. Palpation along the course of dilated veins may reveal
tenderness. The presence of active or healed ulcers, typically in a
distribution near the medial aspect of the ankle with GSV reflux or lateral
aspects of the ankle with small saphenous vein reflux, may be seen with
more advanced disease.
Differential Diagnosis
There is a broad differential for the most common presenting
symptoms of limb swelling and discomfort that are seen in CVI. The initial
task is to exclude an acute venous problem, such as deep vein thrombosis.
Then, systemic causes of edema need to be considered, such as heart
failure, nephrosis, liver disease, or endocrine disorders. Importantly,
adverse effects of medication should be considered, such as those with
calcium channel blockers, nonsteroidal anti-inflammatory agents, or oral
hypoglycemic agents. Critical disorders to consider are lymphedema,
lipedema, and the combined disorder of lipolymphedema. Lymphedema
because of obstruction of lymphatic drainage leads to fluid accumulation
that extends into the foot and toes, in contrast with CVI, which relatively
spares the foot. The edema may be pitting early in the course of the disease
but as the disease progresses becomes nonpitting. In contrast, lipedema is
characterized by fatty tissue accumulation rather than fluid, thus, it is not
pitting. It usually spares involvement of the feet, often with a cuff of tissue
at the ankle. Finally, other regional considerations should be made, such as
ruptured popliteal cyst, soft tissue hematoma or mass, exertional
compartment syndrome, or gastrocnemius tear. The use of examination
findings and noninvasive testing should allow for the proper diagnosis to
be established.
Noninvasive Testing
Venous Duplex Imaging
 Venous duplex imaging is currently the most common technique
used to confirm the diagnosis of CVI and assess its etiology and anatomy
and is highly recommended in the CPG (grade 1A) V.enous duplex
imaging combines B-mode imaging of the deep and superficial veins with
pulsed Doppler assessment of flow direction with provocative maneuvers.
The presence of venous obstruction because of chronic deep vein
thrombosis or venous stenosis may be directly visualized or inferred from
alteration in spontaneous flow characteristics. The direction of flow may
also be assessed in the reverse Trendelenburg position during a Valsalva
manuver or after augmenting flow with limb compression. However, the
preferred method to assess for reflux involves the use of a cuff inflation-
deflation technique with rapid cuff deflation in the standing position. This
provides information about the anatomic distribution of reflux disease
involving the deep and superficial venous systems, as well as perforator
veins.
The presence of reflux is determined by the direction of flow,
because any significant flow toward the feet is suggestive of reflux (Figure
3). The duration of reflux is known as the reflux time. A reflux time of
>0.5 seconds for superficial veins and 1.0 second for deep veins is
typically used to diagnose the presence of reflux.54 A longer duration of
reflux implies more severe disease but does not correlate well with clinical
manifestations.55Venous duplex imaging provides information about local
valve function to construct an anatomic map of disease in terms of the
systems and levels of involvement. This is often sufficient data to help
guide therapy, but if the contribution of the reflux to global hemodynamics
is required, then further testing, such as plethysmographic techniques,
should be considered.
 Figure 3. Venous duplex ultrasound demonstrating reflux in the
great saphenous vein. Blood flow direction is determined after increasing
central venous return with rapid cuff inflation then deflation. Flow in the
direction of the feet is because of incompetent valves, as shown in red in
the color image and above the baseline in the pulse Doppler. The Doppler
spectrum quantifies the duration of reflux, and in the example above it is
≈4 seconds.

Air Plethysmography
Air plethysmography (APG) has the ability to measure each
potential component of the pathophysiologic mechanisms of CVI,
including reflux, obstruction, and muscle pump dysfunction. Changes in
limb volume are measured by air displacement in a cuff surrounding the
calf during maneuvers to empty and fill the venous system (Figure 4).
Venous outflow is assessed during rapid cuff deflation on an elevated limb
that has a proximal venous occlusion cuff applied. The venous outflow at 1
second, expressed as a percentage of the total venous volume, is used to
evaluate the adequacy of outflow. The limb is then placed in the dependent
position to evaluate venous filling. The rate of refill, expressed as the
venous filling index, is used to determine the presence and severity of
reflux. A normal venous filling index is <2 mL/s, whereas higher levels
(>4 mL/s) are abnormal. Abnormal venous filling indices have excellent
test characteristics to detect reflux (with sensitivity of 70% to 80% and
positive predictive value of 99%) and have been found to correlate with
the severity of CVI. The function of the calf muscle pump in ejecting
blood is determined after 1 and 10 repetitive contractions during toe raises.
The volume of blood ejected with 1 tiptoe maneuver divided by the venous
volume is called the ejection fraction. Complications of CVI, including
ulceration, have been shown to correlate with the severity of venous
disease assessed with the venous filling index and ejection capacity. This
technique provides quantitative information about several aspects of global
venous function and may be used in the selection of intervention and
assessment of the response to intervention.

Figure 4. Air plethysmography (APG) measure changes in venous

volume of the lower extremity over time. The ejection fraction (EF) is the
amount of ejected volume (EV) after 1 tiptoe over the total venous volume
(VV). The EF is a measure of the calf muscle pump function. The residual
volume fraction (RVF) is the residual volume (RV) after 10 tiptoes over
the venous volume (VV) and is the noninvasive measure of ambulatory
venous pressure. The venous filling index (VFI) is 90% of the venous
volume (VV90%) that fills within the venous filling time (VFT90) at 90%
of the VV. The VFI measures venous valvular function and severity of
global reflux. Reprinted with permission from Christopoulos et al.
Computed Tomographic or Magnetic Resonance Venography
 Advances in imaging with computed tomography and magnetic
resonance have allowed for their use in the evaluation of venous disease.
These techniques are most useful to evaluate more proximal veins and
their surrounding structures to assess for intrinsic obstruction or extrinsic
compression. Optimal imaging of the venous system requires the use of
intravenous contrast material, with appropriate timing of image acquisition
on the basis of venous filling to obtain a venogram. Proper technique is
required to avoid artifacts with inadequate venous opacification, with
refinements allowing for better visualization to assess for obstructive
disease, varicose veins, perforating veins, and other venous malformations.
Invasive Testing
Contrast Venography
Venography may be used to directly visualize the venous system by
either an ascending or descending approach (Figure 5). Ascending
venography involves injection of contrast in the dorsum of the foot with
visualization of contrast-traveling cephalad in the deep venous system of
the limb. Ascending venography provides details of venous anatomy that
may be useful with surgical interventions and can help to distinguish
primary from secondary disease. Descending venography involves
proximal injection of contrast in a semivertical posture on a tilt table with
the use of the Valsalva maneuver. It is most useful to identify reflux in the
common femoral vein and at the saphenofemoral junction but may be used
to evaluate other locations. A grading scheme has been developed on the
basis of the anatomic extent of reflux. These modalities have been largely
replaced by venous duplex imaging but may be performed if venous
reconstruction is being contemplated.
 Figure 5. A, Venography of the iliocaval segment to assess for
patency. B, Descending venography of the left lower extremity
demonstrating reflux into the femoral vein in a postthrombotic vein.
Intravascular Ultrasound
Intravascular ultrasound is rapidly gaining acceptance in the
management of venous disease and is increasingly being used to help
guide interventions (Figure 6). The technique uses a catheter-based
ultrasound probe to visualize periluminal vascular anatomy to assess for
obstructive or stenotic disease of the venous system. Intravascular
ultrasound appears to be superior to venography in estimating the
morphology and severity of central venous stenosis and in visualizing the
details of intraluminal anatomy. This improvement in detection of the
severity and significance of stenosis has led to greater consideration of
venous percutaneous interventions in the treatment of CVI.

Ambulatory Venous Pressure

 Ambulatory venous pressure monitoring is the gold standard in
assessing the hemodynamics of CVI. The technique involves insertion of a
needle into the dorsal foot vein with connection to a pressure transducer.
The pressure is determined in the upright posture at rest and after exercise,
such as during toe raises. The pressure is also monitored before and after
placement of an ankle cuff to help distinguish deep from superficial reflux.
Ambulatory venous pressure has been shown to be valuable in assessing
the severity and clinical outcomes in CVI. The mean ambulatory venous
pressure and refill time are the most useful parameters. This technique
provides information on global competence of the venous system.
However, there is some concern that this pressure may not accurately
reflect the pressure within the deep system. This technique is seldom used
in clinical practice because of its invasive nature, potential limitations, and
alternative diagnostic modalities.
Treatment of CVI
Conservative Management
The initial management of CVI involves conservative measures to
reduce symptoms and prevent development of secondary complications
and progression of disease. The use of compressive stockings is the
mainstay of conservative management and is further described below. If
conservative measures fail or provide an unsatisfactory response, further
treatment should be considered on the basis of anatomic and
pathophysiologic features (Figure 7).
 Figure 7. A simplified overview for the diagnosis and treatment of
chronic venous insufficiency (CVI) on the basis of pathophysiologic
mechanism. Multiple pathophysiologic mechanisms may contribute to CVI
within the same patient and require a combination of treatment options. †
indicates better assessment by air plethysmography (APG) as more limited
information obtained from venous duplex imaging.
A healthy lifestyle including maintaining an ideal body weight or
weight reduction if overweight may improve manifestations of CVI.
Obesity is a well-established risk factor for the development of CVI and its
complications. Weight reduction after bariatric surgery has been shown to
improve manifestations of CVI, including edema and ulcers. It may be
extrapolated that weight reduction by other means might also assist in the
treatment of CVI.

Compressive Leg Garments

A therapeutic consideration for all of the CEAP clinical classes is
compression therapy. The objective is to provide graded external
compression to the leg and oppose the hydrostatic forces of venous
hypertension. A number of compression garments are available, including
graded elastic compressive stockings, paste gauze boots, layered
bandaging, and adjustable layered compression garments. The use of
graded elastic compressive stockings (between 20 and 50 mm Hg of
tension) is a mainstay in the treatment of CVI. Treatment with a 30- to 40-
mm Hg compression stocking seems to result in significant improvement
in pain, swelling, skin pigmentation, activity, and well being if compliance
of 70% to 80% is achieved.77 In patients with venous ulcers, graded
compression stockings and other compressive bandaging modalities are
effective in both healing and preventing recurrences of ulceration. With a
structured regimen of compression therapy, complete ulcer healing can be
achieved in >90% of patient with ulcers at a mean of 5.3 months. 78 Several
studies have investigated the hemodynamic benefits of compression
therapy in patients with CVI. Compression stockings have been shown to
reduce the residual volume fraction, which is an indicator of improving the
calf muscle pump function, and reduce reflux in vein segments Recently,
studies evaluating reverse compression (antigraduated stockings or
progressive elastic compression with higher pressure in the calf than the
ankle), found improved calf muscle pump function on ambulation and
reduced edema in severe CVI. Further studies are required to determine
whether reverse compression has a similar effectiveness to graduated
compression stockings.

Pharmacologic Therapy
Four groups of drugs have been evaluated in the treatment of CVI,
including coumarins (α-benzopyrenes), flavonoids (γ-benzopyrenes),
saponosides (horse chestnut extracts), and other plant extracts. These drugs
with venoactive properties are widely used in Europe but are not approved
in the United States. The principle for using these venoactive drugs is to
improve venous tone and capillary permeability, although a precise
mechanism of action for these drugs has not been full elucidated. It is
thought that the flavonoids act on leukocytes and endothelium to modify
the degree of inflammation and reduce edema. A micronized purified
flavonoid fraction has been shown to reduce edema-related symptoms as
either primary treatment or in conjunction with surgical therapy. A
combination of coumarin and troxerutin (a flavonoid), with compression
garments, was shown to reduced edema and pain compared with placebo
at 12 weeks. In addition, a meta-analysis found that micronized purified
flavonoid fraction added to compression therapies aided in venous ulcer
healing. Horse chestnut seed extract has been found to be as effective as
compression stockings in the short term at reducing leg edema and pain
from CVI, but the long-term safety and efficacy have not been established.
In general, venoactive drugs, which provide relief of pain and swelling or
accelerate venous ulcer healing, carry a moderate recommendation in the
CPG when used in conjunction with compression therapy but are not
approved by the US Food and Drug Administration.
There have been several trials to suggest that pentoxifylline may
improve healing rates of venous ulcers, although the magnitude of the
effect appears to be small, and its role in patient management is unclear.
The use of pentoxifylline in conjunction with compression therapy is also
recommended in the CPG, although it is not approved by the US Food and
Drug Administration for this purpose. The use of other agents, such as
aspirin and platelet-derived growth factor, has been reported to promote
healing or prevent the recurrence of venous ulceration, but no large
randomized studies have been conducted. It should also be mentioned that
there have been data to support the use of aspirin in the prevention of
recurrent thromboembolic events in those with unprovoked thrombosis.
Sulodexide has been used in Europe to treat venous ulcers with relative
success and has a modest recommendation by the CPG, but further studies
are required to determine its clinical efficacy long term.11

Deep Vein ThrombosisDeep Vein Thrombosis

A. Definition of
 (DVT) is a blood clot that occurs in the veins (veins) inside. The
inhibition of the return of arterial flow is the cause that often initiates
TVD. The causes can be heart disease, infection, or long
immobilization of the limbs.

B. Epidemiology
The incidence of DVT in the United States is 159 per 100 thousand
or around 398 thousand per year. The fatality rate of TVD is largely
due to pulmonary embolism of 1% in young patients to 10% in older
patients. Without prophylaxis, the incidence of TVD obtained in
hospitals is 10-40% in medical and surgical patients and 40-60% in
major orthopedic surgery. Of the approximately 7 million patients who
were treated in 944 hospitals in America, venous thromboembolism
was the second most medical complication, the cause of increased
length of stay, and the third leading cause of death.

C. Pathogenesis
The main cause of venous thrombosis is unclear, but there are three
groups of supporting factors that are considered to play an important
role in the formation known as TRIAS VIRCHOW namely abnormal
blood flow, blood vessel walls and coagulation factor components

Venous
stasis Stasis of venous blood flow, occurs when blood flow slowing
down, as in heart failure or shock; when the vein is dilated, as a result
of drug therapy, and if the skeletal muscle contractions are reduced,
such as at long rest, limb paralysis or anesthesia. These things
eliminate the effect of peripheral venous pumps, increasing stagnation
and collecting blood in the lower extremities. TVD in stroke patients
occurs in the limbs that have paralysis.

Damage to blood vesselsblood vessel

 Injury towalls, is known to initiate thrombus formation. The cause
is direct trauma to the arteries, such as soft tissue fractures and
injuries, and intravenous infusions or irritating substances, such as
potassium chloride, chemotherapy, or high-dose antibiotics.

Hypercoagubility
The balance between natural coagulation factors, fibrinolysis and
its inhibitors serves to maintain the balance of normal hemostasis.
Hypercoagulability of blood, occurs most often in patients with
sudden cessation of anticoagulant drugs, use of oral contraceptives
and replacement hormone estrogen and cancer, especially types of
adenocarcinoma can activate clotting factors thereby increasing the
risk of TVD.

D. Risk Factors
TVD sometimes occurs in normal veins, however risk factors that
can cause TVD are:
Immobility (lack of movement)
Immobility will cause slowing of blood flow to the veins and
increase the occurrence of blood clots. For example:
1. Post-surgery for more than 30 minutes, because during anesthesia
the venous blood flow decreases. Therefore postoperatively,
injections of heparin are usually given to prevent the occurrence of
TVD.
2. Pain and care can cause immobilization such as stroke
3. pregnancy, including 6-8 weeks post partumLong
4. Obesity
5. trips by train or plane can increase the risk of TVD

TVD that occurs before and venous damage

If the inside of the vein is damaged, the possibility of becoming
TVD increases, such as:
1. Vasculitis (inflammation of the vein wall) and conditions such as
chemotherapy can damage the veins and increase the risk of TVD.
 2. Leg fractures
3. Complications of invasive actions in veins

Hypercoagulability
In this condition blood clots are faster than normal as in:
1. Treatment (family planning pills, estrogen)
2. Cancer
3. Smoking
4. Polycytha

Medical and Genetic Conditions

In some conditions cancer and therapy produce substances in the
blood which can cause clots . Heart failure where damage to the heart
causes the heart pump to be abnormal and effective so that pooling and
clots can occur. Genetic diseases such as V Leiden thrombophilia factor
which can cause abnormal clots.

E. Diagnosis
The standard gold standard for the diagnosis of TVD is intravenous
venography, where contrast material is injected into the vein then
photographed x-ray to see where there is venous obstruction. This is
invasive so it is rarely done.

Symptoms and signs

Symptoms and signs on TVD are associated with the obstruction of
blood flow back to the heart which causes blood to collect in the arms
or legs. Classic symptoms and signs:
1. Tenderness in the legs or calves if they occur in the limbs and arms
or neck when it comes to the upper extremities.
2. Swelling is localized to the affected area accompanied by edema.
For TVD distal swelling to below the knee and TVD proximal to
the buttocks area.
3. Warming and redness of the skin around the TVD area, especially
in the back and knees, there is superficial venous dilation and
severe obstruction of the skin appears cyanosis.
4. Sometimes TVD does not provide real symptoms, symptoms occur
after complications such as emboli into the lungs.

Diagnosis based on physical findings alone cannot be relied on,

while optimal management of TVD requires an objective diagnosis. In
order to facilitate the diagnostic approach, a scoring system is used to
determine the likelihood of clinical diagnosis and laboratory
examination, Compression ultrasonography, and venography, which
are proofs of objective diagnosis.

Investigations carried out for diagnosis of TVD:

1. Compression Ultrasonography
CU is the preferred non-invasive examination to help
establish a diagnosis of suspected TVD clinically. This procedure is
quite thorough for detecting symptomatic proximal TVD (femoral,
popliteal, calf bifurcation) with a sensitivity of 97% and specificity
94% .12. If the results are abnormal, a diagnosis of venous
thrombosis can be made, if normal results are repeated the
following week. Conversion from normal to abnormal at repeated
CU examination is in 2% of patients. CU is less sensitive for distal
TVD, asymptomatic TVD and recurrent TVD.

2. D-dimer
Examination of d-dimer levels (the result of the breakdown
of crosslinked fibrin broken down by plasmin), is an additional
examination of CU to improve the accuracy of the diagnosis of
TVD. D-dimer levels usually increase in TVD and / or EP
(Pulmonary Embolism). Increased ddimer levels indicate
abnormally high levels of fibrin degradation products. This
 increase in levels means that there has been a meaningful thrombus
and solution in the body, but it has not been able to show
location13. Normal levels can help to get rid of TVD, but elevated
levels are not specific and have a low positive predictive value.
Increased levels of d-dimer can be a non-specific response to the
disease that occurs together.

3. Venography
Venography is the gold standard inspection of TVD. The
advantage of venography is being able to detect proximal
thrombosis and isolated calf veins. The disadvantages of this
examination are:
a. Invasive
b. Cause pain
c. Expensive and requires special expertise in the technique
d. Takes a long time
e. Possible thrombotic complications
f. Allergies and renal impairment due to contrast fluids
For this reason, non-invasive examinations such as CU and d-
dimer, combined with physical examination, are widely used
instead of venography.

4. MRI (Magnetic Resonance Imaging)

MRI is very accurate for the diagnosis of TVD, including
distal (calf), pelvic and asymptomatic thrombosis in pregnant
women. This technique is very potential to distinguish between
old and new thrombus, and does not require contrast. But the
price is still relatively expensive.

F. Management
Management of TVD is to prevent increased clot size, prevent
pulmonary embolism, post thrombosis syndrome and recurrent TVD.

Pharmacological therapy used is usually anticoagulants and

thrombolytics. Namely:
1. Anticoagulants
 Anticoagulants are used to prevent larger clots from
occurring, and prevent the formation of blood clots. If
anticoagulant therapy is given immediately after TVD is formed,
it will reduce the risk of pulmonary embolism. Commonly used
anticoagulants are heparin and warfarin. Subcutaneous heparin
can be given to patients who require long-term anticoagulant
treatment but warfarin should not be given (for example during
pregnancy). A total dose of about 35,000 U / day is given as a
divided dose every 8 or 12 hours. To prevent deep vein
thrombosis and thromboembolism in sensitive patients, low-dose
heparin is used, it is recommended that 5000 U heparin be given
subcutaneously every 8-12 hours.

2. Thrombolytics
In contrast to anticoagulants that function to prevent the
expansion and recurrence of thrombosis, thrombolytic drugs such
as steptokinase, urokinase and tissue plasminogen activator work
to dissolve thrombin. This drug is mainly used in patients with
extensive pulmonary embolism accompanied by cardiorespiratory
disorders and a small risk of bleeding. Streptokinase drugs can be
given by injection or infusion. 1,500,000 IU IV infusion within 60
minutes. For the treatment of pulmonary embolism, deep venous
thrombosis (DVT). Infusion is given for 72 hours for DVT.

In addition to pharmacological therapy, non-

pharmacological therapy for mechanical prevention is also carried
out, namely:
1. Compression elastic stockings. Used in the morning and all
day during activity, released when going to sleep, can also be
used at rest with the position of raising the legs when lying
down.
 2. Raising the legs, namely the position of the feet and calves
higher than the hips, this position is expected to facilitate
venous blood flow.
3. Intermittent pneumatic compression, this device can give
regular external pressure to the lower limbs or lower limbs
and thighs; the pressure is 35-40 mmHg for 10 seconds /
minute.
4. Initial mobilization to increase venous blood flow under
stasis conditions.12,13

7. What is the first treatment based on the scenario?

THERAPY
1. General: Stocking gradients or elastic stabs
2. Specifically:
a. Clinical degree (C) 0-4 symptomatic: MPPForal 2x1 per day for 6
months (reticular veins or varicose veins can be done sclerosing
therapy).
b. Clinical degree (C) 5-6: MPPF 2x1 per day, if the ulcer does not
improve it is necessary to combine sclerosing / stripping /
valvuloplasti / EVLT.
Education
1. Control of risk factors.
2. Supervision of complications due to venous thrombosis which can
result in pulmonary embolism.
3. Monitoring complications due to venous ulcer infection.10
 Daftar Pustaka
1. Slide dr. Cahyono Kaelan, Ph.D., SpPA(K)., Sp.S. 2018. Gangguan
Hemodinamik dan Syok

2. Price, Sylvia A. Patofisiologi Volume II Edisi 6. Jakarta: EGC

3. Sudoyodo AW,Setiyohadi B,Alwi I, Simadibrata M, Setiati S. Buku Ajar

Ilmu Penyakit Dalam.Jilid I edisi V.Jakarta.Internal Publishing:2009.

4. Dono Antono,Hamonangan Rachmat. 2014.Diagnosis penyakit

vascular.Buku Ajar Ilmu Penyakit Dalam jilid II edisi
VI.Jakarta:Internapublishing.hal 1503,1504.
5. Disease textbooks in volume II edition VI p. 1692
6. Edema patofisiologi & penanganan. Ian effendi, Restu pasaribu (ed). BAIP
D. Jilid I. Edisi IV. Jakarta : FKUI.
7. Muscle cramp symptoms, causes. Treatment-Do all muscle cramps fit into
the above categories on medicine Net Archived. 2008-08-24.
at.The.Wayback. Machine.
8. internapublishing buku ajar ilmu penyakit dalam jilid II edisi IV hal 1503-
1508
9. Kalim, Harmani. 2015. Crash Course Kardiologi dan Kelainan Vaskular.
Singapore : Elsevier. Hal. 410-412
10. Panduan Praktik Klinis & Clinical Pathway Penyakit Jantung dan
Pembuluh Darah.
11. Robert T. Eberhardt, MD; Joseph D. Raffetto, MD,. 2014. Chronic Venous
Insufficiency. American Heart Association, Inc
12. Lestarini, IA. 2017. Deep vein thrombosis. Faculty of Medicine,
University of Mataram
13. Wijaya, WL. 2013. Deep Vein Thrombosis. Diponegoro University Journal