Download Purpura

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Q1. What is purpura?
Purpura is purplish discoloration caused by spontaneous
bleeding within the skin or mucous membranes. The
word purpura is derived from the Greek word porphyra,
the purple fish, a gastropod secreting a purple dye.
Q2. What are the clinical manifestations of purpura?
A. Petechiae which are small, tiny pinpoint (<3mm
across) purpuric lesions often occurring in crops. OR
B. Ecchymoses (bruises) which are larger than 3 mm
purpuric lesions.
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Q3. How do you differentiate purpura from erythema?
The hallmark of purpura is inability of pressure to blanch
the red purple color of the lesion i.e. the lesions do not
blanch with pressure by finger or diascopy, whereas
erythematous lesions are blanched with such pressure.
Q4. What is the colour of purpuric lesions?
Extravasated blood is usually broken down to various
other pigments derived from haem within 2 or 3 weeks.
This accounts for a series of characteristic color changes,
purple, orange, brown and even blue and green, which
occur in many purpuric lesions.
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Q5. What are the physiologic mechanisms that prevent
bleeding within the skin or mucous membranes after an
injury to a blood vessel?
RBCs can only carry out their functions within the vascular lumen,
and capillary endothelium is normally impermeable to them. The
factors concerned in preventing escape of blood after injury to a
vessel are extremely complex. They include:
1. Contraction of the vessel wall.
2. Plugging of small defects by platelets.
3. The complex series of events leading to coagulation of blood.
Often all three mechanisms operate together and the precise role
which each plays in any one instance varies.
Purpura may arise from a disturbance of one or more of these
mechanisms.
Clotting Mechanisms
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Broken lines signify
inhibitory activity.
TFPI: Tissue Factor
Inhibitory Pathway
Normal haemostatic mechanisms: Clotting factors
of the intrinsic and extrinsic pathways
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Q6. How do you clinically classify purpura?
It is important to carefully palpate purpuric lesions to
determine if they are raised (Palpable purpura) or flat
(non-palpable purpura).
Q7. How do you classify purpura etiologically?
Purpura is a physical sign rather than distinct disease
entity and it may result from many causes. However,
classification of purpura, like that of eczema or urticaria
is in the unsatisfactory stage of being based partly on
etiology and partly on morphology. It is not surprising
that there is considerable overlap and often difficulty in
classifying any individual case.
Etiologic Classification
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PURPURA
PLATELET
DEFECTS
COAGULATION
DEFECTS
VASCULAR
DEFECTS
IDIOPATHIC
A popular alternative classification (Clinical classification) is to
subdivide purpura into inflammatory and non-inflammatory, or
what comes to almost the same thing, into palpable or nonpalpable.
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Q8. What are the platelets disorders causing purpura?
Platelets disorders
Quantitative defects
Qualitative defects
(Changes in platelet no.)
(Platelet dysfunction)
Thrombocytopenia
Thrombocythemia*
* Too many platelets may also cause purpura; many cases are pre-leukemic.
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Thrombocytopenia
I.
II.
1.
2.
3.
4.
5.
6.
7.
8.
9.
Idiopathic thrombocytopenic purpura (ITP). [Auto Abs]
Secondary causes of thrombocytopenia: due either to
decreased production or increased destruction. Examples:
Medications (quinine, aspirin, thiazides & sulphonamides).
Bone marrow disease: cytostatic drugs, leukaemia, Ca.
Disseminated intravascular coagulation (DIC).
Hemolytic anemia
Splenomegaly (Hypersplenism)
Connective tissue disorders, especially LE
Severe viral infections
Beta hemolytic streptococcal infections
Giant hemangiomas (Kasabach–Merritt syndrome) due to
increased destruction of platelets.
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Platelet dysfunction
1.
2.
3.
4.
Wiskott–Aldrich syndrome.
Thrombosthenia.
Drugs (e.g. aspirin)
von Willebrand’s disease
In von Willebrand’s disease, in addition to platelets
dysfunction, there is factor VIII deficiency and
vascular fragility.
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Q9. What are the non- platelets causes of purpura?
Coagulopathies
Purpura due to coagulative defects (abnormalities
in the coagulation factors) may be due to:
1. Inherited defects (e.g. hemophilia, Christmas
disease and von Willebrand’s disease).
2. Disseminated intravascular coagulation (DIC)
including purpura fulminans.
3. Paraproteinaemia (e.g. macroglobulinemia).
4. Connective tissue disorders
5. Acquired defects: e.g. anticoagulant therapy,
vitamin K deficiency and liver disease.
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Purpura due to vascular defects
1. Vasculitis (including Henoch–Schönlein purpura)
2. Dysproteinemic purpura: Vasculitis with purpura and
arthralgias is seen in cryoglobulinemia and
cryofibrinogenemia.
3. Vascular malformations: hereditary hemorrhagic
telangiectasia (Osler–Weber–Rendu disease).
4. Raised intravascular pressure: (coughing, vomiting,
venous hypertension, gravitational or stasis purpura).
5. Septic purpura (e.g. meningococcal septicemia, Rocky
Mountain spotted fever).
6. Drug-induced purpura (carbromal, aspirin, quinine,
sulphonamides, phenylbutazone and gold salts).
* Both septic purpura and drug-induced purpura are called
Toxic purpura and due to toxic vessel damage.
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Purpura due to collagen-vascular disorders
[due to decreased support from surrounding dermis]:
1. Senile purpura (confined to severely actinically
damaged skin of arms and face).
2. Steroid purpura (topical or sys. corticosteroids).
3. Scurvy (perifollicular purpura)
4. Lichen sclerosus et atrophicus
5. Systemic amyloidosis
6. Several genodermatoses:: examples:
 Pseudoxanthoma elasticum
 Marfan syndrome
 Ehlers–Danlos syndrome
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Idiopathic purpuras
Synonyms
Progressive pigmented purpuras
Capillaritis of unknown cause
Purpuric oddities
1. Schamberg's disease (Progressive pigmented purpuric
dermatosis)
2. Majocchi disease (Purpura anularis telangiectodes)
3. Gougerot–Blum syndrome (Pigmented purpuric lichenoid
dermatitis)
4. Doucas–Kapetanakis syndrome (Eczematoid purpura)
5. Lichen aureus
* All patients with purpura should be evaluated for underlying
disease before deciding that the purpura is an idiopathic.
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Miscellaneous Clinical Syndromes
These syndromes having varying aetiology:
1. Painful bruising syndrome
2. Purpura simplex
3. Neonatal purpura
Q10. Is there another approach to classify the
causes of purpura?
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1. Non-palpable purpura
Non-palpable purpura
1. Platelet abnormalities
2. Severe physical exertion
3. Progressive pigmentary
purpura
4. Scurvy
5. Dysproreinemia
6. Viral infections
7. Wiskott-Aldrich syndrome
8. Histiocytosis X
Non-palpable Ecchymoses
1.
2.
3.
4.
5.
6.
7.
8.
9.
Trauma
Senile purpura
Venous stasis
Clotting abnormalities
Cushing’s syndrome
Corticosteroid usage
Chronic renal disease
Primary amyloidosis
Psychogenic purpura
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2. Palpable purpura: may occur as a shower of numerous
lesions or as sparse, scattered lesions.
Sparse Acral Lesions
1.
2.






3.
4.
SBE
Septicemia
Gonococcal
Meningococcal
Pseudomonal
Staphylococcal
Candidal
Mucoraceous
Rheum. arthritis & SLE
Atheroembolism
Multiple Lesions
1.
2.






Consumption coagulopathy
Leukocytoclastic vasculitis
Drug-related
Henoch-Schonlein purpura
Allergic vasculitis
Collagen vascular disease
Dysproteinemia
Thrombotic thrombocytopenic
purpura
 Idiopathic
3. Rocky Mountain spotted fever
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Q11. Mention the general guidelines in the manage. of purpura?
Guidelines
To avoid doing all possible investigations in all cases of purpura, the following
broad generalizations may be made:
1. Thrombocytopenia is often associated with petechiae but there may be
external or internal hemorrhages and bruising. Petechiae or ecchymoses
usually occur in traumatized sites, dependent areas and acral sites +
mucous membranes. The lesions may be in straight lines in areas of trauma.
2. Coagulation defects usually present as large ecchymoses and external or
internal bleeding but not petechiae.
 Purpura, petechiae, epistaxis, and ecchymosis are commonly seen in
platelet abnormalities, whereas clotting factor defects or deficiency
(hemophilia A and B and von Willebrand disease) can lead to palpable
ecchymoses, hematomas, hemarthrosis, or unstoppable bleeding during
minor surgeries.
 External bleeding and large ecchymoses are due to coagulation or platelet
defects or to diseases of connective tissue such as Ehlers-Danlos syndrome.
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Guidelines
3.

4.

5.

6.
Vasculitis is seldom the cause of external bleeding or ecchymoses but it is
the commonest cause of persistent and localized purpura. An erythematous
inflammatory component is often present. Vasculitis of small vessels causes
purpura, often palpable and painful, but not bleeding.
In general it is the vascular or palpable purpuras (raised or palpable purpura
means vasculitis) which dermatologists consider their special province,
although they do need to have a passing knowledge of other types. Most of
the causes of palpable purpura are very serious.
The most common cause of purpura is trauma, especially to the thin sundamaged skin of elderly forearms.
Purpura on the legs of the elderly, in association with other skin diseases,
is common and seldom requires extensive investigation.
Cryoglobulinemia is a rare cause of purpura, which is most prominent on
exposed parts. It may also cause cold urticaria and livedo reticularis.
The condition may be idiopathic, or secondary to myeloma, leukemia, a
previous hepatitis C infection or an autoimmune disease.
Splinter hemorrhages of the nails are due to purpura of the nail bed and are
not diagnostic of any one condition.
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Q12. How do you investigate a case of purpura?
When purpura has no obvious cause, investigations should include:
1. Platelet count
2. Bleeding time
3. Prothrombin time
4. Activated partial thromboplastin time
5. Thrombin time.
6. Full blood count and Peripheral blood smear (blood film)
7. Platelet release assays
8. Coagulation factor assays (Coagulation screen): to detect a consumptive
coagulopathy,, including measurement of fibrinogen and fibrin
degradation products.
9. Electrophoresis is needed to exclude hypergammaglobulinaemia and
paraproteinaemia. Cryoglobulinemia should also be excluded.
10. Biochemical screen
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1. Platelets count
Normal count varies from 150-400 × 109/l. It varies greatly even in health
from person to person, and from time to time in the same person. It may be
affected by numerous external factors, hormonal factors-including
menstruation and minor infections.
 Purpura due to thrombocytopenia seldom occurs with a platelet count
above 50 × 109 /l.
 Thrombocytosis may also be a cause of bleeding.
 A full blood count should always be undertaken in the investigation of
purpura.
Platelet function may be assessed by performing a standardised template
bleeding time test. A small standardized incision is made on the forearm
below a sphygmomanometer cuff inflated to 40 mmHg. The bleeding time is
prolonged in those with platelet functional defects, thrombocytopenia or
von Willebrand disease. Platelet function can be further assessed by
measuring aggregation in vitro in response to various agents, e.g. adrenaline
(epinephrine) and collagen, or measuring the constituents of the
intracellular granules, e.g. ATP/ADP.
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2. Capillary resistance
 Capillary fragility depends upon numerous factors, including
the integrity of the capillary endothelium itself and also the
ability of platelets to fill any gaps which may arise in it.
 The simplest clinical test is the Hess test, not so much used
these days. A standardized increase in capillary pressure is
produced by inflating a sphygmomanometer cuff around the
upper arm to a constant pressure of 80mmHg (or less if this
approaches the systolic blood pressure) for 5min. Petechiae
may develop in the presence of abnormalities of vascular
wall, thrombocytopenia or platelet dysfunction, and can be
counted after releasing the pressure. Up to five in a
measured area 5cm across just below the antecubital fossa
may be considered normal.
 Capillary fragility is normal in coagulation defects.
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3. Bleeding time
 This is the time taken for bleeding to cease after a standardized
tiny incision in the skin. This type of bleeding normally ceases
because of contraction of the small vessels aided by production
of platelet thrombus. It is normal in disorders of coagulation .
 Techniques can be standardized in various ways, for example
with a sphygmomanometer cuff at 40mmHg the bleeding time is
usually given as 4-10 min. It is usually prolonged in
thrombocytopenia below 80 × 109/l and becomes progressively
prolonged as the count falls, being 30min at counts less than 10
× 109/l. It is also often prolonged in von Willebrand's disease and
some other disorders of platelet function.
 It is a rather insensitive test of limited use, even as a screening
test, although by careful standardization of technique it can give
useful clinical information.
 The bleeding time, and a Hess tourniquet test for capillary
fragility, help less often.
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4.
Coagulation screen
 Major coagulation defects can be excluded by a clotting screen including
prothrombin time, kaolin cephalin clotting time, thrombin clotting time and
fibrinogen.
 Clinical considerations and the results of the screening tests may suggest
further laboratory tests, including individual clotting factors.
Coagulation tests usually measure the length of time a plasma sample takes
to clot after the clotting process is initiated by activators and calcium. The
result of the test sample is compared with normal controls.
 The PT assesses the extrinsic system. The patient's plasma is incubated
with tissue factor and calcium. The reaction proceeds with the activation of
factor X by factor VIIa.
 The intrinsic system may be assessed by the APTT, sometimes known as
the partial thromboplastin time with kaolin, PTTK). The APTT is determined by
adding an activator to plasma-for instance, a suspension of kaolin-along with
an extract of phospholipid (to mimic the platelet membrane).
Special tests of coagulation including fibrinogen levels and individual
clotting factor assays can be performed as indicated by the screening tests.
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COAGULATION SCREENING TESTS
Investigation
Normal range
Platelet count
150-400 × 109/l Thrombocytopenia
Bleeding time
< 8 minutes
Thrombocytopenia, Abnormal platelet
function, Deficiency of von Willebrand
factor and Vascular abnormalities
Prothrombin time (PT)
12-15 seconds
Deficiencies of factors II, V, VII or X
Activated partial
thromboplastin time
(APTT)
30-40 seconds
Deficiencies of factors II, V, VIII, IX, X,
XI, XII, Heparin, Antibodies against
clotting factors, Lupus anticoagulant
Fibrinogen concentration 1.5-4.0 g/l
Situations (tests may be abnormal)
Hypofibrinogenaemia
International normalized ratio (INR) is not a coagulation screening test. It is used only to
assess the control of oral anticoagulant treatment. It is the ratio of the patient's PT to a
normal control based on an international reference thromboplastin which ensures
standardization of anticoagulation between different centers.
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5. Capillary microscope
Direct microscopic examination of capillaries is disappointing in
the elucidation of hemorrhagic and purpuric diseases. Purpura
may at times be seen in the nailfold capillaries when not present
elsewhere in the skin. It may also be possible to see the exact
point in the capillary at which extravasation of blood occurs. This
may occur at the junction of the precapillary arteriole with the
capillary, at the tip of the capillary or more usually at the venous
end.
6. Histology
Histological examination of purpuric lesions is relatively unhelpful.
When purpura is due to disease of the vessel wall, evidence of
this may be found, but often there is no hint as to the underlying
cause. Skin biopsy will confirm a small vessel vasculitis, if the
purpura is palpable.
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Schamberg’s disease
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Gougerot-Blum syndrome
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Purpuric drug eruption due
to NSAID “Ibuprofen”
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Senile purpura
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ITP
Platelets’ count:30X109/l
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Allergic Vasculitis, Drug ? Carbromal Purpura
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