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Purpura
Purpura
ALEXANDER K.C. LEUNG, M.B.B.S., University of Calgary Faculty of Medicine, Alberta, Canada
KA WAH CHAN, M.B.B.S., University of Texas M.D. Anderson Cancer Center, Houston, Texas
Purpura is the result of hemorrhage into the skin or mucosal membrane. It may rep-
resent a relatively benign condition or herald the presence of a serious underlying
disorder. Purpura may be secondary to thrombocytopenia, platelet dysfunction,
coagulation factor deficiency or vascular defect. Investigation to confirm a diagno-
sis or to seek reassurance is important. Frequently, the diagnosis can be established
on the basis of a careful history and physical examination, and a few key labora-
tory tests. Indicated tests include a complete blood cell count with platelet count, a
peripheral blood smear, and prothrombin and activated partial thromboplastin
times. (Am Fam Physician 2001;64:419-28.)
P
urpura results from the extrava- vessel wall and, in response to the exposed
sation of blood from the vascula- subendothelial collagen, release adenosine
ture into the skin or mucous diphosphate (ADP) and thromboxane A2.3
membranes. Therefore, purpuric The released ADP and thromboxane A2 cause
lesions do not blanch with pres- further platelet aggregation and the formation
sure. Depending on their size, purpuric of a platelet plug that is responsible for pri-
lesions are traditionally classified as petechiae mary hemostasis.2,3
(pinpoint hemorrhages less than 2 mm in Secondary hemostatic mechanisms consist
greatest diameter), purpura (2 mm to 1 cm) of a series of sequential enzymatic reactions
or ecchymoses (more than 1 cm).1 Although involving various coagulation factors and
purpura itself is not dangerous, it may be the leading to the formation of a fibrin clot. The
sign of an underlying life-threatening disor- intrinsic pathway is activated by the exposed
der. This article reviews the etiology of pur- collagen, and the extrinsic pathway is activated
pura in children and suggests an approach to by tissue thromboplastin (Figure 1).3
evaluating the problem. The integrity of the vascular system depends
on three interacting elements: platelets, plasma
Normal Hemostasis coagulation factors and blood vessels. All three
The normal hemostatic mechanisms are elements are required for proper hemostasis,
vascular response, platelet plug formation and but the pattern of bleeding depends to some
activation of coagulation factors with the for- extent on the specific defect. In general, platelet
mation of fibrin to stabilize the platelet plug. disorders manifest petechiae, mucosal bleed-
Following a vascular injury, vasoconstric- ing (wet purpura) or, rarely, central nervous
tion and retraction usually occur immediately system bleeding; coagulation disorders present
and decrease blood flow to the affected area. as ecchymoses or hemarthrosis; and vasculitic
Factor VIII–von Willebrand’s factor (factor disorders present with palpable purpura.1
VIII–vWF) is released from endothelial cells
and adheres to the exposed collagen matrix.2 Platelet Disorders
Facilitated by factor VIII–vWF, platelets Simple purpura strongly indicates the pres-
adhere to the endothelial cells of the damaged ence of a qualitative or quantitative platelet
disorder.
THROMBOCYTOPENIA
Because purpura results from extravasation of blood into the
Thrombocytopenia may be caused by in-
skin, the lesions do not blanch with pressure.
creased platelet destruction, decreased platelet
production or sequestration of platelets.
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Increased Platelet Destruction. Immune respiratory tract infection, is common. The
thrombocytopenia is the most frequent cause peak incidence is between two and four years
of increased platelet destruction. Idiopathic of age. Both genders are equally affected.
(immune) thrombocytopenic purpura is by Fever, lethargy, weight loss, bone pain, joint
far the most common etiology of thrombocy- pain, pallor, lymphadenopathy and hepato-
topenia in childhood. The disorder is caused splenomegaly are characteristically absent.
by the development of IgG autoantibodies to Minimal splenomegaly occurs in about 5 to 10
platelet membrane antigens as a result of an percent of symptomatic children.5 Idiopathic
unbalanced response to an infectious agent or thrombocytopenic purpura is usually a tem-
autoimmunity.4 The characteristic presenta- porary disorder, with 80 to 90 percent of chil-
tion is the sudden onset of bruises, purpura, dren recovering within six to 12 months, usu-
mucosal hemorrhage and petechiae in a child ally within a few weeks.6 Chronic idiopathic
who is otherwise in excellent health. An thrombocytopenic purpura is more likely to
antecedent viral infection, especially an upper present in teenage girls and children with
Coagulation Cascade
XI XIa
IX IXa
VIII
Common pathway
X
Prothrombin (II)
Xa + V
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Purpura
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Purpura fulminans is an acute, often lethal recurrent infections secondary to immuno-
syndrome of disseminated intravascular coag- deficiency.9 The disorder is transmitted as an
ulopathy. The skin lesions are rapidly progres- X-linked recessive trait. The thrombocytopenia
sive and characterized by microvascular results from abnormal platelet formation or
thrombosis in the dermis, which ultimately release, despite quantitatively adequate num-
results in perivascular hemorrhage and bers of megakaryocytes in the bone marrow.
necrotic gangrene with minimal inflamma- Congenital amegakaryocytic thrombocyto-
tion. Purpura fulminans may develop because penia is a rare cause of isolated thrombocy-
of a severe bacterial infection, notably menin- topenia in the neonatal period.9 Both autoso-
gococcal disease, or because of protein C or S mal dominant and recessive modes of
deficiency.10 inheritance have been described. In some chil-
Decreased Platelet Production. A number of dren, the condition may be due to thrombo-
rare or uncommon congenital syndromes are poietin deficiency.
associated with decreased platelet production. Acquired causes of decreased platelet
Thrombocytopenia–absent radii (TAR) formation include drug reactions, infections
syndrome is inherited as an autosomal reces- and malignancies. Drugs such as alkylating
sive trait. Purpura may present in the first few agents, antimetabolites, anticonvulsants,
days of life or may be delayed for weeks.9 chlorothiazide diuretics and estrogens can
Fanconi anemia, also an autosomal inhibit platelet production by suppressing
recessive disorder, is characterized by pancy- megakaryocyte production.2,3
topenia, hyperpigmentation and café au lait Thrombocytopenia resulting from bone
spots, short stature, skeletal abnormalities and marrow suppression is a common complica-
a wide array of integumentary and systemic tion of viral and bacterial infections, especially
abnormalities. Although the condition is con- septicemia. Intrauterine infection with
genital, hematologic abnormalities are not TORCH organisms (toxoplasmosis, other
usually observed until the affected child is two [viruses], rubella, cytomegalovirus, herpes
to three years of age.9 [simplex] viruses) may lead to thrombocy-
Wiskott-Aldrich syndrome is characterized topenia in the neonatal period.9
by microthrombocytopenia, eczema and Infiltration of bone marrow in patients with
leukemia, histiocytosis, storage diseases,
neuroblastoma, myelofibrosis and granulo-
matosis may result in thrombocytopenia. In
The Authors osteopetrosis, the bone marrow space is
ALEXANDER K.C. LEUNG, M.B.B.S., is clinical associate professor of pediatrics at the replaced with frank bone formation.2
University of Calgary Faculty of Medicine, pediatric consultant at Alberta Children’s Sequestration of Platelets. Splenomegaly or
Hospital and medical director of the Asian Medical Centre, which is affiliated with the
University of Calgary Medical Clinic, all in Alberta, Canada. Dr. Leung is also honorary giant hemangioma can result in thrombocy-
pediatric consultant to Guangzhou Children’s Hospital, People’s Republic of China. Dr. topenia because of platelet sequestration.
Leung graduated from the University of Hong Kong Faculty of Medicine and com- Normally, approximately one third of the total
pleted an internship at Queen Mary Hospital, Hong Kong. He also completed a resi-
dency in pediatrics at the University of Calgary. platelet mass is in the spleen. Sequestration of
platelets in an enlarged spleen, regardless of
KA WAH CHAN, M.B.B.S., is professor of pediatrics at the University of Texas M.D.
Anderson Cancer Center, Houston. Dr. Chan graduated from the University of Hong the cause, may lead to mild thrombocytope-
Kong Faculty of Medicine and completed an internship at Queen Mary Hospital. In nia. Rarely, accelerated destruction of platelets
addition, he completed a residency in pediatrics at Vancouver General Hospital, British may also occur.
Columbia, Canada, and a residency in pediatric hematology and oncology at Memor-
ial Sloan-Kettering Cancer Center, New York, N.Y. The association of thrombocytopenia and
giant hemangioma is referred to as Kasabach-
Address correspondence to Alexander K.C. Leung, M.B.B.S, Alberta Children’s Hospi-
tal, 1820 Richmond Road SW, Calgary, Alberta, Canada T2T 5C7. Reprints are not Merritt syndrome.9 In addition to platelet
available from the authors. trapping, consumption of coagulation factors
422 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 3 / AUGUST 1, 2001
Purpura
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Henoch-Schönlein purpura is an IgA-medi-
ACQUIRED CAUSES ated systemic vasculitis of small blood vessels.
Acquired causes of vasculogenic purpura The hallmarks are nonthrombocytopenic pur-
include Henoch-Schönlein purpura, infec- pura, abdominal pain, arthritis and nephri-
tions, mechanical causes and psychogenic tis.11,12 This condition is the most common
conditions. form of vasculitis in children.1 Approximately
TABLE 1
Findings of the History and Possible Etiologies of Purpura
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Purpura
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pura. Bruises located only on the arms and laboratory screening studies may include a
legs of an active child are common findings complete blood count, peripheral blood
and probably do not indicate a bleeding disor- smear, prothrombin time (PT) and activated
der. Careful observation, rather than exhaus- partial thromboplastin time (aPTT). With few
tive investigation, should be employed. exceptions, these studies should identify most
When the history and physical examination hemostatic defects (Figure 2).3
suggest the presence of a bleeding disorder, A low hemoglobin level is indicative of
Diagnosis of Purpura
Yes No
Yes No Yes No
FIGURE 2. Algorithm for the diagnosis of purpura in children. (PT = prothrombin time; aPTT =
activated partial thromboplastin time)
Adapted with permission from Cohen AR. Rash—purpura. In: Fleisher GA, Ludwig S, et al., eds. Textbook of
pediatric emergency medicine. 3d ed. Baltimore: Williams & Wilkins, 1993:430-8.
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Purpura
blood loss, hemolysis or bone marrow failure. of the immaturity of hepatic synthesis of
The presence of schistocytes points to coagulation factors, infants have physiologic
hemolytic-uremic syndrome, thrombotic prolongation of aPTT until they are three to
thrombocytopenic purpura or disseminated four months of age. Patients with von Wille-
intravascular coagulopathy. An elevated retic- brand’s disease often have mild and variable
ulocyte count is found in hemolytic anemia.8 prolongation of PT and aPTT.3
Neutrophilia and increased numbers of Additional tests should be performed when
band forms or toxic granulations suggest a indicated by the findings of the history, phys-
bacterial infection. Atypical lymphocytosis is ical examination or screening laboratory
seen in patients with infectious mononucleo- tests. Measurements of coagulation factors
sis or cytomegalovirus infection. This finding (VIII, IX or vWF) are needed to confirm a
may sometimes be confused with the blast specific diagnosis.
cells of leukemia. Platelet-associated antibodies may be pres-
Anemia with thrombocytopenia indicates ent in patients with immune thrombocytope-
leukemia, systemic lupus erythematosus or nia, but they are not sensitive enough for diag-
aplastic anemia. If the platelet count is low but nostic purposes. If a platelet function defect is
the rest of the complete blood count is nor- suspected, the following tests should be con-
mal, idiopathic thrombocytopenic purpura is sidered: platelet aggregation tests using activa-
the most likely diagnosis. tors (e.g., ADP, collagen, epinephrine, throm-
The mean platelet volume (MPV), now rou- bin and/or ristocetin), clot retraction,
tinely reported by the automated cell counter prothrombin consumption test (for platelet
(Coulter counter), can be of diagnostic signifi- factor III) and serotonin release.18
cance. Macrothrombocytes (MPV greater than A bone marrow examination may be indi-
10 fL) are seen in patients with idiopathic cated if the cause of thrombocytopenia is not
thrombocytopenic purpura, Bernard-Soulier obvious, but it should definitely be performed
disease or May-Hegglin anomaly, whereas if a second bone marrow cell line (i.e., red
microthrombocytes (MPV less than 6 fL) are blood cells or white blood cells) is depressed.
seen in patients with aplastic anemia, Wiskott- On the other hand, it has been shown that
Aldrich syndrome, TAR syndrome and some bone marrow aspiration rarely reveals an
forms of storage pool disease.9 unexpected diagnosis when the clinical and
Bleeding time is a measure of the interval laboratory findings are typical for idiopathic
required for bleeding to stop after a standard- thrombocytopenic purpura.19
ized superficial incision is made on the fore- Hematuria may be present in Henoch-
arm. This test is rarely indicated in children. Schönlein purpura, systemic lupus erythe-
The PT is the time taken for citrated plasma matosus and hemolytic-uremic syndrome.
to clot after the addition of tissue factor Rheumatoid factor and antinuclear antibody
(thromboplastin) and calcium. A prolonged tests should be ordered if a patient has signif-
PT indicates a deficiency involving coagulation icant prominent arthralgia or arthritis.
factors II, V, VII, X or fibrinogen.17 The aPTT Appropriate laboratory tests should be per-
is the time taken for citrated plasma preincu- formed if kidney or liver failure is suspected.
bated with kaolin to clot after the addition of Abdominal ultrasonography or computed
calcium and platelets. A prolonged aPTT is tomographic scanning with contrast medium
found in deficiencies involving coagulation is appropriate when organomegaly is present.
factors II, V, VIII, IX, X, XI, XII or fibrinogen. Cranial ultrasound examination is appropri-
It should be remembered that an abnormal ate if the neonatal platelet count is less than 50
PT or aPTT only occurs when coagulation 103 per µL (50 109 per L), even in the
factor levels are less than 40 percent. Because absence of neurologic abnormalities.
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Purpura
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