Evaluating the Child with 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 Center, Houston, Texas

Purpura is the result of hemorrhage into the 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 , dysfunction, 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 , and a few key labora- tory tests. Indicated tests include a complete cell count with platelet count, a peripheral blood smear, and prothrombin and activated partial thromboplastin times. (Am Fam Physician 2001;64:419-28.)

urpura results from the extrava- vessel wall and, in response to the exposed sation of blood from the vascula- subendothelial , release adenosine 3 ture into the skin or mucous diphosphate (ADP) and thromboxane A2.

membranes. Therefore, purpuric The released ADP and thromboxane A2 cause lesions do not with pres- further platelet aggregation and the formation Psure. Depending on their size, purpuric of a platelet plug that is responsible for pri- lesions are traditionally classified as petechiae mary .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: , 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 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 , 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 ; and vasculitic Factor VIII–von Willebrand’s factor (factor disorders present with .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.

AUGUST 1, 2001 / VOLUME 64, NUMBER 3 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 419 Increased Platelet Destruction. Immune respiratory tract , 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) is by Fever, lethargy, weight loss, bone pain, 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 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 , 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

Intrinsic pathway Extrinsic pathway

Vascular surface changes Tissue thromboplastin XII XIIa VII VIIa

XI XIa

IX IXa

VIII Common pathway X Prothrombin (II)

Xa + V

Thrombin XIIIa XIII

Fibrinogen (I) Fibrin monomer Fibrin polymer Stable fibrin Clot formation

FIGURE 1. A simplified version of the coagulation “cascade.” An abnormality in the extrinsic pathway results in a prolonged (PT). An abnormality in the intrinsic pathway results in a prolonged activated partial thromboplastin time (aPTT). An abnormality in the com- mon pathway results in prolongation of PT and aPTT. Adapted with permission from Cohen AR. —purpura. In: Fleisher GA, Ludwig S, et al., eds. Textbook of pediatric emergency medicine. 3d ed. Baltimore: Williams & Wilkins, 1993:430-8.

420 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 3 / AUGUST 1, 2001 Purpura

underlying immune disorders. It has a more insidious onset. Idiopathic thrombocytopenic purpura is the most common Drugs that act as a hapten with platelet sur- cause of thrombocytopenia in children. antigens to form an immunologic moiety can also cause an immune thrombocytopenia. This has been shown to occur with penicillin, valproic acid (Depakene), quinidine, sulfon- Escherichia coli O157:H7. The pathologic amides, cimetidine (Tagamet) and . process is initiated by toxin-induced endothe- Thrombocytopenia secondary to immune lial injury and is followed by fibrin deposition destruction may rarely be the presenting fea- in the renal microvasculature and destruction ture of human immunodeficiency virus, of red blood cells and platelets. In addition, cytomegalovirus and herpesvirus .5 vasoactive and platelet-aggregating substances It also occurs in approximately 10 percent of are released from damaged endothelial cells patients with systemic erythematosus; and result in the formation of platelet at times, thrombocytopenia may be the pre- thrombi.8 senting manifestation. In hemolytic-uremic syndrome, thrombo- Post-transfusion purpura is characterized cytopenia may result from platelet destruc- by the acute onset of thrombocytopenia tion, increased consumption of platelets, approximately five to 14 days after a transfu- intrarenal aggregation of platelets, sequestra- sion.7 Previous transfusions may sensitize tion of platelets in the liver or spleen, or a patients to foreign platelet antigens. combination of these factors.8 The remaining Neonatal isoimmune (alloimmune) throm- platelets in the circulation appear to be bocytopenia develops when the mother pro- “exhausted” and circulate in a degranulated duces alloantibodies in response to a fetal form, depleted of nucleotide and granule con- platelet antigen, most commonly P1A1, which tents. From a functional perspective, these is not present on maternal platelets. These IgG platelets demonstrate a pattern characteristic antibodies cross the placenta and cause of impaired aggregation. thrombocytopenia in the fetus. The condition Thrombotic thrombocytopenic purpura occurs most commonly in P1A1-negative and hemolytic-uremic syndrome have gener- women who have been previously sensitized ally similar clinical and laboratory findings. to P1A1-positive platelets.2,5 However, thrombotic thrombocytopenic pur- Neonatal autoimmune thrombocytopenia pura occurs more often in adults, and neuro- may be caused by idiopathic thrombocyto- logic (rather than renal) symptoms are more penic purpura, systemic lupus erythematosus prominent. or drug-related immune-mediated purpura. Disseminated intravascular is In these disorders, maternal autoantibodies characterized by generalized activation of the cross the placenta, bind to fetal platelets and plasma coagulation pathways within small cause their destruction.5 blood vessels, with the formation of fibrin Nonimmune thrombocytopenia may occur and the depletion of all coagulation factors because of hemolytic-uremic syndrome, and platelets. This disorder may result from thrombotic thrombocytopenic purpura or overwhelming , incompatible blood disseminated intravascular coagulopathy. transfusion, snake bite, giant hemangioma Hemolytic-uremic syndrome is characterized and malignancy. Children with disseminated by the triad of microangiopathic hemolytic intravascular coagulopathy are generally , thrombocytopenia and acute renal quite ill and may present with extensive pur- injury. The syndrome is most often associated puric lesions and petechiae, as well as multi- with infection by verocytotoxin-producing focal hemorrhage.9

AUGUST 1, 2001 / VOLUME 64, NUMBER 3 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 421 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 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 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 , also an autosomal inhibit platelet production by suppressing recessive disorder, is characterized by pancy- megakaryocyte production.2,3 topenia, 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 , histiocytosis, storage diseases, , 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 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- 9 tal, 1820 Richmond Road SW, Calgary, Alberta, Canada T2T 5C7. Reprints are not Merritt syndrome. 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

and an increase in fibrin degradation products may also be present. Henoch-Schönlein purpura is the most common form of in children, and the purpuric rash is almost always PLATELET DYSFUNCTION palpable. Congenital Etiologies. Glanzmann’s throm- basthenia is an autosomal recessive disorder caused by congenital deficiency in the platelet membrane IIb and IIIa.9 The Hereditary deficiencies of virtually all coag- result is defective binding of platelet fibrino- ulation factors have been described, but most gen and a decrease in platelet aggregation with are quite rare. The most commonly encoun- all stimulants except . tered disorders are coagulation factor VIII Bernard-Soulier disease is an autosomal deficiency, coagulation factor IX deficiency recessive disorder caused by a congenital defi- and von Willebrand’s disease. Coagulation ciency in platelet membrane Ib factor VIII deficiency and coagulation factor and coagulation factors X and V.9 Affected IX deficiency (hemophilia type A and B) are patients have large platelets and decreased ris- inherited as an X-linked recessive trait. Spon- tocetin-induced platelet aggregation. taneous hemarthrosis is common in patients Storage pool disease is a deficiency of dense with these deficiencies but is rarely encoun- granules, alpha granules, or both types of gran- tered in other coagulation factor deficiencies. ules.9 Patients with storage pool disease have Types I and II von Willebrand’s disease are defective platelet release of ADP and serotonin. autosomal dominant, whereas type III is auto- Acquired Causes. Drugs such as can somal recessive. Type I disease is most com- cause inhibition of prostaglandin synthetase mon. Its severity is quite variable, and labora- and thereby prevent the release of endogenous tory findings in the individual patient may 9 ADP and thromboxane A2, which are essential vary over time. for platelet aggregation. Other drugs that may Acquired deficiencies of coagulation factors impair platelet function include furosemide may be due to disseminated intravascular (Lasix), nitrofurantoin (Furadantin), heparin, coagulopathy, circulating , liver sympathetic blockers, clofibrate (Atromid-S) disease, vitamin K deficiency or .3 and some nonsteroidal anti-inflammatory drugs (NSAIDs).9 Vascular Factors Reduced platelet adhesiveness has been CONGENITAL CAUSES demonstrated in uremic patients. Postulated Hereditary hemorrhagic , an causes include a nonspecific inhibitor or autosomal dominant disorder, is character- increased proteolytic activity in the circulation, ized by the development of fragile telangiecta- which may enhance the catabolism of vWF. sia of the skin and mucous membranes. Deficiency of coagulation factors and a variety Because these blood vessels do not have suffi- of abnormalities in platelet function have been cient muscle or connective tissue in their described in patients with chronic liver disease. walls, hemostatic control is poor. Epistaxis The impairment of fibrinolysis and the accu- and purpura are common presenting features. mulation of degradation products Ehlers-Danlos syndrome, a group of genet- can inhibit platelet aggregation.9 ically heterogenous connective tissue disor- ders, is characterized by skin hyperelasticity, Coagulation Factor Deficiencies joint hypermobility and fragility of the skin Purpura can be the presenting symptom of and blood vessels. Type IV is the ecchymotic congenital or acquired deficiency of coagula- form of the syndrome, and the collagen has a tion factors.3 deficiency of hydroxylysine.9

AUGUST 1, 2001 / VOLUME 64, NUMBER 3 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 423 Henoch-Schönlein purpura is an IgA-medi- ACQUIRED CAUSES ated of small blood vessels. Acquired causes of vasculogenic purpura The hallmarks are nonthrombocytopenic pur- include Henoch-Schönlein purpura, infec- pura, abdominal pain, 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

Historical data Possible etiology Historical data Possible etiology

Age of onset Drug use Birth Intrauterine infection, maternal Alkylating agents Thrombocytopenia idiopathic thrombocytopenic Antimetabolites Thrombocytopenia purpura, maternal systemic lupus erythematosus, maternal Past health medication, TAR syndrome, Antecedent viral infection, Idiopathic thrombocytopenic congenital amegakaryocytic especially an upper purpura, Henoch-Schönlein thrombocytopenia respiratory tract infection purpura 2 to 4 years Idiopathic thrombocytopenic Systemic lupus erythematosus Systemic lupus erythematosus purpura Liver disease Cirrhosis or chronic hepatitis 4 to 7 years Henoch-Schönlein purpura Renal disease Chronic renal failure Onset/chronicity Family history Acute onset Idiopathic thrombocytopenic von Willebrand’s disease von Willebrand’s disease purpura, Henoch-Schönlein purpura, medication, TAR syndrome TAR syndrome mechanical cause Wiskott-Aldrich syndrome Wiskott-Aldrich syndrome Long duration Abnormality of platelets, Maternal history coagulopathy Maternal idiopathic Immune thrombocytopenia Pattern of bleeding thrombocytopenic purpura Mucosal bleeding Thrombocytopenia, Maternal systemic lupus Immune thrombocytopenia von Willebrand’s disease erythematosus Intramuscular and Hemophilia intra-articular bleeding Associated symptoms Abdominal pain, blood Henoch-Schönlein purpura in stools, joint pain Lethargy, fever, bone pain Leukemia Intermittent fever, Systemic lupus erythematosus musculoskeletal symptoms Lethargy, polyuria, polydipsia, Uremia failure to thrive Purpura, but otherwise Idiopathic thrombocytopenic healthy purpura

TAR = thrombocytopenia–absent radii.

424 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 3 / AUGUST 1, 2001 Purpura

75 percent of cases occur in children between tion syndrome or Gardner-Diamond syn- two and 11 years of age.1 The condition is drome) is characterized by spontaneous twice as prevalent in males as in females.11 painful ecchymoses in patients who often have From 60 to 75 percent of patients with psychologic instability.16 Henoch-Schönlein purpura have a history of a preceding upper respiratory tract infection. Clinical and Laboratory Evaluation is the most common infecting A thorough history (Table 1) and a careful organism.13 Palpable purpura is present in physical examination (Table 2) are critical first almost 100 percent of patients with Henoch- steps in the evaluation of children with pur- Schönlein purpura. It is the presenting sign in 50 percent of patients.12 Some patients present with predominantly petechial lesions, some TABLE 2 present with mainly purpuric lesions, and oth- Physical Findings and Possible Etiologies of Purpura ers present with a mixture of lesion types. Some patients have target-like lesions, with each lesion consisting of a central punctate Physical findings Possible etiology hemorrhage surrounded by circumferential General findings regions of pallor and hemorrhage.12 The rash Poor growth Chronic disorder is gravity and pressure dependent.14 Fever Infection Drugs such as atropine and chloral hydrate Chronic renal failure, renal vasculitis may occasionally cause a purpuric lesion sec- Characteristics of purpura ondary to vascular involvement. This vascular Location on lower extremities Henoch-Schönlein purpura purpura usually subsides when the drug is dis- Location on palms and soles Rickettsial infection continued. Patients receiving long-term cortico- steroid therapy may develop purpura sec- Palpable purpura Vasculitis ondary to defective vascular supportive tissue. Associated signs Mild transient nonthrombocytopenic pur- Arthritis, abdominal tenderness, Henoch-Schönlein purpura pura may result from measles, or subcutaneous , scrotal swelling typhoid. Meningococcemia and rickettsial diseases may cause direct damage to blood Hemarthrosis Hemophilia vessels, with resultant purpura. Butterfly rash, pallor, arthritis, Systemic lupus erythematosus Increased venous back pressure following lymphadenopathy violent coughing, vomiting or strangling may Lymphadenopathy Infection, drugs, malignancy cause petechiae in the head and neck area. Jaundice, spider angioma, palmar Liver disease Linear lesions limited to readily accessible , hepatosplenomegaly areas should raise the suspicion of factitious Pallor, lethargy, generalized bone Leukemia purpura. Some ecchymoses of bizarre shape tenderness, hepatosplenomegaly, are the result of religious rituals or cultural lymphadenopathy practices (e.g., cupping, coin rubbing or Skeletal anomalies TAR syndrome, Fanconi’s syndrome spoon scratching).15 Pallor, café au lait spots, Fanconi’s syndrome Child abuse should be suspected if short stature petechiae and bruises are widespread or found Telangiectasia Hereditary hemorrhagic telangiectasia on areas of the body not normally subjected to Hyperelasticity of skin, Ehlers-Danlos syndrome injury. Typically, the platelet count and coagu- hypermobility of lation studies are normal in such children.5 Psychogenic purpura (also termed painful TAR = thrombocytopenia–absent radii. bruising syndrome, autoerythrocyte sensitiza-

AUGUST 1, 2001 / VOLUME 64, NUMBER 3 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 425 pura. Bruises located only on the arms and laboratory screening studies may include a legs of an active child are common findings , 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 level is indicative of

Diagnosis of Purpura

History and physical examination

Etiology clear Etiology unclear

Trauma, drug, Complete blood cell count, infection, peripheral blood smear, hemangioma, PT and aPTT malignancy, syndrome Thrombocytopenia

Yes No

Prolonged PT and aPTT Prolonged PT and aPTT

Yes No Yes No

Sepsis Idiopathic thrombocytopenic Coagulation factor Bleeding time Disseminated purpura deficiency intravascular Hemolytic-uremic syndrome von Willebrand’s coagulopathy Thrombotic disease thrombocytopenic purpura Circulating Normal Prolonged Systemic lupus erythematosus Liver disease Bone marrow aplasia Child abuse Platelet dysfunction Sequestration of platelets von Willebrand’s von Willebrand’s disease disease Vascular purpura

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.

426 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 3 / AUGUST 1, 2001 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- . 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 , 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 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 or 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.

AUGUST 1, 2001 / VOLUME 64, NUMBER 3 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 427 Purpura

thrombocytopenic purpura. Diagnosis and treat- Management ment. Clin Pediatr 1995;34:487-94. 6. George JN, Woolf SH, Raskob GE, Wasser JS, Ale- The treatment of purpura should always be dort LM, Ballem PJ, et al. Idiopathic thrombocy- directed at its underlying cause. Specific treat- topenic purpura: a practice guideline developed by explicit methods for the American Society of ment of the various causes of purpura is Hematology. Blood 1996;88:3-40. beyond the scope of this article but is discussed 7. McCrae KR, Herman JH. Post-transfusion purpura: in standard pediatric hematology textbooks.9,20 two unusual cases and a literature review. Am J Hematol 1996;52:205-11. Children with bleeding tendencies generally 8. Robson WL, Leung AK, Kaplan BS. Hemolytic-ure- should not participate in strenuous activities mic syndrome. Curr Probl Pediatr 1993;23:16-33. or contact sports. In most instances, they 9. Karayalcin G, Paley C, Redner A, Shende A. Disor- ders of platelets. In: Lanzkowsky P. Manual of should not receive intramuscular injections. pediatric hematology and oncology. 2d ed. New The use of aspirin and other NSAIDs also York: Churchill Livingstone, 1995:185-238. should be avoided. Transfusion of platelets or 10. Smith OP, White B. Infectious purpura fulminans: diagnosis and treatment. Br J Haematol 1999; coagulation factors may sometimes become 104:202-7. necessary. Genetic counseling is useful in fam- 11. Kraft DM, McKee D, Scott C. Henoch-Schönlein ilies with inherited bleeding disorders. purpura: a review. Am Fam Physician 1998;58:405- 8,411. 12. Robson WL, Leung AK. Henoch-Schönlein purpura. The authors thank Dianne Leung and Eleanor Sit for Adv Pediatr 1994;41:163-94. expert secretarial assistance and Sulakhan Chopra, 13. Robson WL, Leung AK. The frequency of preceding University of Calgary Medical Library, Alberta, infection with group A beta-hemolytic streptococ- Canada, for assistance in preparing the manuscript. cus in patients with Henoch-Schönlein purpura. J Singapore Paediatr Soc 1993;35:168-72. 14. Robson WL, Leung AK, Lemay M. The pressure- The authors indicate that they do not have any con- dependent nature of the rash in Henoch-Schönlein flicts of interest. Sources of funding: none reported. purpura. J Singapore Paediatr Soc 1992;34:230-1. 15. Leung AK. Ecchymosis from spoon scratching sim- REFERENCES ulating child abuse. Clin Pediatr 1986;25:98. 16. Moll S. Psychogenic purpura. Am J Hematol 1997; 1. Baselga E, Drolet BA, Esterly NB. Purpura in infants 55:146-7. and children. J Am Acad Dermatol 1997;37(5 pt 17. Sallah S, Kato G. Evaluation of bleeding disorders. 1):673-705. A detailed history and laboratory tests provide 2. Duerst RE. Petechiae and purpura. In: Hoekelman clues. Postgrad Med 1998;103(4):209-10,215-8. RA, Friedman SB, Nelson NM, Seidel HM, eds. Pri- 18. Corrigan JJ. Hemorrhagic and thrombotic diseases. mary pediatric care. 2d ed. St. Louis: Mosby Year In: Nelson WE, Behrman RE, Kliegman RM, Arvin Book, 1992:1023-7. AM, eds. Nelson Textbook of pediatrics. 15th ed. 3. Cohen AR. Rash—purpura. In: Fleisher GA, Ludwig Philadelphia: Saunders, 1996:1422-4. S, et al., eds. Textbook of pediatric emergency med- 19. Medeiros D, Buchanan GR. Current controversies icine. 3d ed. Baltimore: Williams & Wilkins, 1993: in the management of idiopathic thrombocy- 430-8. topenic purpura during childhood. Pediatr Clin 4. Kuhne T, Elinder G, Blanchette VS, Garvey B. Cur- North Am 1996;43:757-72. rent management issues of childhood and adult 20. Lusher JM. Approach to the bleeding patient. In: immune thrombocytopenic purpura (ITP). Acta Nathan DG, Orkin SH, et al., eds. Nathan and Paediatr Suppl 1998;424:75-81. Oski’s Hematology of infancy and childhood. 5th 5. Souid A, Sadowitz PD. Acute childhood immune ed. Philadelphia: Saunders, 1998:1574-83.

428 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 64, NUMBER 3 / AUGUST 1, 2001