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As a accepted pediatrician, it is not aberrant to accept to triage patients who present with platelet abnormalities. Typical scenarios run the area from a able-bodied asymptomatic accommodating who presents and is activate to accept an abnormally low platelet calculation on accepted class tests, to a accommodating who presents accurately for astute access of accessible bruising.

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Platelets, calm with von Wille-brand factor, tissue factor, and collagen, are an capital basic of primary hemostasis. Accustomed platelet counts ambit from 150–450×103/mcL, although about pathologic thrombocytopenia is advised back the platelet calculation is agilely beneath than 100×103/mcL. Nonetheless, patients are not advised to be at an added accident for ad-lib bleeding, decidedly intracerebral hemorrhage, unless their platelet calculation is beneath than 10–20×103/mcL. In the ambience of moderately invasive procedures or surgery, a platelet beginning of at atomic 50×103/mcL is about recommended. These norms advice adviser back platelet transfusions may be needed, although accepted administration for thrombocytopenia ultimately depends on the analytic adherence of the accommodating and the basal analysis of the thrombocytopenia. Furthermore, it has been accustomed that for the aforementioned platelet count, there is an added accident of bleeding in thrombocytopenic patients with age-old or old platelets (such as in leukemia or bottom infiltrative processes) as compared to patients with platelets that are rapidly axis over and are about adolescent (such as in allowed thrombocytopenic purpura [ITP]).

Other factors that accord to a patient’s bleeding risk, afar from the platelet calculation itself, are platelet action modifiers such as biologic acknowledgment to ibuprofen or aspirin, activation or burnout of platelets such as in the ambience of prosthetic valves, and the attendance of added hemostatic defects including alarmist or renal disease.1

General attack in compassionate and cerebration about thrombocytopenia circumduct about the basal apparatus abaft the low platelet count. This can be disconnected into several categories as credible in Table 1.

Table 1.

Mechanisms Abaft Analytic Thrombocytopenia

Patient history is a admired antecedent of advice that can advice accommodate clues as to which of the mechanisms listed in Table 1 is best likely. It is decidedly accessible in adapted amid thrombocytopenia as allotment of an basal systemic ataxia adjoin abandoned thrombocytopenia. Factors to accede accommodate the astute adjoin abiding attributes of the antecedent presentation, attendance of bleeding symptoms, accepted ancestors history, claimed medical history of autoimmunity or added abiding illness, acknowledgment to accordant medications, and whether bleeding affection are in acknowledgment to a accepted hemostatic claiming such as surgery, trauma, or injury.

Medications such as diuretics (specifically chlorothiazides), quinines, hormone analysis with estrogen, booze abuse, and abounding antibiotics including sulfonamides accept all been alive in anon suppressing megakaryocytic admeasurement and differentiation.2,3 Added drugs that accept been alive in accessory allowed thrombocytopenia, which after-effects in added borderline abolition and aloofness of platelets, accommodate gold, digoxin, cimetidine, valproic acid, penicillin, and alpha-interferon.1

Infection is a accepted activate for clinically cogent acquired thrombocytopenia because it anon suppresses the bottom and impairs thrombopoiesis. Viral etiologies to accede accommodate adenovirus, hepatitis, measles, mumps, varicella, cytomegalovirus, Epstein-Barr virus, HIV, and parvovirus B19. Bacterial and protozoal infections accept additionally been adroit in thrombocytopenia, accurately malaria.3

Personal and ancestors bleeding history are additionally acutely important. Specific capacity to analyze about accommodate above-mentioned charge for claret transfusions, abiding bleeding with surgeries or in the post-partum period, and history of menorrhagia in accompanying changeable ancestors members.

The analytic actualization of thrombocytopenia is about bark and close film bleeding, with the best accepted actuality epistaxis or gingival bleeding but additionally including gastrointestinal bleeding and menorrhagia. One concrete assay award that is specific for platelet disorders is petechiae, although purpura and able-bodied can be articular on assay as well. Added concrete assay allegation such as leukoplakia, bark hyperpigmentation, and dystrophic nails may point adjoin dyskeratosis congenita, a cartilage bottom abortion affection associated with an added accident for malignancy. Hypotelorism, ample nasal bridge, microphthalmia, deride anomalies, and ashen and vertebral abnormalities may be manifestations of Fanconi anemia. Genitourinary abnormalities, including hypogonadism, micropenis, and undescended testes, can be credible in several affiliated cartilage bottom abortion syndromes.4 Thrombocytopenia absent radii and radial-ulnar synostosis are two orthopedic altitude associated with thrombocytopenia in the ambience of limb anomalies.

Physical assay allegation such as a bloated acme may advance a abysmal venous thrombosis, which can be associated with thrombocytopenia accessory to consumption. Collective or beef bleeds, on the added hand, are acutely aberrant and would point adjoin addition analysis such as hemophilia. Of note, collagen vascular disorders, such as Ehlers-Danlos syndrome, which about present with accessible able-bodied or bleeding but accept no basal platelet calculation abnormalities, should be advised if a accommodating presents with collective hypermobility and bark hyperextensibility.

The class allegation associated with thrombocytopenia are a key basic in accurately anecdotic and managing the basal diagnosis. To begin, there are several actualization of the complete claret calculation (CBC) and borderline claret apply to focus on, as categorical in Table 2. Authentic estimation of the CBC and borderline apply can not abandoned affirm the severity of the thrombocytopenia, but additionally can advice analyze whether it is macro- or microcytic, aphorism out artificially decreased platelets, and accommodate advice apropos abeyant systemic disorders. If necessary, barometer to Pediatric Hematology for a cartilage bottom aspirate and biopsy can accommodate added information, including bottom cellularity and signs of bottom infiltration.

Table 2.

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Helpful Allegation on a Complete Claret Calculation and Borderline Claret Apply in the Ambience of Analytic Thrombocytopenia

Additional class studies that can advice analyze the basal analysis for thrombocytopenia are listed in Table 3.

Table 3.

Additional Class Studies That Can Advice Analyze the Basal Analysis for Thrombocytopenia

See Figure 1, Figure 2, and Figure 3 for accepted guidelines apropos the appraisal and analysis of a adolescent or adolescent with thrombocytopenia.

Figure 1.

Thrombocytopenia in a well-appearing child. ANC, complete neutrophil count; hx, history; ITP, allowed thrombocytopenic purpura; MDS, myelodysplastic syndromes; TAR, thrombocytopenia absent radii; WBC, white claret cell. Adapted from Cris Johnson and de Alarcón.17

Figure 2.

Thrombocytopenia in an ill-appearing child. ALL, astute lymphoblastic leukemia; APML, astute promyelocytic leukaemia; DIC, broadcast intravascular coagulation; HUS, hemolytic uremic syndrome; INR, all-embracing normalized ratio; MDS, myelodysplastic syndromes; PT, prothrombin time; PTT, fractional thromboplastin time; TTP, thrombotic thrombocytopenic purpura. Adapted from Cris Johnson and de Alarcón.17

Figure 3.

Thrombocytopenia in a neonate. ANC, complete neutrophil count; DIC, broadcast intravascular coagulation; Hgb, hemoglobin; HTN, hypertension; ITP, allowed thrombocytopenic purpura; NEC, necrotizing enterocolitis; PT, prothrombin time; PTT, fractional thromboplastin time; RDS, respiratory ache syndrome; SLE, systemic lupus erythematosus; TAR, thrombocytopenia absent radii; WBC, white claret cell. Adapted from Waldron and de Alarcón.18,19

ITP is an important analytic appliance back a accommodating presents in the outpatient ambience with new able-bodied or purpura but is contrarily well-appearing. It is important to verify that the accommodating does not accept any apropos built-in affection such as fever, weight loss, cartilage pain, or night sweats, and to affirm that the accommodating does not accept any credible lymph-adenopathy, hepatosplenomegaly, or added aberrant allegation on concrete assay abreast from bruising, purpura, or petechiae. Typically, the CBC should not accept any added aberrant allegation abreast from an abandoned low platelet count, about <100×103/mcL; however, anemia may be present if cogent bleeding was clinically credible at the time of diagnosis. Cartilage bottom appraisal is not all-important as continued as the accommodating meets the aloft belief and has no added awkward findings. If the accommodating has circumstantial neutropenia and anemia, absolutely blight charge be disqualified out and a barometer to pediatric hematology-oncology is warranted. Added analytic considerations would again accommodate Evans syndrome, an autoimmune action affecting red claret beef (often Coombs positive), platelets, and white claret cells.

In patients with ITP, ascertainment abandoned is recommended if the accommodating is asymptomatic with no alive bleeding, alike in the ambience of able-bodied or petechiae. First-line analysis for patients with alive bleeding (with specific absorption to gastrointestinal hemorrhage, articulate mucosal bleeding or “wet purpura,” or accident of intracranial drain [ICH] with arch agony or headache) includes corticosteroids, intravenous allowed globulin (IVIG), and Rho(D) allowed globulin (anti-D immunoglobulin). IVIG (0.8–1 g/kg × 1 dose) is about anticipation to aftereffect in a added accelerated and affecting acceleration in the platelet calculation compared to steroids (prednisone, 2–4 mg/kg/day). The continuance of corticosteroids has not been associated with a cogent appulse on platelet counts in the continued term, so the dosage is about cone-shaped and chock-full afterwards 3 to 6 weeks behindhand of platelet counts. Rho(D) allowed globulin should not be administered in the ambience of anemia or crumbling claret because it can activate hemolytic anemia, which could added admixture the patient’s hemodynamic stability. Platelet transfusions should abandoned be accustomed for approaching or accustomed ICH. Action does not charge to be belted extensively, but acquaintance sports (hockey, football, lacrosse, conceivably soccer and basketball) as able-bodied as activities astute a trampoline, bicycle, skateboard, or helmet, should be abhorred until the platelet calculation is at atomic >30×103/mcL.

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Most patients accept a bound advance in the aboriginal 3 months or sooner, although some patients can accept a added abiding remitting course. Best cases of adolescence ITP are self-limited, and 80% abide ad-lib absolution aural 6 to 12 months.1 Thus, in children, added invasive or ascent therapies (rituximab, splenectomy, immunosuppressive medications, thrombopoietin receptor agonists) are not adumbrated initially and should be delayed for at atomic 12 months. If the accommodating is not responding to first-line analysis as expected, barometer to pediatric hematology is reasonable for added analytic investigation.

The best accepted triggers for ITP accommodate contempo viral infection but vaccines are addition accepted trigger, decidedly the measles, mumps, and rubella (MMR) vaccine. Nonetheless, it has been approved that built-in infection can account ITP at a college amount than the vaccine itself. Therefore, the aboriginal MMR vaccine is still recommended for all pediatric patients, including those accouchement with a above-mentioned history of ITP. In accouchement with ITP who accept already accustomed one dosage of MMR, vaccine titers can be arrested so that, if able amnesty is present, the added dosage can be abhorred in an attack to anticipate a echo blaze of ITP. If the adolescent does not accept able immunity, the added dosage of MMR should be accustomed at the adapted age.5,6 One abstraction advised the accident of ITP in acknowledgment to added adolescence vaccinations and activate that there was no added accident of ITP afterwards any added vaccine in aboriginal adolescence except for MMR.7 For accouchement age 11 to 17 years, there was possibly an added accident of ITP afterwards hepatitis A, varicella, and Tdap vaccines; however, the cardinal of apparent cases was acutely small, so added analysis is required.

Other immune-mediated processes, such as neonatal alloimmune and autoimmune thrombocytopenia, should be advised if low platelet counts (<50×103/mcL) are encountered in the bairn period. Affectionate antibodies adjoin fetal platelet antigens affiliated from the ancestor cantankerous the placenta and account fetal thrombocytopenia in neonatal alloimmune thrombocytopenia; affectionate antibodies to animal platelet antigen 1a (HPA-1a) accept been articular in 80% of neonatal alloimmune thrombocytopenia cases in white children, admitting HPA-4 and HPA-5 are added acceptable culprits in Asian children. Above-mentioned history of an afflicted bairn with ICH is the accomplished accident agency for issues in a consecutive pregnancy, and approaching pregnancies tend to be added acutely afflicted in general. Infusion of affectionate platelets (HPA negative) is the recommended first-line therapy, although donor platelets, IVIG, or corticosteroids can be accustomed if affectionate platelets are not available. Infants should accept a circadian CBC to chase the platelet calculation with a ambition of advancement platelets >30×103/mcL as able-bodied as an antecedent arch ultrasound to appraise for ICH. Neonatal autoimmune thrombocytopenia is primarily a appliance if there is a absolute affectionate history of autoimmune disease, alike if the mother is in absolution during pregnancy. Bleeding affection are about abundant milder than those in neonatal alloimmune thrombocytopenia. Ascertainment is about recommended, although IVIG can be administered for bleeding symptoms.

Congenital thrombocytopenia syndromes should be advised if thrombocytopenia is assiduous and articular at a adolescent age. That said, it is not aberrant for complete thrombocytopenia syndromes to be diagnosed abandoned in adulthood, as abounding patients may not present with astute or aboveboard bleeding symptoms. Hereditary thrombocytopenias are usually characterized by platelet counts <50×103/mcL, basal to no symptoms, and no adapted administration on a circadian basis. Exceptions to this accommodate Wiskott-Aldrich affection (WAS), thrombocytopenia absent radii (TAR), and Chediak-Higashi syndrome, which can all accept a added astringent bleeding phenotype.

If abandoned thrombocytopenia progresses to astringent aplastic anemia with cartilage bottom failure, complete amegakaryocytic thrombocytopenia is added acceptable and cartilage bottom displace is the abandoned accepted alleviative option. In the ambience of ashen abnormalities including absent radii, TAR is added likely, and because the thrombocytopenia improves with age, common transfusions are about not required. WAS is characterized by the archetypal accord of immunodeficiency, micro-thrombocytopenia, and eczema. Platelet half-life is bargain due to splenic removal, and although splenectomy can access platelet counts in WAS, cartilage bottom displace is adapted for adapted analysis of the basal immunodeficiency. Table 4 provides a abrupt overview of the best acclaimed and articular complete or affiliated syndromes.

Table 4.

Congenital Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a attenuate but important analysis to accomplish as it is a analytic emergency. The accident is decidedly lower in pediatric patients as compared to adults and ranges from 0.05% to 3% of all pediatric patients apparent to unfractionated heparin.8–10 HIT should be doubtable in patients who accept been apparent to heparin either in the aftermost 5 to 10 canicule or anytime in the aftermost 3 months who accept accomplished added than a >50% bead in platelet calculation (which about is in the 50–80×103/mcL ambit and not usually <20×103/mcL).11 Analytic scoring systems such as the “4 T’s” (thrombocytopenia, thrombosis, timing, and added causes of thrombocytopenia) can advice analyze patients in whom HIT is added likely, because cat-and-mouse for antibiotic testing (heparin/platelet agency 4) is not applied or safe.12 The 4 T’s scoring arrangement has a aerial negative-predictive amount (0.998), but aerial array are not associated with a aerial positive-predictive amount (0.14).13 Immediate cessation of heparin with admission of a nonheparin anticoagulant is recommended.

Hemolytic uremic affection (HUS) and thrombotic thrombocytopenic purpura (TTP) are two diseases on a spectrum characterized by broadcast micro-vascular barge occlusion with platelet microthrombi that aftereffect in broadcast endothelial damage. HUS is best acclaimed for the analytic accord of thrombocytopenia, microangiopathic hemolytic anemia, and astute renal failure. It is best frequently credible in patients adolescent than age 3 years with an communicable prodrome of gastroenteritis involving Escherichia coli or shiga toxin. Supportive care, including renal dialysis, is the mainstay of treatment. Aberant HUS (aHUS), which is not associated with a prodromal diarrheal affliction (D- subtype), is credible in earlier patients and has been associated with Streptococcus pneumoniae. aHUS is associated with a worse prognosis, and patients are added apt to accept a abiding alternate advance with end-stage renal failure. TTP is associated with a archetypal analytic accord of fever, adapted brainy status, and thrombocytopenia with added actualization including hemolytic anemia and astute branch injury. The pathogenesis revolves about abortive or amiss ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs), which causes boundless platelet clumping due to non-cleaved ultra-long von Willebrand agency (vWF) multimers. Lactate dehydrogenase, reticulocyte count, and absolute bilirubin are elevated. Coombs testing is negative. Plasmapheresis is the gold accepted and should be accomplished anon afterwards cat-and-mouse for acknowledging ADAMTS13 levels (which should usually be <5%–10%). That said, it is accepted that up to 30% of patients with accessory TTP may accept accustomed ADAMTS13 levels and added specific qualitative testing with enzymatic action may be required.14,15 Overall, adapted amid aHUS and TTP can be challenging. Astringent thrombocytopenia (platelet calculation <20–50×103/mcL) is about added constant with TTP, admitting aHUS is added acceptable to accept college platelet counts. Astute branch abrasion astute abiding dialysis is added about credible with aHUS than TTP. Genetic testing for aHUS can advice differentiate amid familial and non-familial aHUS. TTP is about acquired, but a complete anatomy does abide that presents aboriginal in life.

Treatment of abounding thrombocytopenic disorders is accompanying to the analysis or abolishment of the basal disorder, decidedly in sepsis, broadcast intravascular coagulation, or drug-induced thrombocytopenia. The administration of allowed thrombocytopenias such as ITP or neonatal allo- or autoimmune thrombocytopenia has been discussed added in detail above. Barometer to pediatric hematology-oncology is absolutely consistently accessible and reasonable in any of the diagnoses discussed aloft accustomed the nuances of the controlling action and to get advice with the admission of treatment.

General attack in the administration of advancing bleeding accommodate bounded ascendancy with pressure, ice, or packing, and depending on the situation, the use of desmopressin, aminocaproic acid, tranexamic acid, and/or platelet transfusions if needed. Patients who crave common platelet transfusions should accept leukocyte-depleted platelet articles to abatement alloimmunization. In the ambience of menorrhagia, estrogen and articulate contraceptives accept been acclimated with acceptable efficacy. A humidifier and aerosol with bounded petroleum clabber can additionally advice with alternate epistaxis. For hypersplenism, splenectomy can be considered. Splenectomy has been credible to be able in WAS as able-bodied but does access the accident of infection with encapsulated bacilli in a subset of patients who are already at added accident for infection due to basal immunodeficiency. To abode this, patients with WAS usually accept penicillin prophylaxis forth with account IVIG. Nonetheless, cartilage bottom displace is the adopted and abandoned alleviative treatment. All patients with platelet disorders, both quantitative and qualitative, should abstain platelet function-inhibiting medications such as aspirin, nonsteroidal anti-inflammatory drugs, and the penicillins.

Platelets are an capital basic of the hemostatic pathway. As such, thrombocytopenia is an important award to analyze and diagnose, admitting accepting a ample cogwheel diagnosis. The history, concrete examination, and class allegation are all important clues abaft the analysis of thrombocytopenia, and authentic identification of the basal analysis is astute to free the adapted management. Barometer to pediatric hematologyoncology is acceptable for all patients in whom bleeding is clinically significant, the analysis is unclear, or acknowledgment to analysis is suboptimal, as able-bodied as for all patients who charge abiding subspecialty aftereffect and management.

Mechanisms Abaft Analytic Thrombocytopenia

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Helpful Allegation on a Complete Claret Calculation and Borderline Claret Apply in the Ambience of Analytic Thrombocytopenia

Additional Class Studies That Can Advice Analyze the Basal Analysis for Thrombocytopenia

Comprehensive metabolic console to appraise alarmist and branch function

  Liver disease, uremia, and renal displace bounce can all be associated with thrombocytopenia

  Evidence of astute branch abrasion may point appear sepsis or basal thrombotic microangiopathy

Lactate dehydrogenase to appraise for added corpuscle about-face as credible with infection, malignancy, sepsis, or thrombotic microangiopathy

Immature platelet atom to appraise bottom production

  Low adolescent platelet atom would advance cartilage bottom abortion (ie, aplastic anemia)

  High adolescent platelet atom would advance cartilage bottom advantage for added borderline abolition (ie, allowed thrombocytopenic purpura)

Coagulation console (prothrombin time, all-embracing normalized ratio, fractional thromboplastin time, and fibrinogen to appraise for coagulopathy, bleeding risk, and/or basal broadcast intravascular coagulation)

Hemolysis class after-effects (haptoglobin, fractionated absolute bilirubin, reticulocyte count, lactate dehydrogenase, and Coombs [direct antiglobulin test]) to appraise for basal thrombotic microangiopathy as able-bodied as to appraise for circumstantial hemolytic anemia (as would be present in Evans syndrome)

Thyroid action tests to appraise for hypo- or hyperthyroidism

Congenital Thrombocytopenia

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