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Idiopathic Thrombocytopenic Purpura, Emergency Medicine

Basics

Description

- Chronic ITP: - Occurs mostly in adults - Young women are most susceptible in adult onset ITP - Characterized by variable response to corticosteroids and other immune suppressants - 60-70% respond to splenectomy

- Impaired bone marrow production: - Bone marrow fibrosis - Bone marrow infiltration owing to malignancy - Cytotoxic drugs used in chemotherapy - Congenital/acquired bone marrow abnormalities

- Splenic sequestration: - Portal hypertension - Neoplastic infiltration - Sickle cell disease

- Accelerated destruction of platelets: - Vasculitis - TTP/HUS - Disseminated intravascular coagulation (DIC) - HELLP syndrome - Cardiac valvular disease

- Drug induced: - Decreased platelet production: - Chemotherapy - Thiazide diuretics - Ethanol - Estrogen

- Hemorrhagic shock: - 2 large-bore IVs - Direct pressure for hemostasis - Resuscitation with blood transfusions and isotonic crystalloid - Medications and platelets for acute life-threatening episodes of bleeding: - IV high-dose dexamethasone or methylprednisolone - IVIG infusion - Platelet transfusions: 2-3 times the normal amount

- Initial treatment options for ITP are based on: - Degree of thrombocytopenia - Severity of illness - Duration of symptoms - Age - Risk factors for bleeding (hypertension, peptic ulcer disease, vigorous lifestyle) - Hematologist preference

- Differential diagnosis of thrombocytopenia during pregnancy: - Gestational thrombocytopenia (75%): - Usually of no clinical significance - Does not cause neonatal thrombocytopenia - Remits 1-2 wk after delivery - Platelets typically >50 K

- Glucocorticoids (high dose over 2-3 wk): - Dexamethasone: 40 mg PO daily - Prednisone: 1-2 mg/kg/24 hr PO/day - Methylprednisolone: 1 g IV q8h (30 mg/kg/24 hr pediatric dose)

- Other: - Rituximab: Monoclonal antibody directed against B cell antigens - Danazol: Antiandrogen

- Experimental: - Other monoclonal antibodies directed at B cells - Stem cell transplants - Thrombopoietin and thrombopoietin-like agonists

  • Idiopathic thrombocytopenic purpura (ITP) is thrombocytopenia without apparent cause or abnormalities in other celllines.
  • Incidence is ~2-5/100,000/yr-may be an underestimate owing to undetected, subclinical cases.
  • Acute ITP:1/2 of cases involve children.80% of children recover within 8 wk with or without therapy.Adult recovery is delayed and requires specific therapy to achieve remission.
  • Chronic ITP:Occurs mostly in adultsYoung women are most susceptible in adult onset ITPCharacterized by variable response to corticosteroids and other immune suppressants60-70% respond to splenectomy
  • Chronic refractory ITP:Platelet counts may often wax and wane.Often do not respond to therapyNo clear optimal course of treatment
  • Genetics:ITP appears to run in families, as do variations in response to corticosteroids for treatment.

Etiology

  • Autoantibodies produced by B cells and plasma cells cause immune-mediated destruction of circulating platelets
  • Macrophages in spleen and liver mediate destruction of platelets via IgG autoantibodies
  • IgM and IgA rarely have been seen
  • Some patients do not possess autoantibodies, suggesting a role for T cell-mediated cytotoxicity.
  • C3 and C4 complements have also been shown to play a role in patients that lack autoantibodies
  • Poor platelet production may also play a role especially in chronic or refractory cases of ITP
  • Eradication of Helicobacter pylori can sometimes be associated with platelet recovery (unclear mechanism).

Diagnosis

Signs and Symptoms

History

  • Bleeding is the most common complaint:Common:Mucous membrane: Gingiva, epistaxis, conjunctival, menorrhagiaRare (more common in coagulopathies):GI bleeding, hemarthrosis, hematuria, and hematomas
  • 84% of pediatric cases are 2-3 wk following a viral illness:Small percentage found following vaccinations
  • Most adult cases have an insidious onset:Up to 28% of patients are asymptomatic and diagnosed on routine CBC<5% present with life-threatening bleeding

Physical Exam

  • Mucosal bleeding often apparent in symptomatic cases
  • Commonly may follow dental procedures, extraction or trauma
  • Petechiae (nonblanching)
  • Nonpalpable purpura
  • Distinguishes ITP from Henoch-Sch ¶nlein purpura (HSP)
  • Melena, bright red blood per rectum, or hemoccult positive stools
  • Spleen normal size in ITP:Enlarged spleen may be found in leukemia or other platelet sequestration syndromes
  • Neurologic deficits from intracranial hemorrhage (ICH):ICH is the most common cause of death in ITP.Risk of ICH in ITP increases with age:Age <40 yr: 2%Age >60 yr: 48%

Essential Workup

  • Diagnosis of exclusion-other causes of thrombocytopenia must be ruled out.
  • CBC with differential
  • PT and PTT if actively bleeding to exclude other forms of coagulopathy
  • BUN and creatinine to evaluate renal function
  • Liver function to exclude liver disease
  • Type and screen if actively bleeding
  • Pregnancy test if of childbearing age
  • HIV testing should be considered

Diagnosis Tests & Interpretation

Lab

CBC with differential and peripheral smear:

  • Thrombocytopenia
  • Increased mean platelet volume
  • Normal WBC and RBC morphology and size
  • Liver function, coagulation studies, and kidney function should all be within normal limits

Imaging

CT head without contrast to evaluate for ICH if clinically indicated by focal findings, headache, or head trauma.

Diagnostic Procedures/Surgery

Bone marrow biopsy:

  • All adults >60 yr to evaluate for malignancy
  • Atypical symptoms and cases refractory to treatment
  • Patients considering splenectomy
  • Children with persistent thrombocytopenia >6 mo
  • Children unresponsive to intravenous immunoglobulin (IVIG)
  • Antibody testing is of no clinical value

Differential Diagnosis

  • Impaired bone marrow production:Bone marrow fibrosisBone marrow infiltration owing to malignancyCytotoxic drugs used in chemotherapyCongenital/acquired bone marrow abnormalities
  • Splenic sequestration:Portal hypertensionNeoplastic infiltrationSickle cell disease
  • Accelerated destruction of platelets:VasculitisTTP/HUSDisseminated intravascular coagulation (DIC)HELLP syndromeCardiac valvular disease
  • Drug induced:Decreased platelet production:ChemotherapyThiazide diureticsEthanolEstrogenIncreased destruction of platelets:AspirinHeparinChlorpropamideChloroquineGold saltsSulfonamidesInsecticides

Treatment

Pre-Hospital

Stabilize ABCs

  • Significant oral or laryngeal bleeding may affect airway.
  • CNS event may affect ability to control airway
  • Establish IV access for cases of significant bleeding
  • Control any bleeding with direct pressure

Initial Stabilization/Therapy

  • ABCs
  • Stabilize life-threatening bleeding:ICH:Airway controlNeurosurgery consultation: Craniotomy not typically possible until platelet counts >75 KHemorrhagic shock:2 large-bore IVsDirect pressure for hemostasisResuscitation with blood transfusions and isotonic crystalloidMedications and platelets for acute life-threatening episodes of bleeding:IV high-dose dexamethasone or methylprednisoloneIVIG infusionPlatelet transfusions: 2-3 times the normal amountPlatelets typically infused after steroids and/or IVIGMucous membrane bleeding:Topical agentsOther:IV Aminocaproic acid may be consideredIn rare cases, plasmapheresis has been proven helpful

Ed Treatment/Procedures

  • Initial treatment options for ITP are based on:Degree of thrombocytopeniaSeverity of illnessDuration of symptomsAgeRisk factors for bleeding (hypertension, peptic ulcer disease, vigorous lifestyle)Hematologist preference
  • Efficacy of treatment is demonstrated in terms of platelet recovery time and not morbidity or mortality.
  • Specific treatment options:Observation is recommended for children without bleeding complications or profound thrombocytopenia (<20-30 K)Profound thrombocytopenia (<20 K):High-dose corticosteroids: 75% responseIVIG: 80% response, but costly, so reserved in time critical emergenciesAnti-D IG: 70% response (used only in Rh+ patients)Splenectomy:2nd-line therapy if inadequate response to a course of glucocorticoid therapyTwo-thirds of adult patients respond, three-fourths of pediatric patients respond.No specific indications for emergent splenectomy
  • Differential diagnosis of thrombocytopenia during pregnancy:Gestational thrombocytopenia (75%):Usually of no clinical significanceDoes not cause neonatal thrombocytopeniaRemits 1-2 wk after deliveryPlatelets typically >50 K
  • HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)
  • ITP (15%):Platelets typically <50 KMaternal platelet count does not correlate to neonatal thrombocytopenia.Treatment with steroids or IVIG does not alter incidence of neonatal thrombocytopenia.Degree of thrombocytopenia should not alter decision of vaginal birth vs. C-section.Measure neonatal CBC and check brain ultrasound for ICH.Treat neonatal thrombocytopenia with IVIG and steroids

Medication

First Line

  • Glucocorticoids (high dose over 2-3 wk):Dexamethasone: 40 mg PO dailyPrednisone: 1-2 mg/kg/24 hr PO/dayMethylprednisolone: 1 g IV q8h (30 mg/kg/24 hr pediatric dose)
  • IVIG: 1-2 g/kg IV — 1 dose and possibly repeated in 24 hr:Used only for critical bleeding or when the need to acutely raise platelets is required such as emergency surgery
  • Anti-D immunoglobulin: 50 μg/kg/24 hr IV:Used only presplenectomy and in Rh+ patients

Second Line

  • Chronic long-term suppression and steroid bolus therapy
  • Immunosuppressive agents:AzathioprineCyclosporinMycophenolateChemotherapeutic agents:Vinca alkaloidsCyclophosphamideCombinational chemotherapy
  • Other:Rituximab: Monoclonal antibody directed against B cell antigensDanazol: Antiandrogen
  • Experimental:Other monoclonal antibodies directed at B cellsStem cell transplantsThrombopoietin and thrombopoietin-like agonists

Follow-Up

Disposition

Admission Criteria

  • Life-threatening bleeding regardless of platelet count
  • Any bleeding with platelet count <20 K
  • Asymptomatic patient with platelet count <20 K with issues of noncompliance or poor follow-up

Discharge Criteria

  • Asymptomatic patients
  • Patients with minor bleeding and platelets >30 K

Followup Recommendations

Hematology referral is indicated in all cases (either outpatient or inpatient consultation)

Pearls and Pitfalls

  • Before low platelet counts are evaluated, pseudothrombocytopenia should be excluded.
  • Spontaneous bleeding usually does not occur until platelet counts are <10 K.

Additional Reading

  • British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574-596.
  • Fogarty PF, Segal JB. The epidemiology of immune thrombocytopenic purpura. Curr Opin Hematol. 2007;14:515-519.
  • Godeau B, Provan D, Bussel J. Immune thrombocytopenic pupura in adults. Curr Opin Hematol. 2007;14:535-556.
  • Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.
  • Schipperus M, Fijnheer R. New therapeutic options for immune thrombocytopenia. Neth J Med. 2011;69(11):480-485.

See Also (Topic, Algorithm, Electronic Media Element)

HELLP Syndrome; Thrombotic Thrombocytopenic Purpura

Codes

ICD9

287.31 Immune thrombocytopenic purpura

ICD10

D69.3 Immune thrombocytopenic purpura

SNOMED

  • 32273002 Idiopathic thrombocytopenic purpura (disorder)
  • 28505005 acute idiopathic thrombocytopenic purpura (disorder)
  • 13172003 chronic idiopathic thrombocytopenic purpura (disorder)