Definition of Definition of Hemophilia Hemophilia Deficiency characterized by Deficiency characterized by interruption of clot formation interruption of clot formation Hemophilia A (Classic) Hemophilia A (Classic) – decreased factor VIII decreased factor VIII Hemophilia B (Christmas Hemophilia B (Christmas Disease) Disease) – decreased factor IX decreased factor IX
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Definition of HemophiliaDefinition of Hemophilia
Deficiency characterized by interruption Deficiency characterized by interruption of clot formationof clot formation
Hemophilia A (Classic)Hemophilia A (Classic)
– decreased factor VIIIdecreased factor VIII Hemophilia B (Christmas Disease)Hemophilia B (Christmas Disease)
– decreased factor IXdecreased factor IX
Coagulation CascadeCoagulation Cascade
Casella JF, Casella JF, Oski’s Pediatrics: Principles and Practices, 3rd Ed., 1999Oski’s Pediatrics: Principles and Practices, 3rd Ed., 1999
Casella JF, Casella JF, Oski’s Pediatrics: Principles and Practices, 3rd Ed., 1999Oski’s Pediatrics: Principles and Practices, 3rd Ed., 1999
Incidence of HemophiliaIncidence of Hemophilia
Sex-linked inheritance patternSex-linked inheritance pattern 1 in 5000 live male births in U.S.1 in 5000 live male births in U.S. 4:1 ratio Hemophilia A to 4:1 ratio Hemophilia A to
Hemophilia BHemophilia B Many (~ 1/3) cases are new Many (~ 1/3) cases are new
MildMild - - Hemorrhage usually only after severe trauma or surgeryHemorrhage usually only after severe trauma or surgery
ModerateModerate - - Hemorrhage more frequent after moderate traumaHemorrhage more frequent after moderate trauma
SevereSevere - - Hemorrhage frequently after minor or unrecognized Hemorrhage frequently after minor or unrecognized
traumatrauma
Complications of HemophiliaComplications of Hemophilia
Joint diseaseJoint disease
Deep soft tissue bleedingDeep soft tissue bleeding
Neurovascular compromiseNeurovascular compromise
Complications of HemophiliaComplications of Hemophilia
InfectionsInfections
Inhibitor formationInhibitor formation
PsychosocialPsychosocial
FinancialFinancial
Philosophy of CarePhilosophy of Care
Normalization of life style and Normalization of life style and prevention of disabilityprevention of disability
Rx still “on-demand” in most cases, but Rx still “on-demand” in most cases, but prophylactic treatment should be prophylactic treatment should be consideredconsidered
Home therapy whenever possibleHome therapy whenever possible
Evaluation of the patient - GeneralEvaluation of the patient - General
Personal History Personal History Family HistoryFamily History MedicationsMedications Physical examPhysical exam Consider circumstances of the bleedConsider circumstances of the bleed Presence of pain usually enough to initiate therapyPresence of pain usually enough to initiate therapy Avoid I.M. injections, NSAIDs contraindicatedAvoid I.M. injections, NSAIDs contraindicated
Joint Bleeds - GeneralJoint Bleeds - General
Most common complicationMost common complication Often spontaneousOften spontaneous Target jointsTarget joints Early treatment desirableEarly treatment desirable Predictable progression once Predictable progression once
Consider circumstances of bleed Consider circumstances of bleed (spontaneous vs traumatic)(spontaneous vs traumatic)
Presence of pain usually enough to Presence of pain usually enough to initiate therapyinitiate therapy
Physical examPhysical exam X-rays of limited valueX-rays of limited value
Joint Bleed - TreatmentJoint Bleed - Treatment
Factor replacement (40-60%)Factor replacement (40-60%) Immobilization and cold packs may help initiallyImmobilization and cold packs may help initially Mobilization as soon as feasibleMobilization as soon as feasible Physical therapy if indicated (restore normal Physical therapy if indicated (restore normal
forces to joint)forces to joint) Prophylaxis in resistant casesProphylaxis in resistant cases Should see response in 6-12 hrs in average bleedShould see response in 6-12 hrs in average bleed
HematomasHematomas
More common in infantsMore common in infants Treatment dictated by site and extentTreatment dictated by site and extent Treat closed spaces aggressively (e.g. throat, Treat closed spaces aggressively (e.g. throat,
hand, wrist, nerve compressions) hand, wrist, nerve compressions) Blood counts often best indicator of extentBlood counts often best indicator of extent
HematuriaHematuria
Treatment controversialTreatment controversial Often resolves spontaneouslyOften resolves spontaneously Treatment may be indicated in some Treatment may be indicated in some
cases (steroids, factor replacement)cases (steroids, factor replacement) Therapeutic misadventures have Therapeutic misadventures have
occurred (Amicar)occurred (Amicar)
GI BleedingGI Bleeding
Can be due to bleeding into the wall Can be due to bleeding into the wall of the intestinesof the intestines
Requires immediate evaluation Requires immediate evaluation Often due to the common sources of Often due to the common sources of
bleedingbleeding
LacerationsLacerations
PressurePressure Factor replacement, especially with Factor replacement, especially with
suturessutures Epsilon amino caproic acid (Amicar) or Epsilon amino caproic acid (Amicar) or
tranexamic acid may be helpful with tranexamic acid may be helpful with mouth bleedsmouth bleeds
Tooth ExtractionTooth Extraction
Treat before (50% or greater, Treat before (50% or greater, depending on extent of procedure)depending on extent of procedure)
Consider DDAVP for mild Consider DDAVP for mild hemophiliachemophiliac
Epsilon amino caproic acid Epsilon amino caproic acid (Amicar) or tranexamic acid after(Amicar) or tranexamic acid after
CNS Bleeds (Head trauma)CNS Bleeds (Head trauma)
Most common cause of fatal bleedingMost common cause of fatal bleeding May occur in delayed fashionMay occur in delayed fashion Treat even minor head trauma in generalTreat even minor head trauma in general 100% replacement, 100% replacement, beforebefore diagnostic procedures diagnostic procedures CT or MRI may be helpfulCT or MRI may be helpful When in doubt, or if any sign of objective head When in doubt, or if any sign of objective head
trauma (abrasion or external hematoma), trauma (abrasion or external hematoma), treattreat
Life-threatening and Critical BleedsLife-threatening and Critical Bleeds
Central Nervous SystemCentral Nervous System Neck and OropharynxNeck and Oropharynx Major fracturesMajor fractures Multiple traumasMultiple traumas Deep lacerationsDeep lacerations Compartment bleedsCompartment bleeds Gastrointestinal bleedsGastrointestinal bleeds
InfectionsInfections
HIVHIV Hepatitis (A, B and C)Hepatitis (A, B and C) Septic ArthritisSeptic Arthritis
General Approach to TreatmentGeneral Approach to Treatment
Prophylactic treatmentProphylactic treatment Get a clot (provide replacement as needed) Get a clot (provide replacement as needed) Suppress fibrinolysisSuppress fibrinolysis Use adjunctive measures maximallyUse adjunctive measures maximally
– Local pressure, closure of woundsLocal pressure, closure of wounds
– Gelfoam (gelatin sponge), topical thrombin or fibrin glue, Gelfoam (gelatin sponge), topical thrombin or fibrin glue, oxidized cellulose (Oxycel, Surgicel) , other local stimulants to oxidized cellulose (Oxycel, Surgicel) , other local stimulants to coagulationcoagulation
Moderate or Moderate or Factor replacement Factor replacement
Severe Epsilon aminocaproic acidSevere Epsilon aminocaproic acid
Factor Replacement - GeneralFactor Replacement - General
Previously untreated patients - use Previously untreated patients - use recombinant factor when possiblerecombinant factor when possible
Surgery - any significant surgery Surgery - any significant surgery usually requires factor replacement - usually requires factor replacement - keep levels > 50%, need to monitorkeep levels > 50%, need to monitor
Consider constant infusionConsider constant infusion Remember carriers can bleedRemember carriers can bleed
Factor VIII (intermediate purity, Factor VIII (intermediate purity,
monoclonal, recombinant)monoclonal, recombinant)
1Unit/kg produces 2% increase in VIII 1Unit/kg produces 2% increase in VIII
activity (1-1.5 % increase with IX)activity (1-1.5 % increase with IX)
Use to next full vialUse to next full vial
Factor ReplacementFactor Replacement
Factor VIIIFactor VIII
pharmacokinetics:pharmacokinetics:
- first infusion of shorter duration (4-8 hrs),- first infusion of shorter duration (4-8 hrs),
- second longer, usually 8-12 hrs- second longer, usually 8-12 hrs Factor IXFactor IX
pharmacokinetics:pharmacokinetics: - first infusion of shorter duration (2-6 hrs),- first infusion of shorter duration (2-6 hrs),
- second longer, usually 18-24 hrs- second longer, usually 18-24 hrs
Factor IXFactor IX
None in cryoNone in cryo FFPFFP Vitamin K dependent concentratesVitamin K dependent concentrates Purified factor IXPurified factor IX Recombinant factor IXRecombinant factor IX Can also use continuous infusionCan also use continuous infusion
DDAVP for Dental Procedures in Mild HemophiliaDDAVP for Dental Procedures in Mild Hemophilia
InhibitorsInhibitors
Three varieties (low titer 1-5 bethesda Three varieties (low titer 1-5 bethesda units, intermediate 5-10, high >10)units, intermediate 5-10, high >10)
10-15% of patients10-15% of patients Recurrence the rule with high titer Recurrence the rule with high titer
patient, with higher and higher levelspatient, with higher and higher levels Poor response to treatment often the Poor response to treatment often the
first signfirst sign
Treatment of InhibitorsTreatment of Inhibitors
Activated factor IXActivated factor IX FEIBAFEIBA VIIaVIIa Porcine factor VIIIPorcine factor VIII High doses of VIIIHigh doses of VIII ImmunosuppressionImmunosuppression
Factor VIIa for Surgical ProceduresFactor VIIa for Surgical Procedures
PreventivePreventive
Padded cribsPadded cribs Avoid platelet antagonists (e.g., aspirin)Avoid platelet antagonists (e.g., aspirin) No contact sportsNo contact sports HelmetsHelmets Immunization (Hepatitis A and B)Immunization (Hepatitis A and B) Choice of lifestyleChoice of lifestyle
EmergenciesEmergencies
Have a medical alert braceletHave a medical alert bracelet
Conclusions and Final ThoughtsConclusions and Final Thoughts
Comprehensive care is a proven method for the Comprehensive care is a proven method for the care of hemophilia that reduces morbidity and care of hemophilia that reduces morbidity and mortality (Soucie et al., 2000)mortality (Soucie et al., 2000)
Treatment of hemophiliacs requires a Treatment of hemophiliacs requires a multidisciplinary approach – Pharmacy plays a multidisciplinary approach – Pharmacy plays a major role in quality of life for hemophiliacsmajor role in quality of life for hemophiliacs
Further research into cost-effective management Further research into cost-effective management of problems in hemophiliacs is warrantedof problems in hemophiliacs is warranted
Who Supports Comprehensive CareWho Supports Comprehensive Care
Federal Government (MCHB and CDC)Federal Government (MCHB and CDC) State of Maryland (DHMH)State of Maryland (DHMH) HFMHFM
ITPITP
James F. Casella, M.D.James F. Casella, M.D. Chief, Pediatric HematologyChief, Pediatric Hematology The Johns Hopkins University School of The Johns Hopkins University School of
Sometimes referred to as Sometimes referred to as immuneimmune or or autoimmuneautoimmune thrombocytopenic purpura thrombocytopenic purpura (ITP or ATP)(ITP or ATP)
Most commonly encountered acquired Most commonly encountered acquired quantitative platelet disorder of childhoodquantitative platelet disorder of childhood– Overall incidence of ITP is 1:10,000/yrOverall incidence of ITP is 1:10,000/yr
~ ½ of cases in children~ ½ of cases in children
Etiology and PathogenesisEtiology and Pathogenesis
Evidence for an immunologic basisEvidence for an immunologic basis
– Rapid destruction of autologous or heterologous Rapid destruction of autologous or heterologous plateletsplatelets
– Passive transmission by serumPassive transmission by serum
– Demonstration of specific antiplatelet antibodiesDemonstration of specific antiplatelet antibodies
– Transplacental transfer of Transplacental transfer of ““passivepassive”” disease disease
Etiology and PathogenesisEtiology and Pathogenesis
Destruction of platelets in ITPDestruction of platelets in ITP
– Spleen the major site of destructionSpleen the major site of destruction – Less important contribution from the Less important contribution from the
reticuloendothelial system of the liver, bone reticuloendothelial system of the liver, bone marrow, and lungs.marrow, and lungs.
Acute ITPAcute ITP
Often preceded by a viral illnessOften preceded by a viral illness
Viral antigens may trigger antibodies that Viral antigens may trigger antibodies that cross-react with the platelet membrane cross-react with the platelet membrane (e.g. varicella)(e.g. varicella)
Chronic ITPChronic ITP
Often occurs in the setting of other known Often occurs in the setting of other known autoimmune illnessesautoimmune illnesses
Specific anti-glycoprotein IIb/IIIa Specific anti-glycoprotein IIb/IIIa antibodies often demonstratedantibodies often demonstrated
Acute and Chronic ITPAcute and Chronic ITP
Not all platelet-associated IgG (PAIgG) in ITP Not all platelet-associated IgG (PAIgG) in ITP is directed against specific platelet antigensis directed against specific platelet antigens
Other serum proteins (eg albumin) associated Other serum proteins (eg albumin) associated with platelet membranes in increased amountswith platelet membranes in increased amounts
Decreased production of platelets in otherwise Decreased production of platelets in otherwise classic cases of ITP classic cases of ITP
– ? decreased production and increased destruction ? decreased production and increased destruction in some casesin some cases
ITP - Clinical FeaturesITP - Clinical Features
Acute and chronic ITPAcute and chronic ITP
Purpura and mucosal bleeding most prominent symptomsPurpura and mucosal bleeding most prominent symptoms
Children generally appear well, except for purpuraChildren generally appear well, except for purpura
Large submucous hemorrhages in the mouth associated with Large submucous hemorrhages in the mouth associated with increased risk of bleedingincreased risk of bleeding
Hepatomegaly, splenomegaly and lymphadenopathy notably Hepatomegaly, splenomegaly and lymphadenopathy notably absent absent
GI and renal hemorrhage may occurGI and renal hemorrhage may occur
* Central nervous system bleeding the most feared complication* Central nervous system bleeding the most feared complication
Laboratory Diagnosis of ITPLaboratory Diagnosis of ITP
Platelet counts vary from normal to undetectable,Platelet counts vary from normal to undetectable,– (tend to be lower in acute ITP than in chronic ITP)(tend to be lower in acute ITP than in chronic ITP)
Remainder of the CBC should be normalRemainder of the CBC should be normal– (Anemia secondary to bleeding may be seen)(Anemia secondary to bleeding may be seen)
Careful review of the peripheral blood smear Careful review of the peripheral blood smear should be performedshould be performed
Eosinophilia and atypical lymphocytosis may be Eosinophilia and atypical lymphocytosis may be seenseen
Laboratory Diagnosis of ITP Laboratory Diagnosis of ITP
Need to rule out other abnormalities, Need to rule out other abnormalities, including:including:– immature white blood cells immature white blood cells – red cell morphology consistent with red cell morphology consistent with
Laboratory Diagnosis of ITPLaboratory Diagnosis of ITP
PAIgG on the platelet surface (ie, direct test) PAIgG on the platelet surface (ie, direct test) usually positiveusually positive
Patient's serum may or may not increase the Patient's serum may or may not increase the amount of IgG on the surface of control platelets amount of IgG on the surface of control platelets (i.e., indirect test)(i.e., indirect test)
PT and aPTT should be normalPT and aPTT should be normal Bone marrow aspirates show increased Bone marrow aspirates show increased
megakaryocytesmegakaryocytes There is no definitive test for ITPThere is no definitive test for ITP
Laboratory Diagnosis of ITPLaboratory Diagnosis of ITP
ITP is a diagnosis of exclusionITP is a diagnosis of exclusion
When Should You do a Bone Marrow?When Should You do a Bone Marrow?
When there are signs and symptoms of When there are signs and symptoms of possible bone marrow diseasepossible bone marrow disease– Abnormally low or high white blood cell countAbnormally low or high white blood cell count– Immature forms on peripheral smearImmature forms on peripheral smear– Unexplained or severe anemiaUnexplained or severe anemia– MacrocytosisMacrocytosis– Organomegaly or lymphadenopathyOrganomegaly or lymphadenopathy– NotNot when the thrombocytopenia is isolated when the thrombocytopenia is isolated
What is the risk of leukemia?What is the risk of leukemia?
Isolated thrombocytopenia in ALLIsolated thrombocytopenia in ALL
First author and year Number of patients studied of publication With isolated With leukemia
thrombocytopenia
McIntosh (1985) 0 218
Dubansky (1988) 0 2339
Jones (1985) 41 0
Halperin (1988) 127 0 Calpin (1998) 332 0
ITP - Clinical Course and prognosisITP - Clinical Course and prognosis
Frequently benign in young childrenFrequently benign in young children
Excellent prognosis:Excellent prognosis:– >50% of untreated children recover within four weeks>50% of untreated children recover within four weeks
– >80% spontaneously recover within six months>80% spontaneously recover within six months
Resolution of the thrombocytopenia occurs in a variety Resolution of the thrombocytopenia occurs in a variety of patternsof patterns
Improvement of symptoms often precedes a detectable Improvement of symptoms often precedes a detectable rise in the platelet count.rise in the platelet count.
ITP - Clinical Course and prognosisITP - Clinical Course and prognosis
Generally not considered chronic unless Generally not considered chronic unless
symptoms > than 6 monthssymptoms > than 6 months
Relapses common in chronic ITPRelapses common in chronic ITP
Acute ITP tends not to recur, but relapses Acute ITP tends not to recur, but relapses
reported (~3%) reported (~3%)
Treatment of ITPTreatment of ITP
BackgroundBackground– Incidence of serious complications of ITP is Incidence of serious complications of ITP is
very lowvery low– Mortality and morbidity most often associated Mortality and morbidity most often associated
with intracranial hemorrhagewith intracranial hemorrhage– Given the low incidence of intracranial Given the low incidence of intracranial
hemorrhage, no prospective, randomized trials hemorrhage, no prospective, randomized trials to truly estimate the likelihood of prevention to truly estimate the likelihood of prevention
Rx of ITP - General PrinciplesRx of ITP - General Principles
Goal of Rx: reduce the likelihood of bleeding during periods of Goal of Rx: reduce the likelihood of bleeding during periods of maximal riskmaximal risk
Waiting period usually warranted before treating in mild cases Waiting period usually warranted before treating in mild cases (platelet count >20,000/mm3, no bleeding other than purpura)(platelet count >20,000/mm3, no bleeding other than purpura)
Platelet counts < 20,000/mm3 or extensive mucosal bullae suggest a Platelet counts < 20,000/mm3 or extensive mucosal bullae suggest a higher risk for internal hemorrhage and Rx should be consideredhigher risk for internal hemorrhage and Rx should be considered
If serious complications are present or suspected, or if a protective If serious complications are present or suspected, or if a protective environment cannot be guaranteed, Rx should be initiatedenvironment cannot be guaranteed, Rx should be initiated
ITP - Treatment OptionsITP - Treatment Options
CorticosteroidsCorticosteroids
– Historically, the most commonly used therapyHistorically, the most commonly used therapy
– Effectiveness still debated; the following Effectiveness still debated; the following statements are generally considered to be true:statements are generally considered to be true: Steroids at least transiently increase the platelet count in Steroids at least transiently increase the platelet count in
most patientsmost patients
Even if the platelet count is not increased, a lessening of Even if the platelet count is not increased, a lessening of bleeding symptoms may occurbleeding symptoms may occur
Steroids do not change the natural history of the disease Steroids do not change the natural history of the disease
Prednisone for ITPPrednisone for ITP
Usually administered at an initial Usually administered at an initial
dosage of 2 mg/kg/day orallydosage of 2 mg/kg/day orally
Higher or intravenous dosages up to 30 Higher or intravenous dosages up to 30
mg/kg/day of prednisolone for very mg/kg/day of prednisolone for very
short periods may be more effective. short periods may be more effective.
Important not to taper aggressivelyImportant not to taper aggressively
Treatment varies from 0.5-2 g/kg over 1 to 5 days (Most Treatment varies from 0.5-2 g/kg over 1 to 5 days (Most commonly used dose is 1 g/kg, single administration)commonly used dose is 1 g/kg, single administration)
Responses usually rapid and transitory - should not be Responses usually rapid and transitory - should not be expected in all patientsexpected in all patients
Up to 34% of patients may experience transient Up to 34% of patients may experience transient complications (severe headache, nausea, aseptic meningitis) complications (severe headache, nausea, aseptic meningitis)
Some risk of transmission of infection; appears to be quite Some risk of transmission of infection; appears to be quite safesafe
Extremely expensiveExtremely expensive
Anti-D ImmunoglobulinAnti-D Immunoglobulin
Relatively new, but useful therapy for ITPRelatively new, but useful therapy for ITP Mechanism of action incompletely understoodMechanism of action incompletely understood
– Hypothesis: antibody-coated red cells compete Hypothesis: antibody-coated red cells compete with antibody-coated platelets for destruction in with antibody-coated platelets for destruction in the RE-systemthe RE-system
No response in Rh-negative individualsNo response in Rh-negative individuals Splenectomized individuals may respond Splenectomized individuals may respond
suboptimally, but responses seensuboptimally, but responses seen
Anti-D immunoglobulin Anti-D immunoglobulin
Dose varies from 25Dose varies from 25g/kg/dose on two g/kg/dose on two consecutive days to 50-100 consecutive days to 50-100 g/kg x 1g/kg x 1
Can be infused within 1/2 hourCan be infused within 1/2 hour I.M. use also been reportedI.M. use also been reported Response rates similar to that of IVIgGResponse rates similar to that of IVIgG
– (Slightly longer delay in response reported; may be dose (Slightly longer delay in response reported; may be dose related)related)
Major toxicity a predictable fall in Hgb (mean Major toxicity a predictable fall in Hgb (mean decrease 1.3 g/dl)decrease 1.3 g/dl)
Advantages of Anti-D vs IVIgGAdvantages of Anti-D vs IVIgG
Ease of useEase of use
Outstanding safety record of anti-D for other Outstanding safety record of anti-D for other indicationsindications
Significantly lower protein load and expenseSignificantly lower protein load and expense
Smaller donor pool Smaller donor pool
Mechanisms of IVIgG and Anti-DMechanisms of IVIgG and Anti-D
ITP - Blanchette et al. 1993ITP - Blanchette et al. 1993
53 children (7 mos - 11.3 yrs)53 children (7 mos - 11.3 yrs) IVIgG (1g/kg/day x 2), p.o. prednisone IVIgG (1g/kg/day x 2), p.o. prednisone
(4 mg/kg/day), or no treatment (control)(4 mg/kg/day), or no treatment (control) IVIgG > prednisone > control for plts > 20,000IVIgG > prednisone > control for plts > 20,000
(1 day vs 2days vs 4 days)(1 day vs 2days vs 4 days) IVIgG > prednisone > control for plts > 50,000IVIgG > prednisone > control for plts > 50,000
(2 day vs 4 days vs 16 days)(2 day vs 4 days vs 16 days)
No differences in chronic ITP or side effectsNo differences in chronic ITP or side effects
Blanchette et al. 1993Blanchette et al. 1993
Blanchette et al. 1993Blanchette et al. 1993
ITP - Blanchette et al. 1994ITP - Blanchette et al. 1994
146 children (6 mos - 18 yrs)146 children (6 mos - 18 yrs) IVIgG (1g/kg/day x 2 IVIgG (1g/kg/day x 2 oror 0.8 g/kg x 1), p.o. prednisone 0.8 g/kg x 1), p.o. prednisone
(4 mg/kg/day), or I.V. Anti-D (Winrho) (25 u/kg/day (4 mg/kg/day), or I.V. Anti-D (Winrho) (25 u/kg/day x 2) x 2)
IVIgG > prednisone > anti-D for plts > 20,000IVIgG > prednisone > anti-D for plts > 20,000 IVIgG > prednisone > anti-D for plts > 50,000IVIgG > prednisone > anti-D for plts > 50,000 0.8 g/kg IVIgG best overall0.8 g/kg IVIgG best overall
No differences in chronic ITP or side effectsNo differences in chronic ITP or side effects
Blanchette et al. 1994Blanchette et al. 1994
Blanchette et al. 1994Blanchette et al. 1994
Platelet transfusions Platelet transfusions
Generally avoided because of the Generally avoided because of the shortened survival of transfused plateletsshortened survival of transfused platelets
May be effective in immediately reducing May be effective in immediately reducing serious bleedingserious bleeding
SplenectomySplenectomy
Effective in resolving thrombocytopenia Effective in resolving thrombocytopenia in approximately two thirds of patientsin approximately two thirds of patients
Generally used only in emergencies or in Generally used only in emergencies or in extremely resistant casesextremely resistant cases
Other therapeutic approaches for ITPOther therapeutic approaches for ITP
Vinca-loaded platelets or vincristine infusionsVinca-loaded platelets or vincristine infusions Other immunosuppressive agents,Other immunosuppressive agents,
Autosomal dominant, recessive and sex-linked recessiveAutosomal dominant, recessive and sex-linked recessive
thrombocytopenia thrombocytopenia
Research at JHHResearch at JHH
Lehmann, Casella, BuchananLehmann, Casella, Buchanan– Decision analytic approach to treatment of ITP – NIH Decision analytic approach to treatment of ITP – NIH
TMH networkTMH network» Study of the decision to treatStudy of the decision to treat
» Analysis of center to center variationAnalysis of center to center variation
» Assessment of provider and patient preferences and Assessment of provider and patient preferences and perception of riskperception of risk
Summary - ITPSummary - ITP
Common disorderCommon disorder Acute and chronic formsAcute and chronic forms Low overall morbidity and mortalityLow overall morbidity and mortality Dx of exclusionDx of exclusion Routine bone marrows unnecessaryRoutine bone marrows unnecessary Newer treatment modalities have helped Newer treatment modalities have helped
CharacteristicsCharacteristics– onset of thrombocytopenia tends to be abrupt onset of thrombocytopenia tends to be abrupt
(within hrs of ingestion or administration of the drug)(within hrs of ingestion or administration of the drug)
– ceases with clearance of the drugceases with clearance of the drug– tends to recur with repeated administration of tends to recur with repeated administration of
the drugthe drug– rechallenge very dangerousrechallenge very dangerous– in vitro testing availablein vitro testing available
* Many other agents have the potential for causing immune-mediated * Many other agents have the potential for causing immune-mediated thrombocytopeniathrombocytopenia
Nonimmune Causes of ThrombocytopeniaNonimmune Causes of Thrombocytopenia
Infrequent problem, usually adults - severe Infrequent problem, usually adults - severe thrombocytopenia after erythrocyte transfusionsthrombocytopenia after erythrocyte transfusions
Thrombocytopenia typically abrupt, ~1 week after Thrombocytopenia typically abrupt, ~1 week after transfusiontransfusion
Affected patients typically HPA(1b,1b) (ie, PlA1 negative) Affected patients typically HPA(1b,1b) (ie, PlA1 negative) women with Hx of 1 or more pregnancies, transfused with women with Hx of 1 or more pregnancies, transfused with blood from a HPA(1a,1a) or HPA(1a,1b) (ie, PlA1 blood from a HPA(1a,1a) or HPA(1a,1b) (ie, PlA1 positive) donorpositive) donor
Possibly secondary to passive absorption of soluble HPA Possibly secondary to passive absorption of soluble HPA 1a antigen from the donor's plasma to recipient's platelets, 1a antigen from the donor's plasma to recipient's platelets, but pathophysiology may be more complexbut pathophysiology may be more complex
Nonimmune Causes of ThrombocytopeniaNonimmune Causes of Thrombocytopenia
Infectious ThrombocytopeniaInfectious Thrombocytopeniaviral infections (active infection or postinfectious)viral infections (active infection or postinfectious)
varicella, Epstein-Barr virus, cytomegalovirus, other varicella, Epstein-Barr virus, cytomegalovirus, other herpesviruses, infuenza, scarlatina, measles, mumps, herpesviruses, infuenza, scarlatina, measles, mumps, rubella and HIVrubella and HIV