hematology/oncology emergencies
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Hematology/Oncology Emergencies. Ali Mullah-Ali Oct 8 th , 2011. Tumor Lysis Syndrome Bleeding & Coagulation Abnormalities Anemia (neonates & older) including hemolytic Thrombocytopenia (neonates & older ) Thrombocytosis Pancytopenia Leukocytosis Fever & neutropenia Typhlitis - PowerPoint PPT PresentationTRANSCRIPT
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Hematology/Oncology Emergencies
Ali Mullah-AliOct 8th, 2011
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Tumor Lysis SyndromeBleeding & Coagulation AbnormalitiesAnemia (neonates & older) including
hemolyticThrombocytopenia (neonates & older)ThrombocytosisPancytopeniaLeukocytosisFever & neutropeniaTyphlitisMediastinal mass +/- SVC obstruction
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Tumor Lysis Syndrome
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Tumor Lysis Syndrome• Oncological emergency• Release of large amounts
Potassium Hyperkalemia Phosphate Hyperphosphatemia Nucleic acids Hyperuricemia
Results from tumor necrosis OR fulminant apoptosis ◦ Spontaneous◦ Treatment-related
Comlications:◦ Hypocalcemia◦ ARF
Due to uric acid & Calcium phosphate deposition in renal tubules
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Pre TLS◦Rapid cell breakdown Nucleic acid
Catabolized to uric acid◦Hyperuricaemia
Established TLS◦Urate nephropathy + ARF◦Hyperphosphataemia◦Hyperkalaemia◦Hypocalcaemia
Prevention is best management
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Typically starts after induction of Rx ◦ May occur prior to Rx to 5/7 after Rx
Risk factors:◦ High cell count leukemia (WBC >100)◦ Burkitt’s lymphoma◦ Large tumour bulk◦ Bulky T cell lymphoma◦ Bulky lymphoproliferative disease ◦ Evidence of renal infiltration with tumor◦ Evidence of renal impairment◦ Cancer with high sensitivity to chemoRx◦ High uric acid ◦ High LDH
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Prevention of TLSHydration
◦3 L/m2/day (0.45% NaCl/2.5% Glu)◦No potassium additives
If no evidence of fluid overload◦Tachycardia◦Tachypnoea◦Gallop rhythm◦Desaturation◦O2 requirement
May increase to 4 L/m2/day
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Allopurinol ◦ If no high risk features◦ 100 mg/m2 8 hrly PO◦ Reduce dose by 50% or more in renal failure
Rasburicase◦ If
High risk Poor response to allopurinol
◦ 200 mcg/kg once per day◦ Risk of haemolysis in G6PD deficiency◦ For very high risk patients with rapid tumour lysis
May increase the frequency (18 hrly, max 12 hrly) for 2-3 days
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Review pt clinically at least q 4 hrsCheck v/sLook for oliguria / fluid overloadFluid balanceBiochemistry
◦ Na, K, Ca, PO4, TCO2, urate, urea and creatinine (q 4-6 hrs)
◦ If very high risk, monitor biochemistry 2-3 hrlyIf signs of fluid overload
◦ Furosemide 1-2mg/kg (up to 5 mg/kg)Cardiac monitor
◦ Peaked T waves and dysrhythmias
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Treatment Established TLS:
◦ Haemodialysis (HD) preferred in acute phase
Absolute indications for HD include:◦ Potassium > 5 mmol/l◦ Phosphate > 4 mmol/l◦ Pulmonary oedema
Oxygen and consider ventilation◦ Anuria
Relative indications for HD include:◦ Rapid rise in K, phos or urate◦ Oliguria unresponsive to furosemide◦ Urea > 15 mmol/L OR creatinine > 150 μmol/L
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Bleeding & Coagulation Abnormalities
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Definition of Clinically Significant Bleeding• Recurrent nose bleeds (> 30 min)• Oral Bleeds (>30 min)
• Restarting over next days• Bleeding from skin laceration (> 30 min) • Prolonged bleeding related to dental extraction• Menorrhagia requiring Rx • Spontaneous GI bleeding• Hemarthrosis
• Spontaneous or after minor trauma• Petechiae, Ecchymosis
• Unusual sites• With minor trauma
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Hemostasis OverviewPrimary phase Platelet plug
◦Adhesion◦Activation◦Aggregation
Secondary phase Cross-linked fibrin clot
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Tissue Factor
X, V, Phospholipids
Contact Factors , XI, XII
VIIVIIIIX
Prothrombin
Thrombin
Fibrinogen Fibrin
Cross Linked Fibrin ClotXIII
clot
IntrinsicPathway
Extrinsic Pathway
CommonPathway
CommonPathway
Coagulation Cascade
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Medical History & Clinical Examination
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Duration / QuantityBeyond “routine” bleeding episodes
Previous surgery or dental extractions without bleeding complications
Unlikely underlying congenital hemorrhagic disorder
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Family History Most children not encountered severe challenges
Inherited disorders ? undiagnosed / misdiagnosed for generations, especially when mild
Family members◦ Hemophilia (X-linked) may also result in abnormal bleeding
symptoms in female carriers
Previous ◦ Surgical procedures◦ Dental extractions◦ Transfusions
◦ Menstrual and obstetric Hx of female relatives Up to 20% of girls with menorrhagia beginning at menarche
have an underlying bleeding disorder
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Type of BleedingPlatelet & vWD
◦ Mucosal bleeding Gingival hemorrhage Epistaxis Menorrhagia
◦ Petechiae◦ Bruising
Factor deficiencies (hemophilia)◦ Spontaneous, deep muscle, and joint
bleeding
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Time of Onset No rule Acute onset (days/weeks) Acquired disorder:
◦ Immune (previously idiopathic) thrombocytopenic purpura (ITP)◦ Vitamin K deficiency
Longer duration are indicative of a congenital disorder:◦ VWD◦ Coagulation-factor deficiencies
Infants with congenital coagulation disorders◦ At birth (following circumcision)◦ 1st months of life (with immunizations)◦ When mobile and begin to experience mild trauma (most
common) Severe inherited bleeding disorder may not manifest until 6-12 months of age
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Significant challenges to hemostatic system◦ Surgery, dental extractions, trauma, or menstruation
Good initial hemostasis followed by persistent oozing
Due to failure to form a firm clot Characteristically is seen with??
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Overall HealthOtherwise well
◦ Congenital bleeding disorders◦ ITP
Sick individuals +/- comorbid conditions◦ DIC
Liver disease◦ Impaired factor production
Malabsorbtion / GI disease◦ Impaired vit K absorption◦ Impaired factor synthesis
Renal disease ◦ ?Platelet function
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Physical ExaminationPetechiae
◦ Almost pathognomonic of platelet-related bleeding -/+Involvement of the mucosal membranes with purpura or
hemorrhageNares
◦ Gently examined in epistaxis cases◦ Excoriations and damaged vessels may be indicative of trauma
Ecchymoses ,,,,, unusual sitesBruises
◦ Excessively large for degree of trauma Joint swelling without h/o significant traumaDeep tissue and intramuscular bleeds
** Physical abuse
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PT and aPTTScreening tests for the second phase of
hemostasis
PT ◦ Extrinsic and common pathways◦ Reported as an international normalized ratio (INR)
A standard allowing for comparison of results between different laboratories
aPTT ◦ Intrinsic and common pathways
Factor level at which PT or aPTT prolonged varies:◦ Usually ~ 40% N pooled plasma level
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VII
X
VII
Fgn
PT
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XIIXIIX
VIII
XVII
Fgn
PTT
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aPTT & PT Mixing StudiesFor abnormal PT or aPTTMixing pt's plasma with N plasma
◦ Factor deficiency corrects ~ 50%◦ Normalization Factor deficiency◦ Persistent prolongation Inhibitors
If factor deficiency◦ Measure
FVIII FIX FXI
Associated with clinical bleeding
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Thrombin Clotting TimeTime required to form a clot when thrombin
added to plasmaA measure of fibrin formation
If prolonged◦ Low fibrinogen activity◦ Presence of fibrin split products◦ Heparin contamination
Reptilase clotting time◦ Similar to thrombin time◦ Not inhibited by heparin
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TCT
Fgn
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Expected Results of For Hemostatic Functions
Fibrinogen TT APTT PT BT Disorder
N N N / Long N LongVasculopathies, Connective Tissue Disease
N N N N Long Thrombocytopenia
N N N N Long Thrombocytopathy
N N Long N N Hemophilia
N N Long N Long VWD
Low Long Long Short Long DIC
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Management of Bleeding DisorderLaboratory Investigations:
◦ CBC◦ Platelet morphology◦ INR, PT, APTT ◦ Mixing study◦ Bleeding time◦ TCT◦ Clotting Factor assay◦ Factor XIII assay◦ Platelet Aggregation studies
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ManagementABCLocal measures whenever possiblePlts + PRBCs as neededTranexemic acid (cyklokapron):
◦PO 20-25 mg/kg (max 1.5 g) q8hr◦ IV 10 mg/kg (max 1g) q8hr
As indicated:◦FFP◦Factor replacement◦Cryo◦Novoseven
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Fresh Frozen Plasma (FFP) ◦Frozen within 8 hrs of separation, at ≤ -18 ْ C
Frozen Plasma (FP) Frozen within 24 hrs◦Contain all clotting factors (low fibrinogen)◦Dose 10-15 ml/kg over 30-120 min◦Transfuse slowly in 1st 15 min (50ml/hr)
Cryoprecipitate◦Contains all clotting factors◦Contains 150mg fibrinogen/unit◦Dose 1 unit / 5-10 kg
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FVIII◦ 1 unit incease level by 2%◦ Half-life
1st dose 6-8 hrs ,,, Subsequent doses 8-12 hrs◦ Dose
Minor bleeds .. Increase level to 20-30 % of normal Major bleeds .. Increase level to 70-100 % of normal
FIX◦ 1 unit incease level by 1%◦ Half-life
1st dose 4-6 hrs ,,, Subsequent doses 18-24 hrs◦ Dose
Minor bleeds .. Increase level to 20-30 % of normal Major bleeds .. Increase level to 70-100 % of normal
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NovoSevenrFVIIDose 90 mg/kg IV every 2 hrsRarely …. Risk of thrombosis
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Thank you