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Hematology/Oncology Emergencies

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

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Hematology/Oncology Emergencies

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  1. Hematology/Oncology Emergencies Ali Mullah-Ali Oct 8th, 2011

  2. Tumor Lysis Syndrome • Bleeding & Coagulation Abnormalities • Anemia (neonates & older) including hemolytic • Thrombocytopenia (neonates & older) • Thrombocytosis • Pancytopenia • Leukocytosis • Fever & neutropenia • Typhlitis • Mediastinal mass +/- SVC obstruction

  3. Tumor Lysis Syndrome

  4. 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

  5. Pre TLS • Rapid cell breakdown Nucleic acid Catabolized to uric acid • Hyperuricaemia • Established TLS • Urate nephropathy + ARF • Hyperphosphataemia • Hyperkalaemia • Hypocalcaemia • Prevention is best management

  6. 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 celllymphoma • Bulky lymphoproliferative disease • Evidence of renal infiltration with tumor • Evidence of renal impairment • Cancer with high sensitivity to chemoRx • High uric acid • High LDH

  7. Prevention of TLS • Hydration • 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

  8. 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 tumourlysis • May increase the frequency (18 hrly, max 12 hrly) for 2-3 days

  9. Review pt clinically at least q 4 hrs • Check v/s • Look for oliguria / fluid overload • Fluid balance • Biochemistry • Na, K, Ca, PO4, TCO2, urate, urea and creatinine (q 4-6 hrs) • If very high risk, monitor biochemistry 2-3 hrly • If signs of fluid overload • Furosemide 1-2mg/kg (up to 5 mg/kg) • Cardiac monitor • Peaked T waves and dysrhythmias

  10. 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

  11. Bleeding & Coagulation Abnormalities

  12. 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

  13. Hemostasis Overview • Primary phase  Platelet plug • Adhesion • Activation • Aggregation • Secondary phase  Cross-linked fibrin clot

  14. Coagulation Cascade Contact Factors, XI, XII Tissue Factor Extrinsic Pathway Intrinsic Pathway IX VIII VII X, V, Phospholipids Common Pathway Common Pathway Thrombin Prothrombin Fibrinogen Fibrin clot XIII Cross Linked Fibrin Clot

  15. Medical History & Clinical Examination

  16. Duration / Quantity • Beyond “routine” bleeding episodes • Previous surgery or dental extractions without bleeding complications  Unlikely underlying congenital hemorrhagic disorder

  17. 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

  18. Type of Bleeding • Platelet & vWD • Mucosal bleeding • Gingival hemorrhage • Epistaxis • Menorrhagia • Petechiae • Bruising • Factor deficiencies (hemophilia) • Spontaneous, deep muscle, and joint bleeding

  19. 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

  20. 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 ??

  21. Overall Health • Otherwise 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

  22. Physical Examination • Petechiae • Almost pathognomonic of platelet-related bleeding +/- Involvement of the mucosal membranes with purpura or hemorrhage • Nares • Gently examined in epistaxis cases • Excoriations and damaged vessels may be indicative of trauma • Ecchymoses ,,,,, unusual sites • Bruises • Excessively large for degree of trauma • Joint swelling without h/o significant trauma • Deep tissue and intramuscular bleeds ** Physical abuse

  23. PT and aPTT • Screening 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

  24. PT VII X V II Fgn

  25. PTT XII XI IX VIII X V II Fgn

  26. aPTT & PT Mixing Studies • For abnormal PT or aPTT • Mixing 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

  27. Thrombin Clotting Time • Time required to form a clot when thrombin added to plasma • A 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

  28. TCT Fgn

  29. Expected Results of For Hemostatic Functions

  30. Management of Bleeding Disorder • Laboratory Investigations: • CBC • Platelet morphology • INR, PT, APTT • Mixing study • Bleeding time • TCT • Clotting Factor assay • Factor XIII assay • Platelet Aggregation studies

  31. Management • ABC • Local measures whenever possible • Plts + PRBCs as needed • Tranexemic 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

  32. Fresh Frozen Plasma (FFP) • Frozen within 8 hrs of separation, at ≤ -18ْ 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

  33. 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

  34. NovoSeven • rFVII • Dose 90 mg/kg IV every 2 hrs • Rarely …. Risk of thrombosis

  35. Thank you

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