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

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Hematology/Oncology Emergencies

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Hematology oncology emergencies

Hematology/Oncology Emergencies

Ali Mullah-Ali

Oct 8th, 2011


Hematology oncology emergencies

  • Tumor Lysis Syndrome

  • Bleeding & Coagulation Abnormalities

  • Anemia (neonates & older) including hemolytic

  • Thrombocytopenia (neonates & older)

  • Thrombocytosis

  • Pancytopenia

  • Leukocytosis

  • Fever & neutropenia

  • Typhlitis

  • Mediastinal mass +/- SVC obstruction


Tumor lysis syndrome

Tumor Lysis Syndrome


Tumor lysis syndrome1

Tumor Lysis Syndrome

  • Oncological emergency

  • Release of large amounts

    • PotassiumHyperkalemia

    • PhosphateHyperphosphatemia

    • Nucleic acidsHyperuricemia

  • Results from tumor necrosis OR fulminant apoptosis

    • Spontaneous

    • Treatment-related

  • Comlications:

    • Hypocalcemia

    • ARF

      • Due to uric acid & Calcium phosphate deposition in renal tubules


  • Hematology oncology emergencies

    • Pre TLS

      • Rapid cell breakdown Nucleic acid Catabolized to uric acid

      • Hyperuricaemia

    • Established TLS

      • Urate nephropathy + ARF

      • Hyperphosphataemia

      • Hyperkalaemia

      • Hypocalcaemia

    • Prevention is best management


    Hematology oncology emergencies

    • 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


    Prevention of tls

    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


    Hematology oncology emergencies

    • Allopurinol

      • If no high risk features

      • 100 mg/m28 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


    Hematology oncology emergencies

    • 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


    Treatment

    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


    Bleeding coagulation abnormalities

    Bleeding & Coagulation Abnormalities


    Definition of clinically significant bleeding

    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


    Hemostasis overview

    Hemostasis Overview

    • Primary phase  Platelet plug

      • Adhesion

      • Activation

      • Aggregation

    • Secondary phase  Cross-linked fibrin clot


    Hematology oncology emergencies

    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


    Medical history clinical examination

    Medical History & Clinical Examination


    Duration quantity

    Duration / Quantity

    • Beyond “routine” bleeding episodes

    • Previous surgery or dental extractions without bleeding complications

       Unlikely underlying congenital hemorrhagic disorder


    Family history

    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


    Type of bleeding

    Type of Bleeding

    • Platelet & vWD

      • Mucosal bleeding

        • Gingival hemorrhage

        • Epistaxis

        • Menorrhagia

      • Petechiae

      • Bruising

    • Factor deficiencies (hemophilia)

      • Spontaneous, deep muscle, and joint bleeding


    Time of onset

    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


    Hematology oncology emergencies

    • 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 ??


    Overall health

    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


    Physical examination

    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


    Pt and aptt

    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


    Hematology oncology emergencies

    PT

    VII

    X

    V

    II

    Fgn


    Hematology oncology emergencies

    PTT

    XII

    XI

    IX

    VIII

    X

    V

    II

    Fgn


    Aptt pt mixing studies

    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


    Thrombin clotting time

    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


    Hematology oncology emergencies

    TCT

    Fgn


    Expected results of for hemostatic functions

    Expected Results of For Hemostatic Functions


    Management of bleeding disorder

    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


    Management

    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


    Hematology oncology emergencies

    • 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


    Hematology oncology emergencies

    • 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


    Novoseven

    NovoSeven

    • rFVII

    • Dose 90 mg/kg IV every 2 hrs

    • Rarely …. Risk of thrombosis


    Thank you

    Thank you


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