Hematology/Oncology Emergencies

Ali Mullah-AliOct 8th, 2011

Tumor Lysis SyndromeBleeding & Coagulation AbnormalitiesAnemia (neonates & older) including

hemolyticThrombocytopenia (neonates & older)ThrombocytosisPancytopeniaLeukocytosisFever & neutropeniaTyphlitisMediastinal mass +/- SVC obstruction

Tumor Lysis Syndrome

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

Pre TLS◦Rapid cell breakdown Nucleic acid

Catabolized to uric acid◦Hyperuricaemia

Established TLS◦Urate nephropathy + ARF◦Hyperphosphataemia◦Hyperkalaemia◦Hypocalcaemia

Prevention is best management

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

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

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

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

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

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 OverviewPrimary phase Platelet plug

◦Adhesion◦Activation◦Aggregation

Secondary phase Cross-linked fibrin clot

Tissue Factor

X, V, Phospholipids

Contact Factors , XI, XII

VIIVIII

IX

Prothrombin

Thrombin

Fibrinogen Fibrin

Cross Linked Fibrin Clot

XIII

clot

IntrinsicPathway

Extrinsic Pathway

CommonPathway

CommonPathway

Coagulation Cascade

Medical History & Clinical Examination

Duration / QuantityBeyond “routine” bleeding episodes

Previous surgery or dental extractions without bleeding complications

Unlikely underlying congenital hemorrhagic disorder

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 BleedingPlatelet & vWD

◦ Mucosal bleeding Gingival hemorrhage Epistaxis Menorrhagia

◦ Petechiae◦ Bruising

Factor deficiencies (hemophilia)◦ Spontaneous, deep muscle, and joint

bleeding

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

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 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

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

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

VII

X

V

II

Fgn

PT

XII

XI

IX

VIII

X

V

II

Fgn

PTT

aPTT & PT Mixing Studies

For 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

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

TCT

Fgn

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

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

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

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

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

NovoSevenrFVIIDose 90 mg/kg IV every 2 hrsRarely …. Risk of thrombosis

Thank you