Haematological Emergencies (Part 1) Ray Mun Koo Haematology Advanced Trainee Canberra Hospital

Haematological Emergencies (Part 1) Ray Mun Koo Haematology Advanced Trainee Canberra Hospital

Case Number 1 43 year old male presenting with fevers, abdominal distension and weight gain over 2 weeks. No past medical history of significance. Physical examination: Tense ascites CT-Abdo/Pelvis: Multiple enlarged para-aortic, mediastinal, mediastinal and epicardial lymph nodes. Abnormal thickening of jejunum

Other investigations PET-CT: Intense FDG avid lymph nodes above and below the diaphragm, with bone marrow involvement Bone marrow biopsy: 90% marrow infiltration with Burkitt s lymphoma FISH: MYC rearrangement detected

?

Tumour Lysis Syndrome (TLS) Rapid breakdown of malignant tumour cells causing metabolic derangements Release of intracellular metabolites End-organ dysfunction Morbidity, mortality and increased length of stay!

TLS Pathogenesis

TLS Biochemical Manifestation Hyperkalaemia Hyperphosphataemia (Secondary) hypocalcaemia Hyperuricaemia Creatinine Lactate dehydrogenase

TLS Clinical Manifestation Nausea/vomitting Anorexia Lethargy Muscle cramps Signs of heart failure and renal failure Oliguria/anuria Death

TLS Definition Cairo-Bishop definition (2004) Laboratory TLS Clinical TLS Laboratory TLS + Creatinine, seizures, cardiac arrhythmias or sudden death

TLS Risk Factors Haematological malignancies High tumour cell proliferation rate Chemosensitive malignancies Large tumour burden High WCC (> 50) prior to treatment Examples: Burkitt s lymphoma, acute lymphoblastic leukaemia or acute myeloid leukaemia (with high WCC)

TLS Risk Factors Patient predisposition Baseline renal impairment Hyperuricaemia Dehydration or inadequate fluid resuscitation during treatment

TLS Risk Factors Non-Haematological malignancies (rare) Breast cancer SCLC Neuroblastoma Sarcoma

Spontaneous TLS Occurs prior to initiation of therapy. Burkitt s lymphoma, acute leukaemias and diffuse large B-cell lymphomas (DLBCL) with large tumour burden.

TLS Management Prevention is better than cure!

TLS Management (cont.) Pharmacological management Allopurinol Xanthine oxidase inhibitor 300mg daily (if Cr normal) 100mg daily (if renal impairment) Rasburicase Urate oxidase 6mg IV flat dose Risk of: Haemolysis in G6PD deficiency Anaphylaxis in repeat dosing

TLS Management (cont.) Intravenous fluid resuscitation Normal saline 1L over 8-10 hours Avoid Hartmann s solution Twice daily bloods UEC, CMP, LFT, LDH and uric acid LDH should be <60 Strict fluid balance monitoring No PUIT! Aim UO 80-100mls/hour

Allopurinol started on 10/6/17

Rasburicase given at 1700 hours Chemo started at 1200 hours Admitted to ICU for CRRT

Take home messages Prevention is better than cure. Consider TLS as a differential in Haem/Oncology patients with unexpected renal failure and dyselectrolytaemia If suspecting a Haematological diagnosis, always ask for Flow Cytometry.

Case Number 2 23 year old carpenter apprentice, transferred from peripheral hospital with undifferentiated septic shock to ICU. Complicated by: Anuric renal failure (Cr 426) Refractory hypotension Septic encephalopathy Type 1 respiratory failure - intubated Returned from Melbourne after celebrating NYE: Snorted cocaine with some mates 3 day history of fevers, rigors and headaches

Macular-papular rash appears

?

Disseminated Intravascular Coagulation (DIC) Dynamic, procoagulant and pro-thrombotic state. Characterised by intravascular coagulation and fibrinolysis due to procoagulant exposure, with resultant end-organ damage.

Pathogenesis

Two types of DIC Acute DIC = Decompensated Significant generation of thrombin, rapid consumption of coagulation factors Therefore: Thrombocytopaenia Elevated PT and APTT Elevated XDP Bleeding > thrombosis Seen in: Sepsis Trauma Acute promyelocytic leukaemia (APML)

Two types of DIC (cont.) Chronic DIC = Compensated Therefore +/- Normal PT and APTT +/- Thrombocytopaenia Elevated XDP Thrombosis > Bleeding Seen in: Advanced malignancy Pancreas Primary brain Gastric Ovarian

Clinical manifestations Bleeding and thrombosis Organ dysfunction Laboratory abnormalities

Causes of DIC Sepsis Malignancy Trauma Obstetric complications Intravascular haemolysis

DIC mimics Chronic liver disease Heparin-induced thrombocytopaenia Thrombotic thrombocytopaenic purpura (TTP) Thrombotic microangiopathies Haemolytic uraemic syndrome Complement-mediated HUS

DIC Treatment Supportive Treat the sepsis Transfuse as required PRBCS if Hb < 70g/L Pooled platelets if Plts < 10 (with exceptions) Cryoprecipitate if fibrinogen < 1.0g/L Liberal FFP transfusion to correct coagulopathy not recommended (Cure the cancer)

Take home messages (2) Two types of DIC Suspect acute DIC in unexplained coagulopathy with thrombocytopaenia Chronic DIC is under-diagnosed, suspect in thromboembolism in certain malignancies Transfuse judiciously

Topics Tumour Lysis Syndrome Disseminated Intravascular Coagulation Hyperviscosity Syndrome Hyperleukocytosis Hypercalcaemia? Febrile Neutropaenia? Other topics (JMO driven)