Emergencies in hematological mallignancy..life saving if diagnosed early..time and tide saves nine

1. HEMATOLOGICAL
EMERGENCIES – 1
Ajay Kumar Yadav
PGY3,Medicine
IOM-TUTH, Kathmandu

2. LAYOUT
• Classification of hematological/oncological emergencies
• Tumor lysis syndrome
• Presentations
• Diagnosis
• Treatment
• Superior vena cava syndrome
• Diagnosis
• Management

3. CLASSIFICATION
• Classified into 5 groups
 Structural-obstructive oncological emergencies
 Paraneoplastic syndrome
 Treatment related complications
 Metabolic complications
 Miscellaneous

4. Cont..
 STRUCTURAL-OBSTRUCTIVE
EMERGENCIES
 TREATMENT RELATED
COMPLICATIONS
 METABOLIC EMERGENCIES
 Superior vena cava syndrome
 Pericardial
effusion/tamponade
 Intestinal obstruction
 Urinary obstruction
 Malignant biliary obstruction
 Spinal cord compression
 Increased ICP
 Airway obstruction
 Febrile neutropenia
 Tumor lysis syndrome
 Pulmonary infiltrates
 Human antibody infusion
reactions
 Hemorrhagic cystitis
 Hypersensitivity reaction
 Neutropenic enterocolitis
 Hemolytic uremic syndrome
 Hypercalcemia
 SIADH
 Lactic acidosis
 Hypoglycemia
 Adrenal insufficiency

5. Cont..
• Paraneoplastic syndrome
• Miscellaneous
• Neoplastic meningitis
• Seizure
• Leucostasis
• Bleeding :Hemoptysis/Hematemesis

6. TUMOR LYSIS SYNDROME

7. INTRODUCTION
• TLS is characterized by pentad of
• Hyperuricemia,
• Hyperkalemia,
• Hyperphosphatemia,
• Hypocalcemia and
• Acute renal failure
• Caused by the destruction of a large number of rapidly proliferating neoplastic cells.

8. CAIRO BISHOP LABORATORY DEFINITION OF TLS

9. CAIRO BISHOP CLINICAL DEFINITION OF TLS

10. TLS cont..
• TLS is most often associated with the treatment of Burkitt’s leukemia/lymphoma, ALL, and other
rapidly proliferating lymphomas, but it also may be seen with chronic leukemias and, rarely, with
solid tumors.
• TLS usually occurs during or shortly (1–5 days) after chemotherapy.
• Rarely, spontaneous necrosis of malignancies causes TLS.

11. Cont..

13. • Effective treatment kills malignant cells  Nucleic acid turnover  increased serum uric acid.
• Owing to the acidic local environment, uric acid can precipitate in the tubules, medulla, and
collecting ducts of the kidney, leading to renal failure.
• Lactic acidosis and dehydration may contribute.
• The finding of uric acid crystals in the urine is strong evidence for uric acid nephropathy.
• The ratio of urinary uric acid to urinary creatinine is >1 in patients with acute hyperuricemic
nephropathy and <1 in patients with renal failure due to other causes.

15. • Hyperphosphatemia is caused by the release of intracellular phosphate pools by tumor lysis, producing a
reciprocal depression in serum calcium.
• Deposition of calcium phosphate in the kidney and hyperphosphatemia may cause renal failure.
• Hyperkalemia in patients with renal failure may rapidly become life-threatening by causing ventricular
arrhythmias and sudden death.
• High leukocyte and platelet count may artificially elevate potassium levels  Pseudohyperkalemia.
• Hyperkalemia Vs Pseudohyperkalemia
• Plasma K+
• ECG changes

16. CLINICAL MANIFESTATIONS
• The symptoms a/w TLS largely reflect the associated metabolic abnormalities
(hyperkalemia, hyperphosphatemia, and hypocalcemia).
• They include nausea, vomiting, diarrhea, anorexia, lethargy, hematuria, heart
failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and
possible sudden death .
• Flank pain can occur if there is renal pelvic or ureteral stone formation.

17. PROGNSOTIC FACTOR FOR TLS
• The likelihood that TLS will occur in patients with Burkitt’s lymphoma is related to the tumor
burden and renal function.
• Hyperuricemia and high Sr. levels of LDH >1500 U/L correlate with total tumor burden, also
correlate with the risk of TLS.
• Factors which can predispose to TLS
• Pretreatment hyperuricemia (serum uric acid >7.5 mg/dL ) or hyperphosphatemia
• Preexisting nephropathy or exposure to nephrotoxins
• Oliguria and/or acidic urine
• Dehydration, volume depletion, or inadequate hydration during treatment

18. RISK STRATIFICATION

19. TREATMENT
• The standard preventive approach consists of hypouricemic drugs, urinary alkalinization, and
aggressive hydration.
• Hypouricemic drugs : Allopurinol , Febuxostat
• Febuxostat > Allopurinol in renal failure
• Urinary alkalization with sodium bicarbonate is controversial.
• It increases uric acid solubility, but decreases calcium phosphate solubility.
• If it is used, it should be discontinued when hyperphosphatemia develops.
• May worsen hypocalcemia by induction of alkalosis.
• HD may be necessary for rapidly progressive renal failure.

21. • Indications for RRT in patients with TLS :
 Severe oliguria or anuria
 Intractable fluid overload
 Persistent hyperkalemia
 Hyperphosphatemia-induced symptomatic hypocalcemia
 A calcium-phosphate product ≥70 mg2/dL2

22. • RASBURICASE
 Recombinant urate oxidase.
 Catalyzes the conversion of poorly soluble uric acid to readily soluble allantoin.
 Indication
 Renal failure is present.
 High-risk patients for TLS as prophylaxis.
 Rapid reduction of uric acid is desired (within hours)
 S/E : May cause HSR s/a bronchospasm, hypoxemia, and hypotension.
 C/I : G6PDH deficiency  unable to break down H202.

24. SUPERIOR VENACAVA SYNDROME

25. NORMAL ANATOMY

26. INTRODUCTION
• SVC syndrome results from any condition that leads to obstruction of blood flow through the SVC
with severe reduction in venous return from the head, neck, and upper extremities.
• Mechanism of Malignant SVC Obstruction:
• Direct invasion of tumor into the SVC, or
• External compression of the SVC by an adjacent pathologic process involving the right lung,
lymph nodes, and other mediastinal structures, leading to stagnation of flow and thrombosis

27. CAUSES OF SVCC
• Lung cancer, particularly of small-cell and squamous cell histology, accounts for approximately 85% of all
cases of malignant origin.
• In young adults, malignant lymphoma is a leading cause of SVCS.
• Hodgkin’s lymphoma involves the mediastinum more commonly than other lymphomas but rarely
causes SVCS.
• When SVCS is noted in a young man with a mediastinal mass, the differential diagnosis is lymphoma
• Metastatic cancers to the mediastinal lymph nodes, such as testicular and breast carcinomas, account for a
small proportion of cases.
• Other causes include benign tumors, aortic aneurysm, thyromegaly, thrombosis, and fibrosing mediastinitis
from prior irradiation, histoplasmosis, or Behcet's syndrome.

28. CLINICAL FEATURES
• The rapidity of onset of symptoms depends on the time course of SVC invasion or
compression, and the severity of luminal compromise.
• The presence and severity of S/S of SVC obstruction in turn depends on whether
recruitment of venous collaterals has compensated for the narrowing.
• Dyspnea is the most common presenting symptom.
• Facial swelling or head fullness : exacerbated by bending forward or lying down.

30. Cont..
• Swelling of the head and neck.
• Edema can narrow the lumen of larynx or pharynx  dyspnea, stridor, cough,
hoarseness, and dysphagia.
• Respiratory distress can also be related to pleural effusion or pulmonary restriction from
severe chest or breast swelling.
• Occ. c/o cerebral edema : headaches, confusion, or visual/auditory disturbances ; can
also lead to brainstem herniation, and possibly death.

31. • Increased number of collateral veins covering the anterior chest.
• The clinical picture is milder if the obstruction is located above the azygos vein.
• Seizures are more likely related to brain metastases than to cerebral edema from venous
occlusion.
• Cardiorespiratory symptoms at rest, particularly with positional changes, suggest significant
airway and vascular obstruction and limited physiologic reserve.

32. • Rarely, Esophageal varices may develop : Downhill varices  depend on level of
obstruction
• Proximal to the azygous vein : Upper 1/3rd of the esophagus.
• At or distal to the azygous vein : Entire length of the esophagus.
• Bilateral breast edema with bilateral enlarged breast. Unilateral breast dilatation
may be seen as a consequence of axillary or subclavian vein blockage.

33. GRADING OF SEVERITY

34. Cont..

35. DIAGNOSIS
• The diagnosis of SVCS is a clinical one.
• CXR :
• Widening of the superior mediastinum(>8 cm ),most commonly on the right side.
• Pleural effusion : 25% of pts, often on the right side ; exudative and occasionally chylous.
• CT provides the most reliable view of the mediastinal anatomy.
• The diagnosis of SVCS requires diminished or absent opacification of central venous
structures with prominent collateral venous circulation.

36. Cont..
• MRI has no advantages over CT.
• Invasive procedures : bronchoscopy, percutaneous needle biopsy, mediastinoscopy, and even
thoracotomy.
• Endobronchial or esophageal USG guided needle aspiration.

39. TREATMENT
• GOALS OF MANAGEMENT
 To alleviate symptoms and
 Treat the underlying disease.
 Depends on the type of cancer, extent of disease, and overall prognosis.

40. MEDICAL EMERGENCY ??
• Pts. who present with stridor due to central airway obstruction or severe laryngeal edema, or
coma from cerebral edema, represent a true medical emergency.
• These patients require immediate intervention (endovenous recanalization with SVC stent
placement, as needed) to decrease the risk of sudden respiratory failure and death.

42. • SUPPORTIVE CARE AND MEDICAL MANAGEMENT
 Thrombus present : systemic anticoagulation to limit thrombus extension
 Obstruction of the SVC resulting from intravascular thrombus associated with an indwelling
catheter : removal of the catheter in conjunction with systemic anticoagulation

43. • GLUCOCORTICOIDS
 Pts. receiving RT on an emergency basis for severe airway obstruction that is not amenable to
stenting.
 Reversing symptomatic SVC syndrome caused by steroid-responsive malignancies, such as
lymphoma or thymoma.
• DIURETICS AND HYDRATION
 Overhydration of the patient should be avoided if possible.
 Diuretics can be used, as needed, but not at the expense of intravascular volume depletion

44. ALGORITHMIC APPROACH TO MANAGEMENT

48. REFERENCE
• Harrison 19th edition
• UpToDate 2018
• Wintrobe’s clinical hematology 13th edition

49. THANK YOU